Emulgel for improved topical delivery of Tretinoin: Formulation design and characterization

Abstract

Objectives: The chief objective of the present research was to reduce local side effects by reducing the dose, controlling the release, and improving the stability by developing and optimizing tretinoin (TRT)-loaded topical emulgel formulation.

Methods: TRT emulgel (TE) was prepared and optimized at varying ratios of excipients and using 3² optimal response surface design (ORSD). The TRT emulgel was optimized based on TRT content and in vitro release profile of TRT from formulated emulgel batches. The optimized TRT was characterized for physical properties, pH, viscosity, spreadability, extrudability, photomicroscopy, in vitro anti-acne, in vivo skin irritation, in vivo anti-inflammatory activity, and stability study.

Results: The FTIR and DSC analysis revealed the compatibility between TRT and formulation excipients of emulgel. The batch F5 of emulgel formulation displayed maximum drug content (98.69±1.26%), and controlled TRT release (78.27±0.69%). Thus, batch F5 was selected as an optimized batch for further characterization. The photomicroscopic analysis of optimized TE exhibited the presence of spherical globules. The pH and viscosity of optimized TE were found to be 6.20±0.12 and 3240cP respectively. Besides, the optimized TE showed good spreadability and extrudability. The in vitro anti-acne activity against Propionibacterium acne (P. acne) of optimized TE (diameter of zone of inhibition 34.54±0.26mm) was found to be the comparatively same as that of marketed Sotret® gel (diameter of zone of inhibition 36.13±0.43mm). Moreover, no sign of irritation was observed in rats treated with optimized TE indicating the safety of TE. Furthermore, the optimized TE displayed significant (p<0.01) in vivo anti-inflammatory activity when compared to marketed gel. Besides, optimized TE was found to be stable when stored in cool conditions for three months.

Conclusion: Thus, the emulgel could be a promising approach for the topical delivery of TRT with improved performance and reduced side effects.

Keywords: Activité anti-acnéique in vitro; Activité anti-inflammatoire in vivo; Conception de l’expérience; Design of experiment; Emulgel; In vitro anti-acne activity; In vivo anti-inflammatory activity; Skin irritation study; Tretinoin; Trétinoïne; Émulgel; Étude d’irritation cutanée.