Evaluation of hot -melt extrusion technology to improve dissolution rates of poorly water soluble drugs

Rina Chokshi, University of Rhode Island

Abstract

The bioavailability of orally administered drugs mainly depends on solubility and permeability. Since the advent of high throughput screening (HTS) in drug discovery process the resultant compounds are often high molecular weight and highly lipophilic, that show poor solubility. Scientists have tried to address solubility issues by various pharmaceutical interventions. Today amongst many methods available to improve solubility and dissolution rate, preparation of solid dispersions and solid solutions has gained enormous attention. ^ Hot-melt extrusion is one of the most widely applied processing technologies in the plastic, rubber and food industry. Today this technology has found its place in the array of pharmaceutical manufacturing operations. Melt extrusion processes are currently applied in the pharmaceutical field for the manufacture of a verity of dosage forms and formulations such as granules, pellets, tablets, implants, transdermal systems and ophthalmic inserts. In this study the melt extrusion process is evaluated to formulate solid dispersion and solid solution of poorly water soluble model drug. ^ The primary objective of this study is to evaluate the utility of hot-melt extrusion (HME) in improving the dissolution rate of a poorly water-soluble model drug (Indomethacin) using suitable hydrophilic polymers such as Eudragit EPO (EPO), Polyvinyl pyrrolidone-vinyl acetate copolymer (PVP-VA), Polyvinylpyrrolidone K30 (PVPK30), Poloxamer 188 (P188). The secondary objective is to characterize physical and viscoelastic properties of materials prior to the actual melt extrusion process to assess their suitability for HME process and to establish correlation between these assessments with HME process parameters. To achieve these objectives, the research plan is mainly divided in to three broad sections: (1) Physico-mechanical evaluation of drug and polymer binary mixtures prior to hot-melt extrusion (thermal analysis, viscoelastic evaluation and solubility parameters). (2) Evaluation of hot-melt extrusion process parameters (such as barrel temperatures, motor load, screw speed, feed rate, melt pressure etc.) for the various formulations. (3) The performance attributes of hot-melt extrudate such as solid state characterization (differential scanning calorimetry, powder x-ray diffraction, FTIR spectroscopy), intrinsic dissolution rate studies and stability studies. ^

Subject Area

Chemistry, Pharmaceutical

Recommended Citation

Rina Chokshi, "Evaluation of hot -melt extrusion technology to improve dissolution rates of poorly water soluble drugs" (2004). Dissertations and Master's Theses (Campus Access). Paper AAI3145415.
http://digitalcommons.uri.edu/dissertations/AAI3145415

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