Transdermal Drug Delivery (TDD) PDF

Objectives Transdermal Drug Delivery (TDD) Be able to name the major layers of the skin. Understand what the rate limi...

Objectives Transdermal Drug Delivery (TDD) Be able to name the major layers of the skin. Understand what the rate limiting step of transdermal drug delivery is. Know and understand the transport processes (transcellular/intracellular, intercellular, and transappendageal. Understand the roles of the components within a transdermal patch. Understand how the attributes of a transdermal (patch) will lead to increased or decreased drug penetration. Same for the biological aspects. Articulate which patches can, in theory, be cut and which cannot be cut? Understand the difference between dissolution controlled and diffusion-controlled implants. Understand (if any) the advantages and disadvantages. Reference: Wong WF, Ang KP, Sethi G, Looi CY. Recent advancement of medical patch for transdermal drug delivery. Medicina. 2023 Apr 17;59(4):778. 2 Be able to generically explain what the LogP ratio is and what our ideal range (polar vs non-polar) is and why? Questions to ask yourself: Explain how the patient (biological) factors negatively or positively affect drug absorption of medications in transdermal patches. Understand the molecular weight, half-life, and melting point 1. What is the largest organ of the body? guidelines for API’s being loaded into a transdermal patch. 2. What does percutaneous absorption mean? 3. Can we measure the drug concentrations within a membrane? 4. What is the dosage (aka the units)? 3 4  Functions of the Skin: 1. Containment 2. Protective: Microbial Chemical Radiation Mechanical and Heat barrier(s) 3. Temperature regulation 5 Transdermal Drug Delivery (TDD) Advantages Can terminate most drug effects rapidly by the removal of the patch.* Diffusion of the medication (drug) through skin into the Avoid GI drug absorption (-pH, drug interactions, systemic circulation for distribution and therapeutic effect. enzymatic activity, GI irritation) The first commercially available prescription patch was Avoids first pass effect approved by the U.S. FDA in December 1979, which administered Scopalmine for motion sickness. Non-invasive Easily and rapidly identified in emergency situations Reduce side effects due to the optimization of the blood concentration time profile V S 7 8  Disadvantages Provides predictable and extended duration of activity Greater patient compliance Most drugs have poor penetration through the skin Reduced dosing frequency (-fail to reach systemic circulation) Self-administration On-set is not quick: can be 24-48 hours+ (some Minimize inter-/intra-patient variation as compared to oral exceptions: nitroglycerin patch… 2-hour onset) drug delivery Local irritation Poor adhesion Requires high drug load/concentration but unsuitable if you require a large amount of drug in systemic circulation 9 10 Human Skin Drugs may affect any of the following levels: The human skin is on average 0.5 mm thick and consists of three major layers: 1. Effect on the skin surface (Ex: protective, zinc oxide cream; a 1. Epidermis moisturizer; cleansing effect; antimicrobial effect) 2. Dermis 2. Effect within the stratum corneum (Ex: moisturizers that soften the skin; salicylic acid; certain drugs like benzocaine) 3. Subcutaneous Tissues 3. Systemic effect 4. A deep effect requiring penetration into the epidermis (-microcirculation than possibly general circulation) The epidermis layer is about 0.05 mm thick in the eyelids and 1.5 mm thick on the palms and soles. 11 12  Transport Mechanism 2. Transappendageal route- through the skin’s appendages: sebaceous glands, sweat glands, hair follicles. Passive diffusion of substances through the epidermis or This route is accessible to polar molecules and diffusion through shunts. occupies only 0.1% of the skin surface. 1. Transepidermal pathway- Drug transport through this route is LIMITED. a. transcellular (aka intracellular): across the cells; lipophilic drugs b. intercellular: between the cells; hydrophilic drugs 13 14 Transdermal: Log P For Transdermals: a log P between 1 and 3 is ideal 16  *This Rate Limiting Step Systemic Absorption applies to semisolids (ointments, creams) too Is dependent on: Stratum Corneum-behaves as a semipermeable 1. The ability of the drug to cross the stratum corneum membrane. It is composed of: (SC) 1. Keratinized tissue (~40% keratin, protein) 2. The potential of the drug to leave the formulation 2. 15-25 layers 3. The influence of the formulation on the SC 3. Thickness= 10 µM 4. Cells 5. Lipids (about 20%, fatty acids, cholesterol) 6. ~40% water 17 18 Attributes of a TDD Formulation/drug Physicochemical Factors Affecting Absorption candidate 1. Drug Concentration Hydration of the skin: hydration = permeability 2. Surface area of the patch: SA= drug absorption 3. Solubility/Ionization: (Review) same rules as before Skin temperature 4. MW; range 100-800; best is