Formulation, Optimization, and In vivo Evaluation of Clozapine Loaded Transdermal Drug Delivery System for the Treatment of Schizophrenia

Mayur M. Patel

Abstract


Introduction: The present research work was intended to develop and optimize transdermal matrix patch of
clozapine using Box–Behnken experimental design (Box–Behnken design [BBD]) for improved bioavailability as
compared to oral formulation. The 3-factor, 3-level BBD was employed to investigate the combined influence of
formulation variables on flux, tensile strength (TS), and in vitro drug release. The generated polynomial equation
was validated and desirability function was utilized for optimization. Materials and Methods: Optimized
formulation evaluated for physicochemical characterization, Fourier transform infrared, differential scanning
calorimetry, in vitro drug release, permeability enhancement potential by ex vivo, skin irritation, and in vivo
pharmacokinetics and stability studies. Results: The results of the optimized formulation (F15) showed TS of 6.84
± 0.64 MPa, flux of 104.80 ± 1.39 (μg/h/cm2), and % drug release after 20 h (Q20) of 82.19 ± 1.12% which was
stable up to 6 months in accelerated condition. Observed and the predicted values of the responses were found
to be in good agreement. Optimized transdermal patch of clozapine found free from skin irritation as per Draize
score method. The pharmacokinetic result had shown the bioavailability of clozapine improved about 2.18-fold
after transdermal drug delivery when compared with oral marketed formulation. Discussion and Conclusion: The
results of the study revealed that the developed transdermal patch of clozapine can be a promising alternative
which provides effective management of schizophrenia in terms of improved patient compliance.


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DOI: http://dx.doi.org/10.22377/ajp.v14i4.3823

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