Design And Evaluation Of Novel Topical, Transdermal And Microneedle Formulations

Abstract

Arunprasad Sivaraman

Design and evaluation of novel topical, transdermal and microneedle formulations

(Under the direction of AJAY K. BANGA, Ph.D)

Purpose: The broad aim of this project was to formulate passive transdermal patches, topical gel and microneedle and evaluate their physical properties and delivery efficiency via skin.

Methods: Polyvinyl alcohol polymer transdermal patch was prepared in combination with DURO-TAKTM 387-2516 acrylate adhesive using oxybutynin and characterized for coating efficiency, matrix structure, rheology, tack, shear, peel adhesion and tested for in vitro permeation using dermatomed human skin for 72 hours.

A semi-synthetic opioid transdermal patch was prepared using a formulation blend of oleic acid, BIO-PSA 7 - 4301 silicone adhesive and an amphiphilic solvent and characterized for coating efficiency, matrix structure, thickness, tack, peel adhesion and tested for in vitro permeation using dermatomed human skin for 72 hours.

In situ forming hydrogel microneedles were investigated using a non-ionic triblock thermosensitive copolymer with methotrexate. The microneedles were characterized for sol-gel transition, geometry, depth of micropores, histology, rheology, methylene blue staining and evaluated for transdermal delivery in full thickness porcine ear skin and dermatomed human skin.

A topical diclofenac gel was prepared using polyvinyl alcohol polymer and characterized for matrix arrangement, pH, adhesion, spreading efficiency, crystallization, rheology, skin irritation and evaluated for in vitro drug distribution and permeation with dermatomed human skin.

Results and Conclusions: The polyvinyl alcohol transdermal patch showed an emulsion matrix formation with an average in vitro cumulative permeation and flux of 343.80 ± 74.36 μg/cm2 and 4.79 ± 1.3 μg/cm2/h respectively with no skin irritation. The semi-synthetic opioid transdermal patch delivered an average drug cumulative permeation and flux of 25.98 ± 0.19 μg/cm2 and 0.28 ± 0.2 μg/cm2/h respectively with no drug crystallization. The in situ formed hydrogel microneedles delivered an average cumulative drug amount of 32.2 ± 15.76 μg/sq.cm and 114.54 ± 40.89 μg/sq.cm for porcine ear skin from 0.2% w/w and 0.4% w/w methotrexate formulations. The topical diclofenac gel delivered an average cumulative drug amount of 22.85 ± 9.41 μg/cm2 and distribution of 10.30 ± 9.09 μg/cm2 for 24 h with no skin irritation. In conclusion, transdermal patches, topical gel and microneedles were formulated and characterized for their physical properties and evaluated for skin delivery.