1st Edition
Assessing Bioavailablility of Drug Delivery Systems Mathematical Modeling
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.
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