Processing of nimesulide-PEG 400-PG-PVP solid dispersions: preparation, characterization, and in vitro dissolution

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Formulation Development

Background:

• Nimesulide, a model active pharmaceutical material, often exhibits poor aqueous solubility, limiting its therapeutic efficacy.
• Enhancing the dissolution rate of poorly soluble drugs is crucial for improving bioavailability and therapeutic outcomes.

Purpose of the Study:

• To investigate the impact of various dissolution enhancers on the in vitro dissolution profile of nimesulide.
• To optimize the formulation of nimesulide using a blend of pharmaceutical adjuvants through a 33 factorial design.

Main Methods:

• Preparation of solid dispersions and physical blends of nimesulide with adjuvants like polyethylene glycol 400, propylene glycol, and polyvinylpyrrolidone K30.
• Utilized solvent evaporation and cogrinding methods for solid dispersion preparation.
• Employed a 33 factorial design to study the influence of key adjuvants on drug dissolution and granule properties.

Main Results:

• Polyvinylpyrrolidone demonstrated superior efficacy in enhancing nimesulide dissolution compared to polyethylene glycol 400 and propylene glycol.
• High concentrations of liquid adjuvants negatively impacted granule flow properties.
• The optimized formulation achieved a significant increase in drug release (Q120 = 70%) compared to pure nimesulide powder (Q120 = 15%), attributed to improved wetting and solubilization.

Conclusions:

• Dissolution of nimesulide can be effectively modulated by incorporating a suitable combination of pharmaceutical adjuvants.
• The study highlights the potential of solid dispersions and pseudosolid dispersions in enhancing the dissolution of poorly soluble drugs.
• Formulation strategies involving dissolution enhancers are vital for improving the performance of active pharmaceutical ingredients.