Availability of Metoclopramide in vitro and in vivo

Abstract

Metoclopramide (4-amino-5-chloro-2-methoxy-N-2-diethyl-aminoethy~-benzamide) is recommended for use in gastrointestinal diagnostics and in treating various types of vomiting and a variety of functional gastrointestinal disorders. The drug increases the motility of the stomach and gastric emptying rates. It may provide symptomatic relief in dyspepsia and possibly in vertigo and reflux oesophagitis'-').When given orally, metoclopramide is readily absorbed but shows a wide range in bioavailability which might be partially due to interindividual first-pass metabolism3). On the other hand, the available formulations could be responsible for these variations. In order to compensate for the latter, new metoclopramide formulations are required; sustained release preparations are of particular interest here. Evaluation of the dissolution model adopted and choice of formulations can be simplified if the relationship between in-vifro dissolution and in-vivo availability is known. In this respect, the mean dissolution time in-vifro Tdiss.vitro and the mean transit time in the organism Tsys were used for the correlation of two different tablet and two different sustained release formulations of metoclopramide. Experimental PartThe dissolution rates of the tablets (n=6) and the sustained release formulations (n=6) were determined by the half-change method4) using rotating bottles. The assembly consists of a motor-driven six bladed wheel (30rpm), with a capacity for a maximum of six 100ml vessels. Each vessel is filled with l00ml simulated gastric fluid (USPXX) without pepsin and the test-dose is added.Once an hour starting 60 min from the beginning of the investigation half of the vol. of the dissolution medium is removed and substituted by simulated intestinal fluid (USPXX) without pancreatin. The temp. was maintained at 37°C throughout the whole investigation period using a water bath with 03654233/84/0202-0185 $ U2.50/0 0 Verlag