Biopharmaceutical Studies on Methaqualone

Abstract

The subjects of biopharmaceutics and pharmacokinetics have been briefly reviewed and a short literature survey of methaqualone knowledge has been presented. Rapid, specific, sensitive and reproducible gas-liquid chromatographic methods using an internal marker technique have been developed for the estimation of methaqualone and diphenhydramine in biological fluids. The presence of diphenhydramine or alcohol did not enhance either the plasma methaqualone concentrations or the rates of absorption or alter the in vivo distribution of methaqualone in blood. The urinary excretion characteristics of methaqualone and diphenhydramine giving the standardised conditions necessary for future biopharmaceutical studies have been correlated with their buccal absorption characteristics in most instances; the influence of diphenhydramine and alcohol on these buccal absorption characteristics have been determined. The influence of methaqualone as base or hydrochloride powder (250mg)or with diphenhydramine hydrochloride (25mg) on plasma methaqualone profiles prior to formulation has been determined. Significant linear relationships were demonstrated between dissolution t50% and logarithm of particle sizes of methaqualone with and without diphenhydramine. The availability of methaqualone from both commercially available methaqualone preparations and experimental Mandrax formulations was determined, Dissolution studies have demonstrated a linear relationship between logarithm of amount undissolved and time. In vivo studies have shown that commercially available Mandrax preparations achieved much higher plasma levels than the other methaqualone preparations marketed in the United Kingdom; tablets being absorbed more efficiently than capsules. Significant correlations between in vitro 1/t50%  or percentage dissolved after 25 minutes and in vivo mean peak plasma methaqualone levels were demonstrated for the majority of formulations investigated. The efficacy of the different drugs as hypnotics corresponded well with their peak plasma methaqualone levels. The bioavailability of methaqualone was shown to be influenced by body weight and specific formulation and manufacturing variables. Preliminary pharmacokinetic parameters for methaqualone have been calculated from a limited study.