In vitro In vivo correlation of sustained release capsules of Metoprolol

ISSN:0976-9374 In vitro in vivo correlation of metoprolol tartrate sustained release capsules were studied in this investigation. The half-life of metoprolol is 3 to 4 hours. Peak plasma concentrations vary widely and occur about 1.5 to 2 hours after a single oral dose. In this study, non pareil seeds were prepared and coated with metoprolol tartrate using polyvinyl pyrollidone and iso propyl alcohol. Drug coated pellets were then coated with different proportion of microcrystalline wax and glyceryl di stearate using carbon tetrachloride as solvent. The release pattern of drug coated pellets and wax coated pellets were evaluated in vitro by dissolution test apparatus. Theoretical sustained release was compared with formulated sustained release. In vivo evaluation of metoprolol sustained release has been studied. A single dose was carried out in six rabbits with two sequences, cross over study. Blood samples were collected at one hour intervals. The plasma concentration of metoprolol was estimated by reverse phase HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of metoprolol and time data. The mean in vitro dissolution curve of the product is compared with the mean in vivo absorption curve generated by Wagner – Nelson method. The mean data for the in vivo percent absorbed were plotted versus time and the in vitro drug release versus time were superimposed on the first plot. The simplest way to demonstrate a correlation is to plot the percentage absorbed in vivo versus the percentage released in vitro at the same time. www.inpharmaworld.com/ijphs Available online @ INTRODUCTION: An in vivo in vitro correlation (IVIVC) is defined as a “predictive mathematical model describing the relationship between an in vitro property of an extended release dosage forms and a relevant in vivo response, e.g. plasma drug concentration or amount of drug absorbed”. The main objective of such a mathematical model is to use data collected in vitro to predict the in vivo response without having to conduct in vivo studies [1]. Three levels of IVIVC have been defined, level A describes the relationship between the entire in vitro and in vivo time profiles, whilst level B and C describe relationship between summary statistics derived from the in vitro and in vivo data. [1, 2, 3]. The level A IVIVC is considered the most informative and is consequently recommended by the food and drug administration as it can be used to predict the entire in vivo time profile [1, 3, 4]. Metoprolol tartrate is a β-adrenergic blocking agent with cardio selective activity. It is safe drug and is effective in the treatment of hypertension either alone or in combination with other anti hypertensive drug. Metoprolol is readily and completely absorbed from the gastrointestinal tract but is subject to considerable first-pass metabolism, with a bioavailability of about 50%. Peak plasma concentrations vary widely and occur about 1.5 to 2 hours after a single oral dose [5, 6]. The half-life of metoprolol is 3 to 4 hours MATERIALS AND METHODS Formulation of Non pareil seeds Non pareil seeds (NPS) were prepared using 18” coating pan. Sucrose, starch, talc and heavy kaolin were used for this preparation. The developed non pareil seeds were sieved through 30/36 meshes and used as core for the preparation of drug coated pellets. Formulation of drug coated pellets: Non pareil seeds were coated with metoprolol (drug) using poly vinyl pyrollidone as binder. In 18” coating pan, non pareil seeds were taken and coated with K.Kannan et al, /Int. J. Pharm. & Health Sci. Vol.1 (1), 2010, 35-39