Haloperidol In Presence Research Articles

Supersolubilization and Amorphization of a Model Basic Drug, Haloperidol, by Interaction with Weak Acids

To present a novel approach of greatly enhancing aqueous solubility of a model weakly basic drug, haloperidol, by using weak acids that would not form salts with the drug and to attain physically stable form of amorphous drug by drying such aqueous solutions. Aqueous solubility of haloperidol in presence of increasing concentrations of four different weak organic acids (malic, tartaric, citric, fumaric) were determined. Several concentrated aqueous solutions with differing drug-to-acid molar ratios were dried in vacuum oven, and dried materials were characterized by DSC, powder XRD, dissolution testing, and stability study. Acids were selected such that they would not form salts with haloperidol. Haloperidol solubility increased greatly with increased concentrations of malic, tartaric and citric acids, reaching >300mg/g of solution. In contrast to the haloperidol HCl aqueous solubility of 4mg/g, this may be called supersolubilization. Fumaric acid did not cause such solubilization as it had low water solubility. Dried solids formed dispersions of amorphous haloperidol in acids that were either amorphous or partially crystalline. Amorphous haloperidol was physically stable and had better dissolution rate than HCl salt. A novel method of drug solubilization in aqueous media by acid-base interaction is presented. Physically stable amorphous systems of drugs may also be prepared by using this organic solvent-free approach.

Zero-crossing derivative spectrophotometry for the determination of haloperidol in presence of parabens

First derivative spectrophotometry with a zero-crossing technique of measurement is used for the quantitative determination of haloperidol in the presence of methylparaben and propylparaben, which is added as antimicrobial preservatives in pharmaceuticals. This technique permits the quantification of haloperidol in the presence of parabens, with closely overlapping spectral bands, and without any separation step. Linear calibration graphs of first derivative values (at 255.2 nm for haloperidol) versus concentration (in the range 4.0–20.0 μg ml −1) were obtained with negligible intercepts. Relative standard deviation of 0.83% was obtained for intra-day precision and 1.86% for inter-day precision. The recovery of haloperidol in synthetic mixtures with parabens and in pharmaceutical dosage forms is also reported.