ASD Formation Prior to Material Characterization as Key Parameter for Accurate Measurements and Subsequent Process Simulation for Hot-Melt Extrusion

Abstract

Process simulation facilitates scale-up of hot-melt extrusion (HME) and enhances proper understanding of the underlying critical process parameters. However, performing numeric simulations requires profound knowledge of the employed materials’ properties. For example, an accurate description of the compounds’ melt rheology is paramount for proper simulations. Hence, sample preparation needs to be optimized to yield results as predictive as possible. To identify the optimal preparation method for small amplitude oscillatory shear (SAOS) rheological measurements, binary mixtures of hydroxypropylmethylcellulose acetate succinate or methacrylic acid ethyl acrylate copolymer (Eudragit L100-55) together with the model drugs celecoxib and ketoconazole were prepared. The physical powder mixtures were introduced into the SAOS as a compressed tablet or a disk prepared via vacuum compression molding (VCM). Simulations with the derived parameters were conducted and compared to lab-scale extrusion trials. VCM was identified as the ideal preparation method resulting in the highest similarity between simulated and experimental values, while simulation based on conventional powder-based methods insufficiently described the HME process.

Evaluation of Printability of PVA-Based Tablets from Powder and Assessment of Critical Rheological Parameters

“…It was shown that vacuum compression modeling (VCM) is a useful tool for the simulation of extruded samples in order to correctly predict extrusion parameters. Also, temperature as a crucial parameter for printability was predicted by melt rheology experiments [ 20 , 33 ].…”

An isocratic RP-HPLC-UV method for simultaneous quantification of tizanidine and lidocaine: application to in vitro release studies of a subcutaneous implant

“…VCM is a technology that can be used for pre-formulation studies of implants and solid amorphous polymer-drug dispersions without using hot-melt extrusion. [63][64][65][66][67][68] This allows the use of small samples. In this case the pre-mixture of drugs with an organic solvent will mimic the mixing of the drugs and polymers within the barrel of a hotmelt extruder.…”