Drug dissolution from pregelatinized corn starch capsules
Abstract
Drug dissolution rates have been observed to be inconsistent in capsule formulations containing pregelatinized corn starch from different vendors, different lots and botanical sources. There is no effective method for screening different sources of pregelatinized starch and predicting its performance in dissolution. The objectives of this research are (1) to understand at molecular/supra molecular level the properties of starch that affect drug dissolution performance, (2) to elucidate the drug release mechanism from pregelatinized starch-drug capsule dosage form, (3) and to develop an effective method for screening commercial pregelatinized corn starch for drug dissolution performance. In this study, the effects of crystallinity and amylopectin fragmentation were investigated separately using laboratory-prepared pregelatinized starch. Different levels of crystallinity of starch were achieved by processing starch and glycol/water mixture at different temperatures. Different levels of amylopectin fragmentation were achieved by ball milling starch for different lengths of time at a laboratory scale. The impacts of crystallinity and amylopectin fragmentation on drug dissolution rate were investigated using these laboratory prepared pregelatinized starches. Analyses of the curve fitting results using Noyes and Whitney equation and Higuchi equation indicated that the drug dissolution is diffusion-controlled for most pregelatinized starch. Two relationships, i.e., (1) the relationship between starch crystallinity and drug dissolution rate constant, and (2) the relationship between amylopectin fragmentation and drug dissolution rate constant were obtained from laboratoryprepared starch. These relationships were applied to commercial pregelatinized normal corn starch and were found to be able to map out the relative contributions of starch crystallinity and amylopectin fragmentation on the drug dissolution rate constant on these commercial pregelatinized normal corn starch. It was found that amylopectin fragmentation is four times more important than starch crystallinity. A linear combination of both processes can be described by the equation Y = .0.58*(0.0061X1-0.0547) + 2.37*(-0.0007X2+0.0428), where Y is the drug dissolution rate constant, X1 is the crystallinity of the starch of and X2 is the normalized amylopectin fragmentation. This model was shown to be able to predict the drug dissolution rate from commercial starch within ±20 percent. The physico-chemical properties of typical commercial starch were characterized, including particle size, degree of crystallinity, degree of gelatinization and amylopectin fragmentation. No apparent relation was observed between particle size, degree of gelatinization and drug dissolution rate in these commercial starches. Amylopectin fragmentation has been observed to follow a negative linear relationship with drug dissolution rate in commercial starch.
Degree
Ph.D.
Advisors
Pinal, Purdue University.
Subject Area
Pharmacy sciences
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