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

Results and discussion

Table II: Theoretical yield, apparent heat of solution, Gibb's free energy of dissolution, aspect ratio, enthalpy of melting, and crystallinity of acetaminophen Form I crystals grown from or dissolved in cosolvent systems.
Out of the 100 cosolvent systems, the authors constructed only 92 solubility curves represented as van't Hoff plots because eight cosolvent systems (i.e., THF and N-butyl alcohol, THF and DMF, methanol and DMSO, methanol and 1,4-dioxane, methanol and ethanol, ethanol and 1,4-dioxane, DMSO and benzyl alcohol, and DMF and benzyl alcohol) had exhibited light pink–orange color, thus indicating the possible formation of two side-products of acetaminophen oxidation (i.e., p-benzoquinonemonoimine and p-benzoquinone) (see Table II) (16).

In general, a cosolvent system was a better solubilizer than a single solvent system (7). The theoretical yield (i.e., the amount of crystalline solids that would result if the saturated solution at 60 C were cooled to 25 C) was approximated from each solubility curve using the following equation:

Table II (Continued).
where S h is the solubility (g/mL) at 60 C, and S L is the solubility (g/mL) at 25 C. The cosolvent system of benzyl alcohol and acetonitrile and the cosolvent system of ethanol and acetone gave a maximum theoretical yield of 71.73% and a minimum of 17.94%, respectively (see Table II). These results implied that the interactions between protic benzyl alcohol and polar aprotic acetonitrile were relatively weak and more sensitive to temperature change than the relatively strong interactions between hydrogen-bond donating ethanol and hydrogen-bond accepting acetone (7).


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