Influence of pressurized carbon dioxide on ketoprofen-incorporated hot-melt extruded low molecular weight hydroxypropylcellulose.

OBJECTIVES: The aim of the current research project was to investigate the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of ketoprofen (KTP)-incorporated hydroxypropylcellulose (HPC) (Klucel™ ELF, EF, and LF) produced using hot-melt extrusion (HME) techniques and to assess the plasticization effect of P-CO2 on the various polymers tested. METHODS: The physico-mechanical properties of extrudates with and without injection of P-CO2 were examined and compared with extrudates with the addition of 5% liquid plasticizer of propylene glycol (PG). The extrudates were milled and compressed into tablets. Tablet characteristics of the extrudates with and without injection of P-CO2 were evaluated. RESULTS AND CONCLUSION: P-CO2 acted as a plasticizer for tested polymers, which allowed for the reduction in extrusion processing temperature. The microscopic morphology of the extrudates was changed to a foam-like structure due to the expansion of the CO2 at the extrusion die. The foamy extrudates demonstrated enhanced KTP release compared with the extrudates processed without P-CO2 due to the increase of porosity and surface area of those extrudates. Furthermore, the hardness of the tablets prepared by foamy extrudates was increased and the percent friability was decreased. Thus, the good binding properties and compressibility of the extrudates were positively influenced by utilizing P-CO2 processing.

Hot-Melt extrusion coupled with pressurized carbon dioxide for enhanced processability of pharmaceutical polymers and drug delivery applications - An integrated review.

Hot-melt extrusion (HME) technology is one of the primary approaches that has been implemented in recent years to overcome poor drug solubility/dissolution issues through the development of solid dispersion systems. Carbon dioxide (CO2) either in supercritical (SupC) or subcritical (SubC) forms has been introduced to HME as a temporary plasticizer, reducing the operating temperature and eventually processing heat-sensitive molecules more efficiently. In this paper, a comprehensive review of CO2-HME processes focused on pharmaceutical polymers and applications is presented. The steps and requirements for the setup of experimental devices are demonstrated, with a detailed influence of CO2 characteristics on HME processes. The most relevant physical and chemical properties of pharmaceutical grade polymers subjected to the CO2- HME process are described. The basic knowledge and main mechanisms of HME process parameters in conjunction with CO2 concentration with regard to process feasibility and final product formation are discussed. HME coupled with CO2 is extensively reviewed to provide a complete understanding of how to optimize the process parameters and conditions to reach optimized characteristics of final outcomes, as well as the sequential relationship between those outcomes (foaming → porosity → milling → tableting). Pharmaceutical applications of CO2-based HME are presented in detailed case studies, including extrusion feasibility, solubility, dissolution rate enhancement, and gastroretentive or floating drug delivery. Finally, the current status of general CO2-based techniques, as well as future perspectives and opportunities for promising applications through the integration of CO2 with HME is presented.