Rational and precise development of amorphous polymeric systems with dapsone by response surface methodology.

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Dapsone (DAP) exhibits poor aqueous solubility, limiting its oral bioavailability.
• Polymeric dispersions (PDs) offer a strategy to enhance the dissolution and solubility of poorly soluble drugs.

Purpose of the Study:

• To design amorphous dapsone (DAP) polymeric dispersions (PD) using design of experiments (DoE) and response surface methodology (RSM).
• To optimize PD formulation for improved oral delivery by tailoring biopharmaceutical properties.

Main Methods:

• A 3(2) factorial design was employed to investigate the impact of PVP K30 and Pluronic F68 on DAP solubility in physical mixtures (PM), kneaded (KN), and freeze-dried (FD) PDs.
• X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were used for characterization.
• In vitro dissolution studies were conducted to assess drug release.

Main Results:

• Increased PVP K30 enhanced DAP equilibrium solubility, particularly in FD PDs.
• Increased Pluronic F68 concentration decreased DAP solubility.
• FD PDs exhibited amorphous characteristics, enhanced homogeneity, increased surface area, and significantly faster in vitro dissolution rates compared to DAP and PM.
• Similarity factors (f2) below 50 confirmed significant differences in dissolution profiles.

Conclusions:

• Polymeric dispersions are effective in improving the dissolution and solubility of dapsone.
• DoE and RSM are successful Quality by Design (QbD) tools for optimizing PD formulation for enhanced oral delivery.