Hot stage extrusion of p-amino salicylic acid with EC using CO2 as a temporary plasticizer

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of the thermally labile p-aminosalicylic acid (p-ASA) and ethylcellulose 20cps (EC 20cps) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer. The thermal stability of the p-ASA was investigated using DSC, TGA and HPLC. The compound decomposes completely upon melting. Below 110 degrees C and under atmospheric conditions, the compound is thermally stabile for 10min. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. Carbon dioxide acted as plasticizer for p-ASA/EC 20cps, reducing the processing temperature during the hot stage extrusion process. HPLC showed that without carbon dioxide injection, approximately 17% of p-ASA degraded, while less than 5% degraded with CO(2) injection. The experiments clearly showed that injecting pressurized carbon dioxide broadens the application of hot stage extrusion to thermally labile compounds in a one step process.status: publishe

The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64

The aim of the current research project was to explore the possibilities of combining pressurized carbon dioxide with hot stage extrusion during manufacturing of solid dispersions of itraconazole and polyvinylpyrrolidone-co-vinyl acetate 64 (PVP-VA 64) and to evaluate the ability of the pressurized gas to act as a temporary plasticizer as well as to produce a foamed extrudate. Pressurized carbon dioxide was injected into a Leistritz Micro 18 intermeshing co-rotating twin-screw melt extruder using an ISCO 260D syringe pump. The physicochemical characteristics of the extrudates with and without injection of carbon dioxide were evaluated with reference to the morphology of the solid dispersion and dissolution behaviour and particle properties. Carbon dioxide acted as plasticizer for itraconazole/PVP-VA 64, reducing the processing temperature during the hot stage extrusion process. Amorphous dispersions were obtained and the solid dispersion was not influenced by the carbon dioxide. Release of itraconazole from the solid dispersion could be controlled as a function of processing temperature and pressure. The macroscopic morphology changed to a foam-like structure due to expansion of the carbon dioxide at the extrusion die. This resulted in increased specific surface area, porosity, hygroscopicity and improved milling efficiency.status: publishe

Self-assembly of cyclodextrins and their complexes in aqueous solutions

Cyclodextrins (CDs) are enabling pharmaceutical excipients that can be found in numerous pharmaceutical products worldwide. Because of their favorable toxicologic profiles, CDs are often used in toxicologic and phase I assessments of new drug candidates. However, at relatively high concentrations, CDs can spontaneously self-assemble to form visible microparticles in aqueous mediums and formation of such visible particles may cause product rejections. Formation of subvisible CD aggregates are also known to affect analytical results during product development. How and why these CD aggregates form is largely unknown, and factors contributing to their formation are still not elucidated. The physiochemical properties of CDs are very different from simple amphiphiles and lipophilic molecules that are known to self-assemble and form aggregates in aqueous solutions but very similar to those of linear oligosaccharides. In general, negligible amounts of aggregates are formed in pure CD solutions, but the aggregate formation is greatly enhanced on inclusion complex formation, and the extent of aggregation increases with increasing CD concentration. The diameter of the aggregates formed is frequently less than about 300 nm, but visible aggregates can also be formed under certain conditions.publisher: Elsevier articletitle: Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions journaltitle: Journal of Pharmaceutical Sciences articlelink: http://dx.doi.org/10.1016/j.xphs.2016.01.019 content_type: article copyright: © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.status: publishe