Design-dependent Drug Content and In-vitro Permeation of Naltrexone Hydrochloride from Dissolving Microneedle Patches

Abstract

Aims: To develop sodium carboxymethylcellulose (CMC)-based dissolving microneedle patches for naltrexone hydrochloride (NTX) and to evaluate the influence of polymer characteristics and drug localisation on formulation performance. Study Design: An experimental formulation study comparing two dissolving microneedle designs differing in NTX localisation and conventional matrix patches. Place and Duration of Study: Department of Technology of Drug Forms with Biopharmaceutics, Faculty of Pharmacy, Medical University – Sofia, Sofia, Bulgaria, between 06.2024 and 09.2026. Methodology: Microneedle patches were prepared using micromoulding using two CMC grades at 5% and 10%. NTX was incorporated either into the microneedle-forming layer (Design A) or into the backing layer (Design B). Conventional matrix patches (Design C) served as controls. Morphology, drug content, and 24-h in vitro permeation across a synthetic membrane were evaluated. Results: Drug localisation markedly affected formulation performance. Design A provided rapid fractional permeation but low drug content (6.66–23.83% of the theoretical value), whereas Design B achieved near-theoretical drug content (99.67–100.83%) with more gradual permeation. CMC 7MF-5/B combined 99.67% drug content with 80.32% permeation over 24 h. Conventional matrix patches showed substantially lower 24-h permeation (19.78–28.08%). Lower CMC molecular weight and concentration also provided more favourable microneedle morphology. Conclusion: Drug localisation within the microneedle patch was a key determinant of NTX content and permeation behaviour. Incorporation of NTX into the backing layer resulted in near-theoretical drug content while maintaining substantial 24-h permeation. CMC 7MF-5/B provided the most favourable overall performance among the investigated formulations.