title: Inulin-based tablet in capsule device for variable multipulse delivery of aceclofenac: optimization and in vivo roentgenography.
abstract: The aim of the study was to develop single-unit tablet in capsule system of aceclofenac for the treatment of late night pain and morning stiffness associated with rheumatoid arthritis. The system was conceptualized as a three-component design (1) a hard gelatin enteric-coated capsule (for carrying two pulses), (2) first-pulse granules (for rapid release in intestine), and (2) second-pulse matrix tablet (for slow release in colon). An appropriate integration of pH-sensitive (Eudragit S100) and bacteria-responsive (inulin) functions, on the basis of 3(2) factorial design, led to formulation of TICS 1-9 that were screened for in vitro release. TICS 2 with biphasic drug release of 98.64% from first-pulse granules in simulated intestinal fluid (12 h) and 97.82% from second-pulse matrix tablet in simulated colonic fluid (24 h) was the optimized formulation that exhibited Fickian diffusion of drug (n=0.363). In vivo fluoroscopy in rats traced the intact tablet to colon in 7.5 h that got eroded at the tenth hour. This demonstrated the colon-specific delivery of the matrix tablet affirming the potential of the system to obviate the need for two-time administration of drug at odd hours. The experimental design was validated by extra design check point, and diffuse reflectance spectroscopy and DSC revealed absence of chemical interaction between the formulation excipients.
authors.affiliation: Department of Pharmaceutics, Rajiv Academy for Pharmacy, P.O. Chattikara, Mathura 281001, Uttar Pradesh, India.
authors.forename: Puja
authors.initials: P
authors.lastname: Sharma
authors.forename: Kamla
authors.initials: K
authors.lastname: Pathak
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000000981:diagnostic imaging; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers; D005471:Fluoroscopy; D005772:Gastrointestinal Transit; D005780:Gelatin / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000737:chemistry; D007422:Intestines / Q000000981:diagnostic imaging*; D007444:Inulin / Q000737:chemistry*; D007700:Kinetics; D015233:Models, Statistical; D011109:Polymethacrylic Acids / Q000737:chemistry; D011817:Rabbits; D015203:Reproducibility of Results; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; D004008:Diclofenac; C038300:methylmethacrylate-methacrylic acid copolymer; D005780:Gelatin; D007444:Inulin; C056498:aceclofenac