title: Time and pH dependent colon specific, pulsatile delivery of theophylline for nocturnal asthma.
abstract: In this study, investigation of an oral colon specific, pulsatile device to achieve time and/or site specific release of theophylline, based on chronopharmaceutical consideration. The basic design consists of an insoluble hard gelatin capsule body, filled with eudragit microcapsules of theophylline and sealed with a hydrogel plug. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. The theophylline microcapsules were prepared in four batches, with Eudragit L-100 and S-100 (1:2) by varying drug to polymer ratio and evaluated for the particle size, drug content and in vitro release profile and from the obtained results; one better formulation was selected for further fabrication of pulsatile capsule. Different hydrogel polymers were used as plugs, to maintain a suitable lag period and it was found that the drug release was controlled by the proportion of polymers used. In vitro release studies of pulsatile device revealed that, increasing the hydrophilic polymer content resulted in delayed release of theophylline from microcapsules. The gamma scintigraphic study pointed out the capability of the system to release drug in lower parts of GIT after a programmed lag time for nocturnal asthma. Programmable pulsatile, colon-specific release has been achieved from a capsule device over a 2-24h period, consistent with the demands of chronotherapeutic drug delivery.
authors.affiliation: KLES College of Pharmacy, JNMC Campus, Belgaum 590010, India. mastiholimath@rediffmail.com
authors.forename: V S
authors.initials: VS
authors.lastname: Mastiholimath
authors.forename: P M
authors.initials: PM
authors.lastname: Dandagi
authors.forename: S Samata
authors.initials: SS
authors.lastname: Jain
authors.forename: A P
authors.initials: AP
authors.lastname: Gadad
authors.forename: A R
authors.initials: AR
authors.lastname: Kulkarni
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism*; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005079:Excipients; D005233:Fatty Alcohols; D005557:Formaldehyde / Q000737:chemistry; D005780:Gelatin; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D011109:Polymethacrylic Acids; D011817:Rabbits; D013667:Technetium; D013806:Theophylline / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D018927:Anti-Asthmatic Agents; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005079:Excipients; D005233:Fatty Alcohols; D020100:Hydrogels; D014677:Pharmaceutical Vehicles; D011109:Polymethacrylic Acids; D005557:Formaldehyde; C038300:methylmethacrylate-methacrylic acid copolymer; D011092:Polyethylene Glycols; D013667:Technetium; D005780:Gelatin; D013806:Theophylline; C400265:1,2,6-hexanetriol