Evaluation of “External” Predictability of an In Vitro–In Vivo Correlation for an Extended‐Release Formulation Containing Metoprolol Tartrate

The purpose of this study was to examine the external predictability of an in vitro–in vivo correlation (IVIVC) for a metoprolol hydrophilic matrix extended‐release formulation, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. In addition,...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2000-10, Vol.89 (10), p.1354-1361
Main Authors: Mahayni, H., Rekhi, G.S., Uppoor, R.S., Marroum, P., Hussain, A.S., Augsburger, L.L., Eddington, N.D.
Format: Article
Language:English
Subjects:
Adrenergic beta-Antagonists - blood
Adrenergic beta-Antagonists - pharmacokinetics
Adult
Antiarythmic agents
Biological and medical sciences
Cardiovascular system
Chemistry, Pharmaceutical
correlation
Cross-Over Studies
drug release
extended-release
Female
Humans
in vitro
in vivo
Linear Models
Male
mechanism
Medical sciences
metoprolol
Metoprolol - blood
Metoprolol - pharmacokinetics
Middle Aged
Pharmacology. Drug treatments
Polymers - pharmacokinetics
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Summary:The purpose of this study was to examine the external predictability of an in vitro–in vivo correlation (IVIVC) for a metoprolol hydrophilic matrix extended‐release formulation, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. In addition, this report evaluated the predictability of the IVIVC for another formulation of metoprolol tartrate differing in its release mechanism. Study 1 examined the scale up of a matrix extended‐release tablet from a 3‐kg small batch (I) to a 50‐kg large batch (II). The second study examined the influence of scale and processing changes [3‐kg small batch with fluid bed granulation and drying (III); 80‐kg large batch with high shear granulation and microwave drying (IV), and a formulation with an alternate release mechanism formulated as a multiparticulate capsule (V)]. In vitro dissolution of all formulations (I–V) was conducted with a USP apparatus I at pH 6.8 and 150 rpm. Subjects received the metoprolol formulations, and serial blood samples were collected over 48 h and analyzed by a validated HPLC assay using fluorescence detection. A previously developed IVIVC was used to predict plasma profiles. Prediction errors (PE) were
ISSN:0022-3549
1520-6017
DOI:10.1002/1520-6017(200010)89:10<1354::AID-JPS13>3.0.CO;2-P