Validation of spectrophotometric method to quantify cabotegravir in simulated vaginal fluid and porcine vaginal tissue in ex vivo permeation and retention studies from thermosensitive and mucoadhesive gels.

Cabotegravir (CAB) is an antiretroviral therapy (ARV) used for Human Immunodeficiency Virus (HIV) treatment. CAB has low solubility, which affects its bioavailability in oral therapy. Moreover, the injection form of CAB has difficulty in the administration process. Therefore, it is essential to develop a new drug delivery system for CAB. Vaginal drug delivery system offers many advantages such as a large surface area, increased drug bioavailability, and improved drug delivery. CAB was developed in thermosensitive and mucoadhesive vaginal gel preparations that provided optimal distribution in the vaginal mucosa. To support the process of formulation development, in this study, UV-visible spectrophotometry method was validated in methanol, simulated vaginal fluid (SVF) and vaginal tissue to quantify the amount of CAB in the gel preparations, in vitro, and ex vivo studies, respectively. The developed analytical method was subsequently validated according to ICH guidelines. The calibration curves in these matrices were found to be linear with correlation coefficient values (R2) ≥ 0.998. The LLOQ values in methanol, SVF and vaginal tissue were 2.15 µg/mL, 2.22 µg/mL, and 5.13 µg/mL, respectively. The developed method was found to be accurate and precise without being affected by dilution integrity. These methods were successfully applied to quantify the amount of CAB in gel preparations, in vitro, and ex vivo studies, showing uniformity of drug content and controlled release manner in the permeation profile for 24 h for both thermosensitive and mucoadhesive vaginal gels. Further analytical method is required to be developed for the quantification of CAB in in vivo studies.