Walter Morozowich

Modifying the diffusion layer of soluble salts of poorly soluble basic drugs to improve dissolution performance.

The dissolution mechanism of soluble salts of poorly soluble bases can be complex because both the dissolution of the salt and precipitation of the free base can occur depending on the experimental conditions and properties of the molecule. The dissolution of three soluble salts of poorly soluble bases is described in this paper. Two of these compounds precipitate as free base under normal stomach pH conditions (pH from 2-4) during dissolution. This free base precipitation is a result of formation of free base on the surface of the dissolving salt. Diffusion Layer modulated (DLM) solids are defined and presented that can effectively counteract this precipitation mechanism. These DLM materials employ excipients in order to modify the pH or solubility conditions at the surface of the dissolving salt to minimize precipitation of the free base that can occur. Rotating disk dissolution data is presented which shows how these formulated solids can act to improve the dissolution profile for these materials.

Detection of prostaglandins by high-performance liquid chromatography after conversion to p-(9-anthroyloxy)phenacyl esters

p-(9-Anthroyloxy)phenacyl bromide (panacyl bromide) undergoes rapid reaction with the carboxyl group of prostaglandins in the presence of N,N-diisopropylethylamine in acetonitrile-tetrahydrofuran (4:1). The resulting prostaglandin panacyl esters are strongly uv absorbing with a lambda max at 253 nm and an epsilon of 174,280 in acetonitrile. The lower limit of detection of prostaglandins was approximately 200 pg with uv detection (254 nm) and about 30 pg with fluorescent detection (exitation 253 and emission 445 nm) using normal-phase HPLC. The reactivity of panacyl bromide with 23 prostaglandins as well as prostaglandins released by human lung tissues was investigated.

SEMIAUTOMATED QUANTITATION AND CHARACTERIZATION OF STEROID PHOSPHATES USING ION‐EXCHANGE CHROMATOGRAPHY

This work was designed to provide a quantitative chromatographic procedure suitable for monitoring the synthesis and formulation of steroid 21 -phosphate esters. The basic procedure involves the chromatography of the steroid esters on a column of DEAE cellulose with the use of concave gradient elution with triethylammonium acetate (TEA) and a continuously recording ultraviolet (UV) spectrophotometer. This report describes two procedures for the quantitation and characterization of ion-exchange chromatograms of steroid 2 I-phosphates. In the first procedure, a semiautomated procedure (Method A), quantitation is achieved by automatic integration of areas under the peaks in the elution chromatogram. An important prerequisite of this method is a constant flow rate throughout the chromatogram, which is achieved by the use of a proportioning pump. In the second procedure, a gravity-flow system (Method B), quantitation is achieved by manual collection and independent determination of the absorbance of the individual peaks. The synthesis of methylprednisolone 21 -phosphate and the identification of the minor impurities in the ion-exchange chromatograms will be the subject of a future publication by one of the authors (W. Morozowich).