Bioequivalence and pharmacokinetic comparison of two fixed dose combination of Metformin/Glibenclamide formulations in healthy subjects under fed condition

@#Aim: This study is conducted to compare the pharmacokinetic profiles of two fixed dose combination of metformin/glibenclamide tablets (500mg/5 mg per tablet). Materials and Methods: This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2- period crossover study with a washout period of 7 days. All 28 adult male subjects were required to fast for at least 10 hours prior to drug administration and they were given access to water ad libitum during this period. Thirty minutes prior to dosing, all subjects were served with a standardized high-fat and high-calorie breakfast with a total calorie of 1000 kcal which was in accordance to the EMA Guideline on the Investigation of Bioequivalence. Subsequently, subjects were administered either the test or reference preparation with 240mL of plain water in the first trial period. During the second trial period, they received the alternate preparation. Plasma levels of glibenclamide and metformin were analysed separately using two different high performance liquid chromatography methods. Results: The 90% confidence interval (CI) for the ratio of the AUC0-t, AUC0-∞, and Cmax of the test preparation over those of the reference preparation were 0.9693–1.0739, 0.9598– 1.0561 and 0.9220 – 1.0642 respectively. Throughout the study period, no serious drug reaction was observed. However, a total of 26 adverse events (AE)/side effects were reported, including 24 that were definitely related to the study drugs, namely giddiness (n=17), while diarrheoa (n=3), headache (n=2) and excessive hunger (n=2) were less commonly reported by the subjects. Conclusion: It can be concluded that the test preparation is bioequivalent to the reference preparation.

Development and evaluation of omeprazole pellets fabricated by sieving-spheronization and extrusion - spheronization process

Pelletized dosage forms can be prepared by different methods which, in general, are time consuming and labor intensive. The current study was carried out to investigate the feasibility of preparing the spherical pellets of omeprazole by sieving-spheronization. An optimized formulation was also prepared by extrusion-spheronization process to compare the physical parameters between these two methods. The omeprazole pellets were consisted of microcrystalline cellulose, polyvinylpyrrolidone K 30, sodium lauryl sulphate and polyethylene glycol 6000. The omeprazole delay release system was developed by coating the prepared pellets with aqueous dispersion of Kollicoat 30 DP. The moisture content, spheronization speed and residence time found to influence the final properties of omeprazole pellets prepared by extrusion-spheronization and sieving-spheronization. The Mann-Whitney test revealed that both methods produced closely similar characteristics of the pellets in terms of, friability [p=0.553], flowability [p=0.677], hardness [p=0.103] and density [bulk, p=0.514, tapped, p=0.149] except particle size distribution [p=0.004]. The percent drug release from the coated formulation prepared by sieving-spheronization and extrusion spheronization was observed to be 84.12 +/- 1.10% and 82.67 +/- 0.96%, respectively. Dissolution profiles of both formulations were similar as indicated by values of f1 and f2, 1.52 and 89.38, respectively. The coated formulation prepared by sieving-spheronization and commercial reference product, Zimore[registered] also showed similar dissolution profiles [f1=1.22, f2=91.52]. The pellets could be prepared using sieving-spheronization. The process is simple, easy, less time- and labor-consuming and economical as compared to extrusion-spheronization process.

BIOEQUIVALENCE STUDY OF GENERIC PENTOXIFYLLINE

The bioequivalence of two oral formulations of pentoxifylline were evaluated. The two products were administered as a single oral dose in a randomized two-way crossover design to 12 healthy Thai male volunteers. The washout period between each treatment was 1 week. After drug administration, serial blood samples were collected over a period of 30 hours. Plasma pentoxifylline concentrations were measured by HPLC with UV detection. The pharmacokinetic parameters were analyzed by non-compart-mental analysis. RESULTS: The maximum pentoxifylline concentrations (Cmax, ng/mL), median time to reach the Cmax (Tmax, hr) for the test and the reference were 225.5 (range 374.9-111.1), 1.0 (0.75-2.0) and 218.4 (390.4-133.7), 0.88 (0.5-1.5), respectively. Analysis of variance for bioequivalence was carried out using logarithmi-cally transformed AUC 0-ฅ and Cmax. The mean (90% CI) of the AUC 0-ฅ and Cmax ratios for the Test : Reference were 0.99 (0.81-1.22) and 1.02 (0.91-1.15), respectively. These values were within the bioequivalence range of 0.80-1.25, thus, our study demonstrated the bioequivalence of the test and reference. Chiang Mai Med Bull 2003;42(1):7-16.