Human skin is the largest organ of the body and is an effective physical barrier keeping it from environmental conditions. This barrier function of the skin is based on stratum corneum, located in the uppermost skin. Stratum corneum has corneocytes surrounded by multilamellar lipid membranes which are composed of cholesterol, free fatty acids and ceramides (CERs). Alterations in ceramide content of the stratum corneum are associated with numerous skin disorders. In recent years, CERs have been incorporated into conventional and novel carrier systems with the purpose of exogenously applying CERs to help the barrier function of the skin. This review provides an overview of the structure, function and importance of CERs to restore the barrier function of the skin following their topical application.

In vitro methods for quality and equivalence assessment of semi-solid products applied to the skin have increasingly garnered attention because in vivo bioequivalence studies is high cost, complexity, and time-consuming. Regulatory authorities established draft guidelines that outline a modular framework demanding qualitative, quantitative, microstructure and product performance equivalence to support generic products. In line with these guidelines, our study aimed to evaluate the relationship between microstructure and performance attributes in both originator and generic semi-solid products applied to the skin. In this context, reference and three generics of ketoprofen gel were selected as models for semi-solid formulations. Microstructure of all products was assessed regarding pH, specific gravity, drying rate, formulation rheology and potential drug polymorphism. Additionally, performance attributes of products were evaluated using in vitro release testing and in vitro permeation testing. Polymorphism and drying rate data showed no significant difference in microstructure of ketoprofen gels. All tested products exhibited pseudo-plastic flow behavior with thixotropic characteristic. However, differences in pH, specific gravity and viscosity values at low shear stress were observed between reference product and generic products, according to EMA guidance. Although IVRT outcomes did not entirely align with Q3 attributes, IVRT results for reference product versus Generic Product-I and Generic Product-II met the acceptance limits according to FDA guidance, which differs from EMA's assessment. Furthermore, in vitro release rate results were consistent with IVPT data. Consequently, it can be concluded that microstructure of semi-solid products applied to the skin may not consistently correlate with performance attributes due to various alternations influenced by manufacturing process parameters and/or formulation components. Graphical Abstract

Background/Objectives: Cyclodextrin inclusion complexation is widely used to improve the dissolution of poorly water-soluble drugs, but its effects on the manufacturability and quality of orally disintegrating tablets (ODTs) remain insufficiently understood. This study investigated how β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes affect the powder properties, tablet quality attributes, and dissolution performance of flurbiprofen ODTs. Methods: Flurbiprofen inclusion complexes with β-CD and HP-β-CD were prepared by freeze-drying and characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). ODTs containing pure flurbiprofen, inclusion complexes, or corresponding physical mixtures were manufactured by direct compression. Powder flowability and compressibility were assessed using the Hausner ratio and Carr’s index. Tablets were evaluated for weight variation, content uniformity, hardness, friability, disintegration, and dissolution at pH 1.2, 4.5, and 6.8. Results: Physicochemical characterization studies confirmed successful inclusion complex formation. β-CD formulations exhibited poorer flowability and compressibility than HP-β-CD formulations and pure drug blends. All ODTs complied with pharmacopeial requirements for weight variation and content uniformity. Inclusion complex-based tablets showed lower hardness and higher friability, whereas physical mixture-based tablets demonstrated greater mechanical strength. HP-β-CD inclusion complexes enhanced dissolution at pH 1.2 and 4.5. At pH 6.8, all formulations released more than 95% of flurbiprofen within 30 min. Conclusions: Cyclodextrin complexation influenced both the quality attributes and dissolution performance of flurbiprofen ODTs, highlighting the importance of cyclodextrin selection during formulation development.