Proniosomes as a carrier system for transdermal delivery of clozapine

Abstract

The current study aimed to formulate the clozapine (CLZ) loaded proniosomal (PN) gel and evaluate its 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 and 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 EE of 90% and the average particle size of approximately 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 CLZ from the PN gel. The ex vivo permeation showed noteworthy permeation of the drug through stratum corneum with a steady state flux of 18.26 μg/cm²/h. The optimized gel was analyzed for pH, spreadability, bioadhesion, and rheology. The results suggested that CLZ could be effectively loaded into PN gel for administration through skin.

Graphical Abstract

Keywords:

• Proniosomes
• clozapine
• bioavailability enhancement
• transdermal gel
• nanocarriers

Acknowledgements

The authors are thankful to the staff and students of Quaid-i-Azam University for their cooperation during the preparation and characterization of the samples.

Ethical approval

All applicable institutional guidelines for the care and use of animals were followed.

Disclosure statement

The authors report no conflict of interest.