Oral sustained delivery of theophylline from thermally reversible xyloglucan gels in rabbits

• Published in: Journal of pharmacy and pharmacology 2001-09, Vol.53 (9), p.1185-1191
• Main Authors: Miyazaki, Shozo, Kawasaki, Naoko, Endo, Kumiko, Attwood, David
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological Availability; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - pharmacokinetics; Delayed-Action Preparations; Gels; Glucans; Kinetics; Male; Polysaccharides - chemistry; Rabbits; Temperature; Theophylline - administration & dosage; Theophylline - pharmacokinetics; Xylans
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/0022357011776621

Thermally reversible gels formed in‐situ following the oral administration of dilute aqueous solutions of an enzyme‐degraded xyloglucan to rabbits were evaluated as sustained‐release vehicles for the delivery of theophylline. In‐vitro release of theophylline from gels formed by warming xyloglucan sols (0.5, 1.0 and 1.5% w/w) to 37°C followed root‐time kinetics over a period of 4 h. Gels formed after oral administration to rabbits of chilled 1.5% w/w aqueous solutions of xyloglucan containing dissolved drug showed sustained‐release characteristics with a maximum plasma concentration at 4.5 h. The theophylline bioavailability from a 1.5% w/w xyloglucan gel was 1.7–2.5 times that of commercial oral sustained‐release liquid dosage forms containing an identical theophylline concentration. It was concluded that dilute solutions of the enzyme‐degraded xyloglucan had suitable rheological properties and in‐situ gelling characteristics for use as sustained‐release vehicles for oral drug delivery. The in‐vivo release characteristics of theophylline in a rabbit model suggested the potential for the use of these vehicles in humans for the oral delivery of this drug.