Preparation and biopharmaceutical evaluation of khellin coprecipitates

Aiming at increasing khellin dissolution and consequently improving its bioavailability, its hydrophilic solid dispersions were prepared. Several amino acids of different nature as well as aspartame gentisic acid ethanol amide [GAEA], certain bile salts and Eudragit polymers were utilized in different techniques. Dissolution studies revealed that most of the additives used gave enhanced khellin dissolution which increased with increasing vehicle concentration with few exceptions, e.g. solid dispersions with L-proline and DL- methionine were additive concentration independent. Most of the coprecipitates prepared were dissolution profile stable for one year while, others are not, e.g. coprecipitate with L-tryptophan. Although most of the products chosen for in vivo studies gave about 60-70% dissolution of khellin dose within the first half hour, in vivo data showed variable increases of khellin bioavailability, especially products FIII and FV. Formula V proved to be superior to product FIII, since it attained, in addition to higher [AUC]08 value [2.46 times that of plain khellin], a comparatively high absorption rate [t max = 30 min.]

In-vitro and in-vivo evaluation of cinnarizine solid dispersions

To solve the problem of cinnarizine dissolution, its solid dispersions with certain amino acids, aspartame, gentisic acid ethanolamide [GAEA], and Eudragit E100 were prepared in different ratios. The prepared solid dispersions were subjected to dissolution rate studies in comparison to plain cinnarizine as well as the drug treated in the same way without additives. Effect of aging on drug dissolution was also investigated. Selected cinnarizine coprecipitates containing 2: 1 w/w Eudragit E100 [FII], 1: 5 M aspartame [FIII] and 1: 3M Dl-phenylalanine [FIV] were subjected to in vivo bioavailability testing compared to plain cinnarizine [FI]. HPLC method was used to quantitate cinnarizine in rabbits' serum