Abstract
The absorption of methaqualone from the gastro-intestinal tract is a dissolution—and not a permeability-rate limited process. Absorption from solution dosage forms can occur throughout the gastro-intestinal tract with maximum absorption from the intestine. Dissolution of solid dosage forms is favoured in the highly-acidic environment of the stomach and absorption of the in situ dissolved drug occurs in both stomach and upper small intestine. Methaqualone is found primarily in the plasma phase of whole blood and is highly bound to plasma proteins. The plasma elimination curve is biexponential with a rapid distributive phase and a slow elimination phase. The principle tissues of distribution are the metabolic and excretory tissues—liver and kidney — and lipid tissue. Metabolism occurs by hydroxylation of the methyl, tolyl and quinazolinone substituents via inducible hepatic microsomal oxidoreductases. Methaqualone is completely bio-transformed and excreted as O-glucuronide conjugates in urine and bile. Enterohepatic recirculation of metabolites occurs and is responsible for the prolonged urinary excretion profile. There is no change in absorption, distribution or elimination kinetics following chronic administration in man.
Tablet and capsule formulations with good in vitro dissolution, stability and bioavailability characteristics were developed. Equivalent bioavailability of these tablet formulations was observed in the fasted and post-prandial state. Techniques were developed to correlate dissolution and absorption profiles of these formulations.
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