A Co-Processed API Approach for a Shear Sensitive Compound Affording Improved Chemical Stability and Streamlined Drug...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Active pharmaceutical ingredient (API) physical properties critically impact drug substance (DS) and drug product (DP) processing and final dosage unit quality.
• High aspect ratio, low bulk density APIs, particularly needle-like crystals, present significant processing challenges.
• Shear sensitivity leading to amorphous phase conversion and degradation further complicates API processing.

Purpose of the Study:

• To address the processing challenges posed by a shear-sensitive, needle-like API with poor physical properties.
• To develop an innovative isolation strategy to improve API morphology, bulk density, and flowability.
• To enhance the chemical stability and processability of the API for direct encapsulation oral dosage forms.

Main Methods:

• Evaluation of API physical properties, including morphology and shear sensitivity.
• Exploration of conventional crystallization routes to modify API morphology.
• Development and application of a thin film evaporation (TFE) process with a water-soluble polymer for API isolation and co-processing.

Main Results:

• Conventional methods failed to improve the API's challenging physical properties.
• The TFE process with a polymer successfully produced a high bulk density, free-flowing API.
• Engineered API exhibited reduced amorphous levels and decreased shear sensitivity due to surface coating by the polymer.

Conclusions:

• The TFE-based particle engineering route effectively overcomes the limitations of conventional API processing.
• This innovative strategy improves API chemical stability and simplifies both DS and DP operations.
• The co-processed API is amenable to direct encapsulation, enabling the development of robust oral dosage forms.