Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue

Hasan Afzaal; Shahiq-Uz-Zaman; Adil Saeed; Syed Damin Abbas Hamdani; Amir Raza; Alvina Gul; Mustafeez Mujtaba Babar; Jayakumar Rajadas

doi:10.3389/fphar.2022.1017549

Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue

Front Pharmacol. 2022 Sep 29:13:1017549. doi: 10.3389/fphar.2022.1017549. eCollection 2022.

Authors

Hasan Afzaal^{1

2}, Shahiq-Uz-Zaman¹, Adil Saeed¹, Syed Damin Abbas Hamdani³, Amir Raza⁴, Alvina Gul⁵, Mustafeez Mujtaba Babar^{2

3}, Jayakumar Rajadas²

Affiliations

¹ Department of Pharmaceutics, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
² Advanced Drug Delivery and Regenerative Biomaterials, Stanford University School of Medicine, Stanford, CA, United States.
³ Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
⁴ Department of Chemistry, Gomal University, D. I. Khan, KPK, Pakistan.
⁵ Department of Plant Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.

Abstract

Purpose: Alternate formulation strategies need to be devised for improving the absorption and bioavailability of drug molecules administered through the intravaginal route. Enhancing the coating of vaginal mucosa can aid the achievement of this goal. The aim of the current study is to develop a mucoadhesive formulation having adequate adhesiveness, spreading, and viscosity profiles that can ensure good tissue absorption of adapalene upon intravaginal application. Method: A combination of mucoadhesive agents has been employed, including Carbopol-934, HPMC K-15M, and xanthan gum, in varying ratios to formulate five different gels. Furthermore, a cost-effective UV-spectroscopic analytical method was developed to quantify the amount of adapalene in tested samples, both of in vitro and in vivo origin. The analytical method was validated for different parameters, including specificity, linearity, range, accuracy, precision, and ruggedness. The modified USP-II apparatus was used for dissolution studies, while in vivo pharmacokinetic validation was performed in a murine model. Result: Of all the tested formulations, on the basis of the rheo-mechanical attributes, ACX3 performed better than the rest, including the commercially available intravaginal reference product. ACX3 had an average adhesion time of 12 min and a spread diameter of 37 mm. It showed 35 mm as average distance travelled by the diluted sample for leakage assessment. The analytical method developed for the adapalene muco-adhesive gel was within the range for all the validation parameters. For further evaluating the performance of the formulation, dissolution studies were conducted in simulated vaginal conditions which showed 94.83% of drug release within 5 minutes, while on completion of 30 min, it was measured to be 92.90%. Moreover, approximately 67% of the administered drug was recovered after 5 min of administration as evaluated through tissue recovery procedures in mice. Conclusion: The study aided in development of a formulation which can enhance the muco-adhesion of the drug molecule, resulting in an improved pharmacokinetic profile. Moreover, it established an efficient assay method which can be employed for in vitro and in vivo quantification of adapalene in simulated and physiological fluids.

Keywords: adapalene; assay development; dissolution; intravaginal drug delivery; mucoadhesion.