Formulation design space for stable, pH sensitive crystalline nifedipine nanoparticles.

Area of Science:

• Pharmaceutical Technology
• Nanotechnology
• Drug Delivery Systems

Background:

• Enteric coatings protect drugs from stomach degradation and facilitate intestinal absorption.
• Optimizing formulation parameters is crucial for developing stable and effective drug delivery systems.
• Nifedipine nanoparticles require careful formulation to ensure stability and targeted delivery.

Purpose of the Study:

• To optimize formulation parameters for pH-sensitive nifedipine nanoparticles using Design of Experiments (DoE).
• To evaluate the stability of optimized nifedipine nanoparticles under various storage conditions.
• To develop a predictive model for the preparation of stable pH-sensitive nifedipine nanoparticles.

Main Methods:

• Application of four Design of Experiments (DoE) models for formulation optimization.
• Preparation of pH-sensitive nifedipine nanoparticles using Eudragit®L 100-55 and polyvinyl alcohol.
• Stability assessment of nanoparticles over three months at 4°C, 25°C, and 40°C, monitoring particle size, polydispersity index, surface charge, and drug release at pH 1.2 and 6.8.
• Multiple linear regression analysis for predictive model development.

Main Results:

• Optimized nifedipine nanoparticles exhibited an average particle size of 131.86±8.21nm, a polydispersity index of 0.135±0.008, and a surface charge of -7.631±0.146mV.
• Formulations stored at 4°C remained stable for three months regarding particle size, homogeneity, surface charge, drug loading, and drug release.
• Nanoparticles stored at 25°C and 40°C showed relative instability over the same period.

Conclusions:

• A combination of Eudragit®L 100-55 and polyvinyl alcohol effectively stabilized the nifedipine nanoparticle suspension.
• Optimal storage at 4°C is critical for maintaining the stability and integrity of these pH-sensitive nanoparticles.
• A predictive model using multiple linear regression was successfully developed for preparing stable pH-sensitive nifedipine nanoparticles.