In vitro–In Vivo Correlations: Tricks and Traps

Cardot, J; Davit, Barbara M.

doi:10.1208/s12248-012-9359-0

Cited by 88 publications

(49 citation statements)

References 24 publications

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“…In the case of poor and nonlinear relationships, Levy plots were drawn. The time for certain percentages of drug dissolved in vitro is on the x axis, while the time for similar percentages to be absorbed in vivo is depicted on the y axis (15,16). The Levy analysis allows correction for different rates or lag times observed between in vivo and in vitro data and leads to a final 1:1 relationship between in vitro and in vivo time points.…”

Section: Level a Ivivcmentioning

confidence: 99%

Optimization of a Dissolution Method in Early Development Based on IVIVC Using Small Animals: Application to a BCS Class II Drug

Deshmukh¹,

Avachat²,

Garka³

et al. 2016

Dissolution Technol.

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The aim of the present study was to develop optimal dissolution conditions for a BCS Class II drug in early development. The model drug efavirenz was formulated in two dosage forms: a classical immediate-release suspension and modified-release cubosomes. Dissolution studies were carried out in classical and biorelevant media adapted to early development using animal models to confirm the in vitro findings. The percentage drug dissolved was calculated in all media, and the percentage absorbed was calculated from in vivo data. Level A IVIVC was investigated in all media, and the best one selected based on the highest r 2 value. Optimal dissolution media that could be used as starting points for further development are 0.5% SLS in water for cubosomes and fasted-state simulated intestinal fluid (FaSSIF) for suspensions. The predicted plasma profiles show appropriate contour, and the internal prediction error was at most 12% for the predicted parameters C max and AUC. Thus, a simple approach was used for developing IVIVC based on animal in vivo data, which can be used as a quick and simple alternative tool in early development stage depending on which dissolution method can be optimized even before human studies.

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Section: Level a Ivivcmentioning

confidence: 99%

Optimization of a Dissolution Method in Early Development Based on IVIVC Using Small Animals: Application to a BCS Class II Drug

Deshmukh¹,

Avachat²,

Garka³

et al. 2016

Dissolution Technol.

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“…For the calculation of the absorption curve, the formulation C (slow) produced questions. The terminal part of the curve is different from those of all the other formulations, and a "flip-flop" model could be discussed (22). In a flip-flop model, rate of absorption approximates rate of elimination; in a simplified sense, rate of absorption is the rate-limiting step in the sequentialparallel processes of drug absorption, distribution, and elimination.…”

Section: Example Of Use Of Level a Ivivc To Optimize A Generic Formulmentioning

confidence: 99%

Use of IVIVC to Optimize Generic Development

Cardot¹,

Garrait²,

Beyssac³

2015

Dissolution Technol.

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During the development of a generic sustained-release dosage form, an in vivo pilot study is often performed. This pilot study could be the starting point to set up an IVIVC. Thanks to the relationship established between in vitro data and in vivo curve, a predictive in vitro model could be determined allowing calculation of an optimal dissolution curve. Based on those available tools, using a design of experiment, the formulation can be optimized with a minimum of effort. The target is to develop a formulation whose dissolution is as close as possible to the calculated optimal dissolution curve. This approach demonstrates that it is possible to improve the selection of the best formulation and minimize the risk in the bioequivalence final study using the in vivo profile observed during the pilot study and the IVIVC.

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“…Jean-Michel Cardot, Ph.D. (Université d'Auvergne) presented two case studies which yielded the conclusion that "we can trust prediction," but only if prediction based on knowledge of the critical quality attributes and a relevant hypothesis based on API characteristics, formulation, and physiology (16). Prof. Cardot also presented data in which an IVIVC had been improved by considering the rate of drug absorption from different segments of the gastrointestinal tract.…”

Section: Ivivc Case Studiesmentioning

confidence: 99%

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

Polli

Cook

Davit

et al. 2012

AAPS J

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Abstract. This summary workshop report highlights presentations and over-arching themes from an October 2011 workshop. Discussions focused on best practices in the application of biopharmaceutics in oral drug product development and evolving bioequivalence approaches. Best practices leverage biopharmaceutic data and other drug, formulation, and patient/disease data to identify drug development challenges in yielding a successfully performing product. Quality by design and product developability paradigms were discussed. Development tools include early development strategies to identify critical absorption factors and oral absorption modeling. An ongoing theme was the desire to comprehensively and systematically assess risk of product failure via the quality target product profile and root cause and risk analysis. However, a parallel need is reduced timelines and fewer resources. Several presentations discussed applying Biopharmaceutics Classification System (BCS) and in vitro-in vivo correlations in development and in post-development and discussed both resource savings and best scientific practices. The workshop also focused on evolving bioequivalence approaches, with emphasis on highly variable products (HVDP), as well as specialized modified-release products. In USA, two bioequivalence approaches for HVDP are the reference-scaled average bioequivalence approach and the two-stage group-sequential design. An adaptive sequential design approach is also acceptable in Canada. In European Union, two approaches for HVDP are a two-stage design and an approach to widen C max acceptance limits. For some specialized modified-release products, FDA now requests partial area under the curve. Rationale and limitations of such metrics were discussed (e.g., zolpidem and methylphenidate). A common theme was the benefit of the scientific and regulatory community developing, validating, and harmonizing newer bioequivalence methodologies (e.g., BCS-based waivers and HVDP trial designs).

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In vitro–In Vivo Correlations: Tricks and Traps

Cited by 88 publications

References 24 publications

Optimization of a Dissolution Method in Early Development Based on IVIVC Using Small Animals: Application to a BCS Class II Drug

Optimization of a Dissolution Method in Early Development Based on IVIVC Using Small Animals: Application to a BCS Class II Drug

Use of IVIVC to Optimize Generic Development

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

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