Pravin D Chaudhari

Gastroretention is advisable for metformin hydrochloride due to its site specific absorption and low bioavailability (60%). Therefore, the attempts have been carried out in present study to formulate bioadhesive microspheres of metformin hydrochloride. Microspheres provide precise control on drug release and bioadhesion is useful to obtain gastroretention for improvement in bioavailability. Drug loaded microspheres of bioadhesive polymers were prepared by ionic gelation method. Hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC) and methyl cellulose (MC) were used as bioadhesive polymers. Microspheres were prepared by using various ratios of sodium alginate to respective polymer(s). One gram of drug was added in 50ml solution of polymers separately. Microspheres were collected in 10% w/v calcium chloride solution with constant stirring. Formulation MS2 (sodium alginate: HPC; 1:1) was found to be the best among all. For MS2, percent yield (65.5%), drug entrapment efficiency (72±0.56%), particle size (851 µm), in vitro wash off test (63.9 %), in vitro drug release (80.77 %) etc. Some process parameters viz orifice diameter of needle used to pass polymer solution, dropping height and stirring speed were studied. It was observed that as the orifice diameter of needle decreased from needle no. 18 to 23, the microspheres were more spherical with retention in their shape and needle no. 20 was found to be optimum. More spherical microspheres were observed with decrease in dropping height and optimum was found to be 6 cm. With increase in stirring speed from 250 to 750 RPM, drug entrapment efficiency decreased. 

The present study was aimed to study the requirements of bioequivalence for registration of pharmaceutical products in various countries. It is essential for pharmaceutical industry to study the guidelines of bioequivalence for respective country where industry would like to apply for ANDA and thus want to enter into generic market. This study gives insight about requirements of bioequivalence with study parameters such as study design, fasting or fed state studies, volunteers recruitment, study dose, sampling points, analytical method validation parameters, moieties to be measured in plasma, pharmacokinetic parameters, criteria for bioequivalence, GCP requirements etc. which are needed for pharmaceutical industry to carry out bioequivalence studies and to file ANDA. Test products for these bioequivalence studies are usually manufactured by a sponsor or manufacturer while reference is provided by the government laboratories of respective countries. Sampling points also varies with respect to the regulatory guidelines of these countries. India follows Indian GCP guidelines, South-Africa MCC GCP guidelines and Australia follows ICH GCP guidelines. Criteria of bioequivalence, for India and South-Africa is 90% CI 80-125% for Cmax, AUCt, AUCo-inf. for Australia 90% CI 80-125% for Cmax, hAUCt, AUCo-inf.