Impact of Data Base Structure in a Successful In Vitro-In Vivo Correlation for Pharmaceutical Products

Abstract

The in vitro-in vivo correlation (IVIVC) (Food and Drug Administration 1997) aims to predict performances in vivo of a pharmaceutical formulation based on its in vitro characteristics. It is a complex process that (i) incorporates in a gradual and incremental way a large amount of information and (ii) requires information from different properties (formulation, analytical, clinical) and associated dedicated treatments (statistics, modeling, simulation). These results in many studies that are initiated and integrated into the specifications (quality target product profile, QTPP). This latter defines the appropriate experimental designs (quality by design, QbD) (Food and Drug Administration 2011, 2012) whose main objectives are determination (i) of key factors of development and manufacturing (critical process parameters, CPPs) and (ii) of critical points of physicochemical nature relating to active ingredients (API) and critical quality attribute (CQA) which may have implications in terms of efficiency, safety, and inoffensiveness for the patient, due to their non-inclusion. These processes generate a very large amount of data that is necessary to structure. In this context, the storage of information in a database (DB) and the management of this database (database management system, DBMS) become an important issue for the management of projects and IVIVC and more generally for development of new pharmaceutical forms. This article describes the implementation of a prototype object-oriented database (OODB) considered as a tool, which is helpful for decision taking, responding in a structured and consistent way to the issues of project management of IVIVC (including bioequivalence and bioavailability) (Food and Drug Administration 2003) necessary for the implementation of QTPP.

Establishment of In Vitro Dissolution Based on Similarity with In Vivo Dissolution: A Case Study on Aripiprazole

“…In addition, the undissolved drugs continue to dissolve during the separation process, while the operation, e.g., centrifuge and ultrafiltration, accelerates the dissolution . The catheter is invasive and may cause duodenogastric reflux . All the above-mentioned factors impair the accuracy of the technique.…”

“…19 The catheter is invasive and may cause duodenogastric reflux. 20 All the above-mentioned factors impair the accuracy of the technique. Moreover, without an accurate estimate of the volume of the gastric/intestinal fluid, the technique only provides the concentration variation of the dissolved drugs in vivo without a definite dissolution percentage.…”

“…However, the establishment of F a -based IVIVC is challenging with a universal acceptance rate of 40%. ,, F a is estimated by a deconvolution of plasma concentration–time profile of the drugs. The bias in the estimate makes it difficult to establish IVIVC. , Therefore, the European Innovative Medicines Initiative and the U.S. Food and Drug Administration (FDA) have organized major research plans to develop in vitro /in silico tools that are predictive for in vivo drug behavior. − However, the accuracy of the tools are impaired from the complicated and changeable gastrointestinal conditions. − The essence of the IVIVC is the correlation between in vitro dissolution and in vivo dissolution. , The in vivo dissolution may be preferable to F a in setting up an in vitro dissolution protocol.…”

Use of IVIVC to Optimize Generic Development

“…IVIVC stresses the importance of the in vitro dissolution (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), which must directly reflect the release and dissolution of the drug from the dosage form and all the aspects related to the formulation work. In contrast to in vivo studies, in vitro methods can be adapted to the dosage form developed as different apparatus could be used (USP Apparatus 1-4) with various media (HCl, buffer solutions, added surfactants or enzymes, complexation media: FaSSIF and FeSSIF), using pre-established technical parameters (e.g., volume, rate, flow).…”