title: Design and optimization of colon-targeted system of theophylline for chronotherapy of nocturnal asthma.
abstract: The objective of the present work was to develop a delayed-onset controlled-release colon-targeted system of theophylline, and to achieve the chronotherapy of nocturnal asthma. The formulation consisted of a core tablet containing hydroxypropyl methylcellulose used for achieving controlled release of drug, and a Eudragit S100:ethyl cellulose (EC) coating capable of delaying the drug release. The system was optimized using a 3(2) full factorial design, wherein two factors [ratio of Eudragit S100:EC and the coating level (% w/w)] were evaluated for lag time, t(50) and t(80) . The optimum formulation consisted of Eudragit S100:EC in a 60:40 ratio and a coating level of 7.5% (w/w). Results showed that the tablets prepared according to the optimized values released no drug in the upper part of gastrointestinal tract; drug release was initiated at pH 6.4 (colon) after a lag time of 5 h. In vivo evaluation (pharmacokinetic studies and roentgenography) in rabbits revealed that the tablet remained intact until it reaches the colon and the drug release was initiated after a lag time of 5 h. Thus, it can be concluded that the developed system exhibited a promising colonic targeting and hence may be used for chronotherapy of nocturnal asthma.
authors.affiliation: Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad 382481, Gujarat, India. drmayurmpatel@gmail.com
authors.forename: Mayur M
authors.initials: MM
authors.lastname: Patel
authors.forename: Avani F
authors.initials: AF
authors.lastname: Amin
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D019454:Chronotherapy; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004355:Drug Stability; D011109:Polymethacrylic Acids / Q000737:chemistry; D011817:Rabbits; D013806:Theophylline / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C013517:ethyl cellulose; D002482:Cellulose; D013806:Theophylline