Bioequivalence of topical drug products: in vitro - in vivo correlations
外用药品的生物等效性:体外-体内相关性
基本信息
- 批准号:9340990
- 负责人:
- 金额:$ 50万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-01 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Project Summary/Abstract. This project responds to the Funding Opportunity, RFA-FD-13-016, "In vitro
release tests for topical dermatological products (U01)". The development of appropriate methods to determine
bioequivalence (BE) of topical dermatological products is a significant objective of the Food & Drug
Administration (FDA). While the agency has identified limited situations - for example when formulations
contain the same inactive ingredients in the same amounts - in which alternatives to clinical endpoint
bioequivalence studies may be possible, the FDA has a long-standing challenge to determine surrogate test
methods (including in vitro techniques) to predict whether formulations, which differ in composition, result in
equivalent drug delivery to and across the skin.
The long-term goal of this project, therefore, is to demonstrate that in vitro measurements related to the
performance of topical drug products are correlated with in vivo outcomes, such that simpler experimental
approaches can be reliably and reproducibly used for the establishment of (in)equivalence between
formulations containing the same active pharmaceutical ingredient (API) for application to the skin.
The proposed research strategy broadly aims to test three hypotheses:
1. That topical BE assessment can be accomplished through the use of appropriately selected in vitro and/or
in vivo surrogate tests.
2. That all surrogate tests have limitations but that they do not all have the same limitations; it follows that the
results of one test complement those of another.
3. That the test(s) chosen depend on the complexity of the formulation and whether or not the inactive
ingredients in the product are quantitatively and/or compositionally equivalent.
The project has been designed in two phases, with individual specific aims: [A] An initial, intensive, 12-month
program of work focused on econazole, betamethasone valerate (BMV) and diclofenac. For the anti-fungal
and BMV, to generate in vitro skin penetration and release test data for comparison and correlation with
published in vivo data, specifically, dermatopharmacokinetic (DPK) information for both, and vasoconstriction
measurements for the corticosteroid. For diclofenac, to complement in vivo DPK experiments with blood level
determinations using highly sensitive liquid chromatography/mass spectrometry methods and to correlate
these results with in vitro skin penetration and release test studies. [B] A further 4-year investigation to validate
the predictability of in vitro tests when appropriate, and to identify the potential of simpler in vivo approaches as
alternative surrogates for the default assessment of topical (in)equivalence using a clinical trial. A systematic
examination of several key classes of topical drug products will be undertaken including, but not limited to
lidocaine, triamcinolone acetonide, tretinoin, acyclovir and metronidazole.
项目摘要/摘要。该项目响应资助机会 RFA-FD-13-016,“体外
局部皮肤科产品的放行测试(U01)”。制定适当的方法来确定
局部皮肤科产品的生物等效性 (BE) 是 FDA 的一个重要目标
管理(FDA)。虽然该机构已经确定了有限的情况 - 例如当配方
含有相同数量的相同非活性成分 - 其中临床终点的替代品
生物等效性研究或许是可能的,FDA 在确定替代测试方面面临着长期的挑战
方法(包括体外技术)来预测成分不同的配方是否会导致
等效的药物递送至和穿过皮肤。
因此,该项目的长期目标是证明体外测量与
局部药物产品的性能与体内结果相关,因此更简单的实验
方法可以可靠且可重复地用于建立之间的(内)等价
含有相同活性药物成分(API)的制剂,适用于皮肤。
拟议的研究策略主要旨在检验三个假设:
1. 局部BE评估可以通过使用适当选择的体外和/或
体内替代测试。
2. 所有替代测试都有局限性,但并非都具有相同的局限性;由此可见
一项测试的结果与另一项测试的结果相辅相成。
3. 所选择的测试取决于配方的复杂性以及非活性成分是否有效。
产品中的成分在数量和/或组成上是等效的。
该项目分两个阶段设计,具有各自的具体目标: [A] 初始、强化、为期 12 个月的
工作计划的重点是益康唑、戊酸倍他米松(BMV)和双氯芬酸。对于抗真菌
和 BMV,生成体外皮肤渗透性并发布测试数据,以便与
已发表体内数据,特别是两者的皮肤药代动力学 (DPK) 信息和血管收缩
皮质类固醇的测量。对于双氯芬酸,用血液水平补充体内 DPK 实验
使用高灵敏度液相色谱/质谱方法进行测定并关联
这些结果是体外皮肤渗透和释放测试研究的结果。 [B] 进一步为期 4 年的调查来验证
适当时体外测试的可预测性,并确定更简单的体内方法的潜力
使用临床试验对局部(内)等效性进行默认评估的替代替代方案。一个系统的
将检查几个关键类别的外用药品,包括但不限于
利多卡因、曲安奈德、维A酸、阿昔洛韦和甲硝唑。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Topical bioavailability of diclofenac from locally-acting, dermatological formulations.
- DOI:10.1016/j.ijpharm.2017.06.063
- 发表时间:2017-08-30
- 期刊:
- 影响因子:5.8
- 作者:Cordery SF;Pensado A;Chiu WS;Shehab MZ;Bunge AL;Delgado-Charro MB;Guy RH
- 通讯作者:Guy RH
Raman Spectroscopic Tools to Probe the Skin-(Trans)dermal Formulation Interface.
- DOI:10.1021/acs.molpharmaceut.2c00480
- 发表时间:2022-11-07
- 期刊:
- 影响因子:4.9
- 作者:Garvie-Cook, Hazel;Hoppel, Magdalena;Guy, Richard H.
- 通讯作者:Guy, Richard H.
Investigator Impact on Reproducibility of Drug Bioavailability in Stratum Corneum Sampling by Tape Stripping.
研究人员通过胶带剥离对角质层采样中药物生物利用度的重现性的影响。
- DOI:10.1007/s11095-022-03199-w
- 发表时间:2022
- 期刊:
- 影响因子:3.7
- 作者:Shukla,Sagar;Bunge,AnnetteL;Hassan,HazemE;Stinchcomb,AudraL
- 通讯作者:Stinchcomb,AudraL
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{{ truncateString('ANNETTE L BUNGE', 18)}}的其他基金
Bioequivalence of topical drug products: in vitro - in vivo correlations
外用药品的生物等效性:体外-体内相关性
- 批准号:
8924788 - 财政年份:2013
- 资助金额:
$ 50万 - 项目类别:
Bioequivalence of topical drug products: in vitro - in vivo correlations
外用药品的生物等效性:体外-体内相关性
- 批准号:
8693308 - 财政年份:2013
- 资助金额:
$ 50万 - 项目类别:
DERMAL ABSORPTION OF CHEMICALS FROM LIQUID MIXTURES
皮肤从液体混合物中吸收化学物质
- 批准号:
7071783 - 财政年份:2004
- 资助金额:
$ 50万 - 项目类别:
DERMAL ABSORPTION OF CHEMICALS FROM LIQUID MIXTURES
皮肤从液体混合物中吸收化学物质
- 批准号:
6951885 - 财政年份:2004
- 资助金额:
$ 50万 - 项目类别:
DERMAL ABSORPTION OF CHEMICALS FROM LIQUID MIXTURES
皮肤从液体混合物中吸收化学物质
- 批准号:
6732555 - 财政年份:2004
- 资助金额:
$ 50万 - 项目类别:
DERMAL ABSORPTION FROM SOILS--EVALUATION AND PREDICTION
皮肤从土壤中的吸收——评估和预测
- 批准号:
2155731 - 财政年份:1994
- 资助金额:
$ 50万 - 项目类别:
DERMAL ABSORPTION FROM SOILS--EVALUATION AND PREDICTION
皮肤从土壤中的吸收——评估和预测
- 批准号:
2155732 - 财政年份:1994
- 资助金额:
$ 50万 - 项目类别:
DERMAL ABSORPTION FROM SOILS--EVALUATION AND PREDICTION
皮肤从土壤中的吸收——评估和预测
- 批准号:
2155730 - 财政年份:1994
- 资助金额:
$ 50万 - 项目类别:
DERMAL ABSORPTION FROM SOILS--EVALUATION AND PREDICTION
皮肤从土壤中的吸收——评估和预测
- 批准号:
2444224 - 财政年份:1994
- 资助金额:
$ 50万 - 项目类别:
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