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生物豁免专著:速释固体口服剂型-卡马西平

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Carbamazepine.

机构信息

Pharmaceutical Technology and Biopharmaceutics, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.

Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA.

出版信息

J Pharm Sci. 2021 May;110(5):1935-1947. doi: 10.1016/j.xphs.2021.02.019. Epub 2021 Feb 18.


DOI:10.1016/j.xphs.2021.02.019
PMID:33610571
Abstract

Literature relevant to assessing whether BCS-based biowaivers can be applied to immediate release (IR) solid oral dosage forms containing carbamazepine as the single active pharmaceutical ingredient are reviewed. Carbamazepine, which is used for the prophylactic therapy of epilepsy, is a non-ionizable drug that cannot be considered "highly soluble" across the range of pH values usually encountered in the upper gastrointestinal tract. Furthermore, evidence in the open literature suggests that carbamazepine is a BCS Class 2 drug. Nevertheless, the oral absolute bioavailability of carbamazepine lies between 70 and 78% and both in vivo and in vitro data support the classification of carbamazepine as a highly permeable drug. Since the therapeutic and toxic plasma level ranges overlap, carbamazepine is considered to have a narrow therapeutic index. For these reasons, a BCS based biowaiver for IR tablets of carbamazepine cannot be recommended. Interestingly, in nine out of ten studies, USP dissolution conditions (900 mL water with 1% SLS, paddle, 75 rpm) appropriately discriminated among bioinequivalent products and this may be a way forward to predicting whether a given formulation will be bioequivalent to the comparator product.

摘要

评估基于生物药剂学分类系统(BCS)的生物豁免是否可应用于含有卡马西平作为唯一活性药物成分的即释(IR)固体口服剂型的相关文献进行了回顾。卡马西平用于癫痫的预防治疗,它是一种非离解药物,不能被认为在通常在上胃肠道遇到的 pH 值范围内“高度溶解”。此外,开放文献中的证据表明,卡马西平是 BCS 分类 2 药物。然而,卡马西平的口服绝对生物利用度在 70%至 78%之间,体内和体外数据均支持将卡马西平分类为高渗透性药物。由于治疗和毒性血浆水平范围重叠,卡马西平被认为具有狭窄的治疗指数。因此,不能推荐基于 BCS 的卡马西平 IR 片剂的生物豁免。有趣的是,在十项研究中有九项研究中,USP 溶出条件(900 mL 水加 1%SDS,桨板,75 rpm)适当地区分了生物不等效产品,这可能是预测给定制剂是否与参比产品生物等效的一种方法。

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引用本文的文献

[1]
Novel Drug-Drug Cocrystalline Forms of Carbamazepine with Sulfacetamide: Preparation, Characterization, and In Vitro/In Vivo Performance Evaluation.

Pharmaceutics. 2025-5-21

[2]
Establishing Clinically Relevant Specifications for Carbamazepine Tablets Using Physiologically Based Pharmacokinetic Modeling.

AAPS J. 2025-5-2

[3]
An Investigation into the Effect of Maltitol, Sorbitol, and Xylitol on the Formation of Carbamazepine Solid Dispersions Through Thermal Processing.

Pharmaceutics. 2025-3-2

[4]
Polymorphism and Pharmacological Assessment of Carbamazepine.

Int J Mol Sci. 2024-9-11

[5]
Material extrusion 3D-printing technology: A new strategy for constructing water-soluble, high-dose, sustained-release drug formulations.

Mater Today Bio. 2024-7-14

[6]
Applying Physiologically Based Pharmacokinetic Modeling to Interpret Carbamazepine's Nonlinear Pharmacokinetics and Its Induction Potential on Cytochrome P450 3A4 and Cytochrome P450 2C9 Enzymes.

Pharmaceutics. 2024-5-30

[7]
Coupling Drug Dissolution with BCS.

Pharm Res. 2024-3

[8]
Integration of Biorelevant Pediatric Dissolution Methodology into PBPK Modeling to Predict In Vivo Performance and Bioequivalence of Generic Drugs in Pediatric Populations: a Carbamazepine Case Study.

AAPS J. 2023-6-29

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