Optimization of budesonide compression-coated tablets for colonic delivery.
The purpose of this study was to formulate budesonide (BUD) compression-coated tablets for colonic specific delivery. Pectin and guar gum were used as enzyme-dependent polymers. For comparison purposes, both pH- and time-dependent polymers were also tried. In vitro release studies were carried out at different pH (1.2, 6.8, and 7.4). Therapeutic efficacy of the prepared tablets compared to commercially available capsules and enema were evaluated in trinitrobenzenesulfonic acid-induced rabbit colitis model. In pH-dependent polymers, Eudragit (EUD) S100/EUD L100 (1:1) released 45.58% in the target area (colon). For time-dependent polymers, decreasing cellulose acetate butyrate (CAB) ratio increased the release in both pH 6.8 and 7.4 till it reached 40.58% and 93.65%, respectively, for 25% CAB. In enzyme-dependent polymers, increasing pectin ratio to 75% retarded the release (4.59% in pH 6.8 and 54.45% in pH 7.4) which was significantly enhanced to 99.31% using pectinolytic enzyme. Formula F14 coated with 75% pectin significantly reduced the inflammatory cells in the connective tissue core of the colon of the treated group and significantly decreased myeloperoxidase activity (3.90 U/g tissue weight). This study proved that BUD compression-coated with 75% pectin may be beneficial in the treatment of inflammatory bowel disease.
Yehia
Soad A
SA
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Elshafeey
Ahmed H
AH
Sayed
Ibrahim
I
Shehata
Ahmed H
AH
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D019819:Budesonide / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D005685:Galactans / Q000737:chemistry / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007700:Kinetics; D008297:Male; D008351:Mannans / Q000737:chemistry / Q000378:metabolism; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D010368:Pectins / Q000737:chemistry / Q000378:metabolism; D053149:Plant Gums / Q000737:chemistry / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000737:chemistry; D011817:Rabbits; D012212:Rheology; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical / Q000379:methods; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005685:Galactans; D005765:Gastrointestinal Agents; D008351:Mannans; D053149:Plant Gums; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; D065347:Hypromellose Derivatives; D019819:Budesonide; D010368:Pectins; D014302:Trinitrobenzenesulfonic Acid; D002482:Cellulose; C014396:cellulose acetate-butyrate; D008747:Methylcellulose; C007894:guar gum