The hot melt extrusion (HME) is a novel technology to prepare pharmaceutical dosage forms by embedding a drug in a polymer while shaping the composite material to form a pharmaceutical product. The use of polymeric carriers generally requires the incorporation of a plasticizer into the formulation to improve the processing conditions of certain high molecular weight polymers. With liquid plasticizers, non uniform mixing, unstable mass flow, loss and evaporation of plasticizers during high temperature processing may lead to variable process and product performance. To overcome the shortcomings of liquid plasticizers, it is important to evaluate solid-state plasticizers as HME processing aid. Therefore, objective of this study was to judiciously select solid-state plasticizers (SSP) and evaluate of their impact on HME process and product performance including, the physicochemical stability.
Indomethacin (INM) and Eudragit E PO (EPO) were selected as the model drug and the polymer, respectively. Stearic acid, glyceryl behenate and PEG 8000 were selected as SSP using solubility parameter. Various binary (polymer: plasticizer) and ternary (drug: polymer: plasticizers) physical mixtures were prepared and evaluated for thermal and rheological evaluation for HME process. The various INM/EPO/plasticizer mixtures were processed using twin screw extruders. Percentage-torque was monitored as a response variable from the processing aspects and the extrudates were characterized using differential scanning calorimetry, powder x-ray diffraction, Fourier Transform Infrared Spectroscopy, solubility, chemical assay and intrinsic dissolution rate studies. The physicochemical stability of the extrudates were monitored at 40°C/75% RH for 1 month and 30°C/60% RH for 6 months in open HDPE bottles.
All plasticizers were effective in reducing the percentage-torque even at the lower concentrations. Plasticizers at lower concentrations appeared to have no effect on product performance at lover concentrations. The formulation containing higher concentration of plasticizer (>5%) had adverse effect on the Tg but had no effect on the PXRD or IDR suggesting that mechanism of solid-state stabilization of amorphous INM may not be sensitive to the mobility of the system. Judicious use of plasticizer may help in HME processing without affecting the solid state stability of extruded formulations.
