Peer-Reviewed Journal Details
Mandatory Fields
Bueno, RA,Crowley, CM,Hodnett, BK,Hudson, S,Davern, P
2017
April
Organic Process Research & Development
Influence of Process Parameters on the Heterogeneous Nucleation of Active Pharmaceutical Ingredients onto Excipients
Published
()
Optional Fields
PROTEIN CRYSTALS POLYMORPH SURFACES DESIGN CRYSTALLIZATION PARACETAMOL
21
559
570
It is known that chemical and physical compatibility between a heterosurface and the crystallizing, molecule promotes heterogeneous nucleation. In this work, acetaminophen (AAP), alpha/beta-lactose (alpha/beta-Lac), and methanol (MeOH) were selected as, the model active pharmaceutical ingredient, excipient, and solvent, respectively. The excipient-suspended in a supersaturated solution of AAP in MeOH-was used as a heterogeneous surface ("seed"), and parameters influencing the heterogeneous nucleation of the AAP such as (a) AAP solution/excipient contact time, (b) AAP supersaturation, and (c) AAP to excipient loading, were varied to, demonstrate how,the nucleation rate and the degree of crystallization can be manipulated to control the particle site and the balance between nucleation and growth. In this regard, the crystallizations were performed at a supersatutation which was shown not to promote nucleation of AAP up to 2 h in the absence of alpha/beta-Lac. There after, during the heterogeneous crystallizations of AAP in the presence of alpha/beta-Lac, AAP particles nucleated on the alpha/beta-Lac surface and then grew uniformly, producing small AAP particles (<15 mu m) in a robust manner such that the particle size distribution was maintained constant over a range of contact times, supersaturations, and AAP loadings (%).
10.1021/acs.oprd.6b00425
Grant Details