Stability screening of pharmaceutical cocrystals

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry

Background:

• Cocrystals are crucial for enhancing active pharmaceutical ingredient (API) stability and solubility.
• Assessing both chemical and physical stability is vital for drug product development and shelf-life prediction.

Purpose of the Study:

• To propose an efficient protocol for evaluating the chemical and physical stability of API cocrystalline forms.
• To establish a method for predicting a minimum one-year shelf-life for cocrystal formulations.

Main Methods:

• Preparation of low-dose tablets from cocrystalline material, mimicking wet granulation.
• Designed stress testing (temperature, RH) followed by degradant formation modeling using ASAPprime®.
• Physical stability assessment using kinetic solubility changes under selected stress conditions.

Main Results:

• The protocol effectively models degradant formation to predict shelf-life.
• Kinetic solubility changes indicate potential physical instability risks during long-term storage.
• The method was successfully exemplified using model API cocrystals.

Conclusions:

• The proposed protocol offers an efficient approach to assess cocrystal stability.
• This method aids in determining the shelf-life and physical stability of cocrystal formulations.
• The protocol supports the development of stable and effective cocrystal-based drug products.