Hot melt extrusion (HME) was evaluated as a continuous processing technology for the manufacture of solid dispersions. The aim of the current research project was to study the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of three different grades of cellulose polymers, Klucel™ ELF, EF and LF hydroxypropylcellulose (HPC) resulting from hot melt extrusion techniques, and to assess the plasticization effect of P-CO2 on the tested polymers. The physico-mechanical properties as well as the tablet characteristics of the extrudates with and without injection of P-CO2 and with non-extruded polymers were examined. P-CO2 acted as plasticizer for Klucel™ LF, EF and ELF and allofor a reduction in processing temperature during the extrusion process by 20°C as compared to the processing temperature without injecting P-CO2. Furthermore, the CO2 served as a pore former and produced foam-like structure extrudates. This morphological change resulted in an increase in bulk and tap density as well as surface area and porosity. Additionally, the hardness of the tablets of the polymers with P-CO2 was increased compared to polymer processed without P-CO2 and the non-extruded polymer. Moreover, the % friability of the tablets improved using P-CO2 processed polymer. Thus good binding properties and compressibility of the extrudates were positively influenced utilizing P-CO2 processing. The interest to incorporate a model was increased to investigate the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties as well as the drug release behavior. Ketoprofen (KTP), used as a model drug, was incorporated with hydroxypropylcellulose (HPC) (Klucel™ ELF, EF and LF) as a polymeric carrier to produce KTP amorphous solid dispersion using HME technique. Thermal gravimetric analysis (TGA) was used to evaluate and confirm the formulations thermal stability. Differential Scanning Calorimetery (DSC) was performed to evaluate the physical state of KTP in the extrudates. The microscopic morphology of the extrudates was 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 in porosity and surface area of those extrudates. The moisture content of the extrudates processed with P-CO2 was slightly increased and this played a significant role in increasing KTP tablet hardness and decreasing percent friability. A concern with HME is the limitation of the drug loading due to drug-polymer miscibility. In order to solve this issue, we investigated the effect of foam like structure produced by pre P-CO2 on the drug loading and the dissolution profile of carbamazepine (CBZ) and low molecular weight hydroxypropylcellulose (HPC) matrices using HME technique. The resulted extrudates with P-CO2 injection exhibited higher surface area and porosity compared to the extrudates processed without P-CO2. Moreover, the CBZ release profile of the 20-50% drug load formulations processed with P-CO2 injection shoalmost complete drug release within 2 hours. In contrast, the drug release profiles of 20%, 30%, 40% and 50% CBZ/ Klucel™ ELF formulations processed without P-CO2 injection exhibited 90%, 86%, 80% and 73% CBZ drug release, respectively. In conclusion, HME processing assisted with P-CO2 increased the drug loading capability of CBZ in KlucelTM ELF polymeric matrix as well as optimized CBZ drug- release profiles. Drug permeability and dissolution rate are considered as key to predict the drug bioavailability. HME was used as an approach to improve solubility and permeability of the psychoactive natural product piperine. Piperine 10–40% w/w formulated in Eudragit® EPO/ Kollidon® VA 64 or Soluplus® formulation was used in this study to investigate the efficiency of various polymers to enhance the solubility and permeability of piperine via HME technique to ultimately increase its systemic absorption of the compound. Scanning electron microscopy (SEM) images shoabsence of crystals in 10% w/w piperine/Soluplus® indicating that piperine was dispersed in the Soluplus® polymer carrier in its amorphous form. However, crystals were evident in all other formulations with different ratios. Solubility of 10% and 20% piperine/Soluplus® was increased more than 160 and 45 folds in water, respectively. Furthermore, permeability studies using non- everted rat intestinal sac model demonstrated the enhancement in piperine absorption of the 10% w/w piperine/Soluplus® extrudates up to 158.9 ?g/5mL compared to 1.4 ?g/5mL in the case of pure piperine within 20 minutes
