Investigation of viscosity, pH and dielectric constant of the microenvironment surrounding a dissolving enteric polymer film
Date of Completion
January 1998
Keywords
Chemistry, Physical|Health Sciences, Pharmacy
Degree
Ph.D.
Abstract
The effects of bulk parameters on the dissolution of enteric coatings have been investigated, but there has been no attempt to study the microenvironment surrounding the dissolving enteric polymer film which may be playing a significant role. The goal of this investigation was to explore this microenvironment using a laser to excite fluorescent probes homogeneously distributed in the dissolution medium. Fluorescent probes, p-(N-dimethylamino cinnamylidene) malononitrile (CMN) and 6-propionyl-2-(dimethylamino) naphthalene (PRODAN) were shown to be sensitive to and specific for microviscosity and dielectric constant, respectively. A correction procedure was developed to account for the effect of the dielectric constant on the second pK$\sb{a}$ of fluorescein.^ A laser spectrometer was modified and validated to investigate the microenvironment accurately. Using the fluorescent probes and the modified laser spectrometer, the microenvironment near dissolving hydroxypropylmethylcellulose phthalate (HP) films was investigated under various conditions of bulk pH and convection. A moderately concentrated viscous polymer layer was observed 0.25 mm from the HP film surface under unstirred and stirred conditions at pH 6.5 and 7.0. A linear relationship was shown to exist between the concentration of HP dissolved in the microenvironment and the increase in microviscosity of the medium. This increase in microviscosity of the medium decreased the diffusivity of protons released from HP at the film surface causing a decrease in pH. This was consistent with the linear relationship that existed between the decrease in pH and microviscosity of the medium. Moreover, a non-linear relationship between the decrease in pH and average flux of protons generated suggested that the rate of release of protons from the dissolving HP was not the sole factor responsible for the decrease in pH. The microviscosity also played an important role in determining the pH near the film surface. In addition, steady state dissolution was observed for the protons released from the dissolving HP. However, over two hours, steady state was not achieved for HP concentration, microviscosity, dielectric constant and pH near the dissolving surface. In general, the properties of the microenvironment near dissolving HP films were shown to be very different from those in the bulk of the dissolution medium. ^
Recommended Citation
Harianawala, Abizer Ismail, "Investigation of viscosity, pH and dielectric constant of the microenvironment surrounding a dissolving enteric polymer film" (1998). Doctoral Dissertations. AAI9909109.
https://digitalcommons.lib.uconn.edu/dissertations/AAI9909109