Transdermal Drug Delivery Systems (TDDSs)

Transdermal Drug Delivery Systems (TDDSs)

• Definition: Transdermal drug delivery (TDD) is the delivery of active pharmaceutical ingredients (APIs) through the skin into the bloodstream to produce systemic effects.
• Advantages:
  • Avoid first-pass metabolism, enhancing bioavailability and therapeutic efficacy of certain drugs
  • Avoidance of GIT irritation and degradation
  • Minimizing undesirable side effects
  • Providing controlled drug release, reducing the frequency of dosing and enhancing patient compliance
  • Easy to terminate drug input by simply removing the transdermal patch
  • Suitable for self-medication and avoiding the risk and inconvenience of parenteral therapy
  • Providing a substitute when oral medication is not suitable (e.g., in cases of vomiting and diarrhea)
• Disadvantages:
  • Local skin reaction can occur due to irritancy of some drugs
  • Limited to potent drugs (therapeutically effective in small doses) and drugs of low molecular weight (Molecules lower than 500 Daltons)
  • Skin enzymes may metabolize some drugs
  • May be non-economical, and patch failure may occur

Mechanism of Drug Release from TDDSs

• The drug is released from the vehicle
• Then, diffusion of the drug through the lipophilic stratum corneum and crossing to the more aqueous viable epidermis
• Then, continuing from the avascular epidermis to the highly perfused dermis layer
• Uptake to the microcirculation to the systemic circulation, then to the affected area

Factors Affecting Drug Release from TDDSs and Skin Penetration

• Skin barrier properties
• Physicochemical properties of the drug
  • Drug solubility
  • Drug partition coefficient
  • Surface area of the applied drug
  • Drug concentration
  • Diffusional path length of the drug across the skin layers
  • Molecular weight of drug molecules

Fick's First Law of Diffusion

• J = P.D.A.ΔC/h
• Where J is the flux (rate of drug permeation across the skin), P is the partition coefficient, D is the diffusion coefficient, A is the surface area of the applied drug, ΔC is the drug concentration gradient across the skin, and h is the diffusional path length across the skin layers

Types of Transdermal Patches

• Drug-in-Adhesive System
  • Examples: Isosorbidedinitrate- (Frandoltape) for treatment of angina pectoris, Zolmitriptan TDDS for treatment of migraine
• Reservoir System
  • Examples: Nitroglycerine (Deponit patches) for angina pectoris, Scopolamine (Transderm Scop) for prophylaxis from motion sickness
• Matrix System
  • Examples: Nitro-Dur patch for treatment of angina pectoris, Glimepiride patches for treatment of diabetes mellitus
• Micro-Reservoir System
  • Combination of reservoir and matrix dispersion system

Some Transdermal Drugs for Systemic Delivery Launched in the USA and EU

• Asenapine (Secuado, 2009) for antipsychotic treatment
• Buprenorphine (Butrans, 2010) for chronic pain
• Clonidine (Catapres-TTS, 1984) for hypertension
• Oestradiol (Estraderm, 1986) and Oestradiol (Climara, 1994) for female HRT