ABSTRACT
PURPOSE: To study the biorelevant drug release from novel starch-based polyvinyl alcohol capsules (S-PVA-C). The effect of the shell material is studied by considering microstructural formulation changes during hydration. METHODS: Two different self-emulsifying systems containing either fenofibrate or probucol were filled in S-PVA-C, as well as capsules of gelatin (SGC) and starch (VegaGels®). Release analysis employed a BioDis® apparatus, while disintegration was studied by texture analysis. For microstructural analysis we used small angle x-ray scattering (SAXS). RESULTS: S-PVA-C opened only partially in biorelevant media compared to completely opened SGC and VegaGels®. In case of the fenofibrate formulation, this opening mechanism caused only a short lag time, while the probucol formulation in S-PVA-C resulted in a sustained release. The latter formulation demonstrated much higher viscosity upon hydration compared to the fenofibrate system. Such a rheological effect on drug release was barely noted for SGC or VegaGels® and SAXS revealed differences in the hydrated microstructure. CONCLUSIONS: Even though S-PVA-C are highly attractive for encapsulation of rather hydrophilic formulations, some care is needed regarding an immediate release form. The type of formulation hydration must be considered for adequate selection of the capsule material.
Subject(s)
Capsules/chemistry , Chemistry, Pharmaceutical/methods , Delayed-Action Preparations/chemistry , Emulsions/chemistry , Fenofibrate/chemistry , Gelatin/chemistry , Hydrophobic and Hydrophilic Interactions , Particle Size , Polyvinyl Alcohol/chemistry , Probucol/chemistry , Scattering, Small Angle , Starch/chemistry , X-Ray Diffraction/methodsABSTRACT
For decades, gelatin has been used in the rotary die process as a shell-forming material of soft capsules because of its unique physicochemical properties. However, with respect to the encapsulation of comparatively hydrophilic lipid-based formulations, gelatin has one considerable drawback: Immediately after production, the capsule shell contains a large amount of water (up to 35%). There is the potential for water to migrate from the capsule shell into the formulation, which will lead to a decrease in drug solubility and, in turn, the potential for drug crystallization. The present study introduces a novel capsule material that was obtained from extrusion. The starch-based polyvinyl alcohol thermoplastic capsules (S-PVA-C) mainly comprised a blend of starch and PVA. Gelatin and the novel material were used to encapsulate a hydrophilic lipid-based system of fenofibrate. Considerable water migration was observed from the soft gelatin shell to the hydrophilic formulation during drying and drug crystallization resulted in soft gelatin capsules. In contrast, S-PVA-C displayed no substantial water exchange or drug crystallization upon storage. The thermoplastic capsule material further exhibited more surface roughness and higher resistance to mechanical deformation compared with gelatin. In conclusion, S-PVA-C provided a robust drug product following encapsulation of a rather hydrophilic lipid-based formulation.
