Day 1 :
Director, Merck KGaA, Germany
Time : 12:20-13:00
Dr. Dieter Lubda is director of R&D Operations of Actives and Formulation within Merck KGaA (Germany) Life Science business unit. The Formulation R&D teams at global sites within the franchise are mainly focusing on the development and solid and liquid formulations of excipients for oral and parental administration of drugs. During his career of more than 30 years with Merck KGaA/ Germany mainly working in R&D and “Global Operations” Dr. Dieter Lubda has contributed to 77 Peer-reviewed publications and as one of the inventors to more than 50 patents filed or granted.
Dr. Dieter Lubda holds a Ph.D. degree in Chemistry from the University of Vienna, Austria and had got the degree “Diploma Engineer of Chemistry” after finalizing his thesis at the Technical University of West-Berlin, Germany
The requirements of customers with regard to convenience and range of application for oral and liquid administration of active pharmaceutical ingredients (APIs) have increased significantly in recent years. In addition, solubility and bioavailability of APIs for oral administration has become a main issue of pharmaceutical industry.
Nearly all new chemical entities (NCE’s) under development are suffering in aqueous solubility during pharmaceutical drug product development therefore showing limited oral bioavailability. At least, in the preclinical stage every 3rd drug candidate offers poor bioavailability. Different strategies to enhance the drug's bioavailability are commonly used showing beneficial effect. Therefore, technologies to address these challenges have never been more important! But although there are a number of approaches to improving solubility, bioavailability and dissolution rates, they have, for the most part, remained unchanged for decades. The use of drug carriers (such as mesoporous silica), spray drying and hot melt extrusion (HME) are all effective technologies, but as we move into a new era of pharmaceutical development, the excipients used in formulation should be as advanced as the emerging techniques being seen in other areas of the pharma industry. For example, future trends and key drivers of the industry point towards continuous manufacturing, personalized medicine, 3D printing, and increased importance on amorphous solid dispersion, with the goal of dispersing or dissolving an API in a polymeric matrix in the amorphous state. These technologies have the potential to disrupt the market as we know it.
The presentation will give an overview about trends of products and technologies used nowadays to address delivery challenges of small and biomolecules focusing on excipients and technologies for oral administration. Technologies exemplary described increasing bioavailability through enhancement of solubility or trying to address user convenience.
Senior Researcher, Kazakhstan, Almaty
Keynote: DIFFERENTIAL EFFECT OF IODINE BIOORGANIC MOLECULAR COMPLEX ON HOST DEFENSE IN BALB/c and C57BL/6 MICE
Time : 14:00-14:30
In 2004 she graduated from Kazakh National University. Al-Farabi, Faculty of Biology, Department of Human and Animal Physiology and Biophysics with a Master of Biology. The total scientific experience is more than 16 years. The main research areas are in the field of cell and molecular biology. She is an experienced specialist in conducting cultural work with tumor cell lines, hematopoietic stem cells, and the isolation and cultivation of immunocompetent cells.
Statement of the Problem: Long experience in the use of various iodine preparations has shown that while possessing pronounced antibacterial and antiviral properties, wide-spectrum antimicrobial activity, and lacking mutagenic and teratogenic effects, they are toxic when introduced to the human body, which significantly narrows the scope of their clinical application. The search for alternative ways to solve the problem of high toxicity of inorganic iodine compounds has led to the development of iodine-containing organic complexes. The manifestation of the phagocytic response is a significant indicator of the body reactivity state and level of its immune activity. The coordination compound of iodine with alpha-dextrin and polypeptides was synthesized at the Scientific Center for Anti-Infectious Drugs JSC, the effect of which on the phagocytic activity of granulocytes and monocytes in BALB/c and C57BL/6 mice was studied. Phagocytosis is considered as one of the major host defense function, which is a fundamental component of the innate immune response /1/.
Materials and methods: The animals of each line were divided into 3 groups of 10 mice, including 5 females and 5 males. Two doses of the drug were used in the study: 1/20 of maximum tolerated dose (MTD) is 125 mg/kg and 250 mg/kg (1/10 MTD) of animal weight. Blood was collected on day 14 after the administration of the drug. The analysis was performed by flow cytometry. Findings: It was shown that a new complex of iodine with bioorganic molecules upon repeated oral administration for 14 days in the examined doses did not affect the phagocytosis in BALB/c mice. The findings indicated that a new complex of iodine with bioorganic molecules at a dose of 250 mg/kg increased the phagocytic activity of both granulocytes and monocytes in C57BL/6 mice.
Conclusion & Significance: One of the explanations for the differential effect of a new complex of iodine with bioorganic molecules on different lines of mice may be based on the genetic characteristics of these animals. Macrophages of BALB/c mice are known to be of M-2 type, which inhibits inducible NO synthesis and stimulates cell division. Macrophages of C57BL/6 mice are of M-1 type, which produces NO and inhibit cell division, and increases the cytostatic or cytotoxic activity of phagocytes
/2 - 4/. We can therefore conclude that a new complex of iodine with bioorganic molecules enhances the cellular factors of the natural resistance in the prototype mouse strains Th1 (C57BL/6), but not Th2 (BALB/c). This, in turn, fits into the single mechanism of action of the studied complex, namely, the activation of phagocytic cells through the induction of IFN-γ production and the ability of the complex to switch T cells to the Th1-type response path.
Associate Professor, Dr Harisingh Gour University, India
Dr. Abhinav Mehta is currently Associate Professor at R C Patel Institute of Pharmaceutical Education and Research at Shirpur, Maharashtra, India. He has 26 publications in peer reviewed journals. He has h-index of 13 and an i10-index of 16 with more than 570 citations. He has supervised 12 M. Pharm students and co-supervised 1 PhD student. He has to his credit 1 Govt. sponsored project on Drug delivery system and Tuberculosis. He has 1 year postdoctoral experience. His current recent research interest is on the development of stimuli responsive drug delivery system
Tuberculosis (TB) caused by the bacterium Mycobacterium tuberculosis remains a major health problem worldwide. Although BCG seems to provide protection against miliary tuberculosis, its effect on pulmonary TB in adults is poor, and needs a better vaccine regimen to combat the disease. Various strategies have been postulated for the development of the tuberculosis vaccine viz. improving the current BCG vaccine, over expression of the immunodominant antigens, endosomal escape, recombinant fusion proteins and a hybrid approach which is a multiphase vaccine that can be administered regardless of the infection status of the individual and with activity both in naïve and already infected individuals.
The present investigation was aimed to develop liposome based DNA prime-protein boost vaccine regimen against pulmonary tuberculosis. The rationale behind the use of liposomes as delivery systems in intracellular infections such as mycobacteria is selective uptake by the macrophages, following systemic administration and versatility to engineer to target the specific site in the body via binding to specific receptors.
Two types of multilamellar liposomes (MLVs) were prepared, one ligand directed while the other pH sensitive cationic. Liposomes were developed using DRV (dehydration-rehydration vesicles) and film hydration technique using trehalose dibehenate (TDB) as a protein stabilizer. O-palmitoyl mannan (OPM) was used to coat the ligand directed liposomes to impart them the desired targetability for the alveolar macrophages. Plasmid DNA encoding genes for Ag85A were adsorbed on the preformed pH sensitive cationic liposomes whereas rAg85A was entrapped in the ligand directed (OPM coated) liposomes.
The optimized formulation was evaluated for various physico-chemical parameters such as vesicle size, shape, entrapment/loading efficiency of the bioactive, their structural integrity by SDS-PAGE followed by confirmation with the western blot and agarose gel electrophoresis and in vitro release. In-vivo immune responses were obtained in terms of antibody responses, isotype titers as well as cytokine profile.