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| Cell Membranes, Epithelial Barriers and Drug Absorption | |
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| Introduction | |
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| The Plasma Membrane | |
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| The phospholipid bilayer | |
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| Dynamic behaviour of membranes | |
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| Modulation of membrane fluidity by sterols | |
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| Models of cell membranes | |
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| Membrane proteins | |
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| Membrane asymmetry | |
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| Epithelia | |
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| Cell junctions | |
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| Transport Across Cell Membranes | |
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| Passive diffusion | |
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| Facilitated and carrier mediated diffusion | |
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| Cotransport | |
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| Uptake of macromolecules and particles | |
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| Intercellular Routes of Absorption | |
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| Persorption | |
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| Mucus | |
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| Conclusions | |
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| References | |
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| Parenteral Drug Delivery | |
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| Introduction | |
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| Intravenous Delivery | |
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| Physiology | |
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| Advantages and disadvantages of intravenous delivery | |
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| Formulation considerations | |
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| Devices and technologies | |
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| Injected particulates | |
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| Intravenous oxygen carriers | |
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| Intramuscular Delivery | |
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| Physiology | |
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| Pharmacokinetics | |
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| Formulation considerations | |
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| Subcutaneous Delivery | |
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| Physiology | |
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| Subcutaneous colloidal delivery systems | |
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| Tissue Damage and Biocompatability | |
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| Drug Distribution Following Parenteral Administration | |
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| Protein Binding | |
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| The Blood-Brain Barrier | |
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| Physiology | |
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| Uptake by diffusion | |
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| Receptor-mediated transport | |
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| Colloidal delivery | |
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| References | |
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| Drug Delivery to the Oral Cavity or Mouth | |
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| Anatomy and Physiology | |
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| The oral cavity | |
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| The palate | |
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| The tongue | |
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| The teeth | |
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| Organisation of the oral mucosa | |
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| Functions of the oral mucosa | |
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| Salivary secretion | |
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| Migration and Clearance of Substances from the Oral Cavity | |
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| Absorption of Drugs across the Oral Mucosa | |
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| Disadvantages of oral mucosal delivery | |
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| Effect of position on drug delivery | |
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| Gingival penetration | |
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| Improving penetration through the mucosa | |
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| Measurement of Oral Mucosal Drug Absorption | |
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| Dosage Forms for the Oral Cavity | |
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| Chewable formulations | |
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| Fast-dissolving dosage forms | |
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| Bioadhesive dosage forms | |
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| Dental systems | |
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| Drugs Administered Via the Oral Mucosa | |
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| Nitrates | |
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| Steroids | |
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| Analgesics | |
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| Antibiotics | |
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| Antifungals | |
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| Others | |
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| Conclusions | |
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| References | |
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| Oesophageal Transit | |
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| Introduction | |
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| Anatomy and Physiology | |
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| Oesophagus | |
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| Gastro-oesophageal junction or cardia | |
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| Motility of the Oesophagus | |
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| Oesophageal Transit of Dosage Forms | |
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| Measurement | |
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| Typical transit times | |
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| Oesophageal Adhesion of Dosage Forms | |
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| Factors predisposing formulations to adhere | |
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| Consequences of Adhesion of Dosage Forms | |
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| Delay in drug absorption | |
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| Oesophageal damage | |
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| Effect of Ageing | |
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| Patient Preference and Ease of Swallowing | |
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| Effect of Diseased States on Transit | |
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| Targeting the Oesophagus | |
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| Conclusions | |
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| References | |
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| The Stomach | |
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| Anatomy and Physiology | |
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| Organisation of the stomach | |
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| Gastric secretion | |
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| Digestion and absorption | |
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| Gastric pH | |
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| Circadian rhythm of acidity | |
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| pH and gender | |
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| pH and age | |
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| pH and smoking | |
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| Gastric Motility | |
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| The fasted state | |
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| The fed state | |
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| Physiological factors which influence gastric emptying | |
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| Effect of disease on gastric emptying | |
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| Dispersion of Dosage Forms in the Stomach | |
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| Hard gelatin capsules | |
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| Soft gelatin capsules | |
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| Gastric Emptying of Dosage Forms | |
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| Time of dosing relative to a meal | |
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| Retention of formulations in the stomach | |
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| Posture effects | |
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| Drug-induced effects on gastric emptying | |
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| Gastric pH and Enteric Coatings | |
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| Drug/Formulation Induced Ulceration | |
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| Animal Models for Gastric Emptying | |
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| References | |
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| Drug Absorption from the Small Intestine | |
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| Anatomy and Physiology of the Small Intestine | |
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| Gross morphology | |
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| Mucosa | |
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| Organisation of the mucosa | |
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| The gastrointestinal circulation | |
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| The lymphatic system | |
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| Secretions into the small intestine | |
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| Secretion and absorption of water | |
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| Digestion and absorption of nutrients | |
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| Patterns of Motility in the Small Intestine | |
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| Stagnation at the ileocaecal junction | |
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| Small Intestinal Transit Times | |
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| Methods for measuring small intestinal transit | |
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| Small intestinal transit times of food | |
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| Physiological and pathophysiological effects on small bowel transit | |
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| Small intestinal transit time of dosage forms | |
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| Density and small intestinal transit | |
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| Absorption of Drugs | |
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| Absorption and delivery of macromolecules | |
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| Intestinal pH | |
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| Solvent drag and intestinal permeability | |
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| P-glycoprotein | |
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| Cytochrome P450 3A4 (CYP3A4) | |
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| Intestinal reserve length | |
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| Interaction with food | |
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| First-pass metabolism | |
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| Relationship Between Drug Absorption and Position of Dose Form | |
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| Radio controlled capsule | |
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| Absorption of drugs and foreign substances through the lymphatic system | |
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| Drug Induced Damage | |
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| References | |
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| Drug Delivery to the Large Intestine and Rectum | |
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| Introduction | |
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| Anatomy and Physiology of the Colon | |
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| Interspecies differences in structure | |
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| Colonic structure | |
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| Gut wall metabolism | |
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| Blood supply | |
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| Nervous and humoral control | |
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| Colonic environment | |
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| Colonic motility | |
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| Drug absorption from the colon | |
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| Drug Delivery | |
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| Transit | |
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| Dietary factors | |
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| Temporal factors | |
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| Targeting the proximal colon | |
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| Effect of disease and co-medication on colonic drug absorption | |
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| Rectal Administration of Drugs | |
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| Drug absorption and avoidance of first-pass metabolism | |
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| Dosage forms for rectal delivery | |
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| Adjuvants and enhancers | |
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| Spreading of rectal dosage forms | |
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| Therapeutic agents administered rectally | |
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| Rectal irritation and damage | |
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| Conclusions | |
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| References | |
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| Transdermal Drug Delivery | |
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| Introduction | |
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| Structure of the Skin | |
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| Epidermis | |
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| Dermis | |
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| Subcutaneous fat layer | |
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| Hair and nails | |
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| Sebaceous glands | |
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| Eccrine sweat glands | |
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| Surface characteristics | |
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| Passage of Drug Through the Skin | |
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| Model systems for skin | |
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| Routes of absorption | |
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| Advantages and disadvantages of transdermal delivery | |
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| Factors Affecting Percutaneous Absorption | |
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| Individual variation | |
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| Age | |
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| Site | |
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| Occlusion | |
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| Temperature | |
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| Race | |
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| Disease | |
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| Vehicles and Devices | |
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| Penetration Enhancers | |
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| Iontophoresis | |
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| Electroporation | |
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| Sonophoresis | |
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| Conclusions | |
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| References | |
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| Nasal Drug Delivery | |
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| Anatomy and Physiology | |
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| Nasal epithelia | |
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| Nasal lymphatic system | |
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| Nasal secretions | |
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| The nasal cycle | |
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| Mucociliary clearance of inhaled particles | |
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| Pathological effects on mucociliary function | |
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| External factors affecting mucociliary clearance | |
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| Chemical-induced changes | |
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| Intranasal Administration of Drugs | |
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| Drugs administered for local action | |
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| Drugs administered for systemic effect | |
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| Drug Delivery Systems and Deposition Patterns | |
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| Mechanisms to increase nasal residence time of formulations | |
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| Excipient and drug effects on clearance | |
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| Effect of formulation pH | |
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| Interspecies Comparisons | |
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| Conclusions | |
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| References | |
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| Pulmonary Drug Delivery | |
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| Structure and Function of the Pulmonary System | |
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| The lung | |
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| Upper airway | |
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| Structure of the tracheo-bronchial tree | |
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| Epithelium | |
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| Lung permeability | |
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| Lung mucus | |
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| Lung defenses | |
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| Lung surfactant | |
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| Blood supply | |
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| Lymphatic system | |
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| Nervous control | |
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| Biochemical processes which occur in the lung | |
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| Breathing | |
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| Respiratory disease | |
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| Dosage Forms for Pulmonary Drug Delivery | |
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| Pressurized inhalation aerosols | |
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| Dry powder inhalers | |
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| Nebulizers | |
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| Spacer devices and ancillary equipment | |
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| Assessment of Deposition by Gamma Scintigraphy | |
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| Choice of radiolabel | |
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| Labeling inhalation formulations | |
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| Labeling dry powder inhalers | |
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| Validation | |
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| Factors Affecting Particle Deposition in the Lung | |
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| Physicochemical properties | |
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| Deposition patterns from different dose forms | |
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| Physiological variables | |
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| Drug Absorption | |
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| Pharmacokinetics | |
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| Drugs Administered Via the Pulmonary Route | |
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| Anti-allergy agents | |
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| Beta receptor agonists | |
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| Adrenocorticosteroids | |
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| Leukotriene inhibitors | |
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| Other bronchodilating agents | |
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| Mucolytics | |
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| Systemically-absorbed drugs | |
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| References | |
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| Ocular Drug Delivery | |
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| Introduction | |
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| Structure of the Eye | |
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| The cornea | |
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| The conjunctiva and sclera | |
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| The choroid and retina | |
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| The aqueous humor | |
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| The eyelids | |
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| The precorneal tear film | |
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| Blood-eye barriers | |
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| Factors Affecting Drug Permeation | |
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| Ionization and pH | |
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| Protein binding | |
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| Pigmentation and drug effects | |
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| Drug distribution in the eye | |
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| Drug penetration through the sclera and conjunctiva | |
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| Factors Influencing Drug Retention | |
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| Proper placement of the eyedrops | |
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| Influence of instilled volume | |
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| Preservatives | |
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| Effect of systemically administered drugs | |
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| Routes of Drug Administration | |
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| Topical administration | |
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| Intraocular drug delivery | |
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| Systemic administration | |
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| Conclusions | |
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| References | |
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| Vaginal and Interuterine Drug Delivery | |
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| Anatomy and Physiology | |
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| Mucosa | |
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| Blood and nerve supply | |
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| Uterine and vaginal fluid | |
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| pH | |
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| Enzymatic activity | |
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| Mucus | |
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| Menstruation | |
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| Menopause | |
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| Disorders of the vagina | |
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| Drug Absorption Through the Vagina/Uterus | |
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| Drug Delivery | |
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| Vaginal | |
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| Intrauterine Devices | |
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| Conclusion | |
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| References | |
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| Glossary | |
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| Index | |