Formulation development, optimization, and in vitro assessment of thermoresponsive ophthalmic pluronic F127-chitosan in situ tacrolimus gel

Abstract

To overcome problems associated with topical delivery of tacrolimus (TCS), a thermoresponsive in situ gel system containing pluronic F127 (PL), and chitosan (CS) was developed, to enhance the precorneal retention, and to sustain the release of the drug. The PL-CS in situ gel was optimized using a 2-factor-3-level central composite experimental design by selecting the concentration of PL and CS as independent variables while gelation time, gelation temperature, and spreadability as dependent variables. The optimized formulation was developed using 22.5 g PL and 0.3 g CS, gels at 33.6 °C, in 22.93 s, and showed the spreadability of 6.2 cm. In vitro studies conducted for the optimized gel revealed the sustained release of TCS (81.73% in 4 h) and improved corneal permeation (74.13% in 4 h), compared with TCS solution. The mechanism of release of TCS followed the Higuchi model with Fickian diffusion transport. Further, histopathology and HET-CAM studies revealed that the developed gel was non-irritating and safe for ocular administration.

Keywords:

• Tacrolimus
• pluronic F127
• chitosan
• thermoresponsive in situ gel
• ocular drug delivery system

Acknowledgments

The authors are thankful to DST for granting KIRAN WOS-A fellowship [SR/WOS-A/LS-414-2018], also to CRF, SPER, Jamia Hamdard, New Delhi, and CIL, Guru Jambheshwar University of Science and Technology, Hisar for the infrastructural and equipment facilities.

Disclosure statement

The authors declare no conflict of interests.