(306d) High Throughput Solvent Screening for Ethylcellulose Barrier Membranes in Pharmaceutical Applications

High Throughput Solvent Screening for
Ethylcellulose Barrier Membranes in Pharmaceutical Applications

Cody
A. Schoener, Jaime Curtis-Fisk, True L. Rogers

Dow Pharma and
Food Solutions, The Dow Chemical Company, Midland, MI, USA

Purpose: Solvent is a process variable
that can influence barrier membranes composed of ethylcellulose for
modified-release pharmaceutical applications. Due to a wide variety of solvents
used in barrier membrane coating, high throughput research (HTR) can be utilized
to quickly screen and identify successful or unsuccessful solvent systems. 
Therefore, HTR screening was used to explore a variety of solvent systems
wherein a subset of those solvent systems were used for rheological,
mechanical, and performance testing of ethylcellulose barrier membranes.  

Methods: HTR robots were used to prepare
31 formulations in a Design of Experiments approach. The solvent systems were
composed of ethanol, isopropanol, methanol, acetone, and/or water in which 10
wt% of ethylcellulose 10 cps (ETHOCEL^TM Std 10 Premium, Dow
Chemical) was dissolved by shaking overnight.  Phase Identification and
Characterization Analysis HTR instrumentation was used to image and analyze
clarity of the solutions. A subset of these samples was selected that
represented the range of clarity observed for Dynamic Light Scattering (DLS)
analysis. From this set, samples that exhibited unique light scattering
characteristics were subjected to rheological measurements, tensile tests,
water permeation, and drug transport studies.

Results: Using HTR, the 31 formulations (solvent +
ethylcellulose) were developed and imaged to determine their clarity. Samples
ranged from nearly translucent to hazy, and in some cases the ethylcellulose
remained un-dissolved (Figure 1). 10 samples ranging from translucent to hazy
were further tested with DLS. DLS enabled characterization of monomodal and
bimodal distributions of ethylcellulose conformation and reduced the DLS subset
to 4 samples for further investigation (Figure 1). The pre-screening HTR
methods resulted in formulations exhibiting unique properties, and allowed us
to focus on four formulations for film tensile and permeation testing. Further
results will be presented demonstrating how altering solvent combinations alter
final modified-release performance.

Conclusion: This research will demonstrate
relationships between solvent selection and modified release performance, and
results can help pharmaceutical formulators identify harmful or advantageous
formulation parameters.  Furthermore, HTR reduces research time significantly,
whether it is used to explore unique polymer/active pharmaceutical ingredient
interactions or to optimize barrier membrane formulations.