130 exam 2

• Transdermal Drug Delivery System (TDDS)


  Administration of drugs systemically by the application of a drug formulation on the skin

  
• TDDS can be accomplished using transdermal patches, which are adhesive patches formulated with active pharmaceutical ingredients (API) and varying excipients

  
• These patches are applied to the skin and eventually deliver a given dose of the drug systemically through the layers of the skin

  
• Types of transdermal patches

  • Reservoir system
  • Matrix dispersion system
  • Drug-in-adhesive system

  
• Reservoir System


  The drug in the form of solutions, suspensions, gels, or dispersion in a polymer matrix is contained in a reservoir. The rate of drug input into the circulation is dependent on the rate-controlling membrane.
• Matrix System


  The drug is directly formulated with the lipophilic or hydrophilic matrix without using a distinct compartment. Matrix patches can be further classified as drug-in-adhesive or matrix dispersion.
• Examples of reservoir patches

  • Transderm-Scop
  • Catapres
  • Transderm-Nitro
• Examples of matrix patches


  • NicoDerm
  • Climara
  • Nitro-Dur
• Skin structure and properties

  • Transappendageal routes (through sweat glands and hair follicles)
  • Transcellular route (through corneocytes)
  • Intercellular route (through lipid matrix)

  
• Permeation process


  1. Permeation of drug molecules in the skin

  2. Partitioning to the aqueous epidermis from the stratum corneum

  3. Diffusion of molecules into the upper dermis

  4. Permeation through layers with varying properties, functions, and structures

  5. Absorption in the systemic circulation

  
• Basic components of TDDS


  • Active Pharmaceutical Ingredient (API)
  • Polymer
  • Rate-controlling membrane
  • Penetration enhancer
  • Pressure-sensitive adhesives
  • Release liner
  • Backing laminate
  • Plasticizer
• Drug candidates for TDDS

  • Lipophilic with a partition coefficient from 1 to 5
  • Melting point of < 250 °C
  • Molecular weight of < 500 Daltons
  • Exhibit low oral bioavailability
• Classification of polymers


  • Synthetic elastomers
  • Natural polymers
  • Semi-synthetic polymers
  • Synthetic polymers
• Rate-controlling membrane


  Controls the release of the API through the diffusion properties of the membrane
• Classification of permeation enhancers

  • Hydration of the stratum corneum
  • Solubilization of lipids in the stratum corneum
  • Increased permeability and fluidity of the stratum corneum
• Pressure-sensitive adhesives (PSA)


  Materials that adhere to the skin by the application of slight force
• Release liner


  Protective material that is removed before the transdermal patch is applied to the skin
• Backing laminate


  Provides occlusion for the TDDS, should be flexible, facilitate oxygen and vapor transmission, and be nonreactive to the API and excipients
• Plasticizer


  Incorporated in TDDS mainly to improve the flexibility of transdermal films
• Physicochemical characterization is done to define and evaluate the physicochemical properties and performance of TDDS
• Backing laminate


  • Flexible
  • Facilitate oxygen and vapor transmission
  • Nonreactive to the API and excipients
• Backing laminate


  In direct contact with the TDDS from fabrication to skin application
• Backing laminate prevents the leaching of additives

  May result in the diffusion of TDDS components onto this layer
• Plasticizers


  Incorporated in TDDS mainly to improve the flexibility of transdermal films
• Plasticizers


  Reduce the tensile strength and glass transition temperature of the polymer by decreasing intermolecular forces between polymeric chains
• Ideal plasticizer


  • Compatible with the chosen polymer
  • Durable
  • Effective under drastic temperature changes and ultraviolet radiation
  • Has decent mechanical and thermal-electrical properties
  • Inexpensive
• Characterization of TDDS


  • Physicochemical characterization
• Physicochemical characterization


  To define and evaluate the physicochemical properties and performance of critical quality attributes in transdermal patches

  
• Basic transdermal patch specifications

  • Thickness
  • Weight variation
  • Folding endurance
  • Tensile strength
  • Moisture content
  • Moisture uptake
  • Drug content

  
• Thickness


  Physical property of transdermal patches that can be evaluated at multiple locations, usually with a micrometer or screw gauge during manufacturing
• Patch thickness


  Affects drug permeation in matrix-type transdermal patches

  
• Thicker matrix


  Able to deliver higher amount of drug to the skin over relatively longer application time due to higher amount of drug available for permeation from the patch
• Thicker matrix


  Has a higher tendency to cause cold flow, which is the migration of adhesive beyond the boundaries of the patch and may lead to the decrease in drug flux across the skin
• The thickness of a transdermal patch can neither be too thick nor too thin, thus, must be deemed constant to ensure low variability in terms of drug flux
• Weight variation


  Test of transdermal patch physicochemical properties wherein each patch in a set is weighed and stored in a desiccator with molten calcium chloride at room temperature for 24 hours, then recording the final weight when there is no further change for each patch
• The weight of each patch should not deviate significantly from the average as this indicates the uniformity of the patches as well as the reproducibility of the manufacturing process
• Folding endurance


  Essential physical property that checks the ability of the transdermal patch to withstand folding, expressed as the number of times a patch is folded at the same place either to break the patch or to develop visible cracks
• Moisture content


  Studies used to estimate the presence of moisture in the formulated patches after drying, which has been found to affect both the mechanical properties and drug release patterns of TDDS
• Moisture content is required to maintain stability, reduce brittleness, prevent bulkiness, and reduce susceptibility to microbial contamination of patches
• Adhesion


  The adhesive properties of transdermal patches are found to directly affect the performance of the drug-delivery systems