Camptothecin (
CPT), a potent
antitumor drug, exhibits poor aqueous solubility and rapid conversion from the pharmacologically active
lactone form to inactive carboxylate form at physiological pH. Solid dispersion of
CPT in Soluplus®, an amphiphilic polymeric solubilizer, was prepared to increase the aqueous solubility of
CPT and the resultant solid dispersion along with
citric acid was formulated as hard
gelatin capsules that were subsequently coated with
Eudragit S100
polymer for colonic delivery. FTIR spectrum of the solid dispersion confirmed the presence of
CPT. PXRD and DSC revealed the semicrystalline nature of solid dispersion. The solubility of the
drug was found to increase ~40 times in the presence of
Soluplus and ~75 times in solid dispersion. The capsules showed no drug release in 0.01 N HCl but released 86.4%
drug in
lactone form in
phosphate buffer (pH 7.4) and the result appears to be due to
citric acid-induced lowering of pH of
buffer from 7.4 to 6.0. Thus the presence of
citric acid in the formulation led to stabilization of the
drug in its pharmacologically active
lactone form. Cytotoxicity studies conducted with the formulation of solid dispersion with
citric acid, utilizing cell cytotoxicity test (MTT test) on Caco-2 cells, confirmed cytotoxic nature of the formulation.