Development of vitamin loaded topical liposomal formulation using factorial design approach: Drug deposition and stability

Abstract

Long-term exposure of the skin to UV light causes degenerative effects, which can be minimized by using antioxidant formulations. The major challenge in this regard is that a significant amount of antioxidant should reach at the site for effective photoprotection. However, barrier properties of the skin limit their use. In the present study, Vitamin E acetate was encapsulated into liposome for improving its topical delivery. However preparation of liposomes is very difficult due to number of formulation variables involved therein. In the present work systematic statistical study for the formulation of liposomes for topical delivery of Vitamin E using the factorial design approach was undertaken. Amount of phospholipid (PL) and cholesterol (CH) were taken at three different levels and liposomes were prepared using ethanol injection method. Liposomes were characterized for encapsulation efficiency, vesicle size, zeta potential, and drug deposition in the rat skin. Gels containing liposomal dispersion (batch with higher skin deposition of VE) were prepared in Carbopol ® 980 NF and were characterized for gel strength, viscosity and drug deposition in the rat skin. Stability of liposome dispersion and gel formulation was studied at 30 °C/65% RH for 3 months. Results of regression analysis revealed that vesicle size and drug deposition in the rat skin were dependant on the lipid concentration and lipid:drug ratio. Drug deposition in rat skin had an inverse relationship with respect to PL and CH concentration. Prepared liposomal dispersion (50 mg PL:6 mg CH) showed seven-fold increase in drug deposition compared to control (plain drug dispersion). Gel formulation demonstrated six-fold and four-fold increase in drug deposition compared to control gel and marketed cream, respectively. Liposome dispersion and gel formulation were found to be stable for 3 months. Factorial design was found to be well suited to identify the key variables affecting drug deposition. Improved drug deposition from liposomal preparations demonstrates its potential for dermal delivery.