Design and Evaluation of Compritol®-Based Mesalazine Pellets and Tablets for Sustained Release Throughout the Gastrointestinal Tract

Abstract

Background/Objective

Drug delivery to the gastrointestinal tract (GIT) has become very important for the local treatment of digestive diseases such as inflammatory bowel disease (IBD). Mesalazine is an anti-inflammatory drug used as the first-line treatment for IBD. The current study aims to prepare mesalazine controlled-release pellets/tablets based on Compritol^® 888 ATO for the gradual release of the drug throughout the intestine.

Methods

Formulations were designed using Design Expert software based on Central Composite Design (CCD). The independent variables were the ratio of Compritol^® 888 ATO to Microcrystalline cellulose (MCC) in the pellet/tablet formulations and the curing temperature. The dependent variables were the drug release percentages in media simulating the stomach and various sections of the intestine. Pellets were manufactured using the extrusion-spheronization method and tablets were prepared using the wet granulation method. The optimal pellet formulation was evaluated by image analysis, SEM, FTIR, and DSC, as well as the drug release was continuously evaluated in simulated gastric media (pH 1.2), simulated intestinal media (duodenum, jejunum and terminal ileum with pHs of 6.5, 6.8, 7.2, respectively), and colon with pH 6.8.

Results

Increasing the amount of Compritol^® 888 ATO and the curing temperature in the formulation significantly controlled the drug release. The optimal pellet formulation, consisting of 40% mesalazine, 58% Compritol^® 888 ATO, and 2% PVP K30, cured at 75 °C for 24 h, successfully achieved the desired results. In contrast, the tablet formulations failed to deliver the expected outcomes. Image analysis of the pellets showed that the aspect ratio and sphericity of the optimal pellets were 1.12 ± 0.04 and 0.88 ± 0.03, respectively, indicating a spherical shape. The evaluation of SEM images also confirmed the results obtained from the image analysis software. According to the DSC and FTIR results, there was no interference between the drug and excipients. The dissolution test results demonstrated that incorporating Compritol^® 888 ATO in the tablet structure resulted in minimal drug release, whereas the optimal pellet gradually released the entire drug content over approximately 15 h.

Conclusion

The optimal pellet formulation controlled the drug release in the simulated media of different parts of the GIT. Its release profile was similar to Pentasa^®’s, suggesting that it could be considered for extended drug delivery throughout the GIT.

Graphical Abstract