Particle design of three-component system for sustained release using a 4-fluid nozzle spray-drying technique

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Chitosan (Cht) exhibits pH-dependent solubility, dissolving in acid and precipitating in alkali.
• Hydroxypropylmethylcellulose phthalate (HPMCP) shows inverse solubility, dissolving in alkali and precipitating in acid.
• These contrasting properties offer potential for developing controlled-release drug delivery systems.

Purpose of the Study:

• To prepare and characterize composite particles of acetaminophen (Act) with Cht and HPMCP using a 4-fluid nozzle spray-dryer.
• To investigate the formation of solid dispersions and analyze the physical properties and drug-carrier interactions.
• To evaluate the controlled-release potential of the composite particles across different pH conditions.

Main Methods:

• Preparation of solid dispersions using a 4-fluid nozzle spray-dryer.
• Morphological analysis via scanning electron microscopy (SEM).
• Physical characterization using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier-transform infrared (FT-IR) spectroscopy.
• Dissolution rate analysis at various pH values.

Main Results:

• Spray-dried composite particles were spherical and micron-sized.
• PXRD and DSC indicated that acetaminophen became amorphous in the composite particles, forming a solid dispersion.
• FT-IR analysis confirmed hydrogen bonding between acetaminophen and both chitosan and HPMCP.
• The Act-Cht-HPMCP system (ratio 1:2.5:2.5) demonstrated sustained release of acetaminophen in all tested pH solutions.

Conclusions:

• The 4-fluid nozzle spray-dryer effectively produced amorphous solid dispersions of acetaminophen with chitosan and HPMCP.
• The composite particles exhibited sustained drug release, indicating potential for controlled drug delivery applications.
• The pH-dependent solubility of the carriers and drug-carrier interactions contribute to the controlled release mechanism.