Mass Transport Analysis of the Enhanced Buffer Capacity of the Bicarbonate-CO Buffer in a Phase-Heterogenous System: Physiological and Pharmaceutical Significance.

The bicarbonate buffer capacity is usually considered in a phase-homogeneous system, at equilibrium, with no CO transfer between the liquid buffer phase and another phase. However, typically, an in vitro bicarbonate buffer-based system is a phase-heterogeneous system, as it entails continuously sparging (bubbling) the dissolution medium with CO in a gas mixture, at constant ratio, to maintain a constant partial pressure of CO and CO molarity at a prescribed value, with CO diffusing freely between the gas and the aqueous phases. The human gastrointestinal tract is also a phase-heterogeneous system, with CO diffusing across the mucosal membrane into the mesenteric arterial blood, which serves as a sink for CO from the intestinal lumen.

Solution-mediated phase transformation of salts during dissolution: investigation using haloperidol as a model drug.

Soluble salts can undergo solution-mediated phase transformation to a lower solubility form due to pH gradients in the gastrointestinal tract. Therefore, dissolution rate rather than solubility may be the best predictor of bioavailability for such compounds. The purpose of this project was to examine the kinetics of the conversion of a basic compound, haloperidol, and its salt forms using a flow-through dissolution apparatus and rotating disk method in neutral conditions.

Toward an in vivo dissolution methodology: a comparison of phosphate and bicarbonate buffers.

The purpose of this research was to evaluate the difference between the pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in dissolution of ketoprofen and indomethacin, to illustrate the dependence of buffer differential on biopharmaceutical properties of BCS II weak acids, and to recommend phosphate buffers equivalent to bicarbonates. The intrinsic dissolution rates of ketoprofen and indomethacin were experimentally measured using a rotating disk method at 37 degrees C in USP SIF/FaSSIF and various concentrations of bicarbonates. Theoretical models including an improved reaction plane model and a film model were applied to estimate the surrogate phosphate buffers equivalent to the bicarbonates.

Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API.

Purpose: The bioavailability of a development candidate active pharmaceutical ingredient (API) was very low after oral dosing in dogs. In order to improve bioavailability, we sought to increase the dissolution rate of the solid form of the API. When traditional methods of forming salts and amorphous material failed to produce a viable solid form for continued development, we turned to the non-traditional approach of cocrystallization.

Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs.

Purpose: The aim of this study was to examine if sparging with CO2(g) could be used to establish stable biorelevant bicarbonate buffers, in aqueous medium, for use in dissolution characterization of low-solubility ionizable drugs.

Methods: Preparation of the bicarbonate-containing dissolution medium was monitored by use of a commercially available fiberoptic probe to measure the concentration of dissolved CO2(aq). Intrinsic dissolution measurements at 100 rpm, 37 degrees C for indomethacin and dipyridamole were performed using a rotating disk and UV detection at pH 6.