Box-Behnkenov eksperimentalni dizajn u izradi pektin-kompritol ATO 888 obloženih tableta za ciljanu isporuku mesalamina u kolon

The aim of this study was to investigate the combined influence of 3 independent variables in the compression coated tablet of mesalamine for ulcerative colitis. A 3-factor, 3-level Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were: percentage of polymers (pectin and compritol ATO 888) in compression coating (X1), coating mass (X2) and coating force (X3). Fifteen batches were prepared and evaluated for percent of drug released in 5 h (Y5), time required for 50 % mesalamine to disolve (t50) with rat cecal (RC) content and without rat cecal content (t50), percent of drug released in 24 h in the presence of rat cecal content (Y24 with RC). Transformed values of independent and dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation. The computer optimization process and contour plots predicted the levels of independent variables X1, X2, and X3 (0, 0.2 and –0.15 respectively) for colon targeting and total percent of drug released up to 24 h.Cilj rada bio je ispitati utjecaj tri nezavisne varijable u obloženim tabletama mesalamina za ulcerativni kolitis. 3-faktorijalni, Box-Behnkenov dizajn na 3 nivoa upotrijebljen je za dobivanje polinomske jednadžbe drugog reda i konstruiranje konturnih krivulja za predviđanje odgovora. Izabrane nezavisne varijable bile su: udio polimera (pektin i kompritol ATO 888) u oblaganju kompresijom (X1), masa tvari za oblaganje (X2) i sila za oblaganje (X3). Izrađeno je petnaest pripravaka kojima su ispitani sljedeći parametri: udio lijeka oslobođenog nakon 5 h (Y5), vrijeme potrebno za otapanje 50 % mesalamina (t50) uz i bez prisutnosti crijevnog sadržaja štakora (RC), postotak oslobođenog lijeka tijekom 24 h u prisutnosti crijevnog sadržaja (Y24 uz RC). Transformirane vrijednosti nezavisnih i zavisnih varijabla podvrgnute su višestrukoj regresijskoj analizi da se odredi polinomska jednadžba drugog reda potpunog modela. F vrijednost izračunata je da se potvrdi izostavljanje neznačajnih članova iz jednadžbe potpunog modela. Kompjutorski optimizirani proces i krivulje predviđaju nezavisne varijable X1, X2 i X3 (0, 0,2, odnosno –0,15) za ciljanu isporuku u kolon i ukupni postotak lijeka oslobođenog tijekom 24 h

Box-Behnken experimental design in the development of pectin-compritol ATO 888 compression coated colon targeted drug delivery of mesalamine

A novel oral colon-specific drug delivery system (CDDS) has been developed as one of the site-specific drug delivery systems. This delivery system, by means of combining one or more controlled release mechanisms, hardly releases the drug in the upper part of the gastrointestinal (GI) tract, but rapidly releases drug in the colon following oral administration. The necessity and advantage of CDDS have been recognized and reviewed recently (1-3). Owing to CDDS specifically delivering the drug to the colon, many bene- The aim of this study was to investigate the combined influence of 3 independent variables in the compression coated tablet of mesalamine for ulcerative colitis. A 3--factor, 3-level Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were: percentage of polymers (pectin and compritol ATO 888) in compression coating (X 1 ), coating mass (X 2 ) and coating force (X 3 ). Fifteen batches were prepared and evaluated for percent of drug released in 5 h (Y 5 ), time required for 50 % mesalamine to dissolve (t 50 ) with rat cecal (RC) content and without rat cecal content (t 50 ), percent of drug released in 24 h in the presence of rat cecal content (Y 24 with RC). Transformed values of independent and dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full-model equation. The computer optimization process and contour plots predicted the levels of independent variables X 1 , X 2 , and X 3 (0, 0.2 and -0.15, respectively) for colon targeting and total percent of drug released up to 24 h