Wednesday, 12 November 2025

Formulation and Design of Metformin and Glibenclamide in Controlled-Release Osmotic Capsules | Chapter 2 | Pharmaceutical Science: New Insights and Developments Vol. 9

 

Background: Diabetes mellitus (DM) is a disorder of carbohydrate metabolism characterised by chronic hyperglycemia, although lipid and protein metabolism are also affected. Underlying its pathophysiology is a deficit in insulin secretion or action, or there may be a simultaneous deficit in both insulin secretion and activity. 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.

Aims: This study aims to target the improvement of 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 study 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.

Methodology: A compatibility drug-excipient with Raman spectroscopy study at 50°C for four weeks was conducted. A 32 experimental design was successfully developed to obtain controlled-release osmotic capsules containing metformin/Glibenclamide. Pharmaceutical Technology Laboratory, College of Pharmacy, Universidad Autonoma del Estado de Morelos. 2013-2015. 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. The 1:1 Mannitol-Sorbitol mixture in this study showed a reduction in osmotic potential, with Mannitol exhibiting lower osmotic potential and Sorbitol providing the highest osmotic potential. The most important findings indicate that the release rate for both drugs remained linear for 12.5 hours, with the lag time being close to zero. The lag time in the systems was better when the highest level of osmotic agent (sorbitol) and the highest amount of the osmotic agent (100 mg) were present in the osmotic system.

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. The manuscript compares the pharmacological agents used by diabetes patients, and they have to take multiple doses for the efficacy of the treatment with an osmotic system, improving treatment adherence through controlled release, easier and more effective with a lower number of administrations.

 

Author(s) Details :-

Raúl Pineda-Santiago
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.

 

Luz María Melgoza-Contreras
Departamento de Ciencias Biológicas, Universidad Autónoma Metropolitana-Xochimilco, México.

 

Jessica Espinosa-Garcia
Thermo Fisher, CDMX, México.

 

Enrique Amador-Gonzalez
Facultad de Química, Universidad Nacional Autónoma de México, CDMX, México.

 

Efrén Hernandez-Baltazar
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.

 

Please see the book here :- https://doi.org/10.9734/bpi/psnid/v9/6466

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