Drug physical state and drug–polymer interaction on drug release from chitosan matrix films
Introduction
Chitosan, a cationic natural biopolymer produced from deacetylation of chitin, has been widely used for drug carrying devices in controlled drug delivery systems [1]. A drug–polymer dispersion can be utilized to accomplish coating of non-pariel seeds, yielding a matrix for diffusion-mediated controlled drug release. In addition, a drug–polymer matrix film may be adaptable for transdermal drug delivery [2]. The incorporation of a drug into a chitosan matrix to form a monolithic device can expand the use of this biopolymer. Up to date, the study of drug-loaded chitosan films were focused on release behavior of the drug from chitosan matrix films [3], [4], [5], [6]. Depending on the amount of chitosan [4], film thickness [4], [5], and dissolution medium [4], the liberation of drug from the chitosan films varied from fast release to slow release. In case of the sustained release, it was reported that the drug was released from the chitosan film following zero order [5] or first order kinetics [6]. Imai et al. [7] found the interaction of indomethacin with low molecular weight chitosan (MW 3800–25,000) and reported the improved release of the drug.
Many grades of chitosan are available with different molecular weights and degree of deacetylation (%DD) [1], [8]. In the previous paper, we studied the physicochemical characteristics of chitosan films prepared from four types of chitosan derived from crab shell chitin, that is, very low-viscosity grade (VL type, MW 50,000–60,000) with 82%DD; very low-viscosity grade (VL type, MW 50,000–60,000) with 100%DD; high-viscosity grade (H type, MW 800,000–1,000,000) with 80–85%DD; and high-viscosity grade (H type, MW 600,000–800,000) with 100%DD [9]. The characteristics of chitosan films prepared depended on its molecular weight and degree of deacetylation. Therefore, it is of interest to investigate the effect of molecular weight as well as degree of deacetylation of chitosan on the release behavior of drug from chitosan matrix films. In addition, drug physical state and molecular interaction of drugs with chitosan of different grades in the films were also investigated using salicylic acid and theophylline as acidic and basic model drugs, respectively. Crystalline characteristics and thermal behavior of drugs in the chitosan films were studied by powder X-ray diffraction and differential scanning calorimetry. Fourier transform infrared (FTIR) spectroscopy and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy were used for characterization of the molecular interaction between drug and chitosan in the films. Finally, the relation of the molecular interaction of drug with chitosan to the drug release behavior from chitosan matrix film was discussed.
Section snippets
Materials
Four types of chitosan derived from crab shell chitin varying in molecular weight and degree of deacetylation (%DD) i.e. very low viscosity grade (VL type, MW 50,000–60,000) with 82%DD, very low viscosity grade (VL type, MW 50,000–60,000) with 100%DD and high viscosity grade (H type, MW 800,000–1,000,000) with 80–85%DD and high viscosity grade (H type, MW 600,000–800,000) with 100%DD were given as gifts from Dainichiseika Colors and Chemicals Manufacturing, Japan. The H-type chitosan is a high
Morphology study
The scanning electron photomicrographs of VL-82%DD chitosan films loaded with 30% and 40% salicylic acid are illustrated in Fig. 1. The drug crystals were observed at 40% drug loading (Fig. 1b) and they were clearly observed by visual inspection at higher than 40% drug loading. In the films prepared from VL-100%DD, H-80–85%DD, and H-100%DD chitosan, the drug crystals appeared at 50% drug loading and they were also observed by visual inspection at higher than 50% drug loading. The drug crystals
Conclusion
Physicochemical characterization of all chitosan films loaded with salicylic acid and theophylline could reveal the drug physical state and drug–polymer interaction. The solid-state solubility of salicylic acid in chitosan films was about 32–44% at its melting temperature. The higher the molecular weight and degree of deacetylation of chitosan the higher the solid-state solubility was. The drug existed in an amorphous state or monomolecularly dispersed in the films like solid-state solution
Acknowledgements
The authors wish to thank Dainichiseika Colors and Chemicals Manufacturing, Japan, who kindly provided the chitosan. We would like to acknowledge National Metal and Materials Technology Center (MTEC) of Thailand for supporting powder X-ray diffractometer and solid-state 13C NMR spectrophotometer. We also wish to thank Associate Professor Dr Duangdeun Meksuriyen, Department of Biochemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Thailand, for her suggestions in the NMR
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