Adjusting the Release Rate of Mesalazine from Matrix Formulations by Addition of various Excipients

Mesalazine is widely used drug compound to treat inflammations within the gastrointestinal tract (GIT). The APIs is mostly supplied as very fine powder with extremely poor flowability and wet granulation is most often used to meet the challenge. However, mesalazine is prone to degradation by several pathways (e.g. oxidation to oxidation and forms quinoneimine), especially if brought into contact with water [1]. Therefore, dry granulation by roll compaction seems to be a viable alternative. Very often a prolonged release profile or targeting to the large intestine is desired for the delivery profile of this API. To achieve the desired release profile matrix systems containing HPMC (hydroxypropylmethyl cellulose) are often formulated. The release profile is then governed by several factors such as the viscosity grade of the polymer as well as the porosity of the dosage form and the solubility of the drug and other formulation components [2].

Meaningful testing of the API release from such matrix formulations can be challenging. Simulating the pH gradient within the GIT and the use of various compositions of simulated intestinal fluids has been well established [3]. It remains a challenge to reproduce the mechanical stress that a dosage form is exposed to during the passage through the GIT. Garbacz et alt. [4] investigated the effect of mechanical stress on a 8 commercially available dosage forms containing mesalazine and found that the release profiles obtained while putting the dosage forms under mechanical stress differ significantly from those obtained under commonly used dissolution methods described in the pharmacopoeias.

In the presented study it is shown that poorly flowing mesalazine can be formulated into a prolonged release dosage form by roll compaction of the mixture containing a matrix former, such as HPMC and direct compression fillers. Moreover, the influence of several fillers on the drug release profiles in standard dissolution methods is compared to that in bio-relevant, mechanical stress simulating dissolution tests.

Roll compaction proved to be a versatile technique to obtain granules suitable for tableting purposes. It is shown that the addition of insoluble fillers (e.g. calcium hydrogen phosphate) does not only help to adjust the release profile but also provides an easy route to improve the mechanical robustness of the dosage form when exposed to mechanical stress encountered in the GIT.
Download the poster here: adjusting-the-release-rate-of-mesalazine-from-matrix-formulations-by-addition-of-various-excipients-poster-2019.pdf