Formulation Characterization and Optimization of Transdermal Drug Delivery Systems for the Treatment of Schizophrenia

Abstract

The present investigation highlights the prospects of alternate route of drug delivery in the form of transdermal patch for the treatment of schizophrenia. The prevailing studies were carried out to formulate and optimize the transdermal drug delivery of antipsychotic drugs namely clozapine and quetiapine for improved bioavailability as compared to oral formulation. Two types of transdermal drug delivery systems namely matrix patch system and pressure sensitive adhesive patch system were prepared for both the drugs and statistically optimized by applying the experimental design to get the final product. The experimental design was utilized to explore the intermingle impact of critical attributes on tensile strength, peel strength, in vitro drug release and flux. Optimized formulations of above mentioned drugs were characterized for fourier transform infrared, differential scanning calorimetry, in-vivo pharmacokinetics and skin irritation along with stability studies. The results of the optimized formulation of clozapine matrix patch showed tensile strength (TS) of 6.84±0.64 MPa, flux of 104.80±1.39 (and#956;g/h/cm2) and % drug release after 20 h (Q20) of 82.19±1.12%. The inference of the finalized batch of quetiapine matrix patch depicted the flux of 51.81±0.32 and#956;g/h/cm2, TS of 6.46±0.56 MPa and the Q20 of 82.98±1.48%. The results of the optimized formulation of clozapine adhesive patch and quetiapine adhesive patch showed peel strength of 428 ± 3.43 cN/cm and 453 ± 4.86 cN/cm respectively and flux of 106.20±1.21 (and#956;g/h/cm2) and 53.96 ± 1.02 (and#956;g/h/cm2) respectively. All the prepared formulations were stable in the accelerated condition with no remarkable variation even after six months. The optimized transdermal formulations were found to be safe for topical use as they do not exert any symptoms of skin irritation. The bioavailability of clozapine was enhanced about 2.18 and 2.23 times for matrix patch and adhesive patch, respectively, while the same was enhanced about 4.59 and 4.37 times for quetiapine matrix