Design and Optimize a Bilayer Tablet of Antihypertensive Drugs using a 32 Factorial Design

Author: Pooja Kadu, Amar Zalte and Vishal Gulecha

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Abstract

This research aimed to develop a bilayer tablet of telmisartan and Cilnidipine using a 32 factorial design approach. Telmisartan is an angiotensin II receptor antagonist, while Cilnidipine is a calcium channel blocker. By combining these drugs in a bilayer tablet, the physicochemical differences between them could be overcome, reducing the need for frequent dosing. The compatibility of the active ingredients and excipients in each layer is critical to the success of a bilayer tablet. One of the major challenges of bilayer tablet formulation is ensuring that the two layers remain separate and do not mix during manufacturing, storage, or handling. The tablet was formulated using Croscarmellose sodium and sodium starch glycolate as super disintegrants for the telmisartan layer, and HPMC K-100M, methylcellulose, and dicalcium phosphate for the Cilnidipine layer. The optimized batch of immediate-release F7 showed 95.51% drug release, while the sustained-release F5 batch showed 96.46% drug release. Compatibility studies using FTIR and different scanning calorimetry analyses confirmed compatibility between drug and excipients. Evaluation tests, including tablet dimension, hardness, friability, weight uniformity, drug content, and in-vitro dissolution, yielded satisfactory results, indicating the potential effectiveness of the optimized bilayer tablet for treating hypertension.

Keywords

Bilayer tablet, HPMC K100m, Telmisartan, Cilnidipine, Factorial design

Conclusion

In this study, a bilayer tablet formulation of antihypertensive drugs telmisartan and cilnidipine was developed. Telmisartan was incorporated into an immediate-release layer while cilnidipine was formulated into a sustained-release layer to achieve a desired pharmacological effect. The bilayer tablet was prepared using a special technique involving wet granulation, and beta-cyclodextrin was employed to improve the solubility of telmisartan. Various super disintegrants, including sodium starch glycolate and cross-carmellose sodium, were used in different amounts to optimize the immediate-release layer. The best formulation was found to be F7, which demonstrated excellent super disintegrant effect. For the sustained-release layer, HPMC K-100 M was utilized, and it provided satisfactory sustained release up to 12 hours. A 32 factorial design was employed for formulation optimization, and drug-excipient compatibility investigation using DSC showed no interaction between the drug and excipients. FTIR analysis demonstrated the presence of peaks for the drugs. An in vitro drug release study using the USP type II apparatus showed that the telmisartan immediate release optimized batch exhibited 95.51% drug release in 15 minutes, while the cilnidipine sustain optimized release batch showed 96.46% drug release up to 12 hours. The optimized formulation stability study was show the satisfactory result. The optimized formulation maintains the physical and chemical quality. The bilayer tablet demonstrated a synergistic effect and improved patient compliance by combining the two drugs.

References

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How to cite this article

Pooja Kadu, Amar Zalte and Vishal Gulecha (2023). Design and Optimize a Bilayer Tablet of Antihypertensive Drugs using a 32 Factorial Design. Biological Forum – An International Journal, 15(2): 794-803.