Skin Permeability

ISBN-13: 9783540117971 / Angielski / Miękka / 1982 / 356 str.

H. Schaefer; W. Schalla; A. Zesch

Spis treści

Skin Permeability. By Prof. Dr. H. Schaefer, Valbonne/France, Prof. Dr. A Zesch, Berlin, and Prof. Dr. G. Stüttgen, Berlin (With 139 Figures).- I. Introduction.- 1. To the Reader.- 2. Definitions.- II Morphologic Basis of Absorption by Human Skin.- 1. Skin Surface.- 2. Horny Layer.- 3. Epidermis.- 4. Dermis (Corium).- 5. Subcutis.- III. Methods for Measurement of Absorption.- 1. Animal Experiments.- 2. In Vitro Methods.- a) Disappearance Measurements.- b) Penetration Into the Isolated Horny Layer.- c) Diffusion Through Horny Layer and Epidermis Into Dermis.- d) Diffusion Through Horny Layer and Epidermis.- e) Diffusion Through the Total Skin Specimen.- f) Penetration Into Single Layers of the Skin.- g) Inverse Penetration.- 3. In Vivo Methods.- a) Disappearance Measurements.- b) Measurement in the Horny Layer.- c) Appearance in the Skin and Inner Organs (Autoradiography).- d) Measurement of Total Body Content.- e) Measurement of Skin Clearance.- f) Measurement in Exudates.- g) Measurement of Appearance in the Serum.- h) Radioimmunoassay.- i) Determination in the Urine.- j) Determination of Concentration in the Horny Layer, Epidermis and Dermis.- k) Determination of Appearance in the Epidermis and Dermis by Secondary Parameters.- l) Determination of Skin Reactivity.- m) Determination of Allergenic Potency.- n) Determination and Estimation of Therapeutic Efficiency.- o) Determination of Migration From the Vessels of the Underlying Tissue Into the Skin and to the Skin Surface.- 4. Prerequisites for the Measurement of Permeation Parameters With Radioactively Labelled Substances.- 5. Comparison of in Vivo and in Vitro Permeability.- 6. Compartments of Skin Permeation.- a) Skin Surface.- b) Horny Layer.- c) Percutaneous Resorption and Systemic Treatment.- d) Binding to the Skin.- e) Transfollicular Absorption.- 7. Transformation and Metabolism of Drugs in the Skin.- a) Autodisintegration by Radiolysis.- b) Chemical Decomposition.- c) Passive Metabolism.- d) Microbial Transformation.- e) Active Metabolism.- f) Conclusions.- IV. Quantitative and Qualitative Aspects of Absorption.- 1. Theoretic Aspects.- a) Diffusion Through the Horny Layer.- b) Resulting Concentrations in the Epidermis and Dermis.- 2. Kinetics of Penetration, Permeation, Resorption and Excretion.- a) Theoretic and Experimental Prerequisites.- b) Concepts of Optimal Permeation Kinetics in Topical Therapy.- c) Normal Kinetics.- d) Kinetics in the Horny Layer.- e) Barrier Function of the Horny Layer.- f) Reservoir Function of the Horny Layer.- g) Shunt Diffusion.- h) Kinetics in the Epidermis.- i) Kinetics in the Dermis.- j) Percutaneous in Relation to Systemic Absorption.- k) Penetration Into the Subcutis.- 1) Binding of Substances to Cutaneous Constituents.- m) Urinary Excretion.- 3. Chemical Structure and Absorption.- a) Homologous Series of Alcohols.- b) Transport Forms.- c) Steroids.- 4. The Horny Layer as Regulating and Limiting Factor.- a) Barrier and Reservoir Function of the Individual Strata of the Horny Layer.- b) Kinetics of Various Substances in the Horny Layer.- c) Surface Fat and Barrier Effect.- d) Pathologic Alterations of the Barrier Function in Diseased Skin.- e) Regeneration of Barrier Function.- f) Alteration of the Barrier Function of the Horny Layer by “Chemical Stress”.- g) Loss of Barrier Function of the Horny Layer Caused by Stripping.- V. Pharmacy of Topical Drugs.- 1. Pharmaceutical Problems of Externally Applied Drugs.- 2. Availability of Topically Applied Drugs.- 3. Drug Release Into the Stratum Corneum and Optimal Vehicle Properties.- 4. Vehicle Systems.- a) Emulsifying Agents.- b) Pharmaceutical Emulsifying Agents for External Application.- c) Ointment Bases.- ?) Hydrocarbons.- ?) Fats and Oils.- ?) Polyethylene Glycols.- ?) W/O Emulsion Ointments.- ?) O/W Emulsion Ointments.- ?) Hydrogel Ointments.- d) Transparent Gels.- ?) Transparent Oleaginous Gels.- ?) Transparent Microemulsions (“Swinging Gels”).- ?) Transparent Hydrogels.- e) Silicone Ointments.- f) Powders.- g) Solvents as Vehicles.- ?) Penetration of Solvents and Surfactants — Enhancement of Penetration.- ?) Dimethylsulfoxide (DMSO) and Other “Accelerants”.- ?) Solvent Concentration and Particle Size.- ?) Solvent Concentration in Nonvolatile Vehicles.- 5. Drug Release From Vehicles.- a) In Vitro Release Rates.- b) In Vivo Release.- 6. Intrinsic Activity of the Vehicle.- a) Penetration of Vehicle Constituents.- b) Skin Blanching by Vehicle Components.- 7. Drugs and the Accompanying “Appropriate” Vehicles.- a) Partition Coefficient.- b) Concentration of the Applied Substance.- 8. Kinetics of Substance Distribution in the Horny Layer.- a) Shorter Penetration Periods.- b) Intermediate Penetration Periods.- c) Longer Penetration Periods.- d) Horny Layer Kinetic Curves.- ?) Phase I.- ?) Phase II.- ?) Phase III.- ?) Phase IV.- 9. Kinetics of a Drug From Different Vehicles.- a) Aqueous Hydrophilic Ointments.- b) Vaseline.- c) Lipophilic W/O-Emulsion.- d) Polyethylene Glycol.- VI. Therapy and Preparation Form.- 1. Localization.- 2. Application Procedure.- 3. Application Frequency.- 4. Vehicle and Sebum.- VII. The Choice of Vehicle in Skin Diseases.- 1. Acuity of a Dermatosis.- 2. Skin Type, Physiologic Skin Status.- 3. Localization of Dermatosis.- 4. Climatic Factors.- 5. Cosmetic Considerations.- VIII. Pharmacodynamic Activities of Locally Applied Drugs to Normal and Diseased Skin.- 1. Modification by the Dermatosis.- 2. Pharmacoanalysis.- 3. Primary Mode of Action of a Drug and Its Secondary Empiric Therapeutic Effects.- 4. Site of Primary and Secondary Pharmacologic Effects.- 5. Structure and Function in Relation to Pharmacologie Effects.- 6. Antihistamines.- 7. Corticosteroids.- 8. “Vasoconstriction” Test as Bioassay for Corticosteroids.- a) Vasoconstriction and Antiinflammatory Activity.- b) Vasoconstriction (Blanching) as Measure for Penetration.- c) Vasoconstriction and Drug Interaction.- d) Vasoconstriction and Atrophy.- e) Mechanism of Steroid-Induced Vasoconstriction.- f) Further Vasoactive Drugs.- ?) Nicotinic Acid Esters.- ?) Catecholamines.- 9. Caffeine.- 10. Heparin.- 11. Vitamins.- 12. Sex Hormones.- IX. Special Cases and Modifying Factors Related to Topical Therapy.- 1. Drug Interaction.- 2. Combinations with Salicyclic Acid and Derivatives.- 3. State of Skin and Permeation (Childhood, Diseased Skin).- 4. Skin Permeability in Infants and Young Children.- 5. Percutaneous Therapy of Systemic Diseases.- 6. The Permeability of the Vessels of Human Skin.- 7. Penetration From the Blood Into the Skin.- 8. Pharmacokinetics in the Skin (Local Versus Systemic Application).- 9. Penetration From the Undersurface of the Dermis into the Skin (Inverse Penetration).- 10. Permeability of Mucosal Surfaces.- 11. Permeability of Human Nails.- 12. Permeability of the Cornea of the Eye.- X. Factors Influencing the Penetration.- 1. Hydration of the Horny Layer.- 2. Medicinal and Mineral Baths.- 3. Occlusion.- 4. Stripping.- 5. Temperature.- 6. Depilatory Agents.- 7. pH Dependence.- 8. Surface Tension.- 9. Iontophoresis.- 10. Ultrasound (Phonophoresis).- XI. Toxicologic Aspects of Skin Permeability.- 1. Cytostatic Agents.- 2. Antibiotics.- 3. Salicylic Acid.- 4. Hexachlorophene.- 5. Pesticides, Herbicides.- 6. Solvents.- 7. Mercury.- 8. Boron.- 9. Lead.- 10. Contamination and Decontamination of the Skin.- 11. Surfactants, Soaps.- XII. Special Problems Encountered in Penetration.- 1. Permeation of Gases.- a) Permanent Gases.- b) Nonpermanent Gases.- 2. Penetration of Solid Particles.- 3. Water Movement Through the Skin.- 4. Penetration of Electrolytes.- 5. Glucocorticosteroids.- a) Hydrocortisone.- b) Further Literature on Hydrocortisone (HC).- c) Hydrocortisone-17-butyrate (HCB).- d) Betamethasone-17-valerate, Bethamethasone.- e) Desoximetasone (DOM).- f) Fluocinolone (F), Fluocinolone Acetonide (FA), Fluocinolone Acetonide Acetate (FAA).- g) Triamcinolone, Triamcinolone Acetonide (TA).- h) Fluprednylidene-21-acetate.- i) Corticosteroids: Conclusions.- 6. Mineralocorticoids.- 7. Androgens, Antiandrogens and Estrogens.- a) Androgens.- b) Antiandrogens.- c) Estrogens.- d) Conclusions.- 8. Vitamin A Acid and Derivatives.- 9. Psoralens.- a) In Vitro Experiments.- ?) Effects of Different 8-MOP Concentrations on Penetration.- ?) Effects of Solvents on Penetration.- ?) Effects of UV Irradiation on 8-MOP Binding..- b) In Vivo Experiments.- ?) Oral Administration.- ?) Topical Application..- ?) Conclusions Concerning the Photochemotherapy With 8-MOP.- 10. Dithranol (= Anthralin = Cignolin).- 11. Methotrexate (MTX).- XIII. Flux.- XIV. General Rules.- XV. Substances Investigated in Penetration and Related Fields.- References.