Continuous API-crystal coating via coacervation in a tubular reactor

Area of Science:

• Pharmaceutical Technology
• Chemical Engineering
• Materials Science

Background:

• Continuous manufacturing processes offer advantages over batch methods in pharmaceutical production.
• Microencapsulation techniques are crucial for modifying drug release profiles and protecting active pharmaceutical ingredients (APIs).
• Coacervation is a viable method for forming polymer shells around particles.

Purpose of the Study:

• To develop and demonstrate a proof-of-concept for continuous coating of single API crystals using coacervation in a tubular reactor.
• To investigate the feasibility of microencapsulating lipophilic API crystals with enteric polymers.
• To explore the potential of continuous processing for functional API crystal preparation.

Main Methods:

• A continuous coating process was developed in a tubular reactor using coacervation.
• Lipophilic ibuprofen crystals were suspended in aqueous solutions of hypromellose phthalate (HPMCP) or Eudragit L100-55.
• Coacervation was induced by mixing with a sodium sulfate antisolvent, followed by temperature treatment and cross-linking at pH<3.

Main Results:

• The study successfully demonstrated continuous microencapsulation of API crystals.
• Controlled process parameters (flow rates, temperature, ratios) were essential to prevent aggregation and pipe plugging.
• The process yielded coated crystals with potential for modified release and enhanced stability.

Conclusions:

• A tubular reactor design is suitable for continuous API crystal coating via coacervation.
• This continuous process offers a promising alternative to batch coating for pharmaceutical applications.
• Further research can integrate continuous crystallization with this continuous coating method.