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E-grāmata: Predictive Methods in Percutaneous Absorption

  • Formāts: PDF+DRM
  • Izdošanas datums: 01-Jul-2015
  • Izdevniecība: Springer-Verlag Berlin and Heidelberg GmbH & Co. K
  • Valoda: eng
  • ISBN-13: 9783662473719
  • Formāts - PDF+DRM
  • Cena: 106,47 €*
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  • Formāts: PDF+DRM
  • Izdošanas datums: 01-Jul-2015
  • Izdevniecība: Springer-Verlag Berlin and Heidelberg GmbH & Co. K
  • Valoda: eng
  • ISBN-13: 9783662473719

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This book sheds new light on the development and use of quantitative models to describe the process of skin permeation. It critically reviews the development of quantitative predictive models of skin absorption and discusses key recommendations for model development. Topics presented include an introduction to skin physiology; the underlying theories of skin absorption; the physical laboratory-based processes used to generate skin absorption data, which is in turn used to construct mathematical models describing the skin permeation process; algorithms of skin permeability including quantitative structure-activity (or permeability) relationships (QSARs or QSPRs); relationships between permeability and molecular properties; the development of formulation-focused approaches to models of skin permeability prediction; the use of artificial membranes, e.g. polydimethylsiloxane as alternatives to mammalian skin; and lastly, the use of novel Machine Learning methods in developing the next generation of predictive skin permeability models.

The book will be of interest to all researchers in academia and industry working in pharmaceutical discovery and development, as well as readers from the field of occupational exposure and risk assessment, especially those whose work involves agrochemicals, bulk chemicals and cosmetics.

1 Skin Structure and Physiology
1(24)
Introduction
1(1)
The Hypodermis (Subcutaneous Fatty Tissue Layer)
1(1)
The Dermis
2(1)
Skin Appendages
3(1)
The Subcutaneous Sensory Mechanism
4(1)
The Epidermis
5(5)
The Stratum Germinativum
5(1)
The Stratum Spinosum
6(1)
The Stratum Granulosum
7(1)
The Stratum Lucidum
7(1)
The Stratum Corneum
7(1)
The Stratum Corneum Barrier
8(2)
Routes of Permeation of Exogenous Chemicals Across the Stratum Corneum
10(1)
Percutaneous Permeation---Mechanisms of Absorption
10(2)
Theoretical Considerations
12(2)
Physicochemical Properties of the Penetrant
14(3)
Partition Coefficient
14(1)
Molecular Size and Shape
15(1)
Applied Concentration/Dose
15(1)
Aqueous Solubility and Melting Point
16(1)
Ionisation
16(1)
Physiological Factors Affecting Percutaneous Absorption
17(4)
Skin Condition
17(1)
Skin Hydration and Occlusion
17(1)
Skin Age
18(1)
Site-to-Site Variation
19(1)
Race
19(1)
Skin Temperature
19(1)
Vehicle Effects
20(1)
References
21(4)
2 Methods for the Measurement of Percutaneous Absorption
25(18)
Introduction
25(1)
In Vivo and In Vitro Methods: Overview
26(1)
In Vitro Experimental Methods
27(11)
Preamble
27(1)
Membrane Selection
27(4)
Integrity Testing
31(1)
Selection of the Diffusion Cell Apparatus
32(4)
Temperature
36(1)
Formulation and Solubility Factors
36(1)
Detection of the Permeant
37(1)
Conclusions
38(1)
References
39(4)
3 Mathematical Treatments and Early Models of Skin Permeability
43(22)
Introduction
43(5)
Infinite and Finite Dosing
48(13)
References
61(4)
4 The New Breadth of Research in the Field
65(26)
References
87(4)
5 Algorithms for Estimating Permeability Across Artificial Membranes
91(12)
The Role of Artificial Membranes in Studies of Percutaneous Absorption
91(3)
Quantitative Models for Permeability Across Polydimethylsiloxane Membranes
94(6)
References
100(3)
6 Other Approaches to Modelling Percutaneous Absorption
103(14)
References
114(3)
7 Squiggly Lines and Random Dots---You Can Fit Anything with a Nonlinear Model
117(24)
Introduction
117(1)
Application of a Nonlinear Multiple Regression Model to Skin Permeability
118(3)
Fuzzy Logic and Neural Network Methods for the Prediction of Skin Permeability
121(5)
More Machine Learning Methods---Classification and Gaussian Process Models
126(10)
References
136(5)
8 Finite-Dose Models of Transient Exposures and Volatile Formulation Components
141(18)
Introduction
141(3)
Modelling Finite-Dose Experiments
144(6)
Models of Formulation in Finite-Dose Experiments
150(6)
Conclusions
156(1)
References
156(3)
9 The Devil is in the Detail
159(22)
Introduction
159(1)
Experimental Factors in Model Quality
159(8)
Analysis of the Experiments from Which Data Have Been Taken to Develop Models of Skin Absorption
167(6)
Formulation Factors
173(2)
Conclusions
175(1)
References
176(5)
10 Conclusions and Recommendations for Model Development and Use
181(12)
Overview of the Previous
Chapters
181(1)
"Pitfalls" of Model Development and Use
182(2)
Quality of the Source, or Input, Data
184(1)
Outliers
185(1)
Biological Data
185(1)
Descriptor Selection and Interpretation, and Data Set Design
186(1)
Statistical Analysis of Data
187(1)
Data---and Data Set---Quality
188(2)
Conclusions
190(1)
References
191(2)
Index 193