Preparation and evaluation of metastable solid-state forms of lopinavir

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry
• Materials Science

Background:

• Metastable solid-state forms of drugs can significantly impact their therapeutic efficacy.
• Understanding the stability and dissolution behavior of these forms is crucial for drug development.
• Lopinavir, an antiretroviral agent, requires careful formulation to ensure optimal bioavailability.

Purpose of the Study:

• To prepare and characterize novel metastable solid-state forms of lopinavir.
• To investigate the relationship between the structural stability and physicochemical properties of these forms.
• To evaluate the dissolution kinetics and solubility of the newly prepared lopinavir forms.

Main Methods:

• Preparation of partially amorphous crystals, semicrystalline needles, resins, and glasses of lopinavir.
• Characterization using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD).
• Assessment of thermal properties (glass transition temperature, activation energies) and aqueous solubility and dissolution kinetics.

Main Results:

• Successfully prepared and characterized multiple previously unreported metastable forms of lopinavir.
• Each metastable form displayed distinct glass transition temperatures, activation energies for molecular mobility, and equilibrium solubilities.
• Dissolution studies indicated that the release of lopinavir from these forms followed first-order kinetics, with calculated activation energies for dissolution.

Conclusions:

• Multiple metastable solid-state forms of lopinavir can be prepared under varying conditions.
• The stability and dissolution characteristics are intrinsically linked to the specific solid-state form.
• These findings provide valuable insights for the formulation and development of lopinavir-based therapeutics.