Characterization of Tableting Speed-Dependent Deformation Properties of Active Pharmaceutical Ingredients in Powder Mixtures Using Out-of-Die Method

A quantitative evaluation method for determining the effect of tableting speed on the compression properties of pharmaceutical powders was investigated in this study. Cilostazol and ibuprofen were used as active pharmaceutical ingredients (APIs) and mixed with lactose monohydrate and microcrystalline cellulose. Viscoelasticity was examined to evaluate the raw material, and stress relaxation tests were conducted to determine the apparent viscosity and elasticity coefficients of the placebo and two APIs.

Tablets were prepared using a compaction simulator and a rotary tablet press at the tableting speeds ranging from laboratory to commercial. The in-die or out-of-die strain rate sensitivity (SRS) indices were determined as a measure of the compressibility and compactibility. The results showed that the sensitivity of the out-of-die SRS was higher than that of the in-die SRS. The out-of-die SRS of ibuprofen 20% powder, which showed high elasticity and low viscosity, was 13.3–47.9%, whereas that of the placebo and cilostazol 20% (w/w) powder was <7.5%.

A peripheral speed difference of more than 300 mm/s during the out-of-die SRS was sensitive enough to detect the capping tendency. Cilostazol, which has lower elasticity and higher viscosity than ibuprofen, was tested using powder mixtures with the API concentrations of 5–40%; the compressibility SRS was <5% for all API concentrations. In contrast, the compressibility SRS of ibuprofen increased from 4.8 to 81% depending on the API concentration. Using the compressibility SRS as an index, it was possible to extract the tableting speed-dependent compressibility characteristics of API from the powder mixtures containing API.

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Experimental – Materials
Cilostazol (Otsuka Pharmaceutical, Tokyo, Japan), an antiplatelet agent, and ibuprofen (Hachidai Pharmaceutical, Osaka, Japan), a nonsteroidal anti-inflammatory analgesic, were used as model APIs. Lactose monohydrate (Dilactose S; Freund, Tokyo, Japan), microcrystalline cellulose (Ceolus UF-711; Asahi Kasei, Tokyo, Japan), and vegetable-derived magnesium stearate (Taihei Chemical, Osaka, Japan) were used as excipients. A mixture of lactose monohydrate and microcrystalline cellulose (7 : 3) with 1% (w/w) magnesium stearate was used as the placebo mixture. Cilostazol and ibuprofen were added to the placebo mixture at a concentration of 5, 10, 20, and 40% (w/w) powder.

About this article: Characterization of Tableting Speed-Dependent Deformation Properties of Active Pharmaceutical Ingredients in Powder Mixtures Using Out-of-Die Method – Daisuke Mizunaga, Mika Koseki, Naoki Kamemoto, Satoru Watano – Chem. Pharm. Bull. 69, 1184–1194 (2021) – https://doi.org/10.1248/cpb.c21-00665