Correlations between in vitro and in vivo data (IVIVC) are often used during pharmaceutical development in order to reduce development time and optimize the. This presentation gives a bird’s eye view on Dissolution in context with IVIVC. It discusses various levels of Correlations currently in practice. Invitro Invivo study & their correlation shortens the drug development period, economizes the resources and leads to improved product quality. Increased activity.
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Drug absorption from a solid dosage form following oral administration depends on the release of the drug substance from the drug product, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract.
Diffusion-dissolution, matrix retardation, osmosis, etc.
Indexed in Science Citation Index Expanded. Deconvolution is a numerical method used to estimate the time course correlafion drug input using a mathematical model based on the convolution integral.
The in vitro dissolution release of a formulation can be modified to facilitate the correlation development.
The relationship between measured quantities in vitro release and plasma drug concentrations is modeled directly in a single stage rather than via an indirect two stage approach.
Using the NONMEM package, a nonlinear mixed effects model can be fitted to the data with a time-scale model linking the in vitro and in vivo components [ 10 ]. Prediction of generic batch80 profile with linear model built on batch80 and Lipitor. Commonly the following experimental conditions should be considered in this regard. The logical basis for this correlation was the assumption that any dissolved portion of API in vivo would be immediately absorbed due to the nonlimiting permeability of ATV, which allows direct correlation of the ascending part of the dissolution and plasmatic profiles.
This assumed model can be the subject of revision as prototype formulations are developed and characterized in vivo, with the results often leading to a further cycle of prototype formulation and In vivo characterization.
This concept underlying the BCS published finally led to introducing the possibility of waiving in vivo bioequivalence BE studies in favor of specific comparative in vitro testing to conclude BE of oral immediate release IR products with systemic actions [ 32 ].
This level of correlation is the highest category of correlation and represents a point-to-point relationship between in vitro dissolution rate and in vivo input rate of the drug from the dosage form [ 35 ].
Deconvolution results for buffered batches are presented in Figures 11 and The differences between the batches were thus more pronounced here than elsewhere in the apparatus. Further justification as well as 24 hours test duration are required if the percent drug release is less than 80 [ 3437 ]. Thus, the main objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and to support biowaivers.
To generate predicted time courses, the drug input profile is predicted based on In vitro dissolution data and the In vitro-In vivo relationship generated in step 2.
Extended Release Oral Dosage Forms: This research shows that, when the system being modeled is linear, the use of differential equations will produce results that are practically identical to those obtained from the convolution method. From Wikipedia, the ivjv encyclopedia. The instrument is a computer controlled artificial digestive tract, designed for dynamic dissolution testing of oral dosage forms and consisting of four compartments: However, a more complex simulation of the GIT is often needed, and currently only TIM-1 apparatus fully enables in vitro testing in completely biorelevant conditions ranging from stomach to ileum [ 3 ].
In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. Frequently, drug development requires changes in formulations due to a variety of reasons, such as unexpected problems correlatiin stability, development, availability of better materials, better processing results, etc.
In mathematical terminology, dissolution results become an input function and plasma concentrations e. Then, the pharmacokinetic parameters are estimated using a nonlinear regression tool or obtained from literatures reported previously.
In vitro – in vivo correlation: from theory to applications.
corrlation This is the weakest level of correlation as partial relationship between absorption and dissolution is established since it does not reflect the complete shape of plasma drug concentration time curve, which is the critical factor that defines the performance of a drug product.
This paper discusses the application and evaluation of this apparatus, performed with several generic and reference batches of immediate release tablets containing atorvastatin ATV. In general, predictions of were good, but the descending curves could not properly reflect the in vivo behavior resulting in high AUC PE. Moreover, API powder corelation served as uviv control also showed identical dissolution performance to batches 01 and 02, indicating that the dissolution method lacked discriminatory power for these highly dissolving batches.
For an appropriate dissolution test, in general and in particular for developing IVIVC, one requires to conduct the test selecting experimental conditions to simulate an in vivo environment as closely as possible. The starting dissolution medium uviv based on a physiological solution with pH modified by hydrochloric acid or bicarbonate buffer; pepsin was added only to the gastric compartment.
Providing the pharmaceutical industry with oral drug development tools –
It was first introduced into regulatory decisionmaking process in the guidance document on immediate release solid oral dosage forms: This is typically a four or five-arm cross-over study. An individual formulation-related dissolution protocol could thus be an answer to the industrial need for discriminative and at the same time biorelevant dissolution methods, whereas standardization could be achieved on the level of algorithmic approach to the adjustment of the dissolution protocol.
IVIVC can be used correlattion the development of new pharmaceuticals to reduce the number of human studies during the formulation development as the main objective of an IVIVC is to serve as a surrogate for in vivo bioavailability and to support biowaivers. The dissolution behavior of the biobatch maybe used to define the amount to be released at each time point. The mapping process defines boundaries of in vitro dissolution profiles on the basis of iiv bioequivalency criteria.
The pH in stomach compartment was left to change, being influenced by the studied formulation. The research in drug development facilitates corrrelation to uncover and predict many crucial aspects influencing the fate of an administered active pharmaceutical ingredient API iiv the gastrointestinal tract GITwhile employing a wide variety of innovative and special apparatuses, either based on the conventional pharmacopeial tools or having a completely original design [ 1 ].
Beyond this range, the specification should xorrelation supported by bioequivalence studies [ 43 ]. Predictability evaluation was performed by calculating fraction of ATV absorbed versus time with regression equation with in vitro profile as an input.
In Vitro?In Vivo Correlation (IVIVC): A Strategic Tool in Drug Development
The compartments are made from modified common intravenous bags the plastic was tested for interaction with various APIs. Authors would like to thank company-Zentiva Group, a. Fdiss Plots and Levy Plots can be used to ivv determine which of these variables may be applicable.