(355b) Impact of Co-Precipitation Technique on API Physical Properties and Morphology to Enable Continuous Processing

Given the shortening development times for API drug substance development and an increase in needle morphology for final API has made it challenging for final crystallization to enable particle properties for downstream drug product continuous processing. Target properties tend to be the bulk density and morphology which has direct impact on flow needed for continuous direct compression. ¹ Co-precipitation techniques are a new form of process technology to improve API physical properties utilizing wet processes that are directly suitable to crystallization equipment.^2-5 Herein, we present a case study that demonstrates a screening workflow to precipitate an API of poor physical properties with different excipients. The outcome of which is API that is either entirely crystalline or amorphous dependent on the technique used and marked improvement in physical properties.

References

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(2) Erdemir, D.; Daftary, V.; Lindrud, M.; Buckley, D.; Lane, G.; Malsbury, A.; Tao, J.; Kopp, N.; Hsieh, D. S.; Nikitczuk, W. Design and scale-up of a co-processing technology to improve powder properties of drug substances. Org. Process Res. Dev. 2019, 23 (12), 2685-2698.

(3) Rosenbaum, T.; Erdemir, D.; Chang, S.-Y.; Kientzler, D.; Wang, S.; Chan, S. H.; Brown, J.; Hanley, S.; Kiang, S. A novel co-processing method to manufacture an API for extended release formulation via formation of agglomerates of active ingredient and hydroxypropyl methylcellulose during crystallization. Drug Dev. Ind. Pharm. 2018, 44 (10), 1606-1612.

(4) Mann, A. K.; Schenck, L.; Koynov, A.; Rumondor, A. C.; Jin, X.; Marota, M.; Dalton, C. Producing amorphous solid dispersions via co-precipitation and spray drying: impact to physicochemical and biopharmaceutical properties. J. Pharm. Sci. 2018, 107 (1), 183-191.

(5) Trasi, N. S.; Oucherif, K. A.; Litster, J. D.; Taylor, L. S. Evaluating the influence of polymers on nucleation and growth in supersaturated solutions of acetaminophen. CrystEngComm 2015, 17 (6), 1242-1248.