Design and Optimization of Colon-Targeted System of Theophylline for Chronotherapy of Nocturnal Asthma

作者：Patel Mayur M^*; Amin Avani F

来源：Journal of Pharmaceutical Sciences, 2011, 100(5): 1760-1772.

DOI：10.1002/jps.22406

• Chronotherapy
• colonic drug delivery
• diffusion
• controlled release
• factorial design
• lag time
• pharmacokinetics
• roentgenography

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 (R) 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 (R) S100:EC and the coating level (% w/w)] were evaluated for lag time, t(50) and t(80). The optimum formulation consisted of Eudragit (R) 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.

• 出版日期2011-5