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.

Oral sustained release pellets of diltiazem HCL with Kollicoat SR30

An aqueous dispersion of polyvinyl acetate [Kollicoat SR30] was selected for the development and in vitro evaluation of diltiazem sustained release pellets. Five coating levels based on theoretical weight gains of 7, 8, 9, 10 and 11% were examined onto drug pellets using fluidized bed technique. Coated pellets were thermally treated at 37°C, 40°C, 50°C and 60°C for 24 hours. In vitro dissolution tests were performed in distilled water while selected batches were compared to the release data in test media having pH 1, 4 and 7. The release profiles of coated pellets were found to be inversely proportional to the thickness of Kollicoat SR30 coat and desirable controlled release characteristics could be achieved by manipulating the coating levels. Plasticizers [propylene glycol/triethyl citrate] and anti-adherent [magnesium stearate] in the formulation of coated pellets reduced the release rates. Thermally treated pellets also showed reduction in the release rates at 60°C compared to initial release profile at 37°C. However, the drug release rates was found to be fairly independent of dissolution media [pH 1,4 and 7]

Diltiazem release from eudragit NE40 coated pellets and effects of themal treatment

A film coat for diltiazem pellets was applied with aqueous dispersion of Eudragit NE40 using bottom spray Fluidized-bed coater. The effects of thermal treatment, dissolution media and ionic strength of media on drug release from the pellets were evaluated. Coated pellets were treated at 37°C, 40°C, 50°C and 60°C for 24 hours. Thermally treated pellets showed slight reduction in the release rates at 50°C and 60°C compared to initial release profile at 37°C. Curing or thermal treatment of the coat at an appropriate temperature and length of time was found essential to achieve complete coalescence of the polymer particles such that the rate of drug release was stable during prolonged storage. Diltiazem release was fairly independent of pH and the ionic strength of the dissolution media. However, the release rates were slightly decreased with increasing molar concentrations of sodium chloride in the buffer media

Differential scanning calorimetry and surface morphology studies on cated pellets using aqueous dispersions

The present study was conducted to examine the physicochemical changes during passage of drug through polymeric membranes and observe the surface morphology features of the coated pellets using scanning electron microscopy [SEM]. Drug solution was first sprayed around inert pellets to form drug-layered pellets that were coated with two commercial aqueous dispersions namely, Eudragit NE30 and Kollicoat SR30 using bottom-spray fluidized bed technique. Differential scanning calorimetry [DSC] confirmed that no interactions existed between drug and polymers. Small peak of drug was observed in the DSC thermograms of Eudragit NE30 coated pellets indicating that small amount of drug was still present in the polymeric membrane after dissolution. Views of SEM revealed as the coating levels of two types of aqueous dispersions were increased the surface of the pellets become more uniform and compact. Therefore, the diffusion length for dissolution medium to enter the drug layer and dissolved drug to diffuse out would be increased at higher coating levels. The polymer surface of coated pellets after 12 hours dissolution testing seemed to be shrunk and size of the pellets were also reduced indicating the depletion of reservoir layer

In vivo performance of controlled release pellets of dil tiazem HCI

The test formulation of controlled release diltiazem pellets was evaluated in vivo, in comparison with Herbesser SR. Six healthy volunteers participated in the study, conducted according to a randomized, two-way crossover study design. The preparations were compared using the pharmacokinetic parameters plasma concentration-time curve [AUC], peak plasma concentration [Cmax] and time to reach maximum plasma concentration [Tmax] were estimated from the plasma concentration-time profiles for each volunteer. The test formulation was found to be comparable with the Herbesser SR in the extent of bioavailability but differ in the rate of absorption, the test formulation being less sustained. No lag time was observed in any of the volunteers indicating that both formulations started to release their drug content immediately upon rupture of the capsule but in sustained manner. Moreover, the values of pharmacokinetic parameters obtained were comparable to those reported in the literature