(680f) Heterogeneous Nucleation of APIs on Engineered Biocompatible Polymer Surfaces
Microsoft Word - AIChE Abstract.docx
Heterogeneous Nucleation of APIs on Engineered Biocompatible Polymer Surfaces
Li Tan, Rachel M. Davis, Prof. Allan S. Myerson, Prof. Bernhardt L. Trout
Date: May 12th, 2014
Continuous manufacturing of pharmaceuticals have significant advantages over batch processing in terms of economics, reliability, safety, and sustainability. Directly crystallize active pharmaceutical ingredients (APIs) on polymer excipient surfaces can achieve impurity separation and drug-excipient composite formation in a single step, which eliminates many solid handling steps traditionally needed in downstream processing. In order to develop such a process, we must understand the kinetics of heterogeneous nucleation of small molecule drugs on biocompatible polymer surfaces, and study how heterogeneous nucleation affects polymorph formation. The chemical interactions between APIs and polymer substrates plus the effect of surface geometries are the focuses of the present investigation.
We engineered surfaces by first manufacturing a rigid silicon mold using interference lithography to create nanometer-sized and mono-dispersed pillars of varying angles on a flat surface. Negatives of the mold were transferred to polyvinyl alcohol (PVA) films via nano- imprint lithography to create films with nano-pores. The films were submerged in solution as substrates for cooling crystallization of two API compounds, aspirin and indomethacin. A high throughput system was used to collect heterogeneous nucleation kinetics data on the patterned films at low supersaturation settings. Experimental results show that the induction time of aspirin on these surfaces were reduced by more than an order of magnitude with favorable surface chemistry, with further reduction achieved by matching surface geometry. Matching angles on the substrate surface and angles between dominant faces resulted in the greatest reduction in induction time. X-ray diffraction studies revealed favorable interactions between dominant habit faces of aspirin to PVA via hydrogen bonding. Crystallization experiments with indomethacin as the model compound show that in addition to enhancing nucleation rates, polymer chemistry and surface geometry also alters the distribution of polymorphs obtained in the experiments. Correlation between final polymorph distribution on film surface and initial nucleation events were established using Raman spectroscopy. Computational analyses were also used to corroborate experimental results and hypothesis presented.
This paper has an Extended Abstract file available; you must purchase the conference proceedings to access it.
Do you already own this?
Log In for instructions on accessing this content.
|AIChE Graduate Student Members||Free|
|AIChE Undergraduate Student Members||Free|