Betamethasone Dipropionate Nanocrystals: Investigation, Feasibility and In Vitro Evaluation

Abstract

Corticosteroids, such as betamethasone dipropionate (BMD), have been the mainstay in topical therapy as potent glucocorticoid receptor agonist with immune suppression, anti-proliferative, and anti-inflammatory effects. Moreover, they have poor skin penetration, which is a hurdle against its potential therapeutic benefits. In present investigation, nanocrystals as carrier for effective topical delivery of BMD were explored using wet milling as technique and polysorbate 80 as a non-ionic stabilizer. Upon optimizing different process parameters, promising results were observed at stabilizer concentration of 0.9% w/v having particle size analysis (PSA) and PDI as 284 nm and 0.299, respectively. These results were supported by the FTIR and PXRD spectra of BMD-API and BMD nanocrystals, suggesting strong crystal lattice structure of BMD being reduced due to milling. The reduction in particle morphology was evident from the FESEM images. The optimized batch of BMD nanocrystals was incorporated into Carbopol gel base, showing pH 6.2 ± 0.2 and viscosity 87.00 ± 5.2 Pa s at 25°C. A drug diffusion study using Franz diffusion cell proclaimed around ~86% BMD release from nanogel across the membrane. Also, it was observed that the BMD permeation across the skin was 2.39-fold higher with marketed formulation in contrast to BMD nanogel, suggesting prolonged drug release. The skin permeation flux with nanogel was at a much lower rate along with ~50.27% drug retention in different strata of skin, resulting in retention of drug nanocrystals. Thus, in nutshell the prolonged drug release from nanogel would fulfill the aim of once a day application and would aid in reducing the adverse events associated with repeated drug applications.