Solubility, Polymorphism, Crystallinity, Crystal Habit, and Drying Scheme of (R, S)-(±)-Sodium Ibuprofen Dihydrate - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Solubility, Polymorphism, Crystallinity, Crystal Habit, and Drying Scheme of (R, S)-(±)-Sodium Ibuprofen Dihydrate
The racemic compound (R, S)-()-ibuprofen is a popular and well understood active pharmaceutical ingredient, but it has several disadvantageous formulation properties such as poor solubility, low melting point, and potential esterification with excipients containing an hydroxyl group. The authors investigate the use of an (R, S)-()-ibuprofen salt to evaluate these problems using various analytical methods to determine the polymorphism, crystallinity, and drying scheme.


Pharmaceutical Technology


Results and discussion


Figure 3
(R, S)-()-sodium ibuprofen dihydrate dissolved well in nine good solvents in Classes 4 and 5: tetrahydrofuran (THF), n-butyl alcohol, isopropyl alcohol (IPA), benzyl alcohol, N,N-dimethylformamide (DMF), ethanol, dimethyl sulfoxide (DSMO), methanol, and water. The compound only slightly dissolved in n-heptane, xylene, p-xylene, ethyl acetate, toluene, methyl-tert-butyl ether, benzene, methyl ethyl ketone, chloroform, N,N-dimethylaniline, acetone, 1,4-dioxane, nitrobenzene, and acetonitrile with a solubility of <1 mg/mL at 25 C, giving 14 bad solvents in Classes 1, 2, and 3. Only nine solubility curves of (R, S)-()-sodium ibuprofen dihydrate in nine good solvents at 15, 25, 40, and 60 C were constructed and grouped by their similar solubility ranges for ease of comparison (see Figure 3).

If the solute and the solvent formed an ideal solution, a straight line should result when ln x was plotted against 1/T according to the van't Hoff equation (13):











Figure 4
in which x is the mole fraction of (R,S)-()-sodium ibuprofen dihydrate in the solution at a given temperature (T) measured in K, converted from the solubility curves in Figure 3, and Rg was the ideal gas enthalpy constant (8.314 J/mol • K). Any deviation from the ideal solution behavior would be reflected from the correlation coefficient (R) of the linear fit in Figure 4. The relatively high correlation coefficients with values > 0.97 of the solvent systems, except for the one of DMSO, indicated that the solubility measurements by gravimetric titration were quite accurate, and the deviation of the solution from ideality was negligible. The enthalpy of dissolution (ΔHd)and the entropy of dissolution (ΔSd) were estimated from the slope and the y-intercept of the straight lines in Figure 4, respectively.


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