5^th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems March 16-18, 2015 Crowne Plaza, Dubai, UAE

Introduction Silymarin has a short half life (4-6 hours) and hence requires frequent administration. It also undergoes degradation in the intestinal pH. These shortcomings can be overcome by formulating the drug as a novel drug delivery system, viz. gastroretentive drug delivery system. This study aims to develop and evaluate silymarin floating microspheres prepared with polymers like hydroxypropylmethyl cellulose E50 LV and ethyl cellulose.

Since the designs of optimal formulations for resveratrol permeation via the skin are lacking, the aim of this study was to establish the profile of resveratrol permeability into and across human skin. For that, a laboratory-made chromatographic column was used (Zr-PMODS), with its performance being compared to a traditional C18 column. In vitro drug release was conducted with polysulfone membranes, and the flux (JS) was 30.49 μg cm–2 h–1), with a lag time (LT) of 0.04 h, following a pseudo-first-order kinetics. For ex vivo percutaneous absorption using excised female human skin, the kinetic profile was the same, but JS was 0.87 μg cm–2 h–1 and LT was 0.97 h. From the initials 49.30 μg applied to the skin, 9.50 μg were quantified in the receptor medium, 20.48 μg was retained at the stratum corneum (do not account as permeated) and 21.41 μg was retained at the viable epidermis + dermis (account as permeated), totalizing 30.90 μg of resveratrol permeated after 24h of application (62.6%). From these results, one can conclude that a person using the 1-g emulsion dose released by the pump containing 20 mg of resveratrol will have, theoretically, 12.53 mg of it liberated into his bloodstream, gradually and continuously for 24 h.

Ajit Chandra Divedi, a post graduate fellow, Indian Institute of Technology (Banaras Hindu University), India. His current area of research is Nano technology based drug delivery system. Before joining as postgraduate fellow, he had completed bachelor in pharmacy from department of pharmaceutics, IIT (BHU) with distinction. He had worked with Indian Drug and Pharmaceutical Limited (IDPL), India in tablet and capsule manufacturing unit as production trainee. He has qualified GPAT-2013 with All India Rank 375. He received financial assistance, from MHRD, Government of India for his post-graduation research work.

Glioblastoma multiforme (GBM), which is a highly aggressive tumor that invades early into surrounding brain tissue, making cure via surgical resection almost impossible. This study was aimed at developing mebendazole loaded solid lipid nanoparticles (Mbz-SLN) intended for improvement of treatment of GBM. Drug polymer compatibility studied by FTIR, DSC and X-RD studies reveled that drug and polymers are compatible. Modified solvent diffusion evaporation method was selected for preparation of solid lipid nanoparticle. The prepared SLN were evaluated for various characteristics like particle size, zeta potential, entrapment efficiency and drug loading. The in-vitro release study showed biphasic release pattern with initial burst effect followed by sustained release up to 49 hours. The optimized batch follows korsmeyer peppes model of drug release. With increase in lipid-drug ratio, particle size and entrapment efficiency were increased whereas the percent of drug released was decreased. The TEM images for optimized batch exhibited the spherical shape with smooth surface. The X-RD spectra confirmed that the drug inside the SLN has been changed from crystalline form to amorphous. In-vitro cytotoxicity study was performed on U373MG cell line by using sulforhodanmoine B (SRB) assay. The Mbz-SLN showed better activity as compared to pure drug (Mbz) due to enhanced permeation and retention (EPR) effect attributed to its smaller size. This study thus demonstrate that mebendazole loaded SLN are promising for the treatment of GBM.

Saniya Jawed , a post graduate fellow, Indian Institute of Technology (Banaras Hindu University) Varanasi. Her current area of research is “formulation, in vitro evaluation and study of variables on tri- layered gastro-retentive delivery system of Verapamil Hydrochloride. She had completed bachelor in pharmacy from Department Of Pharmaceutics Indian Institute of Technology (Banaras Hindu University) Varanasi India with First class. She has qualified GPAT-2013(conducted by AICTE New Delhi). She received financial assistance, from MHRD, Government of India for his post-graduation research work.

The purpose of study was to formulate mucoadhesive drug delivery system of verapamil hydrochloride to prolong the gastric residence time of dosage form and bioavailability enhancement using HPMC K 100M, carbopol 974 P and alginate as a hydrophilic matrix forming agent, gellan gum as thickening agent and MCC as filler. Drug-excipient compatibility was checked by FTIR study. The direct compression method had been employed to prepared tablets and subjected to various evaluation parameters (drug content, hardness, weight variation, friability, mucoadhesive strength and in vitro drug release study). Carbopol showed floating instead of mucoadhesion so batch made up of carbopol was discarded and study was done using HPMC and alginate alone. Correlation coefficient (r2) values is in the range of 0.96-1.00 indicating zero order release kinetic. The cumulative percentage release over 24 hrs period for marketed preparation ,drug loaded in alginate matrix and drug loaded in HPMC K100M matrix was found to be 98.5%, 86.5% and 94.5% respectively. The stability study of optimized batch indicates that the formulation is stable over the time. The mucoadhesive strength for the batch prepared with HPMC K 100 M showed better performance than the batch having alginate as polymer. The experimental finding suggest that the prepared mucoadhesive tablets of verapamil hydrochloride could overcome the problem of variable and unpredictable lag time of floating drug delivery system, demonstrate effective control over in vitro release of highly water soluble drug and could be cost effective as compared to previously reported gestroretentive formulation of verapamil hydrochloride.

Preformulation studies such as solubility and log D of atypical-antipsychotic drug, Olanzapine (OLN) have been determined in a series of buffers of varying pH, using in-house developed UV-spectrophotometric method. Solubility studies of OLN were carried out using modified-shake flask method in buffered solutions, of pH ranging from 1 to 12, for 48 hr at 37±0.5°C. Analysis was performed using in-house developed UV-spectrophotometric method [(absorbance = 0.0697 × concentration in µgml–1+ 0.008; r2= 0.9999) in 100mM hydrochloric acid]. OLN showed pH-dependent solubility of 0.076±0.012mgml-1 at neutral pH, with maximum solubility in pH 1 (16.561±0.746mgml-1) and minimum solubility in pH 12 (0.028±0.008mgml-1), owing to the fact that Olanzapine, a weak basic drug with pKa 4.6, exists more in ionized form in acidic media and unionized form in basic media. Another significant preformulation study, apparent distribution coefficient was determined using shake flask method with minor modifications. Octanol was selected as organic phase and different buffers with pH ranging from 1 to 12 were used as aqueous phase. It was found that apparent distribution coefficients of OLN also followed pH-dependency with a reverse trend (as compared to solubility studies) of higher log D in alkaline buffers (presence of more unionized species) and lower values in acidic buffers (presence of low unionized species) with a log D value of 1.8±0.12 at neutral pH. These results obtained by preformulation solubility and distribution coefficient studies of OLN in various buffers using in-house developed UV-spectrophotometric method, would help in better formulation development for OLN with maximum efficacy.

Emil Joseph is a senior research fellow in Industrial Research Lab, Department of Pharmacy, BITS Pilani, India with UGC-Government of India fellowship for pursuing doctoral research. He has qualified national level competitive exam, GATE twice and received numerous awards including prestigious Department of Science and Technology-Government of India international travel award for young scientist. He has published numerous articles in reputed journals and presented as well as reviewed posters in international conferences. He also has diverse research experience in central labs such as Central Drug Research Institute of India and Formulation & Development division of reputed pharmaceutical industries.

Prashant Raut, is a research scholar at Department of Pharmacy, BITS Pilani, India, one of the country’s most reputed technical university. He is currently a senior research fellow under the UGC-BSR scheme of Government of India. He is currently working on a research project entitled “Design and Development of Multiple Unit Drug Delivery Systems for Combination of Drugs”.

The present work aimed to design gastroretentive modified release multi-particulate system for Levodopa and Carbidopa for better therapeutic outcome and bioavailability. Multiparticulate system was designed wherein drug loaded Levodopa and Carbidopa pellets, manufactured using extrusion spheronization technique, were coated with four successive coatings: the protective layer (ethyl cellulose), two effervescent layers (tartaric acid layer and sodium bicarbonate layer) and polymeric layer (Eudragit® RL 100) for entrapping the gas evolved. The impact of composition and manufacturing parameters of pellets on their micromeritic properties, floating characteristic and in vitro dissolution properties were studied. The designed pellets showed excellent floating ability (more than 24 h) and physical characteristics. Amount of sodium bicarbonate and Eudragit® RL 100 layered onto pellets influenced floating ability and in vitro drug release rate. Pellets coated with protective layer [weight gain: 3% (w/w)], effervescent layers [weight gain of tartaric acid and sodium bicarbonate layer was 8% (w/w) and 12% (w/w) respectively] and gas-entrapped polymeric membrane [Eudragit® RL 100, weight gain: 20% (w/w)] showed sustained drug release up to 24 hrs. Both the drugs showed similar release profile which was confirmed by calculation of similarity factor. The designed pellets followed zero-order drug release kinetics. The floating characteristics and in vitro release depends on amount of sodium bicarbonate layered on pellets and coating level of ethyl cellulose and Eudragit® RL 100. Floating pellet using multilayer approach is a feasible approach for the controlled delivery of Levodopa and Carbidopa combination. These results need to be further confirmed by in vivo techniques.

Annona vepretorum Mart. (Annonaceae), popularly known as “bruteira”, has both nutritional and medicinal uses. The aim of this study was to investigate the chemical composition and antitumor potential of the leaf essential oil of A. vepretorum alone and complexed with β-cyclodextrin in a nanoencapsulation. The essential oil was obtained by hydrodistillation using a Clevenger-type apparatus and analyzed by GC–MS and GC–FID. In vitro cytotoxicity of the essential oil and some of its major constituents (spathulenol, ocimene, α-phellandrene, α-pinene and o-cymene) for tumor cell lines from different histotypes was evaluated using the alamar blue assay. Furthermore, the essential oil in vivo effectiveness was demonstrated in mice inoculated with B16-F10 mouse melanoma. The essential oil presented bicyclogermacrene, spathulenol, ocimene, α-phellandrene, α-pinene and o-cymene, as major constituents. The essential oil and spathulenol presented promising cytotoxicity. Importantly, the nanoencapsulation of the essential oil led to a higher tumor growth inhibition. In conclusion, the leaf essential oil of A. vepretorum presents bicyclogermacrene, spathulenol, ocimene, α-phellandrene, α-pinene and o-cymene, as major constituents and has both in vitro and in vivo anticancer potential, which was enhanced by nanoencapsulation.

Modern medicine combines new technologies with ancient remedies. Nanotechnology has the potential to impact almost every branch of science. Garlic and mistletoe are medicinal plants that have been known for centuries. These plants help to preserve the function of the blood circulation and so ensure the blood supply of the internal organs, tissues and the brain. In this study, polyurethane nanostructures were synthesized by interfacial polyaddition combined with a spontaneous emulsification between an organic phase (a prepolymer based on an aliphatic diisocyante) and an aqueous phase (mixture of polyethylene glycol, diols with short chains, and Tween®20). Diluted suspensions were characterized by pH, DSC, particles size and stability measurements. The synthesized nanostructures present a proper pH for pharmaceutical substances, heat resistance up to 280 oC, sizes between nano- and micro-scales, and good Zeta potential values. These results indicate that the synthesized polyurethane nanostructures may be a candidate as an enteric carrier (resistant to gastric juices) for garlic and mistletoe and can therefore only dissolve in the small intestine. This means that any annoying odour formation is largely prevented.

Cancer is a major public health problem worldwide. It is considered a major cause of death around the world. The World Health Organization estimates that 84 million people will die of cancer between 2005 and 2015, and the incidence is expected to increase continuously as the world population ages (Danhier et al., 2010). Prostate cancer pertains to the abnormal proliferation of cells of the prostate gland, resulting in the growth of the epithelial lining and eventual blockage of the urinary tract. To date, there is still no efficacious treatment for patients with advanced prostate cancer with metastases. New treatments are therefore critically needed for these patients. Gene therapy holds great promise for the intravenous treatment of prostate cancer. However, its use is currently limited by the lack of delivery systems able to selectively deliver therapeutic genes to tumours by intravenous administration. In our current study, we demonstrated that new tumour-targeted therapeutic systems recognizing receptors specifically over expressed on prostate tumours, were able to improve the in vitro therapeutic effi cacy on PC-3, DU145 and LNCaP prostate cancer cells when compared to the non-targeted delivery system, by up to 100-fold in LnCaP cells. In vivo, the intravenous administration of the tumour-targeted therapeutic system encoding Tumour Necrosis Factor (TNF) α resulted in tumour suppression for 60% of PC-3 and 50% of DU145 tumours. The dendriplex encoding TRAIL led to tumor suppression of 10% of PC-3 tumors. IL-12 mediated gene therapy resulted in tumor regression of 20% of both types of prostate tumors. By contrast, all the tumors treated with DAB-Tf, naked DNA or left untreated were progressive for both tumor types. Th e treatment was well tolerated by the animals, with no apparent signs of toxicity. These transferrin-bearing dendriplexes therefore hold great potential as a novel approach for the gene therapy of prostate cancer.

Amit Sorathiya , a post graduate fellow, Indian Institute of Technology (Banaras HindUniversity) Varanasi. His current area of research is mannosylated lipid based nanoparticulate drug delivery system. Before joining here as a postgraduate fellow, he had completed bachelor in pharmacy studies from well known university of Gujarat (M.S.University of Baroda), India with First class. He has qualified GPAT-2013(conducted by AICTE new Delhi) with All India Rank 26. He received financial assistance, from MHRD, Government of India for his post graduation research work.

The purpose of this study was to investigate the tumor targeting potential of surface tailored mannosylated solid lipid nanoparticles (SLNs) loaded with methotrexate (MTX). MTX-loaded SLNs were prepared by modified solvent injection method using Pluronic F-127 as surfactant and stearyl amine as lipid. The influence of various formulation factors (drug content, surfactant concentration, stirring speed, stirring time ) on particle size, polydispersity index, zeta potential, encapsulation efficiency, in vitro drug release were investigated to optimize formulation. Optimized system mannose-SLNs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and FT-IR . Particle size and polydispersity index of optimized formulation batch was reported as 271nm ; PDI 0.321. Zeta potential of stearyl amine SLNs were found to be +22.1mV. The in vitro studies depicted mannose-conjugated SLNs to be least hemolytic and suitable for sustained drug delivery. Dialysis bag diffusion technique was used to study the in vitro drug release and optimized batch B2 released 56.2%(±1.24%)drug in first 6 hr. and then followed with slow release of drug 87.9%(±1.37%) in remaining 18 hr which is due to slow diffusion of drug across the lipid shell. The release kinetics of optimized batch was studied by zero order,first order,higuchi and korsemeyer –peppas equation. The percentage entrapment of methotrexate in solid lipid nanoparticles were noted as 63.27%. In conclusion, the MTX loaded SLN prevent first pass metabolism,increase bioavilability,Enhanced permeability and retention effect (EPR) and can also provide the control and prolong release of drug.

Ankit Patel, a post graduate fellow, Indian Institute of Technology (Banaras Hindu University) Varanasi. His current area of research is lipid based nanoparticulate drug delivery system. Before joining as postgraduate fellow, he had completed diploma and bachelor in pharmacy studies from Gujarat, India with distinction. He had worked with Alembic Ltd., India in tablet and capsule manufacturing unit as production trainee. He has qualified GPAT-2013 with All India Rank 1. He received financial assistance, from MHRD, Government of India for his post graduation research work. He was felicitated with GPAT Topper Award (Gold Medal) by Indian Pharmacy Graduates Association and received 25,011 INR from Shree Krishna Educational Charitable Trust for his outstanding performance in GPAT-2013.

Currently mixed hyperlipidaemia is acting as a leading cause for aggregation of Coronary Heart Disease and Type 2 Diabetes mellitus and worsening the present status. Present work is introducing a new biodegradable nanoparticulate based approach with a view to improving the efficacy and safety of Atorvastatin calcium-Fenofibrate (ATC-FEN) combination with a single formulation for proper management of mixed hyperlipidaemia. Drug-polymer compatibility was checked by FTIR, DSC and X-RD studies which supported the drug polymer compatibility. Nanoprecipitation method was used for preparation of nanoparticles and the batch contained drug: polymer ratio (1:1), amount of surfactant (200 mg) and aqueous to organic phase ratio (1.5:1) as optimized batch. TEM images for optimized batch exhibited the spherical shape with smooth surface of nanoparticles.XRD results favored the fact that FEN crystallinity reduced in nanoaprticles than pure FEN. In vitro release studies showed sustained release after initial burst for both drugs (for ATC 98.99% and FEN 66.78% release in 24 hrs).Correlation coefficient (R2) values were showing first order release for both drugs while diffusional component (n) values exhibited non-fickian anomalous type and fickian type release mechanisms for ATC and FEN respectively. In vivo lipid profile studies in rats treated with optimized formulation exhibited significant change in all lipid parameters compared to high fat diet (HFD) fed rats (untreated). Histopathological evaluation of hepatic tissue revealed marked degenerative and fatty changes in HFD fed rats (untreated). Whereas rats treated with optimized batch showed positive micro vascular fatty changes in liver tissue, indicating good efficacy of the formulation. This study thus demonstrates that PLGA based nanoparticles improve therapeutic efficacy and safety of ATC-FEN combination for better management of mixed hyperlipidaemia.

Garima Balwani, is a research scholar at Department of Pharmacy, BITS Pilani, India, one of the country’s most reputed technical university. She is currently designated as a senior research fellow under the DST-INSPIRE scheme of Government of India. She is a gold medalist at postgraduate level, with highest CGPA at Department of Pharmacy, BITS Pilani. She is currently working on a research project titled “Design and Evaluation of Novel Drug Delivery Systems for Selected Antiviral Drug” involving extensive laboratory work. She also undertakes practical sessions of Pharmaceutics for both undergraduate and post-graduate students of Pharmacy programme.

Ganciclovir (GAN) is an antiviral drug effective against cytomegalovirus infections that occur frequently in immuno-compromised people. This drug presents a very important drawback of poor oral bioavailability (5-6%) leading to administration of high daily doses (3g/day). To overcome this drawback, solid lipid nanoparticles (SLNs) were developed as potential bioavailability enhancer to improve oral bioavailability of ganciclovir (GAN). The SLNs were prepared by a double emulsion-solvent evaporation method, using glyceryl monostearate as the solid lipid and Vitamin E TPGS as the stabilizer. The SLNs were characterized for shape, size, zeta potential, and percentage drug entrapment and drug release were studied. The effects of varying lipid and stabilizer concentrations on the properties of the formulations such as particle size and entrapment efficiency were investigated. Optimized SLNs had particle size of 151.95 ± 0.41 nm and encapsulation efficiency of 37.86 ± 0.72 %. Morphological analysis using scanning electron microscopy confirmed the nanometer size and suggested a spherical and smooth surface of the nanoparticles. The SLN formulations exhibited biphasic release characteristics with initial burst followed by sustained release upto 8 hours. The release pattern was best described by the Baker-Lonsdale model (R2=0.9786), which describes the release of drugs from spherical matrices by diffusion mechanism. The Fickian diffusion as the mechanism of drug release was further confirmed by fitting the data into Korsemeyer Peppas model (n = 0.323). The in vitro results make these SLNs a suitable system to be developed for the oral GAN delivery.

Emil Joseph is a senior research fellow in Industrial Research Lab, Department of Pharmacy, BITS Pilani, India with UGC-Government of India fellowship for pursuing doctoral research. He has qualified national level competitive exam, GATE twice and received numerous awards including prestigious Department of Science and Technology-Government of India international travel award for young scientist. He has published numerous articles in reputed journals and presented as well as reviewed posters in international conferences. He also has diverse research experience in central labs such as Central Drug Research Institute of India and Formulation & Development division of reputed pharmaceutical industries.

The main objective of the present study was to design and develop novel nanoparticulate delivery systems (NPDS) of widely prescribed anti-psychotic drug, Olanzapine (OLN) for controlled release and better distribution to brain. This paper presents effect of few variables on in-vitro characters of NPDS. Nanoparticulate systems have been prepared using biodegradable polymer polycaprolactone utilizing nanoprecipitation method. A QbD based design was used for formulation development, where amount of surfactant (poloxomer 188) and polymer concentration were selected as significant variables affecting the desired outputs such as particle size and encapsulation efficiency. Surface plots have been made using design expert software and it was found that both the selected variables have significant impact on both the desired outputs. The optimized formulations were further surface modified using tween 80 in order to achieve better brain targeting characteristics since this would inhibit P-glycoprotein and augment endocytosis across blood-brain-barrier. The size and zeta-potential of obtained nanoparticles were found to be <200nm and >20mV (better physical stability) respectively. Drug content and encapsulation efficiency of the optimized formulations, determined using in-house developed HPLC analytical technique were found to be 5.44±0.04%w/w and 82.64±1.41% respectively. Further, in-vitro release studies using dialysis bag technique demonstrated controlled release of OLN from these delivery systems up to 60 hr. These results would help to achieve optimum dopamine-D2 receptor occupancy (60-80%), thereby, better anti-psychotic action with least extra-pyramidal adverse effects and decreased weight gain. Designed formulations are to be further studied for pharmacokinetics and bio-distribution in suitable animal model.

The present study investigates the development and characterization of the surface functionalized pH sensitive liposomes as dry powder inhaler systems using systematic design of experiment approach (DOE) for the targeted delivery of the therapeutics to the lungs. Surface functionalized pH sensitive liposomes were prepared by thin film hydration method for the combined delivery of Isoniazid (INH) and Ciprofloxacin HCl (CIP HCl) using 4-aminophenyl-a-D-mannopyranoside (Man) as surface functionalized ligand. The developed systems were then characterized for their various physicochemical parameters such as aerodynamic diameter, morphology, drug entrapment, drug release, pH sensitivity and cell line study. It was observed that size of the ligand appended liposomes (TPSL) were slightly more than the non-ligand appended liposomes (PSL). It was found that percent drug entrapment (PDE) of TPSL was 70 ± 1.23% (INH), 67 ± 1.38 % (CIP HCl) while PDE of PSL was 66.3 ± 1.05 % (INH) and 65.0 ± 2.31 % (CIP HCl). Drug release was studied at different pH for 24 hrs it was observed that liposomes exhibited sustained release at pH 7.4 as compared to pH 5.5 and pH 5.0 where it increased dramatically due to the destabilization of pH sensitive liposome (PSL). In vitro cellular uptake study showed that much higher concentration was achieved in the alveolar macrophage using ligand appended liposomes as compared to its counterpart. Thus, it was concluded that ligand appended pH sensitive liposome is one of the promising system for the targeted therapy for pulmonary tuberculosis.

Anjala Bulathge has recently completed B.Sc. special degree in Chemistry from University of Peradeniya, Sri Lanka. Her fi nal year research project is on preparation of drug delivery system for can therapy under supervision of Prof. R.M.G. Rajapakse. (Department of chemistry, University of Peradeniya, Sri Lanka). Her current area of research is nanotechnology based drug delivery systems.

pH sensitive drug delivery systems are very important in targeted drug delivery and systemic control release. The studies in this area have been increased in recent years and more attention has been devoted on development of novel and low cost methods for the preparation of new drug delivery systems especially in cancer therapy.Among the metal based anticancer drugs, copper complexes have great potential.There fore, the aim of this study is to synthesize a pH sensitive calcium carbonate-encapsulated copper bis-(8-hydroxyquinoline) anti-cancer drug delivery system starting from naturally occurring dolomite. In this novel preparation method, first, copper bis-(8-hydroxyquinoline) is synthesized using copper(II) chloride dihydrate and 8-hydroxyquinoline as the reactants. Aqueous solutions of sodium carbonate and calcium sucrate prepared by adding calcined dolomite into sucrose are added simultaneously to a template of micelles formed by cetyltrimethyl ammonium chloride(CTAC) on copper bis-(8-hydroxyquinoline) in order to produce the drug delivery system. Th e release of drug is monitored in vitro under the pH values ranging from 2 to 8. According to results, within first four hours, the cumulative release shows 100% in pH 2 and pH4. However, no release is observed in pH 8 for 120 hours. Therefore, it is a good indication that the encapsulated drug releases at the pH trigger point.pH differences can be found at the subcellular level, late endosomes and lysosomes have much lower pH, in the range 4.5-5.5 .Due to high rate of glycolysis, tumors have exhibit pH value 5.7 while the pH value of normal tissue is 7.4. Th is pH gradient is very important in internalization of drugs. Therefore this has potential applications in effective cancer therapy.

Background: In the course of wound healing process metalloproteinases(MMPs)take part already in the infl ammatory phase throughout phagocytosis and process of killing bacteria or removing debris. MMPs participate also in the remodeling phasethereby modulating epithelialization, determining separation of keratinocytesfromthe basal membranes and,supporting the migration of keratinocytes through a network of collagen.During the next stage of remodeling process, angiogenesis,MMPs degrade the basal membranes, promote migration of the endothelial cells and release growth factors sequesteredin ECM.The crucial role of matrix metalloproteinases during wound healing phenomenon as well as the well - known sequence of MMPs changes during the diff erent phases of wound repair, allowed to apply the experimental model of cutaneous wound repair in order to evaluate the therapeutic efficacy of new natural products. Th e aim of the present study was to assess the Propol T therapeutic value in comparison with silver sulfadiazine in the treatment of minor skin burns, inflicted on white domestic pigs. Material and methods: Contact burn wounds were infl icted according to the methods of Hoekstra et al. and Brans et al. The wounds were treated with apitherapeutic agent (propolis), silver sulfadiazine (SSD), propolis vehicle and physiological salt solution,twice a day, for 21 days.Th e assessment of MMPs content in the tissue material derived from healing post-burn wounds was made by immuno enzymatic method. Results: An increased expression of MMP1 throughout ten days of experimental healing process, especially pronounced after Propol T application, was found. Mentioned changes preceded the reduction and further normalisation of MMP1 expression. Burn wounds treatment with SSD caused enhanced accumulation of MMP-1 in the matrix of thermal damage until the tenth day of the experiment, followed by the subsequent content reduction.It was also found that the accumulation of MMP3 in thermal damages increased aft er Propol T and SSD application. The most marked tissue expression of this enzyme was observed in the case of wounds managed with apitherapeutic agent. Th e fact which is of particular interest is that the content of MMP-3 was reducedin the final phase(days15, 21) of burn healing process,aft er application of both apitherapeutic agent and silver sulfadiazine, although the mentioned reduction was more intense in the case of natural product implementation.Increased dynamics of changes and markedly assigned increased content of both MMP1 and MMP-3 after Propol T applicationmay indicate the greater therapeutic efficacy of the natural agent in comparison with SSD, on the modulation of tissue MMPs’ expression. Conclusion: The presented results confirm the therapeutic efficacy of propol is which is connected with generating of favorable biochemical environment supporting healing process.

Prof. Tejal Mehta has more than 17 years of teaching and research experience. She has done her Ph.D. from Saradar Patel University. She has published more than 48 research papers in journals of national & international repute. She has also presented several papers in national & international conferences. She is an author of a chapter in multi-authored book on Novel Drug Delivery Systems. She is recipient of the Best Paper Award 2004 granted by Association of Pharmaceutical Teacher’s of India for publishing paper in Indian Journal of Pharmaceutical Education. She also received prize in the Rajnibhai V. Patel Best Thesis competition for M.Pharm programme supported by Department of Science & Technology in Guide category. She has also authored a book “Practical Manual of Pharmaceutical Engineering” and “Practical Manual of Pharmaceutical Dosage Forms”. She delivered guest lectures in various staff development programmes, symposia, workshops, conferences & seminars. She is a recognized PG and Ph.D. Guide of Nirma University. Her area of research includes formulation development of conventional and various novel drug delivery systems like osmotic, nasal, buccal, transdermal, Injectable, ophthalmics etc, dissolution improvement of APIs and formulation development of fast dissolving drug delivery systems. She is reviewer as well as editorial member of various national & international journal in her research area of interest. She is life member of APTI, IPGA, IPA, and Society of Pharmacovigilence of India.

Silver nanoparticles is one of the paramount model in the gamut of nanotechnology materials due to its insurmountable properties like antimicrobial agents, catalysts etc. which provoked intensive research interest of researchers to use it in various applications. Current research is focused to augment the wound healing and antioxidant activity of aqueous extract of Tridax procumbens in combination of broad anti-bacterial activity of silver nanoparticles. Green synthesis of silver nanoparticles has proven to be better alternate over chemical methods which render product with bio compatible attributes whilst giving a cost effective and environmental friendly process. In the present research, silver nanoparticles were prepared using aqueous extract of Tridax procumbens having polysaccharides constituents which causes stepwise reduction of silver ions to synthesize silver nanoparticles. Nanoparticles were characterized using ultra violet spectrophotometry (surface plasmon resonance) and dynamic light scattering (DLS) methods. Average nanoparticle size was found between 90-120nm and particle size distribution was found narrow. For ease in use of above mixture of nanoparticles and plant extract for wound healing activity, topical gel was prepared using carbopol as polymer. Sprague dolly rat was used as excisional wound model. Rats were divided in four groups, controlled, standard (silver sulfadiazine), plant extract and silver nanogel, having 6 rats in each group. Percentage wound contraction, epithelization time and time taken to remove scar tissue was taken as evaluation parameters and their results were statistically analyzed. It was found that rats treated with silver nanogel shown better and faster wound healing compared to other groups which proves increased wound healing property of Tridax procumbens in combination with silver nanoparticles.

Sue-Ming Chang has completed his PhD from National Taiwan University in 2013 and currently postdoctoral studies from the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Research field: medicinal chemistry; carbohydrate chemistry; natural product chemistry; chemical biology

Our previous study demonstrated that derivatives of bis(hydroxymethyl)- indolizino[6,7-b]indole, a hybrid molecule consisting β-carboline (topoisomerase inhibition moiety) and bis(hydroxymethyl)pyrrole (DNA cross-linking moiety), exhibited multiple modes of action including DNA interstrand cross-linking and inhibition of topoisomerase I and II. To continue the investigation of hybrid molecules bearing multiple modes of action, we synthesized a series of 6,11-dihydro-5H-indolizino[8,7-b]indole-1,2-diyl)dimethanol for antitumor studies. These agents were also designed as a hybrid molecules of β-carboline and bis(hydroxymethyl)pyrrole. The target compounds were synthesized starting from the reaction of tryptamine with glyoxalic acid to give the intermediate pyrido[3,4-b]indole-1-carboxylic acid, which was then converted into the desired target compounds via esterification, N-acylation by treating with various acyl chloride, condensation with DMAD in acetic anhydride to give indolizino[8,7–b]indole–1,2–dicarboxylate derivatives and reduction. The preliminary antitumor studies revealed that these new compounds exhibited significant cytotoxicity against the cell growth of a variety of human tumor cell lines in vitro. Remarkably, we found that the newly synthesized compounds also possessed multiple modes of action comprising induction of DNA interstrand cross-linking and inhibition of topoisomerase I and II. In addition, cell-cycle arrest at the G2/M phase and subG1phase and apoptosis in human lung H460 tumor cells were observed. The present studies suggest that a lead compound having potent antitumor activity and multiple modes of action may be generated for further clinical development.

DorotaWatrobska-Swietlikowska has completed his PhD at the age of 28 years from Medical University of Gdansk. She is aScientistat Department of Pharmaceutical Technology of Medical University. She has published 4 papers, two of them in reputed journals. She collaborated with hospitals to study the physical stability of parenteral admixtures with high electrolytes concentrations.

Lecithin, a mixture of phospholipids, is a commonly used emulsifier in intravenous marketed emulsions. This is due to significant biocompatibility of lecithin with human tissues since phospholipids are natural components of cell membranes.Due to the fact that lecithin is a substance of natural origin, its composition is variable. Lecithins of different origin as well as isolated or modified fractions of phospholipids are available. It is purposeful to investigate them in terms of their applications in preparationof submicron emulsions.The first part of the present work was focused on preparation of stable submicron emulsions in which egg lecithin (Lipoid E80) was replaced with soybean lecithin (Lipoid S100 and Lipoid S75) and isolated phospholipids: PC egg natural (Lipoid E PC), PC egg hydrogenated (Lipoid E PC-3), PC soybean hydrogenated (Lipoid S PC-3). Moreover, attempts have been made to replace half of the amount of lecithin with non-ionic co-surfactant (poloxamer, Cremophor EL, Solutol HS 15, polysorbate).Stable submicron emulsions stabilized with egg lecithin (Lipoid E80; 80% PC) and soybean lecithin (Lipoid S75; 71.5% PC) have been prepared. It was not possible to achieve soybean (Lipoid S100; 97.5% PC) stabilized emulsion due to phase separation during manufacturing. Emulsions stabilized with isolated phospholipids (Lipoid E PC, Lipoid E PC-3, Lipoid S PC-3) were characterized by non-submicron droplet size and emulsion with egg hydrogenated PC was unstable during 2 month storage. Combination of egg lecithin (Lipoid E80) with non-ionic co-surfactant significantly improved physical properties of the emulsions, which first of all were characterized by smaller droplet size of the oily phase in comparison with emulsions without co-surfactant.

The aim of this study was to design and develop Lipid drug conjugated (LDC) nanoparticles for the oral delivery of Pemetrexed as an anitfolate agent for cancer therapy. LDC was produced using cold homogenization technique and was further characterized by various parameters; Particle size, Zeta potential, TEM, DSC, FTIR, AFM and XRD. Moreover, efficacy of the LDC towards the cancer cells was studied by ex vivo gut permeation study, CLSM, and MTT assay. Th e particle size of the optimized LDC was found to be 121.9±0.787nm and Zeta potential of -51.6mV±1.23 indicating a stable formulation. Entrapment efficiency was found to be 81.0%±0.89. TEM images revealed spherical morphology and were in corroboration with particle size measurements. FTIR analysis of LDC proved the presence of amide bond in lipid drug conjugate powder indicating the conjugation between drug and lipid. XRD data had showed the reduced intensity of drug and lipid peaks. In vitro release kinetics indicated the sustained release behavior of the LDC with r2 value of 0.986 for first order release kinetics. Stability studies proved that the formulation was stable with shelf life of 777.134 days. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the LDC as compared to plain drug solution and were confirmed by CLSM. MTT assay conformed significant % toxicity at the end of 24 hrs and 48 hrs. Th e pharmacokinetic data revealed that the LDC (AUC 6345.67±9.47 h/mL) significant enhancement in the oral bioavailability as compared to plain drug solution (AUC 1501.02±12.67 h/mL).

Ramesh Kashi currently is a Sr. Principal Scientist in the Bioprocess Technology and Expression Group at Merck & Co. NJ, USA. He is responsible for external collaborations, scouting and evaluation of novel formulation and delivery technologies for biologics. Ramesh has 25+ years of biotech experience in early and late stages of drug product development and commercialization of biopharmaceuticals. Prior to joining Merck in 2006, he held various scientifi c and leadership positions at Agenus, Baxter Bioscience, Diagnostic Product Corp., and Biogen. Ramesh received PhD in Biochemistry from Indian Institute of Science and conducted postdoctoral studies at Harvard and Tufts Medical Schools.

The development of high concentration antibody solutions is being explored for use both in material logistics and storage as well as for clinical application. Th e design of a robust and high performing solid state formulation platform using a spray dry manufacturing process requires the optimization of spray drying attributes (i.e. nozzle selection and fl ow rates) and selection of appropriate formulation/excipient components including low molecular weight sugars, buff ers and surfactants. Spray drying know-how and an understanding of the protein’s inherent stability can streamline the optimization of these attributes. A historical review of research eff orts in this area reveals themes around process and formulation, but a well characterized platform incorporating process, formulation, and an understanding of protein chemistry is absent. We present a case study wherein we begin dissecting the variables important for the development of a spray dried antibody formulation with a focus on drying kinetics, excipients and protein stability. Th e desirable attributes of resuspended antibody solutions that we focused on in our study included a clear solution with minimal sub-visible aggregates, while maintaining antibody integrity as compared to a non-spray dried sample. Solid state as well as wet lab analytics were utilized in this study. Utilizing the information accrued in this program and other similar programs we have developed a model for platform development of a spray dried monoclonal antibody formulation.

Amani Mohammed El sisi has completed herPh.D at the age of 33 years from Beni-SuefUniversity. She is a lecturer in faculty of pharmacy Beni-Suef University, department of pharmaceutics.

Fast dissolving film is a type of oral drug delivery system, which when placed in the oral cavity it instantly wet by saliva and rapidly disintegrates and dissolveswithout chewing or intake of water. Risperidone, is an atypical antipsychotic drug which is extensively metabolized due to the hepatic metabolism. Although the formulation of Risperidone into oro-dispersible dosage form will improve the release and bioavailability, the bitter taste of the drug will be a great problem. In the current work, the aim was masking the taste by complexation technique, with a formulation into fast dissolving films. The inclusion complex of Risperidone with 2HP-β-CD (1:1 molar ratio) was prepared by solvent evaporation method. Phase solubility showed stability constant 39.13M-1. The prepared complex was evaluated for taste masking and characterized by using Infrared, differential scanning calorimetry, X-ray diffraction, scanning electron microscope and in-vitro drug release. RisperidoneFDFs were successfully prepared by solvent casting method using HPMC-E5, NaCMC and PVP K25 polymers. Propylene glycol was used as a plasticizer in 30% of polymer concentration. Aspartame 1%, menthol 1% and citric acid 1% were used as sweetening agent, flavouring agent and saliva stimulating agent; respectively. The prepared films were evaluated for appearance, thickness and weight variation, folding endurance,tensile strength, in-vitro disintegration and dissolution, pH and drug content.Formula F2 (containing 2% HPMC) showed the shortest in-vitro disintegration time and the highest dissolution rate so it was selected for further stability and bioavailability studies.

Cetirizine is an antihistamine drug used for Allergy and Urticaria. Adherence to medication has been an ongoing problem to patients especially the dysphagic and pediatric patients. The concept of Fast Dissolving Drug Delivery System emerged from the desire to provide patient with easy conventional means of taking their medication. The main objective of the current study was to mask the bitter taste of Cetirizine HCl and make a simple yet effective Fast Dissolving Tablet (FDT). Taste masking was achieved by the preparation of solid dispersions using β- Cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Solid dispersions of different molar: drug ratios were prepared by applying two techniques, the kneading method and the lyophilization method. The most optimal solid dispersion with respect to taste-masking effect was then prepared as tablets by direct compression. Sublimation technique was then applied to obtain porous FDT. Explotab and Gellan Gum were used in tablet formulations as superdisintegrants . Menthol was added in the formulations with the objective of its synergistic taste masking effect and due to its volatility as upon sublimation, it would generates porous structure that facilitate tablet disintegration. Evaluation of tablets was performed and included; weight variation, tablet thickness, friability, wetting time, water absorption ratio, disintegration time and percent drug release. All prepared tablets showed satisfactory results. However, the results slightly favored the Gellan Gum formulation over the Explotab with respect to drug release and disintegration time.

We reported the environmental benign synthesis of chalcones, 2-pyrazolines and cyclohexanones under microwave irradiation. Chalcones were obtained by the condensation of each of 2-hydroxyacetophenone derivatives with α-naphthaldehyde under microwave irradiation. The condensation reactions of each of synthesized chalcones with phenyl hydrazine under microwave irradiation in the presence of dry acetic acid as a cyclizing agent gave 2-pyrazolines. Also, the new cyclohexenone derivatives, valuable intermediates to synthesize fused heterocycles, have been prepared by the cyclocondensation of each of hydroxychalcones with ethyl acetoacetate. The structures of the synthesized compounds were elucidated by infrared(IR) spectrometry, nuclear magnetic resonance(NMR), mass spectrometry(MS) and elmental analysis. The results indicate that unlike classical heating, microwave irradiation results in higher yields with shorter and cleaner reactions. The synthesized compounds were screened for antimicrobial activity against Staphylococcus aureus, Escherichia coli, Candida Albicans and Aspergillus niger. We clarified the effects of different substituents in the tested compounds on the obtaind antibacterial activities and antifungal activities . Keywords Microwave irradiation; 2-Hydroxyacetophenone; α-Naphthaldehyde; Pyrazoline; Cyclohexenone; Antimicrobial activity.

Purpose Letrozole (LZ) is a non-steroidal aromatase inhibitor that is used inthe treatment of breast cancer. Our lab is currently conducting in vitro and in vivo studies on a newly developed dosage formof LZ, which requires the development of a highly sensitive method of analysis. The main objective of this study therefore, was to develop and validate a simple, rapid, stability and bioavailability indicating liquid chromatography–mass spectrometry (LC-MS/MS) method for the determination of LZ in biological fluids. Methods Following liquid phase extraction, the analysis was performed using Agilent 1290 rapid resolution LC-system equipped with zobrax eclipse XDB C18 column (4 µm, 4.6 × 200 mm)maintained at 30oC. The mobile phase consisted of 0.1% Acetic Acid in water as solvent A and acetonitrile solvent B (30/70) using isocratic program with flow rate 1.25 ml/min.The injection volume was 10 µL. Progesterone (PG) was used as an internal standard. All chromatograms were recorded and analyzed on Agilent Mass Hunter software. MS analysis was performed by multiple reaction monitoring (MRM) mode using 6460 triple quadrupole mass spectrometer (Agilent) equipped with a Jet stream electrospray source. The method was fully validated using international on harmonization conference (ICH) and FDA guidelines. Results The retention timeswere 0.89and 2.35 min for LZ and PG respectively. The method was specific and sensitive to LZ and was found linear over the concentration range of 25pg/ml- 200 ng/ml (R2 = 0.999). The limit of detection and the limit of quantitation were found to be 8.7 and 17.5 nM, respectively. The inter-day and intra-day precisions (% RSD) were within acceptable limits. All other validation parameters were in the acceptable range within ICH guidelines. Conclusion The proposed LC/MS/MS method is simple, rapid, accurate, and can be successfully used for the analysis of LZ in blood and urine for assessment of its bioavailability and drug monitoring.

J.M. López-Romero is professor at the University of Málaga from 2000. Postdoctoral studies were carried out at the University Pierre et Marie Curie (Dr. Max Malacria, Paris VI, France) and University of Houston (Dr. Chengzhi Cai, USA). He is founder and director of Icon Nanotech S.L., a Spanish Spin-Off company dedicated to nanotechnology and natural products. He has published more than 50 papers in reputed journals. Research interest includes synthesis of natural products and macromolecules, and their applications on nanotechnology and cosmetics.

Solubility in water and hydrophilic solvents is necessary for biological applications of active compounds. However, organic actives are commonly non-soluble in these media and need to be chemically modified or loaded into nanoparticles in order to increase their bioavailability. , Camptothecin and derivatives like irinotecan, topotecan, diflomotecan, rubitecan and grimatecan are topoisomerase inhibitors that shows very little solubility in water. Only the hydrochloride form of some of them shows an improve solubility. To maintain the maximum activity of the topoisomerase inhibitors the design of new structures is needed, but also alternative administration methods need to be evaluated. In particular, oral administration of some of the newer camptothecin analogues has also shown promising results. On the other hand, paclitaxel and taxanes are a widely used family of anticancer drug that presents very poor solubility and stability in aqueous solution. Encapsulation in cremophor or albumin particles needs to be done for the intravenous administration of the actives. Here we present our results on the preparation of silica nanoparticles of isoindolo[2,1-b]isoquinoline, as a model with similar chemical structure to that of camptothecin. This hybrid material gives very good bioavailability of the active in aqueous systems. Moreover, we present the synthesis, by sonication, of tripalmitin solid lipid nanoparticles of paclitaxel. These nanoparticles were tested against tumoral cell lines MCF-7 (mama) and A549 (lung). AFM, SEM/TEM, Raman and NMR techniques were used to elucidate the structure and composition of the particles and emulsions. Complete results will be reported in the communication.

INTRODUCTION Diclofenac sodium (DS) is a nonsteroidal anti-inflammatory agent useful in the treatment pain and swelling associated with rheumatic disorders since 1974. DS can be considered as one of the few NSAIDs of ‘first choice’ in the treatment of acute and chronic painful and inflammatory conditions (1). In this study DS buccal tablets were prepared with different kinds of polymers namely chitosan, carbopol, HPMC and formulations’ in vitro drug release results compared with in vitro and ex vivo permeation results. MATERIALS AND METHODS Materials: Diclofenac sodium (DS) was a gift from Deva Pharm. Co. (Istanbul, Turkey) and mannitol was a gift from Eczacıbaşı Baxter(Turkey). The following materials were used as received: Carbopol 941 (B.F.Goodrich Chemical Company, USA), cellulose membrane ( Travenol Lab. Inc., USA), chitosan (medium molecular weight) and HPMC (Viscosity of 4% solution 250C; 4000 cps) (Sigma-Aldirch, USA), microcrystalline cellulose 90 M (Penwest Pharm. Co.,USA), Spray Dried Lactose (FlowLac 100) (Meggle Pharma Excipients & Technology (Wasserburg, Germany), Colloidal Silicon Dioxide (Aerosil 200)(Evonik, Germany), sucrallose (Kimetsan, Turkey). Preparation of the Buccal Tablets The formulations compositions of buccal tablets were given in Table I. Each tablet contains 25 mg of DS. Before direct compression, all of the ingredients were screened through sieve and then thoroughly blended in mortar with pestle. The powder was compressed using 8.0-mm punch and dies set, on tablet compress machine (Erweka AR 400, Germany). CONCLUSION Polymer concentration affects the drug permeation from both cellulose membrane and bovine buccal mucosa by affecting the drug release (5). The best release profiles were observed in formulations used with chitosan and HPMC. Due to all of diclofenac sodium was released in 8 hours and better permeability results. D10 formulation which contains 15 % chitosan and 20% HPMC can be a suitable formulation for buccal use.

Genistein (4,5,7-trihydroxyisoflavone) is one of the most abundant isoflavone in soybeans. It is also called a phytoestrogen because structurally similar to the human hormone, 17β-estradiol. Genistein is found to be a potent tyrosine kinase inhibitor, and has been extensively used in the prevention and treatment of many diseases and disorders, including cancer, cardiovascular diseases, osteoporosis and postmenopausal symptoms. Genistein has poor water solubility which is a real problem in terms of formulation. We developed a potential dermally used lyotropic liquid crystal (LLC) with the Genistein. The aim of this work was to investigate the Genistein diffusion and permeation. These systems are usually formed from water and one or two surfactants and possibly co-surfactants and oils. LLCs are characterized by the properties of both liquids and solids. The main advantages of these formulations that show similarity with the lipid bilayer of stratum corneum, thermodynamically stable, exhibit good penetration and they may facilitate the progressive diffusion of biologically active substances into the skin. Therefore we measured the Genistein release and diffusion with a Franz diffusion cell through synthetic membrane in vitro. Furthermore we examined drug permeation with the Franz cell method using excised human epidermis and chick chorioallantoic membrane ex vivo. Chick chorioallantoic membrane model is a new and useful biological membrane model for preclinical permeability study of pharmaceutical substances. The results showed that lyotropic liquid crystal is a potential formulation for local delivery of Genistein. This work supported by Campus Hungary Fellowship.

Csilla Bartos is a PhD student at the University of Szeged, in the Department of Pharmaceutical Technology. Her research work is on the subject of wet milling using different techniques (sonication-acoustic cavitation, planetary ball milling) and development of intranasal formulations (spray, gel); modification of the physico-chemical and biopharmaceutical properties of drugs in order to increase the low bioavailability of nasal preparatoins. Her works were presented on domestic and international conferences.

Nasal administration route is a novel possibility for systemic delivery of pharmaceutical active agents. Intranasal administration offers some advantages including rapid absorption, avoidance of hepatic first-pass metabolism, painless application, avoidance of gastrointestinal side effects and sterility is not a requirement in the case of nasal formulations. In order to achieve systemic effect, the gel is the most suitable form, because applying additives, longer residence time, better mucoadhesion and increased permeability can be achieved. For nasal administration the modification of the physico-chemical and biopharmaceutical properties of drugs is important in the case of the poor soluble pharmaceuticals. Nanonization is being used to improve the delivery of compounds with poor aqueous solubility. The suspension, prepared during wet nanozation is straight usable as a pre-dipersion for further liquid or semisolid formulation development. Our aims were to prepare a pre-dispersion of nanonized meloxicam with wet milling technique for development of a nasal gel. PVA (polyvinyl alcohol) was used as an agglomeration inhibitor polymer. The effects of wet milling on the physico-chemical properties of meloxicam were studied. To prepare the nasal gel, produced directly from the pre-disprsion sodium hyaluronate was used, as a gel-forming agent. In vitro and in vivo characterization of nasal gel containing nanonized meloxicam were carried out.

Many conventional ophthalmic formulations like solution, ointment, suspension are available in market;yet ophthalmic drug delivery is most challenging and interesting to many researchers because of poor availability of the solution caused by drainage and dilution from the eye, to overcome this problem in situ gelling system has been prepared. The in situ gel forming systems that are installed as a drop into the eye undergo phase transition a sol to gel in the cul- de sac. The present study describes the formulation and evaluation of in situgel of Ofloxacin and Diclofenac, based on the concept of gelling agent. Sol to gel system were prepared by utilizing the phase transition property of sodium alginate, a novel ophthalmic gel forming mucoadhesive polymer, which gets converted into gel in the presence of divalent-cations like calcium in lachrymal fluid and HPMC E50and HPMC 4KM which acts as a copolymer and viscosity enhancer.Suitable buffering agents were used to adjust the pH 6.5. The formulations were sterilized in autoclave at 1210C for 15 min and various evaluation tests as well as stability testing of formulation were carried out to identify the ideal formulation. Further the formulation was evaluated for its anti microbial activity and tested in-vivo on rabbits.

Youmna is a senior master student at college of Pharmacy, Qatar University. She got her Bachelor degree from College of Pharmacy, Ain Shams University,Cairo, Egypt. She has presented her graduation projectwork in both international and national conferences such as: 1- American Association of Pharmaceutical Scientists in 2013 San Antonio, Texas, USA. 2- 6th International Conference on Drug Discovery & Therapy in Dubai, February 11th, 2014. 3- ARC’13 Annual Research Conference at Qatar National Convention Center in 2013. She is looking forward to graduation aiming to work and continue in the research field where she finds her passion.

Biodegradable elastomers have attracted recently much attention for their use in biomedical tissue engineering and implantable drug delivery systems. Elastomers possess many advantages over other fabricated tough polymers as their mechanical properties can be manipulated to be as soft as body tissues and withstand the mechanical challenges. To investigate the synthesis and in vitro characterization of a novel family of thermoset biodegradable poly (diol-co- tricarballylate) (PDT) elastomeric polymers for the purpose of their use in implantable drug delivery and tissue engineering applications. PDT prepolymers were synthesized via polycondensation reaction of tricarballylic acid with alkylene diols of varying chain lengths at 140oC for two hours under vacuum; then aft er purifi cation, the formed prepolymers were further crosslinked at 120oC for 18 hours. Th e prepolymers and elastomers were characterized for their structural features, thermal and mechanical properties. PDT elastomeric fi lms were subjected to cytocompatibility studies on human mesenchymal stem cells (MSCs) and Murine renal adenocarcinoma cells (RENCA). 1H-NMR and FT- IR analysis confi rmed the chemical structure and purity of the prepolymers.Th e obtained elastomers were stretchable and rubbery and swell rather than dissolve in most of organic solvents. Mechanical properties were found to be dependent on the number of methylene groups in the chain of precursor diol. Th e cytocompatability studies showed that the elastomeric fi lms supported the growth and adhesion of the cells. Biodegradable, polyester elastomeric matrices were successfully prepared and characterized. Th e family of thermally crosslinked PDT biodegradable polyesters has promising use in drug delivery and other biomedical applications including tissue engineering.

Purpose: Utilization of hydroxybutyl- -cyclodextrin (HB-β-CD) and polyvinyl pyrrolidone (PVP) in the enhancement of glimepiride (GMD) transdermal delivery. Methods: Matrix type transdermal patches containing GMD, drug coprecipitate or its inclusion complex were prepared using different gelling agents. The prepared patches were characterized, and in vitro skin permeation study for the test formulations was conducted using automated diffusion system. Prepared patches were assessed for their hypoglycemic activity and by determination of GMD plasma concentration in rats. Results: GMD- HB-β-CD binary systems (1:2 molar ratio) enhanced GMD aqueous solubility by more than 10 times. Diffusion studies showed improved release of GMD-HB-β-CD inclusion complex compared with its GMD alone. Permeability parameters of the prepared GMD patches, alone or as inclusion complex or co-precipitate through rat skin showed 26.973 and 14.28 g/cm2 as maximum cumulative amounts of GMD permeated from patches, in the form of GMD- HB-β-CD, containing chitosan and HPMC, respectively. GMD complex-chitosan films showed significant (p< 0.05) improvement in permeation data compared with GMD-HPMC data after 6 hours of permeation. Both chitosan and HPMC patches of GMD-HB-β-CD revealed substantial reductions (P< 0.05) in blood glucose levels (192.67±21.18) and (201±15.11) mg/dl from the base line value in 240 minutes, respectively. Conclusion: Application of chitosan and HPMC transdermal patches of GMD-HB-β-CD can be used as a valuable alternative to peroral GMD with improved bioavailability and patient compliance.

Maya N, a post graduate student, Indian Institute of Technology (Banaras Hindu University), India. Her current area of research is Nano technology based drug delivery systems and Semi-solid dosage forms. Before joining as postgraduate fellow, she completed Bachelor of Pharmacy from College Of Pharmaceutical Sciences, Government Medical College, Calicut. She is the winner of All India Pharmacy Quiz Competition 2011 conducted by Government Madras Medical College, Chennai. She has qualified GPAT-2013 with All India Rank 38. She is receiving financial assistance, from MHRD, Government of India for her post-graduation research work.

Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis, which most commonly affects the lungs. The current therapy utilizes higher dose of drugs that cause dose related side effects. The aim of the present study was to formulate, optimize and characterize polymeric nanoparticles of anti-tubercular drugs- rifampicin (RIF), isoniazid (INH), pyrazinamide (PYZ) and ethambutol (ETH) to deliver the anti-tubercular drugs at a sustained rate. The optimization was done using central composite factorial design. The prepared nanoparticles were characterized for physico-chemical properties such as particle size, polydispersity index (PDI) and zeta potential (ZP), % entrapment efficiency (%EE), total drug content and in vitro drug release. The optimized nanoparticles exhibited particle size of 244.1 nm, PDI of 0.299 and smooth and spherical surface morphology, with % EE of RIF, INH, PYZ and ETH 74.93 %, 68.1 %, 70.08% and 64.22 % respectively. The ZP of the optimized batch of polymeric nanoparticles was found to be – 38.42 + 1.91 mV suggesting good stability. The release of drugs from nanoparticles was extended up to 72 hours, while, free drug solutions released 97% of the drugs in less than 3 hours. No significant difference (p<0.05) with respect to size, drug entrapment, PDI and ZP was observed between the stability batch and fresh batch during accelerated stability studies. The qualitative in vivo studies in alveolar macrophages suggested endocytosis of nanoparticles without any adsorption phenomenon. However, further studies should be carried out for establishing the pharmacokinetic potential of the polymeric nanoparticles.

Hardik Solanki, a post graduate fellow, Indian Institute of Technology (Banaras Hindu University), India. His current area of research is Nano technology based drug delivery system. Before joining as postgraduate fellow, he had completed bachelor in pharmacy from Gujarat Technological University (GTU) with first class. He has qualified GPAT-2013 with All India Rank 69. He has received financial assistance, from MHRD, Government of India for his post-graduation research work.

The aim of this study was preparation, optimization and characterization of Efavirenz nanosuspension for dissolution velocity and saturation solubility enhancement to reduce dose amount for pediatric patient. Drug excipient compatibility was checked by FTIR, DSC and XRD studies which supported the drug excipient compatibility. Nano suspension was prepared by using Nano-precipitation (solvent anti solvent method) using PVPK30 (stearic stabilizer) and sodium lauryl sulphate (electrostatic stabilizer). SEM images for optimized batch exhibited smooth surface. In vitro dissolution studies showed release of 75.27%, 39.61% and 23.07% from nanosuspension, micronized powder and physical mixture (drug, PVP K-30 and SLS) respectively in 60 minutes indicating enhancement of the dissolution rate in efavirenz nanosuspension. The saturation solubility studies with lyophilized nanosuspension (LNS), micronized powder and physical mixture was found to be 256±0.5 μg/ml, 31.60±0.9 μg/ml and 17.39±0.98 μg/ml respectively in 24 hours indicating improvement in saturation solubility. The study demonstrates that efavirenz nanosuspension can help to improve the dissolution rate and saturation solubility, which can help to reduce dose of drug in pediatric patients.

Proniosomes propose a multifaceted vesicle delivery system with potential transfer of drugs via topical route. The primary objective of the current research was to develop proniosome gel containing acyclovir for skin delivery. Various formulations were prepared by coacervation techniques with various combinations of non-ionic surface active agents, phospholipids and cholesterol. A 32 factorial design was designed to investigate the effect of Spans to Tweens (X1) ratios and cholesterol to lecithin (X2) ratios on the dependent variables like vesicle size (Y1), entrapment efficiency (Y2) and drug accumulation in the stratum corneum (Y3). The optimized proniosome formulations were evaluated for entrapment efficiency, surface morphology, drug release, in vitro permeation, skin deposition, skin sensitivity and stability studies. In vitro drug release from the optimized formulation was found to be 2.89%, in vitro drug permeation on rabbit skin showed 8.72 g/cm2/hr and percentage drug accumulation in the stratum corneum was 83.43% after 24 hr. The optimized formulation was stable for three month at controlled room temperature (25C and 75% RH). In vitro permeation studies confirmed that the proniosome formulation had accumulated in upper epidermal layers more than conventional acyclovir gel. Based on the promising outcomes, the present investigation concludes that the proniosomes could be a most feasible vesicular delivery system for the effective topical transport of acyclovir.

Currently, there is an increasing attention to produce biodegradable pharmaceuticals using safe solvents during their manufacturing as well as biodegradable ingredients to minimize the amount of byproducts and wastes. Accordingly, we attempted to apply the main principles of green production/chemistry to pharmaceutical formulation in order to obtain drug loaded eco-friendly emulsions devoid of any solvents/cosolvents or synthetic surfactants. In the proposed emulsions, the synthetic emulsifiers that are frequently used to prepare pharmaceutical emulsions, were replaced by in situ inclusion complexes formed between native cyclodextrins and vegetable oil obtained from plant origin. In absence of surfactants, it is expected that the common toxicities and environmental concerns were not problematic. A complete factorial design was employed to study the effect of different formulation variables on emulsions properties that included globule size, drug solubility, zeta potential and polydispersity index. Formulations optimization was conducted using Design-Expert® software. Results revealed the possibility of obtaining stable drug loaded environmental friendly emulsions using an easily scaled up process.

Zogopoulos Panagiotis is a resident of Neurosurgery at the General Hospital of Nikaia-Piraeus “Agios Panteleimon”, Athens, Greece. His ongoing research is in the field of drugs and their interaction with human brain and cerebral vessels. Several of his papers have been published in reputed peer-review journals and he has presented various researches in international conferences.

Cannabinoids are a class of chemical compounds exerting anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types including gliomas, both in vitro and in vivo, after local or systemic administration. Δ9-Tetrahydrocannabinol (Δ9-THC), cannabidiol and cannabinol are the most prevalent natural cannabinoids. Gliomas, the most common primary brain tumors, are highly resistant to available therapeutic approaches, including radiation and chemotherapy. Despite various preparations permitting oral administration of Δ9-THC, their systemic administration has several limitations, partly due to their lipophilicity. Local administration of Δ9-THC reduced the size of tumors generated by intracranial inoculation of glioma cells in rats, without affecting healthy brain tissue. Clinical experimental therapies administered intracranially Δ9-THC via catheter in the resection cavity of glioblastomas and this led to tumor growth inhibition. High concentrations of cannabinoids can easily be delivered by stereotaxic injection (a routine approach for neurosurgeons) directly into human brain tumor masses, thus augmenting their efficacy, while keeping systemic side effects to a minimum. Cannabidiol- and Δ9-THC-loaded microparticles have been used as an alternative delivery system for long-term cannabinoid administration in a rodent model of glioma. This method of microencapsulation facilitated a sustained, prolonged release of the two cannabinoids and reduced tumour growth by enhancing apoptosis and decreasing cell proliferation and angiogenesis. In conclusion, various routes of cannabinoids administration might prove useful in the future treatment of glioma patients.

The damage of peripheral nerve injury is partially treatable. However, it is hindered by several factors. The use of nerve guide conduits showed promising results. In this project a a tubular non-woven nerve guide was prepared and modified, using biodegradable polymers developed at ITV(Institut für Textil- und Verfahrenstechnik Denkendorf), based on ε-caprolactone, trimethylene carbonate and glycolide. The solution blow technique was used for the preparation. The guides were modified to reach the smallest pore size; best results were achieved by minimizing the spraying distance. The cell viability test (MTS) showed that the cells are unable to penetrate the conduits wall, and good biocompatibility especially for thin walls. To enhance the growth of the nerve within the nerve guide conduits microcapsules were prepared. The microcapsules are usually used for drug delivery including growth factors, proteins and others. Microcapsules were prepared from the same polymer using the solvent evaporation method. These microcapsules have a good yield and encapsulation efficiency with very slow or no degradation after several months. The same solvent evaporation method but with some modifications was used to prepare microcapsules from a modified polymer containing glycolide. This polymer showed good degradation results within a shorter period of time. The microcapsules were incorporated within the nerve guide wall using different methods, the best results were achieved by microcapsules spraying during the first two layers of the nerve guide, but a problem of over spraying resulted in all cases. Promising implants for peripheral nerve regeneration could be produced after a further modification of both the polymer used and the method applied.

The aim of this study was to develop a natural cost effective method of bacterial attenuation using indigenous plants to produce a safe live attenuated Salmonella vaccine for poultry salmonellosis. Several indigenous plants were used but garlic and onion gave the expected result of Salmonella attenuation. Chicken were immunized with an attenuated Salmonella cocktail (mixture of five Salmonella strains: S. Montevideo, S. Yeerongpilly, S.Augustenborg, S. Kentucky, and S. Typhimurium). ELISA for Salmonella antibodies showed high titers suggesting that the indigenous plants did not affect the immunogenic capability of the vaccine. Garlic and onion can be considered as natural bacteriostatic agents that inhibited the growth of Salmonella in vitro contributing to a safe and effective vaccine against poultry salmonellosis. ELISA for anti-Salmonella antibodies was effective in immunodetection of specific antibodies and demonstrating that the indigenous plants did not affect the immunogenic capability of the produced live-attenuated vaccine.

Background: Inappropriate Antibiotic (ATB) prescription threatens patients with adverse drug reactions, bacterial resistance, and subsequently elevated hospital costs. Aim was to evaluate ATB prescriptions in an Emergency Department (ED) at tertiary care facility. Methods: A cross-sectional study was conducted by chart-reviewing patients with infectious complaints. Patient characteristics (age, gender, weight, allergy, infection type) and prescription characteristics (class, dose, frequency, duration) were evaluated for appropriateness based on two internationally recognized drug guidebooks. Descriptive and analytic statistics were applied. Results: Sample with equal gender distribution constituted of 5752 cases: adults (61%) & pediatrics (39%). Around (55%) complained respiratory tract infections (RTIs), (25%) urine tract infections (UTIs), and (20%) others. Broad spectrums were prescribed for (77%) of the cases. Prior prescription in pediatrics, (82%) had weight taken, while (8%) had allergy screening. Prevalence of ATB prescriptions with at least one type of error was (58%) in pediatrics and (39%) in adults. Errors were: ATB class selection (2%), Dosage (21%), Frequency (6%), and Duration (25%). Dosage & duration errors were significantly predominant among pediatrics (p=0.0001 & p<0.0001 respectively). Selection error was higher among adults (p=0.002). Age stratification and binary logistic regression were applied. Significant predictors of errors in both age groups were associated with: 1) Penicillin prescriptions: (adult: p<0.001, adj.OR=3.09), (pediatrics: p<0.001, adj.OR=4.10) compared to cephalosporin, 2) RTIs (adults: p<0.001, adj.OR=2.82), (pediatrics: p=0.039, adj.OR=1.37) compared to UTIs, 3) Obtaining weight for pediatrics prior prescription (p<0.001, adj.OR=1.83) compared to those who didn’t. Conclusions: Prevalence of ATB prescription errors in this ED was alerting. Drug guidebooks need to be more accessible. Consulting of infection experts and screening for allergies/weight prior prescriptions is highly recommended.