Abdelazim Zaghloul
Kuwait University, Kuwait
Title: Preparation and in-vitro/in-vivo evaluation of metformin hydrochloride rectal dosage form
Biography
Biography: Abdelazim Zaghloul
Abstract
Metformin hydrochloride (MtHcl) is an oral antidiabetic drug and has been used successfully to treat polycystic ovary and overweight patients. However, the available commercial dosage form is the oral tablets that has poor bioavailability, narrow absorption window and extensive first pass metabolizm in the liver. The aim of this work was to formulate MtHcl as a rectal suppository dosage form to partially bypass the liver metabolism, improve the absorption and bioavailability and to be a good alternative for children and elders who cannot take the oral tablets. For this purpose , suppository fatty bases (Witepsol®, Suppocire® and Massa®; different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppositories each containing 500 mg drug by fusion method. The formulations were characterized for mechanical strength, melting time, penetration time, content uniformity, and in-vitro drug release. Based on the results, three formulations containing Witepsol H12 (F1), Suppocire AP (F2) and Massa Estranium B (F3) were chosen for bioavailability testing in human volunteers using the commercial oral tablets (500mg) as a reference (Ref). The results indicated that the preparation method applied produced suppositories with satisfactory characteristics. The fatty bases were superior compared with PEG bases. The average melting time for F1-F3 was 8 min, the drug content uniformity ranged between 95-105%, the mechanical strength ranged between 7-8kg/cm, the penetration time ranged between 6-8 min and the in-vitro drug release was more than 90% in the first hour of dissolution time. The in-vivo results were: Tmax 0.25, 0.5, 0.25, 3 hr; C max 7254.11, 8319.19, 8423.36, 1125.01 ug/ml for F1, F2, F3 and Ref, respectively The % relative bioavailability for F1, F2, F3 against the Ref. were 76.65, 100.95 and 99.01 respectively. In conclusion, the results indicated that MtHcl rectal suppositories were successfully prepared and characterized and the fatty bases showed better characteristics compared with the PEG bases. F2 and F3 showed comparable bioavailability with the commercial tablets. MtHcl formulated in fatty bases could be a potential alternative to the commercial tablets particularly for pediatric and geriatric patients.
