Sejal Amodwala1, Praveen Kumar1, Hetal P Thakkar2. 1. Shri G. H. Patel Pharmacy Building, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Fatehgunj, Vadodara 390 002, Gujarat, INDIA. 2. Shri G. H. Patel Pharmacy Building, Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Fatehgunj, Vadodara 390 002, Gujarat, INDIA.. Electronic address: hetal.thakkar-pharmacy@msubaroda.ac.in.
Abstract
INTRODUCTION: The long term administration of Meloxicam for the management of arthritis, a chronic disorder, results in gastrointestinal disturbances leading to poor patient compliance. Considering the favorable molecular weight, therapeutic dose, biological half-life and log P value of meloxicam for transdermal delivery, its fast dissolving microneedle patch, with an ability to breach the stratum corneum and efficiently deliver the cargo to deeper skin layers, were developed. METHODS: Microneedle patch of low molecular weight polyvinyl alcohol and polyvinylpyrrolidone was prepared using Polydimethylsiloxane micromolds. The ratio of polyvinyl alcohol to polyvinyl pyrrolidone and solid content of matrix solution was optimized to achieve maximum needle strength. The optimized batch was extensively evaluated for in vitro dissolution, drug release, stability, ex vivo skin permeation/deposition, histopathology and in vivo pharmacodynamic study. RESULTS: The patch containing 9:1 polyvinyl alcohol to polyvinylpyrrolidone ratio with 50% solid content had shown maximum axial needle fracture force (0.9N) suitable for penetrating the skin. The optimized batch was found to be fast dissolving and released almost 100% drug in 60min following dissolution controlled kinetics. The formulation showed a significant drug deposition within skin (63.37%) and an improved transdermal flux (1.60μg/cm2/h) with a 2.58 fold enhancement in permeation as compared to plain drug solution. The formulation showed a comparable anti-inflammatory activity in rats when compared to its existing approved marketed oral tablet. Histopathology and stability evaluations demonstrated acceptable safety and shelf-life of the developed formulation. CONCLUSION: The successful verification of safety, efficacy and stability of microneedle patch advocated the suitability of the formulation for transdermal use.
INTRODUCTION: The long term administration of Meloxicam for the management of arthritis, a chronic disorder, results in gastrointestinal disturbances leading to poor patient compliance. Considering the favorable molecular weight, therapeutic dose, biological half-life and log P value of meloxicam for transdermal delivery, its fast dissolving microneedle patch, with an ability to breach the stratum corneum and efficiently deliver the cargo to deeper skin layers, were developed. METHODS: Microneedle patch of low molecular weight polyvinyl alcohol and polyvinylpyrrolidone was prepared using Polydimethylsiloxane micromolds. The ratio of polyvinyl alcohol to polyvinyl pyrrolidone and solid content of matrix solution was optimized to achieve maximum needle strength. The optimized batch was extensively evaluated for in vitro dissolution, drug release, stability, ex vivo skin permeation/deposition, histopathology and in vivo pharmacodynamic study. RESULTS: The patch containing 9:1 polyvinyl alcohol to polyvinylpyrrolidone ratio with 50% solid content had shown maximum axial needle fracture force (0.9N) suitable for penetrating the skin. The optimized batch was found to be fast dissolving and released almost 100% drug in 60min following dissolution controlled kinetics. The formulation showed a significant drug deposition within skin (63.37%) and an improved transdermal flux (1.60μg/cm2/h) with a 2.58 fold enhancement in permeation as compared to plain drug solution. The formulation showed a comparable anti-inflammatory activity in rats when compared to its existing approved marketed oral tablet. Histopathology and stability evaluations demonstrated acceptable safety and shelf-life of the developed formulation. CONCLUSION: The successful verification of safety, efficacy and stability of microneedle patch advocated the suitability of the formulation for transdermal use.
Authors: David A Castilla-Casadiego; Katherine A Miranda-Muñoz; Jesse L Roberts; Anne D Crowell; David Gonzalez-Nino; Dipankar Choudhury; Frank O Aparicio-Solis; Shannon L Servoss; Adrianne M Rosales; Gary Prinz; Min Zou; Yuntao Zhang; Johann F Coetzee; Lauren F Greenlee; Jeremy Powell; Jorge Almodovar Journal: PLoS One Date: 2022-08-02 Impact factor: 3.752