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Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine.
Int J Pharm. 2006 Nov 06; 324(2):103-15.IJ

Abstract

This paper describes the synthesis of capecitabine-loaded semi-interpenetrating network hydrogel microspheres of chitosan-poly(ethylene oxide-g-acrylamide) by emulsion crosslinking using glutaraldehyde. Poly(ethylene oxide) was grafted with polyacrylamide by free radical polymerization using ceric ammonium nitrate as a redox initiator. Capecitabine, an anticancer drug, was successfully loaded into microspheres by changing experimental variables such as grafting ratio of the graft copolymer, ratio of the graft copolymer to chitosan, amount of crosslinking agent and percentage of drug loading in order to optimize process variables on drug encapsulation efficiency, release rates, size and morphology of the microspheres. A 2(4) full factorial design was employed to evaluate the combined effect of selected independent variables on percentage of drug release at 5h (response). Regression models were used for the response and data were compared statistically using the analysis of variance (ANOVA). Grafting, interpenetrating network formation and chemical stability of the capecitabine after encapsulation into microspheres was confirmed by Fourier infrared spectra (FTIR). Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) studies were made on drug-loaded microspheres to investigate the crystalline nature of drug after encapsulation. Results indicated amorphous dispersion of capecitabine in the polymer matrix. Scanning electron microscope (SEM) confirmed spherical shapes and smooth surface morphology of the microspheres. Mean particle size of the microspheres as measured by the laser light scattering technique ranged between 82 and 168microm. Capecitabine was successfully encapsulated into semi-IPN microspheres and percentage of encapsulation efficiency varied from 79 to 87. In vitro release studies were performed in simulated gastric fluid (pH 1.2) for the initial 2h, followed by simulated intestinal fluid (pH 7.4) until complete dissolution. The release of capecitabine was continued up to 10h. Release data were fitted to an empirical relationship to estimate the transport parameters. Dynamic swelling studies were performed in the simulated intestinal fluid and diffusion coefficients were calculated by considering the spherical geometry of the matrices.

Authors+Show Affiliations

Drug Delivery Division, Center of Excellence in Polymer Science, Karnatak University, Dharwad 580 003, India.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16824710

Citation

Agnihotri, Sunil A., and Tejraj M. Aminabhavi. "Novel Interpenetrating Network Chitosan-poly(ethylene Oxide-g-acrylamide) Hydrogel Microspheres for the Controlled Release of Capecitabine." International Journal of Pharmaceutics, vol. 324, no. 2, 2006, pp. 103-15.
Agnihotri SA, Aminabhavi TM. Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. Int J Pharm. 2006;324(2):103-15.
Agnihotri, S. A., & Aminabhavi, T. M. (2006). Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. International Journal of Pharmaceutics, 324(2), 103-15.
Agnihotri SA, Aminabhavi TM. Novel Interpenetrating Network Chitosan-poly(ethylene Oxide-g-acrylamide) Hydrogel Microspheres for the Controlled Release of Capecitabine. Int J Pharm. 2006 Nov 6;324(2):103-15. PubMed PMID: 16824710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. AU - Agnihotri,Sunil A, AU - Aminabhavi,Tejraj M, Y1 - 2006/06/03/ PY - 2005/11/30/received PY - 2006/04/03/revised PY - 2006/05/28/accepted PY - 2006/7/11/pubmed PY - 2006/12/9/medline PY - 2006/7/11/entrez SP - 103 EP - 15 JF - International journal of pharmaceutics JO - Int J Pharm VL - 324 IS - 2 N2 - This paper describes the synthesis of capecitabine-loaded semi-interpenetrating network hydrogel microspheres of chitosan-poly(ethylene oxide-g-acrylamide) by emulsion crosslinking using glutaraldehyde. Poly(ethylene oxide) was grafted with polyacrylamide by free radical polymerization using ceric ammonium nitrate as a redox initiator. Capecitabine, an anticancer drug, was successfully loaded into microspheres by changing experimental variables such as grafting ratio of the graft copolymer, ratio of the graft copolymer to chitosan, amount of crosslinking agent and percentage of drug loading in order to optimize process variables on drug encapsulation efficiency, release rates, size and morphology of the microspheres. A 2(4) full factorial design was employed to evaluate the combined effect of selected independent variables on percentage of drug release at 5h (response). Regression models were used for the response and data were compared statistically using the analysis of variance (ANOVA). Grafting, interpenetrating network formation and chemical stability of the capecitabine after encapsulation into microspheres was confirmed by Fourier infrared spectra (FTIR). Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) studies were made on drug-loaded microspheres to investigate the crystalline nature of drug after encapsulation. Results indicated amorphous dispersion of capecitabine in the polymer matrix. Scanning electron microscope (SEM) confirmed spherical shapes and smooth surface morphology of the microspheres. Mean particle size of the microspheres as measured by the laser light scattering technique ranged between 82 and 168microm. Capecitabine was successfully encapsulated into semi-IPN microspheres and percentage of encapsulation efficiency varied from 79 to 87. In vitro release studies were performed in simulated gastric fluid (pH 1.2) for the initial 2h, followed by simulated intestinal fluid (pH 7.4) until complete dissolution. The release of capecitabine was continued up to 10h. Release data were fitted to an empirical relationship to estimate the transport parameters. Dynamic swelling studies were performed in the simulated intestinal fluid and diffusion coefficients were calculated by considering the spherical geometry of the matrices. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/16824710/Novel_interpenetrating_network_chitosan_poly_ethylene_oxide_g_acrylamide__hydrogel_microspheres_for_the_controlled_release_of_capecitabine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(06)00446-7 DB - PRIME DP - Unbound Medicine ER -