Amorphous spray-dried hydroflumethiazide-polyvinylpyrrolidone systems: physiochemical properties

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Hydroflumethiazide is a diuretic drug with poor aqueous solubility.
• Amorphous solid dispersions are a strategy to enhance the solubility and bioavailability of poorly soluble drugs.
• Spray drying is a common technique for producing amorphous solid dispersions.

Purpose of the Study:

• To investigate the formation and properties of hydroflumethiazide-polyvinylpyrrolidone (PVP) amorphous systems prepared by spray drying.
• To characterize the physical state, solubility, and thermodynamic properties of these spray-dried systems.
• To understand the influence of PVP content on the amorphous state and drug performance.

Main Methods:

• Spray drying of hydroflumethiazide with varying PVP concentrations (0-30%).
• Differential scanning calorimetry (DSC) to assess thermal properties and physical state.
• Solubility studies to determine apparent solubility in spray-dried systems.
• Dissolution studies using compressed discs to evaluate drug release.
• Thermodynamic analysis of free energy and entropy.

Main Results:

• Spray-dried systems were amorphous and distinct from coprecipitates.
• DSC indicated the presence of both amorphous drug and amorphous drug-PVP complex at low PVP fractions.
• Apparent solubility of hydroflumethiazide increased with PVP content, reaching a plateau ~4x that of crystalline drug.
• Free energy and entropy of the drug increased with PVP content.
• Dissolution data supported the observed increase in apparent solubility.

Conclusions:

• Spray drying hydroflumethiazide with PVP yields amorphous systems with enhanced apparent solubility.
• The extent of amorphous phase organization increases with PVP content.
• These findings suggest potential for improved hydroflumethiazide bioavailability through amorphous solid dispersion formulation.