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fined to the measurement of the rates of disintegration and ultimate dissolution. Although official tests have great practical value, the fact that there is still a need for a test more directly related to bioavailability has been pointed out repeatedly. Since dissolution of a dosage form in vivo is often the rate-limiting factor determining the physiologic availability of a drug, the measurement of the in vitro dissolution rate or some related parameter is more likely to offer a meaningful indication of physiologic availability. If a correlation between the values of good, definite, likely, or poor exists between this parameter and some parameter of bioavailability, then the relatively simple procedure of monitoring the dissolution profile should permit the prediction of in vivo availability. |
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The logic and interest behind correlating in vitro and in vivo dissolution parameters is twofold. First, in vitro values are used to evaluate different lots of a particular pharmaceutical product as a quality control check to ensure a desired physiologic performance. Second, in vitro values are used as a developmental tool for series of dosage forms to obtain a desired in vivo performance. These objectives can be best fulfilled when a relationship between the in vitro and in vivo parameters can be confirmed, but not when dissolution is merely defined under a random set of in vitro specifications. |
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A. Basics of In Vivo-In Vitro Correlations |
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Levy classified in vivo-in vitro correlations as follows: |
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1. Pharmacological correlationsbased on clinical observations; |
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2. Semiquantitative correlationsbased on blood levels or urinary excretion data; and |
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3. Quantitative correlationsresultant to absorption kinetics. |
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While most of the published correlations fall within the second class, the most valuable are those based on absorption kinetics. |
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Essentially, there are two basic types of correlations that are employed while comparing in vivo-in vitro data: |
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Quantitative correlations |
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All correlation techniques require linearity of the complete system under investigation. Erroneous interpretations are likely when absorption of undissolved particles occur or when absorption rate is changed significantly during gastrointestinal passage. Additionally, inter- and intraindividual variability in the bioavailability of the drug will seriously limit the meaningfulness of the correlation. Furthermore, inadequate in vitro test condition(s) without regard to physicochemical characteristics of the drug substance or the drug product |
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