Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection.

Arno A Enose,Sanket M Shah,Priya K Dasan,H Sivaramakrishnan

doi:10.1155/2014/105382

Abstract

Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations. The sulindac-polymer-plasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot melt extrusion process. Hot melt mixing is not a substitute to hot melt extrusion but is an aid in predicting the formation of molecularly dispersed form of a given set of drug-polymer-plasticizer combination in a hot melt extrusion process. The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction. Subsequently, the best drug-polymer-plasticizer combination obtained by hot melt mixing was subjected to hot melt extrusion process to validate the usefulness of hot melt mixing as a predictive tool in hot melt extrusion process.

Highlights

Amorphization of drug increases the solubility of drug because of increased surface area and better ability of the solvent to wet the drug
In case of hydroxyl propyl methyl cellulose (HPMC), a clear and transparent film was obtained with all the plasticizers tested; a representative example with 20% triethyl citrate (TEC) as observed visually (Figure 1(b1)) and optical microscopy (Figure 1(b2))
A representative image of hydroxypropyl cellulose (HPC), 20% w/w TEC, and 20% w/w SUL is shown in Figure 1(c1) and Figure 1(c2)

Summary

Introduction

Amorphization of drug increases the solubility of drug because of increased surface area and better ability of the solvent to wet the drug Such a process can improve the bioavailability of drugs that are poorly soluble, namely, BCS class II and BCS class IV drugs [1,2,3]. Hot melt extrusion is a solvent free process that utilizes heat and pressure to disperse the drug molecularly in a given polymer-plasticizer combination [6,7,8,9,10,11,12,13,14]. Film casting method can be used as preliminary screening technique to determine the right amount of drugpolymer-plasticizer combination that can yield molecularly dispersed drug [16, 17]. Hot melt mixing is another screening technique, described in the current study, which can be used in selection of possible drug-polymer-plasticizer combination for employing in hot melt extrusion (HME) process

Methods

Results

Conclusion