Marian Naguib

Abstract The aim of the present study was the formulation of a novel chewable tablet containing the non-steroidal anti-inflammatory bumadizone calcium (BZ) to deliver the drug to the colon for the local treatment of ulcerative colitis. Colon targeted granules were prepared following 32 full factorial design. The effect of two independent variables, namely, polymer type (Eudragit ® S100, Eudragit ® L100, and a mixture of both in the ratio of 4:1) and drug to polymer ratio (1:1, 1:3& 1:5) on the % of \{BZ\} released for 12 h was studied. In order to produce chewability, candidate formulae were then mixed with different amount of maize starch and mannitol, and compressed into tablets. \{F11\} tablets(composed of drug: Eudragit® \{S100\} in the ratio of 1:3, 250 mg mannitol and 50 mg maize starch with a desirability of 0.925) achieved the required release profile i.e: lowest release before target area (pH 1.2 & 6.8) reaching only 11.00% at the end of the fourth hour, and 100.27% after 12 h (pH7.4). Histopathological studies results declared clearly the ability of the chewable colon targeted tablets \{F11\} to locally treat acetic acid induced colitis. Furthermore, the measurements of myeloperoxidase enzyme activities in colon specimens showed that \{F11\} achieved a significantly lower levels in comparison to both untreated group and group that received the marketed tablets (p<0.05).

The objective of this study was the development of a colon-targeted microspheres which were compressed into tablets containing the non-steroidal anti-inflammatory bumadizone calcium hemihydrate. [corrected]. A 3(2) full factorial design was adopted for the evaluation of the prepared microspheres. The effect of two independent variables namely polymer type (Eudragit RS100, ethyl cellulose and cellulose acetate butyrate), and drug: polymer ratio (1:1, 9:1 and 18:1) was studied on the entrapment efficiency and in vitro drug release for 12 h. Colon targeting aims to minimize the release of the drug off target area (pH 1.2 and 6.8) and to maximize the release of the drug in target area (pH 7.4). Candidate formulae were compressed into core tablets and colon targeting was achieved using the enzyme-dependent polymer (pectin) as coat in three different concentrations 50, 75 and 90%. Candidate formula F15 (microspheres prepared using BDZ:CAB in a ratio of 18:1 and compressed into tablets using 50% pectin and 50% Avicel in the coat) was able to adequately modulate drug release avoiding drug release in the gastric ambient, and reaching the colonic targeting where 99.7% release was achieved within 12 h following zero-order model. In vivo studies showed that F15 achieved significant decrease in myeloperoxidase activity and inflammation with delayed Tmax (4 h) and lower Cmax (2700 ng/ml) when compared to marketed product.