Incorporation of benzoyl peroxide nanocrystals into adapalene-loaded solid lipid microparticles: Part I – Nanocrystalline benzoyl peroxide

• Published in: International journal of pharmaceutics 2019-06, Vol.564, p.171-179
• Main Authors: Brammann, Christoph, Mueller-Goymann, Christel C.
• Format: Article
• Language: English
• Subjects: Benzoyl peroxide; Fully hydrated phosphatidylcholine; Nanosuspension; Wet media milling
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.04.031

[Display omitted] Hair follicles are a promising target for the administration of drugs to treat diseases associated with the pilosebaceous unit, such as acne. For solid lipid microparticle dispersions a successful and selective delivery of adapalene via targeted erosion of the particles in sebum has been shown. By embedding nanoparticulate benzoyl peroxide in lipid microparticles, the therapeutic potency of adapalene can be further increased by improving follicular deposition of benzoyl peroxide and minimizing direct contact between benzoyl peroxide and stratum corneum, which is responsible for the irritating potential of this active agent. The aim of this study was to develop a novel nanoparticulate formulation for benzoyl peroxide suitable for the incorporation in solid lipid microparticles. In this contribution, a wet grinding process using liposomal dispersions of fully hydrated phosphatidylcholine was developed, upscaled and optimized for solid content and stabilizer concentration. The resulting novel nanosuspension was characterized by particle size and morphology and examined for chemical and physical stability as well as solubility and polymorphism. During the process development a dependency between the colloidal microstructure of the stabilizer dispersion and milling efficiency was found: while physical mixtures fail to deliver nanosuspensions, liposomal dispersions succeed with the same amount of stabilizer.