Design-dependent Drug Content and In-vitro Permeation of Naltrexone Hydrochloride from Dissolving Microneedle Patches
Ivaylo Ganchev
Department of Pharmacy and Medical Cosmetics, Burgas State University, 8000 Burgas, Bulgaria.
Teodora Popova
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
Christina Voycheva
*
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
*Author to whom correspondence should be addressed.
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.
Keywords: Naltrexone hydrochloride, dissolving microneedles, sodium carboxymethylcellulose, drug localisation, polymer molecular weight, polymer concentration, micromoulding, drug content, in vitro permeation, synthetic membrane, transdermal drug delivery