Engineering Processing Properties of Acetaminophen by Cosolvent Screening - Pharmaceutical Technology

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Engineering Processing Properties of Acetaminophen by Cosolvent Screening
The authors used common solvents to develop an initial solvent-screening method for laboratory-scale research to determine the solubility, polymorphism, and crystal properties of various active ingredients.

Pharmaceutical Technology
Volume 34, Issue 8, pp. 61-68


Cosolvent screening is a useful and beneficial method for finding ideal cosolvent systems to create the desirable processing properties of acetaminophen crystals because cosolvent systems offered a wide range of choices in solubility, theoretical yield, crystal habit, aspect ratio, and crystallinity. Although small crystal sizes are advantageous for decreasing the force exerted on the roll-bearing blocks for roll compaction and for enhancing the dissolution rate because they lower εn and raise S, respectively (see Table I), small crystal sizes can lengthen the drying rate, the filtration rate, the mixing rate, and the growth rate of granules in the nuclear growth region because of the decreases in R c (which resulted from strong capillary force), D p, k 2, and X a, respectively (see Table I). Crystals with an aspect ratio higher than 3 have needle shapes that are easily broken into pieces of smaller crystal and fines. Therefore, systems produced relatively large crystal sizes, aspect ratios of ~1, and high theoretical yield such as that of the ethyl acetate and acetonitrile system. The authors will carry out similar investigations in the near future for the antisolvent systems represented by the green boxes in Table II and the scale-up effect on the crystal-size distribution.


This work was supported by a grant from the national Science Council of Taiwan, ROC (NSC 97-2113-M-008-006). Suggestions about DSC from Jui-Mei Huang, at Precision Instrument Center in National Central University are gratefully acknowledged.

Tu Lee* is an associate professor, and Gen Da Chang is a graduate student at the Department of Chemical and Materials Engineering, National Central University, 300 Jhong-Da Rd., Jhong-Li City 320, Taiwan, ROC, tel. +886 3 422 7151 ext. 34204, fax +886 3 425 2296,

*To whom all correspondence should be addressed.

Submitted: Aug. 13, 2009. Accepted: Nov. 20, 2009.


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