Multivariate Analysis of Solubility Parameters for Drug-Polymer Miscibility Assessment in Preparing Raloxifene...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Drug solubility is crucial for effective drug delivery.
• Solid dispersions enhance drug solubility but depend on drug-polymer miscibility.
• Predictive methods for selecting appropriate polymeric carriers are needed.

Purpose of the Study:

• To categorize and select polymeric carriers for RX-HCl solid dispersions using solubility parameters.
• To evaluate the miscibility of RX-HCl with various polymers.
• To validate the predictive model through experimental characterization.

Main Methods:

• Calculation of Hansen Solubility Parameters (HSP) for RX-HCl using the group contribution method.
• Multivariate analysis including hierarchical clustering and principal component regression.
• Experimental production of solid dispersions via solvent casting.
• Characterization using X-ray diffraction, infrared spectroscopy, and scanning electron microscopy.

Main Results:

• RX-HCl exhibited a Hansen Solubility Parameter (HSP) of 23.52 MPa^1/2.
• A classification of polymer-drug combinations into miscible (11), partially miscible (15), and immiscible (10) was achieved.
• Significant correlation found between reduced crystallinity and calculated HSP/RED values.
• Spectroscopic analysis indicated hydrogen bonding contributes to amorphization.

Conclusions:

• The group contribution method and HSP analysis effectively predict polymer-drug miscibility for solid dispersions.
• This systematic approach aids in optimal excipient selection for creating solid solutions.
• The findings facilitate the development of enhanced drug solubility formulations.