Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution: pros and cons

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Materials Science

Background:

• Poor aqueous solubility limits the bioavailability of many hydrophobic drugs.
• Developing effective formulations is crucial for enhancing drug efficacy.
• Solid dispersions and solid solutions are strategies to improve drug solubility and dissolution.

Purpose of the Study:

• To compare the efficacy of solid dispersions (SD) and solid solutions (SS) in enhancing the solubility and bioavailability of a model hydrophobic drug.
• To evaluate the physical stability and in vivo performance of these formulations.
• To determine the optimal formulation strategy for poorly water-soluble drugs.

Main Methods:

• Formulation of solid dispersions with poloxamer 188 (P188) and solid solutions with polyvinylpyrrolidone K30 (PVPK30).
• Characterization using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), intrinsic dissolution rate (IDR), and contact angle measurements.
• Accelerated stability studies and in vivo evaluation in beagle dogs.

Main Results:

• Solid dispersions maintained drug crystallinity, forming a two-phase system.
• Solid solutions resulted in an amorphous monophasic system, converting crystalline drug to amorphous state.
• Solid solutions exhibited higher initial dissolution rates, but decreased upon storage due to partial crystallization.
• Solid dispersions demonstrated superior in vivo bioavailability compared to solid solutions.

Conclusions:

• Solid dispersions with P188 are a more suitable approach than solid solutions with PVPK30 for improving the dissolution rate and bioavailability of the studied hydrophobic drug.
• Physical stability and in vivo performance favor solid dispersions for poorly water-soluble compounds.
• Formulation choice significantly impacts drug solubility, dissolution, and ultimately, therapeutic efficacy.