Soluplus-Solubilized Citrated Camptothecin—A Potential Drug Delivery Strategy in Colon Cancer

Abstract

Abstract. 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.

Design of freeze-dried Soluplus/polyvinyl alcohol-based film for the oral delivery of an insoluble drug for the pediatric use

“…resulting in a significant increase in solubility. Similar results were previously reported in several researches (Guns et al, 2011;Linn et al, 2012;Thakral et al, 2012).…”

“…Similar results were previously stated by Sikarra et al (2012) in a study on improving the solubility of different poorly water-soluble drugs. This was also in accordance with Thakral et al (2012) who found that the solubility of camptothecin increased by $40 times in the presence of Soluplus Õ .…”

“…From the previous results, it is clear that the optimized freeze-dried film formula succeeded in improving drug' solubility. This might be attributed to the use of Soluplus Õ which possess an amphiphilic chemical structure with large number of hydroxyl groups which make it an excellent solubilizer for poorly soluble drugs like SL in aqueous media (Thakral et al, 2012). In addition, the use of PVA as a water-soluble polymer possessed a positive synergistic effect in enhancing the drug's saturated solubility.…”

Preparation and Evaluation of Solid Dispersion of Atorvastatin Calcium with Soluplus® by Spray Drying Technique

“…Characteristic IR peaks for crystalline atorvastatin calcium were observed at 3362 cm , and 1631 cm −1 (C= O stretching). 18,19) FT-IR spectra of a physical mixture of atorvastatin calcium and Soluplus ® at a 2 : 8 ratio correspond to a summation of crystalline atorvastatin calcium and Soluplus ® spectra, suggesting that no interactions between the two species or disruption of drug crystallinity occur in the mixtures. Notably, however, the spectra of solid dispersions lack peaks characteristics of crystalline atorvastatin calcium and showed peaks representative of Soluplus ® and amorphous atorvastatin calcium.…”

Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats

“…3 Similar observations have also been made in the management of colon cancer. 4,5 In fact, the deposition and adherence of fluorescent polystyrene particles were greater in the ulcerated regions of the inflamed tissue than in nonulcerated control tissue in experimental models of rodent colitis; this adhesion was size-dependent, the best results being obtained with particle sizes ranging from 25 to 100 nm. 3 Based on this paradigm, different groups have developed the delivery of several drugs, such as tacrolimus and rolipram, delivered on poly(lactic-co-glycolic acid) nanoparticles; dexamethasone on poly(d-lactide) particles; 3 or fluticasone propionate on hydroxypropyl betacyclodextrin.…”