Category: Formulation and Quality
Purpose: Using a direct compression process after dry blending or dry granulation is beneficial compared to wet-granulation methods. It shows higher productivity in terms of simple process and total processing time, and it also gives a better stability when the active pharmaceutical ingredient (API) is sensitive to moisture and heat. However, when the API has a poor compressibility, high API-loaded tablets are not easy to prepare if the binder performance is insufficient. Methylcellulose (MC) is a conventional excipient that has been used for many years for the applications of wet-granulation binder, thickener and film coating. A new grade of MC, that has a smaller particle size and larger surface area, has been developed. The purpose of this study was to evaluate the smaller particle MC as a highly-compressible dry binder for use in a direct compression process.
Methods: Acetaminophen was used for a model of poorly compressible API. Original MC, a viscosity grade of 4 mPa·s (Metolose® SM-4, Shin-Etsu Chemical, Japan, mean particle size, d50: approximately 50 μm) and new-grade MC that has a smaller particle size (SM-4 VF, Shin-Etsu Chemical, Japan, d50: 10 μm) were used as dry binders. Lactose and low-substituted hydroxypropyl cellulose (L-HPC, Shin-Etsu Chemical, Japan) were used as a filler and disintegrant, respectively. Tablets (8 mm in diameter, 200 mg per tablet) were prepared using a rotary tablet press (Virgo, Kikusui, Japan) after dry blending. Tablet properties, tablet hardness, disintegration time and friability of tablets were measured according to the compendial methods. Tablets were stored at 40°C/75% RH and a stability study was also performed.
Results: Bulk density of the new-grade MC was lower than the original MC due to its fine particle size. The new-grade MC showed a sufficient high hardness compared to other binders even at a content of 5 % in the formulation. It was 1.5 - 2 times the hardness compared to the original MC. In the high API-loaded formulation, it kept sufficient tablet hardness. Disintegration time was increased as the tablet hardness increased, and the new-grade MC showed a similar pattern with other binders. Friability of the tablets was lower than the original MC and other binders, and the tablet weight deviation was also showed sufficiently low. In the stability test, the tablet hardness and the disintegration time of tablets composed of MC were sufficiently stable for a long term. On the other hand, they were significantly increased in the other binder formulations.
Conclusion: The new grade of MC was found to significantly improve the compressibility in the direct compression of tablets. It can provide better tablet properties and also sufficient stability compared to other conventional dry binders even at a lower additive amount. It is suggested that the highly compressible MC is an excellent dry binder for use in dry compaction processes.