Design and optimization of colon-targeted system of theophylline for chronotherapy of nocturnal asthma

J Pharm Sci. 2011 May;100(5):1760-72. doi: 10.1002/jps.22406. Epub 2010 Dec 13.


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.

MeSH terms

  • Animals
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / pharmacokinetics
  • Bronchodilator Agents / therapeutic use
  • Cellulose / analogs & derivatives
  • Cellulose / chemistry
  • Chronotherapy*
  • Colon / metabolism*
  • Delayed-Action Preparations / chemistry*
  • Drug Stability
  • Polymethacrylic Acids / chemistry
  • Rabbits
  • Theophylline / administration & dosage*
  • Theophylline / pharmacokinetics
  • Theophylline / therapeutic use


  • Bronchodilator Agents
  • Delayed-Action Preparations
  • Polymethacrylic Acids
  • methylmethacrylate-methacrylic acid copolymer
  • ethyl cellulose
  • Cellulose
  • Theophylline