Controlled API crystallization during additive manufacturing of solid dosage form for flexible integrated...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Conventional solid dosage form manufacturing involves complex unit operations and challenges in handling solids.
• Liquid dispensing offers a potential alternative to overcome manufacturing complexities.
• Additive manufacturing presents an opportunity for flexible and intensified pharmaceutical production.

Purpose of the Study:

• To explore liquid dispensing via additive manufacturing for creating oral solid dosage forms.
• To develop a robust process for generating crystalline solid dispersions.
• To demonstrate a generalizable approach for pharmaceutical formulation.

Main Methods:

• Dispensing a solution of drug substance, solvent, and polymer into a capsule carrier.
• Utilizing controlled solvent evaporation to induce crystallization within a polymer matrix.
• Evaluating critical process parameters (temperature, concentration, evaporation rate, solvent choice) and performance metrics.

Main Results:

• Successfully generated a crystalline solid dispersion of racemic modafinil (MOD) in polyethylene glycol.
• Achieved the desired polymorph form I of MOD.
• The manufactured solid dispersion met quality attributes comparable to commercial modafinil tablets (Provigil®).

Conclusions:

• Additive manufacturing via liquid dispensing provides a flexible approach for solid dosage form production.
• The developed process is generalizable to various drug substance-polymer-solvent systems for both crystalline and amorphous solid dispersions.
• This method supports process intensification and potential applications in personalized medicine and point-of-use manufacturing.