Sustained release microneedle patch for pronounced systemic delivery of doxazosin mesylate

Abstract

Introduction: Microneedle patch is one of the fascinating drug delivery approaches that offers low invasiveness and a painless physical application to enhance the delivery of micro and macro-molecules into the skin.
Methods: Variable contents of chitosan and polyvinyl alcohol were used for the development of doxazosin mesylate containing sustained release microneedle patches via solvent casting technique. The prepared patches were evaluated for microscopic evaluation, mechanical strength, drug loading (%) and Fourier transform infrared spectroscopy (FTIR) etc. The skin penetration study was performed by using pig ear skin and results were captured through confocal microscopy. Ex-vivo release study and pharmacokinetic evaluation were also performed.
Results: Sharp needle tips with a height of 600µm and a base of 200µm were confirmed through microscopic examination. Optimized formulation (SRF-6) exhibited loading of 92.11% doxazosin mesylate with appreciable strength up to 1.94N force. Ex-vivo release studies revealed 87.24% release within 48 hours. Moreover, the pharmacokinetic parameters in case of optimized patch formulation (SRF-6) were markedly improved i.e. MRT (19.46 h), AUC (57.12 μg.h /mL), C_max (2.16 µg /mL), t_max (10.10 h) and t_1/2 (6.32 h) as compared to commercially available tablet. Biocompatibility of the developed patches was validated from skin irritation studies.
Conclusion: Results confirmed the successful fabrication of microneedle patch having sufficient strength and effective penetration ability into the skin to ensure controlled release of incorporated drug for the intended duration. It can be employed as an efficient carrier system for other therapeutics those are prone to bioavailability issues due to first pass effect after their oral administration.

Keywords: Microneedle Patches, Transdermal delivery, Polyvinyl alcohol, Chitosan, Doxazosin mesylate