Engineering Processing Properties of Acetaminophen by Cosolvent Screening - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
23%
Oversee medical treatment of patients in the US.
14%
Provide treatment for patients globally.
7%
All of the above.
47%
No government involvement in patient treatment or drug development.
9%
Jim Miller Outsourcing Outlook Jim MillerOutside Looking In
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAdvances in Large-Scale Heterocyclic Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler New Era for Generic Drugs
Sean Milmo European Regulatory WatchSean MilmoTackling Drug Shortages
New Congress to Tackle Health Reform, Biomedical Innovation, Tax Policy
Combination Products Challenge Biopharma Manufacturers
Seven Steps to Solving Tabletting and Tooling ProblemsStep 1: Clean
Legislators Urge Added Incentives for Ebola Drug Development
FDA Reorganization to Promote Drug Quality
Source: Pharmaceutical Technology,
Click here