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

Latest Issue

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

Figure 5
When the positions of the 23 solvents were located within the 3-D space of a dispersion-force component (δd), a polar component (δp), and a hydrogen-bonding component (δh) according to their corresponding coordinates of (δd, δp, δh, ) in Table I and all the good solvents were represented by yellow and bad solvents by red in the form space (see Table III), a cluster of yellow domains were formed. The contour of these yellow domains outlined a 3-D volume of solubility in space. Good solvents were those solvents within the volume, bad solvents were solvents outside the volume (see Figure 5). This space could be represented by a solubility sphere with center coordinates (δd,API, δp,API, δh,API) and interaction radius (RS-API), for (R, S)-()-sodium ibuprofen dihydrate in the 3-D Hansen plot.

By trial and error, the center coordinates (δd,API, δp,API, δh,API) were determined using the following (15):

Figure 6
in which DS–API was the distance between the solvent location and the center of the sphere. For the 23 solvents listed in Table I with their corresponding sets of Hansen parameters (δd,s, δp,s, δh,s ), 23 DS–API would result for any chosen set of center coordinates (δd,API, δp,API, δh,API). Only one particular set of center coordinates of (δd,API, δp,API, δh,API) giving 9 DS–API values for nine corresponding good solvents that were < the 14 DS–API values calculated from the 14 bad solvents. The largest value among the nine DS–API values was the interaction radius of the solubility sphere. For (R, S)-()-sodium ibuprofen dihydrate at 25 C, the values of δd,API, δp,API, δh,API, and RS–API with respect to the 23 solvents listed in Table I were determined to be 19.89, 16.19, 30.89 and 25.92 MPa1/2, respectively (21, 22).


blog comments powered by Disqus
LCGC E-mail Newsletters

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

FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Source: Pharmaceutical Technology,
Click here