An update on formulation strategies of benzoyl peroxide in efficient acne therapy with special focus on minimizing undesired effects.

Benzoyl peroxide (BPO) in the form of over the counter monotherapeutics or prescription-only combinations is a key component of topical acne therapy, but its unfavourable side effect profile reduces the therapeutic value of this compound. Various galenic approaches have been pursued to resolve this ambivalence, but only a few have managed to enter the market. This article aims to give a comprehensive overview of the published experimental vehicle systems and to identify the fundamental rationales. With regard to the formulation, an increase in the tolerability of BPO can essentially be achieved by combining BPO with re-fattening and moisturizing substances, by incorporating it and controlling its release, as well as by targeted deposition of the active ingredient at the site of action, i.e. drug targeting. Recently, novel particulate formulations have been proposed that combine several of these design principles and are expected to bring new developments in this dynamic field of research.

Incorporation of benzoyl peroxide nanocrystals into adapalene-loaded solid lipid microparticles: Part II - Solid-in-Oil dispersion of nanoparticulate benzoyl peroxide.

Benzoyl peroxide as a monotherapeutic and in combination with adapalene is a cornerstone of current acne therapy, but its unfavourable side effect profile reduces the therapeutic value of this compound. The incorporation into an adapalene-loaded microparticulate lipid matrix, which - via the principle of targeted erosion - allows the targeted release of active substances in the hair follicles, is a promising approach to reduce side effects such as skin redness, increased scaling and allergic reactions. However, there are challenges to the production of such a vehicle which require a galenic solution. That is in particular the redispersion of nanoparticulate benzoyl peroxide in lipids while maintaining its nanodisperse character. In the present work, the lamellar liquid crystalline phase of a binary water/phospholipid system is used to stabilize a nanosuspension during freeze-drying. Both after redispersing in water and after dispersing in nonpolar fat phases, the initial size of the nanosuspension was recovered with only minor deviations. The found cryoprotective effect of purified phospholipid allows the generation of highly concentrated solid-in-oil systems both in fat phases liquid at room temperature and in lipid melts, which after solidification can serve as starting material for the preparation of lipid microparticles loaded with benzoyl peroxide nanocrystals.

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

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.