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.
|Published (Last):||12 February 2008|
|PDF File Size:||6.80 Mb|
|ePub File Size:||5.91 Mb|
|Price:||Free* [*Free Regsitration Required]|
Volume of distribution was calculated with use of the model based upon a modified version of the Poulin and Theil method [ 13 ].
In vitro – in vivo correlation: from theory to applications.
Once a discriminating system is developed, dissolution conditions should be the same for all formulations tested in the biostudy for development of the correlation and should be fixed before further steps towards correlation evaluation are undertaken [ 34 ].
Comparison between dissolution profiles could be achieved using a difference factor f 1 and a similarity factor f 2 which originates from simple model independent approach. The in vitro results are then related to in vivo drug plasma concentration profiles see danazol example below.
For and optimization, only two formulations were used and a middle one with medium dissolution rate was predicted. The Golem dissolution experiments were started with batch80 and its reference product Lipitor, since both products contained the same crystal form of ATV, and both were buffered by CaCO 3as excipient.
While the dissolution profile must be well defined, the simplification in dissolution specification as in Class I is applicable for immediate release dosage forms where drug input to the intestine is gastric emptying rate controlled.
More precisely this is the case where absorption number, An is high and Dissolution number Dn is low. Prediction of in vivo profile of batch82 with nonlinear model built on batch02 and batch The results are more readily interpreted in terms of the effect of in vitro release on conventional bioequivalence metrics [ 5 ]. It is not a formal correlation but it is a semi quantitative qualitative analysis and rank order correlation and is not considered useful for regulatory purpose but can be serves as an aid in the development of a formulation or processing procedure [ 57 ] Table 1.
However this approach is conceptually difficult to use. This objective should guide the choice and cirrelation of evaluation methods. In order to establish a relationship between dissolution test results and actual results from in vivo studies, different modeling approaches were applied.
Once the IVIVC is established and defined it can be then used to guide the final cycle of formulation and process optimization program statistically based experimental design correlatiom looking at critical formulation and process variables. Before one considers relating in vitro results to in vivo, one has to establish as to how one will establish similarity or dissimilarity of in vivo response i.
Frequently, drug development requires changes in formulations due to a variety of reasons, such as unexpected problems in stability, development, availability of better materials, better processing results, etc. Deconvolution results for buffered batches are presented in Figures 11 and This class of drugs present significant problems for effective oral delivery.
It should be, however, pointed out that in order to achieve such a relatively simple mathematical model, it is necessary to provide physiologically relevant dissolution results. Evaluation of external predictability is based on additional test data sets [ 5 ]. As a result, the predictability of an IVIVC model can be evaluated over the entire in vivo time course. IVIVC can be used in the development of new pharmaceuticals to reduce the number of human studies ivviv the formulation development.
In Vitro?In Vivo Correlation (IVIVC): A Strategic Tool in Drug Development
The establishment of a rational relationship between a biological property, or a parameter ifiv from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form [ 2 ]. The research in drug development facilitates dissolution to uncover and predict correlatipn crucial aspects influencing the fate of an administered active pharmaceutical ingredient API in 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 ].
Coupling biorelevant dissolution methods with physiologically based pharmacokinetic modelling to forecast in-vivo performance of solid oral dosage forms. This approach is called direct convolution. Comparison of Lipitor and batch80 predicted and actual plasma concentration profiles. A universal dissolution method was employed which simulated the physiology corelation human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions.
This work should also result in the definitive in vitro method that has been shown to be correlated with in vivo performance and sensitive to the specific formulation variables. October 06, ; Accepted Date: The starting dissolution medium was based on a physiological solution with pH modified by hydrochloric acid or bicarbonate buffer; pepsin was added only to the gastric compartment.
Predicted plasma concentration and consequent AUC and C max could be calculated using convolution or any other appropriate modeling techniques [ 24 ]. The objective of IVIVC evaluation correlaton to estimate the magnitude of the error in predicting the in vivo bioavailability results from in vitro dissolution data. The classification is based on the drug dissolution and absorption model, which identifies the key parameters controlling drug absorption as a set of dimensionless numbers: A typical medium volume is to ml.
Since in the presented case, bioassay protocol did not include such atorvastatin administration, an approximation of i. 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.
Since dissolution apparatuses tend to become less discriminative when operated at faster speeds, lower stirring speeds should be evaluated and an appropriate speed chosen in accordance with the test data.
The plots show dissolution behavior measured in separate compartments, as well as cumulative profile showing the amount of drug dissolved in the whole apparatus including the amount gradually transferred from ileum into the collection canister. To receive news and publication updates ccorrelation BioMed Research International, enter your email address in the box below.
Any appropriate approach related to this objective may be used for evaluation of predictability [ 523 ]. The BCS thus enables manufacturers to reduce the cost of approving scale-up and post approval changes to certain oral drug products without compromising public safety interests [ 33 ].
In Vitro?In Vivo Correlation (IVIVC): A Strategic Tool in Drug Development | OMICS International
The results depicted below follow a general agenda of in vitro – in vivo correlation level A, where fraction absorbed in vivo is directly correlated to the fraction dissolved in vitro. This is typically a four or five-arm cross-over study. Corrslation statistical computing software was used for modeling. Thus, dissolution standard may be necessary for the in-vivo waiver [ 26 ].