High throughput research and evaporation rate modeling for solvent screening for ethylcellulose barrier membranes in pharmaceutical applications.
BACKGROUND
Ethylcellulose is commonly dissolved in a solvent or formed into an aqueous dispersion and sprayed onto various dosage forms to form a barrier membrane to provide controlled release in pharmaceutical formulations. Due to the variety of solvents utilized in the pharmaceutical industry and the importance solvent can play on film formation and film strength it is critical to understand how solvent can influence these parameters.


OBJECTIVE
To systematically study a variety of solvent blends and how these solvent blends influence ethylcellulose film formation, physical and mechanical film properties and solution properties such as clarity and viscosity.


METHODS
Using high throughput capabilities and evaporation rate modeling, thirty-one different solvent blends composed of ethanol, isopropanol, acetone, methanol, and/or water were formulated, analyzed for viscosity and clarity, and narrowed down to four solvent blends. Brookfield viscosity, film casting, mechanical film testing and water permeation were also completed.


CONCLUSIONS
High throughput analysis identified isopropanol/water, ethanol, ethanol/water and methanol/acetone/water as solvent blends with unique clarity and viscosity values. Evaporation rate modeling further rank ordered these candidates from excellent to poor interaction with ethylcellulose. Isopropanol/water was identified as the most suitable solvent blend for ethylcellulose due to azeotrope formation during evaporation, which resulted in a solvent-rich phase allowing the ethylcellulose polymer chains to remain maximally extended during film formation. Consequently, the highest clarity and most ductile films were formed.


CONCLUSIONS
Employing high throughput capabilities paired with evaporation rate modeling allowed strong predictions between solvent interaction with ethylcellulose and mechanical film properties.
a Dow Pharma and Food Solutions, The Dow Chemical Company , Midland , MI , USA ;
Cody A
CA
Schoener
b Formulation Sciences, The Dow Chemical Company , Midland , MI , USA.
Jaime L
JL
Curtis-Fisk
a Dow Pharma and Food Solutions, The Dow Chemical Company , Midland , MI , USA ;
True L
TL
Rogers
b Formulation Sciences, The Dow Chemical Company , Midland , MI , USA.
Michael P
MP
Tate
D019840:2-Propanol / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D000431:Ethanol / Q000737:chemistry*; D012996:Solutions; D012997:Solvents / Q000737:chemistry*; D014783:Viscosity; D014867:Water / Q000737:chemistry*
D012996:Solutions; D012997:Solvents; D014867:Water; D000431:Ethanol; C013517:ethyl cellulose; D002482:Cellulose; D019840:2-Propanol
Controlled release; evaporation; film formation; mechanical strength; modeling; sustained release; water permeability