Site specific solubility improvement using solid dispersions of HPMC-AS/HPC SSL--mixtures

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Many new drugs are weak bases with poor solubility in the gastrointestinal tract, causing variable bioavailability.
• pH-dependent solubility leads to challenges in achieving reliable drug therapy.

Purpose of the Study:

• To design solid dispersions for improved dissolution and sustained supersaturation of poorly soluble weak bases.
• To overcome pH-dependent solubility issues and enhance drug bioavailability.
• To create site-specific drug delivery systems.

Main Methods:

• Solid dispersions of Dipyridamole (DPD) or Griseofulvin (GRI) with hydroxypropylmethylcellulose-acetate succinate (HPMC-AS) and hydroxypropylcellulose (HPC-SSL) were prepared using hot melt extrusion (HME).
• Solid-state characterization and dissolution testing using a three pH-step method were performed.
• Stability studies were conducted.

Main Results:

• HPMC-AS in binary mixtures enhanced solubility and supersaturation, preserving the amorphous state of DPD and GRI.
• The pH-dependent solubility profile of Dipyridamole was inverted, creating a site-specific delivery system.
• Ternary solid dispersions with HPMC-AS and HPC-SSL achieved tailored release profiles and superior supersaturation.
• Both binary and ternary mixtures exhibited favorable stability.

Conclusions:

• Solid dispersions formulated with HPMC-AS offer a promising strategy to improve the bioavailability of poorly soluble weak bases.
• The developed systems provide site-specific drug release and maintain supersaturation across the gastrointestinal pH range.
• Hot melt extrusion is an effective method for creating stable and effective solid dispersions for enhanced drug delivery.