Bumadizone calcium dihydrate microspheres compressed tablets for colon targeting: formulation, optimization andin vivoevaluation in rabbits

Abstract

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 dihydrate. 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 T max (4 h) and lower C max (2700 ng/ml) when compared to marketed product.

Premium ethylcellulose polymer based architectures at work in drug delivery

“…In 2015, Nour and colleagues formulated an optimized microspheres in compressed tablet of bumadizone calcium dihydrate for colon targeting and controlled release. Their findings showed that microspheres based on ethylcellulose N100 displayed the highest entrapment efficiency which was attributed to its higher viscosity and ability to decrease drug diffusion to the outer phase increasing retention within the microsphere core as well as extended in vitro and in vivo release behaviour (Nour et al, 2015). The drug release retarding properties of ethylcellulose also found application in the construction of a once-daily dosing sustained release coated tablet of tolterodine-L-tartrate in the management of overactive bladder.…”

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

“…PS and ZP were not taken into consideration as the results showed statistical insignificant differences (Nour et al, 2015). The highest desirability value obtained was 0.921 and it was associated with the independent variables, namely, X 1 ¼ 50%, X 2 ¼ 40, and X 3 ¼ 10 corresponding to formula PM7.…”

Development of a Multivariate Predictive Dissolution Model for Tablets Coated with Cellulose Ester Blends

“…In the FDA ‘Inactive Ingredient Database’ and the United States Pharmacopeia, CAB is listed as ‘Cellaburate’ [ 17 , 18 ]. The literature has reported its application in fabrication of various drug delivery systems, e.g., nanoparticles [ 19 ], microspheres [ 20 , 21 ], colonic system [ 22 , 23 ], matrix tablets [ 24 ], gastroretentive [ 25 ], osmotic [ 26 ], and so on. It can also be used as a coating polymer for sustained/extended release of drugs.…”