Modification of tapioca starch by hydroxypropyl substitution, crosslinking with phosphate and pregelatinization for use as a matrix for sustained release dosage forms

Abstract

The objective of this study is to develop pregelatinized cross-linked hydroxypropyl starch (PCHS) for using as a matrix for sustained release tablet. The native tapioca starch was modified by substituted reaction with propylene oxide at three levels 2.5, 5.0, 7.5%, cross-linked with 0.1% sodium trimetaphosphate, and then pregelatinized by using drum dryer method. Physical and chemical properties of PCHS were investigated ie. particle morphology, moisture content, viscosity, swelling power, rheology, analysis of hydroxypropyl and phosphate groups by FT-IR & GC. It was found that temperature, pH, and ionic strength of medium had slightly effected on viscosity and the highest degree of substitution (DS) of PCHS 0.106 provided the highest viscosity and swelling power, following with 0.074 and 0.062, respectively. In dissolution testing, it was found that the PCHS matrix of 0.106 DS combined with 10 % of HPMC E4M released 92.64% of propranolol hydrochloride within 12 hrs in DI water, that similar to matrix which consisted only HPMC E4M. In various ionic strength of media at 0.05 and 0.10 had no effect on drug release. However, the PCHS gave slower release rate in 0.20 M NaCl solution when comparing with in DI water (f₂ =45.50). In addition, when comparing drug release in 0.1 N HCl solution with PBS pH 6.8, it was found that the pH of dissolution media had effect on drug released (f₂=32.32). Increasing compression force from 1000-3000 psi and changing the methods of dissolution test from basket to paddle method had no effect on drug release rate that the f₂ was 57.32. Therefore, the PCHS was alternative choices for used as hydrophilic matrix.