(W1030-03-15) The Evaluation of Methacrylic Acid Copolymer as a Direct Compressible Excipient for Erosion Based Sustained Release Matrix Tablets

Purpose: Methacrylic acid copolymer, USP/NF (Kollicoat^® MAE 100-55) has been used for enteric film coating for tablets or pellets to target the drug release at the small intestine. The excipient has also been used for sustained release purposes, typically for weak basic actives to have a more consistent release profile^{1, 2}. In this study, we evaluated Kollicoat^® MAE 100-55 as the sole matrix forming excipient for sustained release effect. Direct compression process was evaluated as an easy to manufacture method for sustained release tablets. Factors such as the diluents used, the particle size of Kollicoat^® MAE 100-55 and compression forces were evaluated for their effect on the drug release profiles.

Methods: Diclofenac sodium was used as the model drug. Sustained release tablets were prepared by direct compression of the active withKollicoat^® MAE 100-55 and other excipients. Drug release was evaluated using the dissolution method specified for Diclofenac Sodium Extended-Release Tablets, USP.

Results: Different levels of Kollicoat^® MAE 100-55 were evaluated for the sustained release effect. 8% of Kollicoat^® MAE 100-55 was enough to match the release profile specified in the USP. The tablets formed a gel in the dissolution media and slowly eroded. Among the diluents evaluated, the combination of microcrystalline cellulose (MCC) and lactose provided good processability for tablet compression. The ratio of MCC and lactose influenced the tablet dissolution. A 5:1 ratio proved to be the best combination to match the USP dissolution profile. Tablet hardness also have an effect on the dissolution. Tablets with an average hardness of 7.5kp showed 15.5% drug release at 1 hour compared with 40% for those with an average hardness of 5.5kp. The effect of the particle size of Kollicoat^® MAE 100-55 was also evaluated. Kollicoat^® MAE 100-55 Fine, a finer grade of the polymer matrix showed slower drug release compared with the regular grade. As an enteric polymer that only dissolves at pH 5.5 and above, the pH of the dissolution media had an effect on the tablet dissolution. As expected, the tablets had slower release in media at pH 1.2 and pH 4.5.

Conclusion: Kollicoat^® MAE 100-55 can be used as a polymer matrix for sustained release. The main mechanism of the drug release is erosion. The selection of other excipients needs to be evaluated carefully as the solubility of some excipients may accelerate the drug release. The particle size of Kollicoat^® MAE 100-55 also affects the drug release, indicating the importance of batch consistency of the polymer matrix. Finally, the pH of the dissolution media needs to be evaluated carefully to have a good correlation of the in vivo performance.

References: 1. US 6,811,794 B2, Sustained release pharmaceutical dosage forms with minimized pH dependent release profiles
2. Bashar M. Al-Taani and Bassam M. Tashtoush, Effect of Microenvironment pH of Swellable and Erodable Buffered Matrices on the Release Characteristics of Diclofenac Sodium, AAPS PharmSciTech 2003; 4 (3) Article 43