Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics

Introduction: In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures. Method: Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C. Results: The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p < 0.01). Conclusion: The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine

Design and study of lamivudine oral controlled release tablets

The objective of this study was to design oral controlled release matrix tablets of lamivudine using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of various formulation factors such as polymer proportion, polymer viscosity, and compression force on the in vitro release of drug. In vitro release studies were performed using US Pharmacopeia type 1 apparatus (basket method) in 900 mL of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using the zero-order model equation, Higuchi’s square-root equation, and the Ritger-Peppas empirical equation. Compatibility of the drug with various excipients was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 60% HPMC 4000 cps were found to show good initial release (26% in first hour) and extended the release up to 16 hours. Matrix tablets containing 80% HPMC 4000 cps and 60% HPMC 15 000 cps showed a first-hour release of 22% but extended the release up to 20 hours. Methematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of lamivudine, with good initial release (20%–25% in first hour) and extension of release up to 16 to 20 hours, can overcome the disadvantages of conventional tablets of lamivudine