Proniosomes as a Carrier System for Transdermal Delivery of Clozapine.

The current study aimed to formulate the clozapine (CLZ) loaded proniosomal gel (PN) and evaluate it's in vitro release, ex vivo permeation and gel properties. CLZ is a BCS class II drug with low bioavailability of 27% and severe adverse drug reactions (ADRs) due to frequent dosing. Proniosomes offer a versatile pro-vesicular approach with potential in transdermal drug delivery. PN-CLZ gel was prepared by the coacervation phase separation method utilizing span-60, cholesterol and lecithin. Optimization of PN gel was done by hit & trial method and the formulations were characterized for particle size, entrapment efficiency (EE), polydispersity index (PDI) and zeta potential (ZP). The optimized formulation had the highest entrapment efficiency of 90% and the average particle size of approx. 325 nm. PDI reflected homogeneity in the formulation. ZP was -59.76 mV, high enough to indicate a stable formulation. The in vitro release studies manifested a sustained release behavior of clozapine from the proniosomal gel. The ex vivo permeation showed noteworthy permeation of the drug through stratum corneum with a steady state flux of 18.26 ug/cm2/hr. The optimized gel was analyzed for pH, spreadability, bioadhesion and rheology. The results suggested that clozapine could be effectively loaded into proniosomal gel for administration through skin.