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

Abstract

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 to 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 & 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 were changed to a foam-like structure due to expansion of the CO2 at the extrusion die. The foamy extrudates demonstrated enhanced KTP release compared to 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.

Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming

“…Up to date, promising new platforms and technologies to produce low density and sustained release formulations were developed. Hot-melt extrusion was successfully used to inflate extrudates with ethanol (9), carbonates (22,23) or pressurised carbon dioxide (24) . However, these processes were done at high temperature and the cutting or spheronisation was done after filament extrusion.…”

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

“…With CO 2 injection, the blend could be extruded at temperatures at or below 110°C, resulting in less than 5% decomposition of p-ASA. Recently, subcritical (pressurized) injection of CO 2 was investigated as a temporary plasticizer for ketoprofen and HPC dispersions (93). Plasticization by injection of CO 2 enabled a decrease of approximately 20°C in extrusion temperature.…”

Melt extrusion with poorly soluble drugs – An integrated review

“…Foam extrusion also facilitates the extrudate milling process because of its porous internal structure and low physical strength. This is especially helpful for minimizing the heat generated during milling that significantly softens the formulation and makes it particularly sticky inside the milling equipment (Ashour et al, 2016).…”