Isotretinoin and Clindamycin Phosphate Combination Gel Preparation for Acne Treatment: Formulation and Stability Evaluation

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Wijittra Malad
Detpon Preechagoon

Abstract

Introduction: Combined formulations of antibiotics and retinoic acid have demonstrated advantageous results for topical acne treatment. The objective of this research was to develop a combination gel formulation of 1% w/w clindamycin phosphate and 0.05% w/w isotretinoin for acne treatment.  Materials and methods: In the preformulation study, eighteen formulations were prepared for the selection of appropriate additives i.e. gel-ling agent, preservative, antioxidant, and chelating agent where a short-termed stability testing was performed. A long-term stability testing for the three most stable formulations was then done including physical, chemical, and biological stability, in vitro release of drug using a Franz’s diffusion cell and zone of inhibition to Propionibacterium acne compared to other marketed products. Results: In the preformulation study it was found that carbopol 940, hydroxypropyl methylcellulose and methylcellulose were the most appropriate gelling agents as a clear gel was obtained and the drug concentration remained unchanged after 1-month of accelerated testing at 45oC and hot and cold temperature cycling conditions. After a long-term stability study at 4+1oC, 45+1oC, room temperature and under light exposure for 3 months, the three developed preparations were found physically and chemically stable. Drug remaining in the developed formulations was between 98-102%. Clindamycin releases of the developed prepara-tions ranged 73-75% whereas those of isotretinoin were approximately 95% after 12 h. These release results were comparable to the commercial products (Ref I® and Ref C®). The release kinetics of the developed and commercial products ftted zero-order and Higuchi equations. The investigation of MIC of clindamycin phosphate (1% w/w) and isotetrinoin (0.05% w/w) against Propionibacterium acne (P. acne) using broth dilution technique revealed the MIC concentration of 31.25 and 625 µg/ml, respectively, and these results showed the combination drug was better than the individual drugs alone. The zone of inhibition to P. acne of the developed formulations was equal to Ref C® and better than Ref I®. Conclusion: The developed formulations demonstrated comparable results on drug release rate and stability under accelerated test condition compared to commercial products whereas inhibition activity gave better results.

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References

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