pH-Enzyme Di-dependent Chronotherapeutic Drug Delivery System of Theophylline for Nocturnal Asthma

• Published in: Chemical & Pharmaceutical Bulletin Vol. 59; no. 2; pp. 191 - 195
• Main Authors: Soni, Murari Lal, Namdeo, Kamta Prasad, Jain, Sunil Kumar, Gupta, Manish, Dangi, Jawahar Singh, Kumar, Manoj, Dangi, Yuvraj Singh
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2011; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Animals; Asthma - drug therapy; Asthma - metabolism; chronotherapeutic; colonic delivery; Drug Chronotherapy; Drug Delivery Systems - methods; Eudragit; Galactans - administration & dosage; Galactans - chemistry; Galactans - pharmacokinetics; guar gum; Hydrogen-Ion Concentration; Mannans - administration & dosage; Mannans - chemistry; Mannans - pharmacokinetics; microsphere; Microspheres; pH-dependent; Plant Gums - administration & dosage; Plant Gums - chemistry; Plant Gums - pharmacokinetics; Polymethacrylic Acids - administration & dosage; Polymethacrylic Acids - chemistry; Polymethacrylic Acids - pharmacokinetics; Rats; Rats, Sprague-Dawley; Theophylline - administration & dosage; Theophylline - chemistry; Theophylline - pharmacokinetics
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.59.191

The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drug delivery system of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit® polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1—4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release.