Improvement of drug processability in a connected continuous crystallizer system using formulation additive.

Area of Science:

• Chemical Engineering
• Materials Science
• Pharmaceutical Technology

Background:

• Continuous crystallization offers advantages over batch processes for active pharmaceutical ingredients.
• Polymer additives can modify crystal properties, potentially simplifying downstream formulation.
• Improving crystal flowability is crucial for efficient pharmaceutical manufacturing.

Purpose of the Study:

• To develop an additive-assisted continuous crystallization process for acetylsalicylic acid using polyvinylpyrrolidone.
• To enhance the flowability of small, columnar crystals by promoting agglomeration.
• To investigate the effect of process parameters on product quality and yield.

Main Methods:

• Utilized a connected ultrasonicated plug flow crystallizer and mixed suspension mixed product removal (MSMPR) crystallizer system.
• Employed polyvinylpyrrolidone as a polymer additive during cooling antisolvent crystallization.
• Evaluated process parameters including temperature, polymer concentration, and flow rate, alongside segmented antisolvent dosing.

Main Results:

• Achieved continuous production of purified acetylsalicylic acid with consistent quality and an 85% yield.
• Demonstrated that higher polyvinylpyrrolidone concentrations (7.5-14%) effectively promoted crystal agglomeration and improved flowability.
• Confirmed that the improved flowability did not negatively impact the dissolution characteristics of the primary particles.

Conclusions:

• The developed additive-assisted continuous crystallization technology is effective for producing high-quality crystalline active ingredients.
• Polyvinylpyrrolidone addition successfully enhances crystal flowability through agglomeration without compromising dissolution properties.
• This approach offers a promising strategy for streamlining drug formulation processes.