Eudragit S-100 entrapped chitosan microspheres of valdecoxib for colon cancer

Abstract

COX-2 inhibitors have demonstrated beneficial effects in colorectal cancer. The purpose of this study was to prepare and evaluate the colon specific microspheres of COX-2 inhibitors using valdecoxib as a model drug. Mucoadhesive core microspheres were prepared using chitosan as polymer and entrapped within Eudragit S 100 for colon targeting. FTIR spectrum of selected, coated microspheres showed peaks of valdecoxib at 3377, 3250, 1334 and 1155 cm(-1). XRD showed amorphous character and DSC showed depressed broad endotherm of valdecoxib at 169.07 degrees C, which may be attributed to dilution effect by the amorphous polymer. The coated microspheres were spherical with an average size of 90 mum. Storage of the microspheres at 40 degrees C/75% relative humidity for 6 months indicated no significant drug degradation. The coated microspheres did neither release the drug in acidic pH of stomach (pH 1.2) nor in small intestinal pH between 5 to 6.8, and the release started at pH 7.4, indicting perfect colonic delivery. The coated microspheres pretreated with phosphate buffer pH 7.4 for 30 min, when applied to mucosal surface of freshly excised goat colon, showed good mucoadhesion. The drug release at pH 7.4 and good mucoadhesive property of the microspheres make the system ideal for colonic delivery.

Untitled

“…[14][15][16] In a typical experiment, a defined quantity of capecitabine was dispersed in aqueous solutions of 1% v/v acetic acid of varying concentrations of chitosan in accordance with a drug polymer ratio as in Table 1. Subsequently, the dispersion was emulsified in light liquid paraffin containing 2% v/v tween 80, with the help of a mechanical stirrer (Remi Instruments Ltd, Mumbai, India) at 1500 rpm for 30 min.…”

The quest for targeted delivery in colon cancer: mucoadhesive valdecoxib microspheres

“…However, it has already been reported that the time required to completely wash-off the valdecoxib-containing chitosan microspheres was quite long (162 minutes) 18 compared with the similarly prepared microspheres of alginate (95 minutes). The better mucoadhesion with chitosan microspheres may be attributed to electrostatic attraction between positively charged chitosan and negatively charged mucin and also to the hydrogen bonding due to the presence of -OH and deprotonated -NH 2 groups in chitosan.…”

“…[16][17][18] In a typical experiment, a defined quantity of valdecoxib was dispersed in aqueous solutions of varying concentrations of sodium alginate in accordance with a drug polymer ratio as in Table 1. Subsequently, the dispersion was emulsified in light liquid paraffin containing 2% v/v Span 80, with the help of a mechanical stirrer (Remi Instruments Ltd, Mumbai, India) at 2000 rpm for 1 hour.…”

“…The drug loading efficiency in core microspheres of VSA-1 was 83.80% ± 1.62%, which is comparable with that of the core microspheres of chitosan, where it was 80.33% ± 2.24%, as reported in a previous publication. 18 In vitro release profile core microspheres…”

“…The total drug release in the present case (88% and 84%) is better than that of coated microspheres of chitosan, where it was 82% and 79%, as reported earlier. 18 …”