Incorrect assumptions for developing an IVIVC and its uses

Developing an IVIVC and its applications are often described in literature as follows (e.g. see link):

“In vitro – in vivo correlation (IVIVC) allows prediction of the in vivo performance of a drug based on the in vitro drug release profiles. To develop an effective IVIVC, the physicochemical and biopharmaceutical properties of the drug as well as the physiological environment in the body must be taken into consideration. Key factors include drug solubility, pKa, drug permeability, octanol-water partition coefficient and pH of environment.”

There are number of deficiencies in the above mentioned description. For example:

  • “in vivo performance of drug”, IVIVC studies are commonly conducted for products (such as tablets and capsules) and not for drugs.
  • An IVIVC does not allow prediction of in vivo performances from in vitro results. In vitro studies (testing) are conducted based on the assumption that the IVIVC already exits.
  • Furthermore, considering the existence of IVIVC, in vitro (dissolution) results are used to reflect or predict expected plasma drug concentration-time profiles.
  • The mathematical approach used for the prediction of plasma concentration-time profiles is not the IVIVC but the convolution technique. This (convolution) is the only technique which can be used or applied for the prediction of plasma drug profiles of products.
  • The parameters mentioned above such as, drug solubility, pKa, drug permeability, and octanol-water partition coefficient, are all drug characteristics, and not those of the products for which dissolution tests are conducted. Therefore, these parameters often remain constant, or are kept constant, to evaluate the impact of formulation and/or manufacturing attributes on release/dissolution characteristics of a product.
  • Regarding the “pH of environment”, this is linked to GI tract physiology and is independent of the drugs and products, thus for drug dissolution testing the environment must also remain constant and independent of products and/or drugs.

Therefore, the IVIVCs as currently conducted or promoted are not of any practical use and can easily be ignored or avoided.

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