THE THERMODYNAMIC CHARACTERIZATION OF THE SOLID-WATER SURFACE INTERACTION FOR THREE TABLET DISINTEGRATING AGENTS
Abstract
Adsorption-desorption studies and immersional calorimetry were used conjointly to characterize the surface properties of three disintegrants: Ac-Di-Sol('R), CLD-2('R), and Amberlite IRP-88('R). The thermodynamic characterization of the water-disintegrant system was investigated to better understand the surface properties of the three disintegrants, since these properties ultimately control the disintegrant's ability to promote tablet disintegration. Adsorption, desorption, and re-adsorption studies resulted in typical type II adsorption isotherms. The adsorption isotherms for Ac-Di-Sol and CLD-2 were found to be characteristic of standard cellulose. Treatment of the adsorption data by the B.E.T. model established an estimated surface area of 305, 342, and 682 meters squared per gram for Ac-Di-Sol, CLD-2, and Amberlite IRP-88, respectively. The surface areas of the disintegrants were also determined for the desorption and re-adsorption processes. The adsorption-desorption isotherms were utilized to calculate the integral and differential Gibbs' free energies. Ac-Di-Sol, CLD-2, and Amberlite IRP-88 samples containing various amounts of adsorbed water vapor were immersed in a non-isothermal calorimeter to determine the heat liberated when water and the disintegrant interacted. From this experimentally determined value, the net integral enthalpy was calculated. The differential enthalpies of adsorption were determined by approximating the slope of the net integral enthalpies of adsorption between two successive points. The integral and differential entropies were calculated once the integral and differential Gibbs' free energy and enthalpy were experimentally determined. Quantification of the energies of interaction between the adsorbate and adsorbent were obtained from the differential enthalpy. These interactions were determined to be -7.5, -7.8, and -9.3 kcal per mole for Ac-Di-Sol, CLD-2, and Amberlite IRP-88, respectively. The premature decrease in the differential enthalpies and entropies was attributed to a swelling process. Swelling was quantified via a light microscope with Ac-Di-Sol increasing in size by 75% and CLD-2 by 90% when under 100% relative humidity conditions. The immersional and adsorption-desorption hystereses were hypothesized to be the result of an irreversible swelling process. The swelling was irreversible, due to the formation of point associations or bonds between neighboring fibers restricting constriction. The disruption of these associations required energy and reduced the observed desorption heats of wetting by -0.9, -0.15, and -1.4 kcal per mole for Ac-Di-Sol, CLD-2, and Amberlite IRP-88, respectively. The differences observed between CLD-2 and Ac-Di-Sol are believed to be due to the higher degree of cross-linking and Ac-Di-Sol. Ac-Di-Sol and Amberlite IRP-88 appear to partially constrict after swelling has occurred, when the powder is re-dried. This suggests that these two compounds may exhibit better disintegration characteristics than CLD-2 when incorporated into the granulating powder.
Degree
Ph.D.
Subject Area
Pharmaceuticals
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.