Description
A novel method for the simultaneous production and formulation of pharmaceutical cocrystals, matrix-assisted cocrystallization (MAC), using hot-melt extrusion by coprocessing the drug and conformer has been developed. Three model drugs were used, a coformer, and matrix, respectively. The MAC product containing 80:20 (w/w) cocrystal:matrix was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. A partial least squares (PLS) regression model was developed for quantifying the efficiency of cocrystal formation. The PLS model estimated that the MAC product was 78% (w/w) cocrystal (theoretical 80%), with ~ 0.3% mixture of free (unreacted) drug, and 21.6% Soluplus (theoretical 20%). A physical mixture (PM) of a reference cocrystal (RCC), prepared by precipitation from solution, and Soluplus resulted in faster dissolution relative to the pure RCC. However, the MAC product with the exact same composition resulted in considerably faster dissolution and higher maximum concentration (~5-fold) than those of the PM. The MAC product consists of high-quality cocrystals embedded in a matrix. The processing aspect of MAC plays a major role on the faster dissolution observed. The MAC approach offers a scalable process, suitable for the continuous production, manufacturing, and formulation of pharmaceutical cocrystals.
Recommended Citation
Boksa, K., Otte, A., & Pinal, R. (2014). Towards continuous production of pharmaceutical cocrystals. In A. Bajaj, P. Zavattieri, M. Koslowski, & T. Siegmund (Eds.). Proceedings of the Society of Engineering Science 51st Annual Technical Meeting, October 1-3, 2014 , West Lafayette: Purdue University Libraries Scholarly Publishing Services, 2014. https://docs.lib.purdue.edu/ses2014/mss/pharmsolids/11
Towards continuous production of pharmaceutical cocrystals
A novel method for the simultaneous production and formulation of pharmaceutical cocrystals, matrix-assisted cocrystallization (MAC), using hot-melt extrusion by coprocessing the drug and conformer has been developed. Three model drugs were used, a coformer, and matrix, respectively. The MAC product containing 80:20 (w/w) cocrystal:matrix was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. A partial least squares (PLS) regression model was developed for quantifying the efficiency of cocrystal formation. The PLS model estimated that the MAC product was 78% (w/w) cocrystal (theoretical 80%), with ~ 0.3% mixture of free (unreacted) drug, and 21.6% Soluplus (theoretical 20%). A physical mixture (PM) of a reference cocrystal (RCC), prepared by precipitation from solution, and Soluplus resulted in faster dissolution relative to the pure RCC. However, the MAC product with the exact same composition resulted in considerably faster dissolution and higher maximum concentration (~5-fold) than those of the PM. The MAC product consists of high-quality cocrystals embedded in a matrix. The processing aspect of MAC plays a major role on the faster dissolution observed. The MAC approach offers a scalable process, suitable for the continuous production, manufacturing, and formulation of pharmaceutical cocrystals.