Transdermal Drug Delivery: Principles and Applications

Transdermal Drug Delivery

Method delivering drugs through skin to bloodstream.

Topical Drug Delivery

Method delivering drugs to local skin tissue.

Systemic Absorption

Drug absorption into systemic circulation.

Ideal Drug Characteristics

Specific properties for effective transdermal delivery.

Dose Deliverable

Maximum dose for transdermal delivery, < 10 mg/day.

Aqueous Solubility

Required solubility for transdermal drugs, > 1 mg/ml.

Lipophilicity

Optimal range for transdermal drugs, 101 < Ko/w < 105.

pH of Saturated Solution

Ideal pH range for transdermal drugs, pH 5-9.

Molecular Weight

Ideal weight for transdermal drugs, < 500 Da.

Melting Point

Ideal melting point for transdermal drugs, < 200°C.

Bioavailability

Extent and rate at which active drug is absorbed.

First-Pass Metabolism

Liver metabolism reducing drug bioavailability.

Short t1/2 Drugs

Drugs with short half-lives, e.g., nitroglycerin.

Rotigotine

Only marketed drug developed for transdermal delivery.

Transdermal Patch Components

Ingredients in patches for effective drug delivery.

Patient Counseling

Guidelines for safe use of transdermal formulations.

Permeation Enhancers

Substances improving drug absorption through skin.

Skin Anatomy

Structure of skin relevant to drug delivery.

Conventional Topical Preparations

Traditional methods for local drug application.

Transdermal Preparations

Formulations designed for systemic drug delivery.

Market Trends

Forecast for transdermal drug delivery market growth.

Challenges in Delivery

Issues affecting reliability of transdermal products.

Steady plasma level

Consistent drug concentration in bloodstream.

Parenteral administration

Drug delivery via injection, bypassing gastrointestinal tract.

Therapeutic effect termination

Ability to quickly stop drug effects.

Patient compliance

Ease of use leading to better adherence.

Potent PK control

Enhanced management of pharmacokinetics for effective dosing.

Transdermal route limitations

Only suitable for potent drugs, not all.

Molecular weight restriction

High molecular weight drugs cannot penetrate skin.

Skin irritants

Drugs causing irritation are unsuitable for patches.

Slow onset action

Delayed therapeutic effects, unsuitable for emergencies.

Patch adhesion issues

Varied skin types affect patch stickiness.

Drug disposal concerns

Residual drug in patches complicates disposal.

Moisture exposure effects

Sweating reduces patch adhesion effectiveness.

Backing layer

Provides flexibility and appearance to the patch.

Drug reservoir

Contains drug with excipients in reservoir systems.

Membrane function

Encloses drug layer, forming a pouch.

Pressure sensitive adhesive (PSA)

Adhesive layer, typically drug-free in reservoir systems.

Release liner

Protective layer removed before patch application.

Permeation enhancer

Substances that improve skin permeability for drugs.

Application site preparation

Skin must be clean, dry, and hair-free.

Patch rotation

Changing application sites to prevent irritation.

Heat exposure precautions

Avoid excessive heat to maintain patch effectiveness.

Crystallization issue

Prolonged storage can cause drug crystallization.

Non-medicated adhesive tape

Used to secure patches for extended wear.

Residual drug delivery

Patches often leave significant drug amounts after use.

Skin irritation causes

Active and inactive ingredients may provoke reactions.

Transdermal Patch

A drug delivery system applied to skin.

Buprenorphine

Used for moderate to chronic pain relief.

Capsaicin

Management of neuropathic pain via patch.

Clonidine

Treats hypertension; available in various doses.

Diclofenac

Short-term pain relief for sprains and bruises.

Estradiol

Hormone therapy for menopause symptoms.

Fentanyl

Reservoir patch for chronic pain management.

Granisetron

Antinauseant for chemotherapy patients.

Lidocaine

Local anesthetic delivered via patch.

Methylphenidate

Treats ADHD; delivered over 9 hours.

Nicotine

Smoking cessation aid via transdermal system.

Nitroglycerin

Treats angina pectoris; various release rates.

Oxybutynin

Antispasmodic for bladder control issues.

Rivastigmine

Used for Alzheimer's disease management.

Selegiline

Antidepressant available in multiple doses.

Scopolamine

Prevents motion sickness via transdermal patch.

Testosterone

Replaces low endogenous testosterone levels.

Iontophoresis

Delivers ionic drugs using electric current.

Heat Effects

Increases drug absorption through skin.

Patch Disposal

Follow specific instructions to prevent reuse.

Patient Consultation

Educate on proper patch application and risks.

MRI Precautions

Metal in patches can cause burns.

Cathode

Electrode that attracts positive ions in iontophoresis.

Anode

Electrode that attracts negative ions in iontophoresis.

Iontophoresis

Technique using electric current to deliver drugs transdermally.

Advantages of Iontophoresis

Noninvasive, minimizes trauma, local action with minimal absorption.

Disadvantages of Iontophoresis

Requires trained professional, potential skin irritation, higher cost.

Electrode Defect

Risk of overdose due to cathode-generated hydroxide.

pH in Iontophoresis

Affects drug ionization; optimal at pH 5 for HCl salts.

Current Density

Must be less than 0.5 MA/cm² to prevent burns.

Extraneous Ions

Compete with drugs, negatively affecting iontophoresis efficiency.

Fentanyl Iontophoretic Patch

Withdrawn in 2009 due to safety concerns after 2006 approval.

Sumatriptan Delivery

Approved in 2013, uses lithium batteries for controlled delivery.

Zecuity

Sumatriptan device, must be removed before MRI.

Electroporation

Experimental method using high voltage pulses to enhance skin permeability.

Phonophoresis

Ultrasound creates microjets to enhance drug delivery through skin.

Microneedles

Tiny needles pierce skin to facilitate drug transport.

Chemical Permeation Enhancers

Substances that temporarily reduce skin barrier permeability.

Skin Irritation

Adverse effect of iontophoresis; can cause discomfort.

Cost Effectiveness

Iontophoresis is more expensive than topical formulations.

Current Intensity

Electric current strength impacting drug delivery safety.

Metal Electrodes

Commonly used electrodes that alter solution pH.

Microjets

High-speed fluid jets created by imploding bubbles in phonophoresis.

Stratum Corneum

Outer skin layer targeted by various drug delivery methods.

Enhancers

Substances that improve drug permeability in skin.

Lipid-protein-partitioning theory

Explains how enhancers affect drug absorption.

Lipid lamellae

Layers of lipids in skin affecting permeability.

Keratin modification

Enhancers alter keratin structure for hydration.

Stratum corneum

Outer skin layer where drugs partition.

USP-NF

United States Pharmacopeia and National Formulary.

Apparatus 5

Paddle over disk method for drug release testing.

Apparatus 6

Cylinder method for evaluating drug release.

Apparatus 7

Reciprocating holder for drug release assessment.