Analysis of multicomponent formulations containing pseudoephedrine HCl and chlorpheniramine maleate using first-derivative spectroscopy on a diode-array spectrophotometer.

Pseudoephedrine HCl and chlorpheniramine maleate are compounds which have overlapping UV spectra in solutions of phosphate buffer (pH 7.2), water, and 0.1 M HCl. The quantitation of both compounds was achieved by using first-derivative spectroscopy on a diode-array spectrophotometer. The application of this method for the analysis of content uniformity testing and measuring dissolution profiles was demonstrated.

N-hydroxymethyl derivatives of nitrogen heterocycles as possible prodrugs I: N-hydroxymethylation of uracils.

Solid samples of 1,3-dihydroxymethyluracil, 3-hydroxymethyl-1-methyluracil, and 1-hydroxymethyl-3-methyluracil were prepared, and their structures were confirmed by spectroscopic analysis. The thermodynamics and kinetics of the formation of N-hydroxymethylated uracils in aqueous formaldehyde solutions also were studied. The equilibrium constants for formation of N-1-hydroxymethyl derivatives were approximately twice those for formation of N-3-hydroxymethyl derivatives, and they were formed more rapidly throughout the pH 3--8 range. Substituents at C-5 of uracil had little effect on the thermodynamics of N-hydroxymethylation. The potential usefulness of N-hydroxymethyl compounds as prodrugs is discussed.

N-hydroxymethyl derivatives of nitrogen heterocycles as possible prodrugs II: possible prodrugs of allopurinol, glutethimide, and phenobarbital.

Solid samples of 1-hydroxymethyl- and 1,5-dihydroxymethylallopurinol, 1-hydroxymethylglutethimide, and 1-hydroxymethylphenobarbital were prepared, and equilibrium constants for their formation from formaldehyde and allopurinol, glutethimide, or phenobarbital were calculated. The N-hydroxymethyl derivatives had higher water solubilities and faster dissolution rates than the parent drugs, and they appear to be potentially useful as prodrugs.

Stability of aqueous solutions of pirbuterol.

The hydrolytic degradation of pirbuterol was investigated under saturated oxygen conditions over a wide range of pH values and at different temperatures. Two of the five observed breakdown products were positively identified. The first-order decomposition rate appeared to depend on the rate constants of the four dissociated ionic species. The most stable region for the drug was pH 1-2, where the diprotonated molecule predominated; appropriate thermodynamic parameters were calculated.

Utilization of an enantiomer as a solution to a pharmaceutical problem: application to solubilization of 1,2-di(4-piperazine-2,6-dione)propane.

An enantiomer of the cytotoxic agent (+/-)-1,2-di(4-piperazine-2,6-dione)propane [(+/-)-I] (ICRF 159) was utilized to overcome a solubility problem in the preparation of a solution suitable for intravenous use. The enantiomers were about five times more soluble and melted at about 40 degrees lower than the racemic compound. This study appears to be the first reported instance in which the difference in the physical properties of a racemic compound and its enantiomers was utilized to improve a pharmaceutical formulation. The expected differences in the physical properties of racemic solids and their corresponding enantiomers are discussed briefly in relation to the three racemic modifications known to exist.