Design of Metformin with Glibenclamide Controlled Release Osmotic Capsules

Abstract

Aims: This article aims to target the improvement for the treatment of people suffering from Diabetes. Rather than using multiple doses and dosage forms for effective treatment, the author provides a robust solution in the form of a combination of drugs as an osmotic capsule, which has a controlled release pattern and aims at treating the disease effectively. This article also presents, for the first time, a compatibility study using a non-destructive methodology with a Raman spectrometer, which can be considered as the article’s novelty Significance: Diabetes represents a global health challenge. In 2021, it was estimated that 536.6 million people suffered from this disease. Today, a wide range of drugs is available for the treatment of Type 2 Diabetes Mellitus. In 2022, in Mexico, the most cost-effective intervention for Type 2 Diabetes was a combined oral treatment of metformin and glibenclamide, with a total cost of USD 951.75, an effectiveness rate of 42.30%, and an effectiveness coefficient of 2.25. Osmotic systems offer clear advantages over conventional pharmaceutical forms, as they allow for the maintenance of constant plasma concentrations over long periods Study Design: A compatibility drug-excipient with Raman spectroscopy study at 50°C for four weeks. A 32 experimental design was successfully developed to obtain controlled release osmotic capsules containing metformin/Glibenclamide. Place and Duration of Study: Pharmaceutical Technology Laboratory, College of Pharmacy, Universidad Autonoma del Estado de Morelos. 2013-2015 Methodology: Compatibility study between Metformin and Glibenclamide with 15 excipients using Raman spectrofotometer during 4 weeks at 50C, then manual encapsulation of the 9 formulations and coating with cellulose acetate in acetone and finally release study in two steps 2.5 hours in gastric medium and ten hours in enteric medium for a total of 12.5 hrs of release study. Results: Capsules free of excipient incompatibilities, with a constant release rate over 12.5 hours, independent of pH and stirring speed. These controlled-release osmotic capsules were sealed and coated with a cellulose acetate membrane, with a weight gain of 3% and a release hole of 635 μm. The best formulation exhibited lag times of 2.09 hours for metformin and 0.18 hours for glibenclamide. Conclusion: For the first time presented a compatibility study was presented using a nondestructive methodology with a Raman spectrometer. The capsules presented constant release for 12.5 hours, the best lag time was 2.09 hours for metformin and 0.18 hours for Glibenclamide. the mixture 1:1 sorbitol– mannitol presented a reduction in osmotic potential. The limited release rate of glibenclamide may be attributed to its solubility constraints. The combination of a high amount of sorbitol as the osmotic agent, along with the use of non-disintegrating capsules, effectively reduced the system's lag time.