Solid lipid microparticles-into-film delivering clobetasol: from buccal formulation design to pilot clinical study in patients with oral lichen planus

Oral lichen planus is a chronic inflammatory disorder of the oral cavity, for which the therapeutic gold standard consists of the topical administration of corticosteroids, such as clobetasol-17-propionate (CLB). Nowadays, there are no commercially available pharmaceuticals intended for CLB delivery within the oral cavity. Then, in clinical practice, the drug is administered via magistral galenic preparations, formulated as adhesive semisolids. As they possess numerous drawbacks (e.g., limited contact time, poor patients’ compliance, inaccurate dosing), the research is still focused on the development of suitable solid buccal drug delivery systems (BDDS). This work aims to: i) combine buccal film and lipid microsystem technologies, thus yielding an innovative composite BDDS and ii) preliminary assess its in vivo effectiveness. Solid Lipid Microparticles containing CLB were designed to possess a softening temperature close to body temperature, thereby facilitating the release of the drug in molecular form by fusion once applied. This lipid matrix, being tissue-affine, may also act as a penetration enhancer. Composite buccal films were then developed to facilitate microparticles administration, converting this powder into a solid mucoadhesive formulation. These Solid Lipid Microparticles-into-Film composites (SiF-composites) resulted homogeneous, highly mucoadhesive and capable of promoting CLB accumulation within the buccal mucosa. The best formulation was subjected to a pilot in vivo evaluation (5 patients per group receiving the SiF-composite or 0.05% CLB in Orafix) resulting in treatment adherence and a reduction in Thongprasom et al. scoring. The preliminary results obtained were extremely promising, thus suggest confirmation through a further larger, randomized double blind clinical trial.