当前位置： SCI文献检索 > JOURNAL OF PHARMACEUTICAL SCIENCES期刊下所有文献 > Evaluation of "external" predictability of an in vitro-in vivo correlation for an extended-release formulation containing metoprolol tartrate.

Evaluation of "external" predictability of an in vitro-in vivo correlation for an extended-release formulation containing metoprolol tartrate.

Abstract：

: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 <10% for C(max) and area under the curve (AUC) of concentration versus time for I, II, and IV. The C(max) for III was slightly underestimated (11.7%); however, the PE of the AUC was <10%. Formulation V displayed a PE for C(max) > 20% and an AUC within 5% of observed values. The low PEs for C(max) and AUC observed for I-IV strongly suggest that the metoprolol IVIVC is externally valid, predictive of alternate processing methods (IV), scale-up (II, III), and allows the in vitro dissolution data to be used as a surrogate for validation studies. However, the lack of predictability for V supports the contention that IVIVCs are formulation specific.

journal_name

J Pharm Sci

journal_title

Journal of pharmaceutical sciences

authors

Mahayni H,Rekhi GS,Uppoor RS,Marroum P,Hussain AS,Augsburger LL,Eddington ND

doi

10.1002/1520-6017(200010)89:10<1354::aid-jps13>3.0

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

1354-61

issue

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)30667-0

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

在线工具

Evaluation of "external" predictability of an in vitro-in vivo correlation for an extended-release formulation containing metoprolol tartrate.