Biomedical subjects

Anthony C Blackburn

Publications and source records attributed to Anthony C Blackburn.

3 recordsLinked to original sources

PubMed2005

Rapid, small-scale determination of organic solvent solubility using a thermogravimetric analyzer.

A rapid gravimetric method for determining drug candidate solubility in organic solvents has been developed. The scale, speed, precision, and accuracy of the method make it ideal for solubility screening of pharmaceutical compounds during early development. The method utilizes a thermogravimetric analyzer to automate drying and weighing. Results for model compounds compare favorably with literature values.

Organic Chemicals↗

PubMed2005

Identifying the stable polymorph early in the drug discovery-development process.

The thermodynamically most stable polymorph under ambient conditions is almost without exception the most desirable crystalline form for development by a pharmaceutical company. It is, therefore, beneficial to discover and to characterize this polymorph at the earliest possible stage of development. A screen for discovering the stable polymorph of a pharmaceutical compound early in the drug discovery-development process is developed and described. In this screen, a small amount of compound is suspended in a diverse group of solvents for two weeks in an effort to crystallize the most stable polymorph. The solubility of the compound in each solvent utilized in the stable polymorph screen is also simultaneously determined using a simple gravimetric method. Ritonavir and an early development candidate (Pfizer compound A) are used as model compounds to demonstrate the utility of the screen for finding the stable polymorph early in the drug discovery-development process.

Anti-HIV Agents↗

PubMed2002

Semi-empirical relationships between effective mobility, charge, and molecular weight of pharmaceuticals by pressure-assisted capillary electrophoresis: applications in drug discovery.

Relationships between effective mobility (m(eff)), calculated charge (Z(c)), and molecular weight (MW) are semi-empirically derived for pharmaceuticals using pressure-assisted capillary electrophoresis (PACE). We determined the m(eff) at 12 different pH points (2.0-11.4) of 66 pharmaceutical-like compounds ranging in MW from 79 to 825 g/mol. Plots of the observed m(eff) values versus Z(c)/MW(x ) (where x is a fractional coefficient) gave linear relationships. For anions, it was found that the best correlation (R(2) = 0.9666) exists when the fractional coefficient is equal to 0.4920, resulting in the equation m(eff) = 0.1853 (Z(c)/MW (0.4920)). For cations, the best linear relationship (R(2) = 0.9861) gave the equation m(eff) = 0.3888 (Z(c)/MW (0.6330)). The m(eff), Z(c)/MW(x) relationships were then applied to: (i) developing a technique for selecting an appropriate pH to achieve optimal separation of pharmaceuticals and (ii) determining the maximum charge of a molecule in the pH range of determination of negative log of the dissociation constants (pK(a)) by PACE, thus enabling the correct choice of model equation to be automated without structure analysis.

Drug Evaluation, Preclinical↗