1st Edition

Assessing Bioavailablility of Drug Delivery Systems Mathematical Modeling

    244 Pages 126 B/W Illustrations
    by CRC Press

    Exploring how to apply in vitro/in vivo correlations for controlled release dosage forms, Bioavailability of Drug Delivery Systems: Mathematical Modeling clearly elucidates this complex phenomena and provides a guide for the respective mathematical modeling. The book introduces mathematical modeling methods for calculating the profiles of plasma levels obtained with controlled release dosage forms and provides examples and case studies to illustrate the techniques employed.

    The author has considerable experience in investigating mathematical fundamentals that are related to pharmaco- and toxicokinetics, modified-release drug products, physiologic pharmacokinetics and statistical treatment in clinical situations. The mathematical models he has developed are particularly powerful because they account for such major parameters as the kinetics of drug release controlled by diffusion or by erosion, and the kinetics of absorption into and elimination out of the plasma. They are also able to solve the problem of determining the drug level in plasma as a result of patient non-compliance, incorrect dosage, and incorrect frequency and to determine the best dosage forms necessary for therapy.

    Using master curves, the book highlights the inter-variability of the patients often expressed by different responses towards a drug. Thus, after evaluating a patient's pharmacokinetic parameters, the dose can be adapted to the patient, with the expectation of decreasing the side effects for each patient. Using dimensionless numbers in repeated doses, either for the time or for the plasma drug concentration, makes the master curves useful for every drug, providing that its pharmacokinetics was linear. These master curves address clear information either to the patients or to the therapists in a didactic and easy way. The patients can see from first look the effects of non-compliance and therapists can see the dramatic effects of inter-variability of patients towards a drug.

    Drug discovery and dosage forms have become an increasingly time-consuming and expensive process. The development of a single drug can leave behind more than 10 to 15 years of work. Discussing time and cost-effective methods as alternatives to conventional in vivo methods, the book helps you analyze and integrate in vitro/in vivo correlations and apply them to patient care and drug consultation situations.

    DEFINITIONS
    Drugs (Active Agents) and Their Supply Forms (Dosage Forms)
    Biopharmaceutics and Its Goal
    Pharmacokinetics
    Pharmacodynamics
    Liberation of the Drug
    Membranes
    Bioavailability
    Absorption of the Drug in the Blood
    Distribution of the Drug
    Elimination of the Drug
    Therapeutic Index
    Determination of the Pharmaceutical Parameters

    INTRAVENOUS ADMINISTRATION
    Administration of a Single Dose
    Repeated Intravenous Injections (DIV)
    Continuous Intravenous Infusion (CIV)
    Repeated Dosage at Constant Flow Rate

    ORAL DOSAGE FORMS WITH IMMEDIATE RELEASE
    Single Dose
    Effect of the Pharmacokinetic Parameters' Values
    Multiple Oral Doses
    Area under the Curve with Oral Dosage Forms
    Comparison Between Oral and I.V. Drug Delivery

    KINETICS OF DRUG RELEASE FROM ORAL SUSTAINED DOSAGE FORMS
    Drug Release Controlled by Diffusion
    Drug Release Controlled by Erosion
    Comparisons and Other Kinetics of Release

    BIBLIOGRAPHY ON IN VITRO-IN VIVO CORRELATIONS
    General Survey on In Vitro-In Vivo Problems
    In Vitro-In Vivo Correlations for Oral Immediate-Release Dosage Forms
    In Vitro-In Vivo Correlations with Oral Sustained-Release Dosage Forms

    PLASMA DRUG LEVEL WITH ORAL DIFFUSION-CONTROLLED DOSAGE FORMS
    Methods of Calculation
    Results Obtained for a Single Dose
    Sustained Release with Repeated Doses
    Prediction of the Characteristics of the Dosage Form

    PLASMA DRUG LEVEL WITH EROSION-CONTROLLED DOSAGE FORMS
    Method of Calculation
    Plasma Drug Profile with a Single Dose
    Plasma Drug Profile with Repeated Multidoses
    Prediction of the Characteristics of the Dosage Forms

    EFFECT OF PATIENT'S NONCOMPLIANCE
    Limited Reliability of the Patient
    Noncompliance with Erosion-Controlled Dosage Forms
    Noncompliance with Diffusion-Controlled Dosage Forms

    DRUG TRANSFER IN VARIOUS TISSUES
    Drug Transfer into and through the Lung and Bronchial Mucus
    Drug Transfer into the Blister Fluid
    Drug Transfer into Endocarditis

    TRANSDERMAL THERAPEUTIC SYSTEMS
    General Mechanisms of Drug Delivery
    Overview of the Skin and Its Role
    Calculation of the Drug Transport
    Results for the Transdermal Delivery of Metropolol
    Effect of the Characteristics of the TTS
    Effect of the Parameters of the Skin

    Biography

    Jean-Maurice Vergnaud, Iosif-Daniel Rosca

    "…it adds new perspectives on topics…[and] gives an overview of the theoretical and experimental work of its senior author."
    -European Journal of Pharmaceutics and Biopharmaceutics