What is the target for dermal therapeutic systems?
Absorption into the skin alone (systemic absorption is not preferred)
What is the target for transdermal therapeutic systems?
Absorption into systemic therapeutic systems is preferred
What are some factors that need to be considered before a patch formulation is finalized?
- Site of Action (local & systemic)
- Bio-activity and physiochemical properties of the drug
- Formulation excipients and adhesion
- Delivery system
- Skin structure
What is the objective for dermal therapeutic systems?
Maximize delivery of drugs from formulations into stratum corneum, upper epidermis, or dermis, and at the same time minimize further absorption into systemic circulation
What are some advantages of dermal therapeutic systems?
- More uniform delivery at site of absorption
- Longer duration (ability to retain drug in subcutaneous and resistance to washing off)
- Deeper penetration (good for anesthetics)
- Reduced side effects (but patients can be more reactive to adhesive)
What is the use of EMLA patches?
They are patches that contain a mixture of anesthetics (lidocaine and prilocaine)
They deliver numbing to a localized area (used before inserting needles for injections or drawing blood)
What are some contraindications for dermal patches?
- Patients with severe circulatory disorders
- Broken skin (can result in undesired systemic absorption)
What is the use of occlusive dressings?
Flexible hydro active dressing
They provide occlusive effects to enhance penetration and absorption of topically applied medications
What is the use of biopatches?
They are a hydrophillic polyurethane foam/sponge containing a broad spectrum anti-microbial agent
Used to reduce catheter-related blood stream infections
Absorbs 8x their weight of percutaneous fluid
What are non-invasive diagnostic patches?
Also known as analyte collection patches
- Can be used to detect drugs like caffeine, theophylline, cocaine, opiates
- Can be used to screen some diseases (cystic fibrosis)
How do DEXCOM monitors work?
These devices are measuring glucose levels in the subcutaenous as a proxy for blood glucose
DEXCOM is a real time CGM, provide continous measurements to app (good for tracking and alerting patient about hyper/hypoglycemic events)
What is the objective of transdermal systems?
Delivery and maintainence of therapeutic levels of drug in the systemic circulation over a long period of time
What are some examples of transdermal patches?
- Fentanyl patches (pain management)
- Nitroglycerin patches
- NRT patches
- Birth control patches
What is the major limitation to drug absorption with transdermal patches?
- Stratum corneum is rate-limiting step
- Some metabolic acitivity in stratum granulosum
What are some advantages of transdermal delivery?
- Reduced first-pass effects vs. oral dosage forms (extends activity of short half life drugs)
- Steadier, sustained release (ex. Duragesic releases at a stable rate for 72h)
- Useful for patients that have difficulties swallowing
- Easy to terminate drug effect (remove patch to end release of drug)
- Less fluctuations in dose due to stable release rate
What are some limitations of transdermal patches over oral dosage forms?
- Local irritation or allergic reaction to adhesice of patch
- High potency drugs only because only small doses can be delivered via transdermal patches
- More expensive, less accessible
- Highly dependent on patient factors (inter-intra individual variability)
- Very few drugs can be delivered at a viable rate using this route due to low permeability
How can oral doses be converted into patch dose?
ex. Hydromorphone
- Step 1: Calculate the total hydromorphone amount patient takes in a day
4mg IR x 6 times/day = 24mg/day
6mg Contin x 2 times = 12 mg/day
Total dose = 36mg/day
- Step 2: Calculate equianalgesic dose of fentanyl patch for replacement
Used table to find 36mg/day = 50mcg/hr fentanyl
What should we counsel patients on for best patch use?
- Prepare skn to remove any dirt, lotions, oils, or powders (affects adhesion)
- Always make sure to remove the old patch before wearing the old patch before wearing a new one (Serious risk of overdosing)
- If you do tear or cut the patch, don’t use it (unpredicatable drug response)
- Using the palm of your hand, press down on the patch. The patch should be smooth, with no bumps or folds (loose fitting will affect drug penetration)
- You may trim the hair if needed but avoid shaving the area of application (increased chances of irritation; broken skin may pre-dispose higher drug exposure)
- Don’t use a heating pad on your body where you are wearing a patch (increase absorption kinetics)
What are some characteristics of drugs that are good candidates for transdermal delivery?
- Drug with high potency (dose requirement of less than 25mg/day)
- Low molecular weight
- Lipophillic
- Short half-life
- Low melting point (correlated with good solubility within the reservoir)
- High skin permeability
- Non-irritating and non-sensitizing to skin
- Low oral bioavailability
- Low therapeutic index (tight control of plasma levels)
What are some types of transdermal delivery systems (TDS)?
- Reservoir type
- Matrix type
- Drug-in-adhesive (DIA) type:
a. single-layer DIA
b. multilaminate DIA - Dot-matrix
What are some characteristics of reservoir type transdermal therpeutic systems (TDS)?
- Separate drug compartment (drug dissolved in solvent, liquid excipients, penetration enhancer) held back by permeable membrane
- Adhesive is applied on the skin facing face of the membrane
- Drug release from reservoir systems normally follow zero-order kinetics (proceed at a constant rate irrespective of concentration)
What are the disadvantages of reservoir type transdermal therapeutic systems?
- Adhesive and drug or adhesice and excipient interactions
- Vulnerable to burst release
What are some characteristics of matrix-type transdermal therapeutic systems?
- Contains drug solution or suspension form in a matrix
- Most simple design: a drug containing semi-solid disc is held in contact with the skin by an adhesive (no membrane)
- Formulation contain:
a. drug dissolved/suspended in a semisolid
b. penetration enhancer
A first-order reaction rate depends on the drug concentration of the drug in the matrix and the statum corneum
What are some disadvantages of matrix-type transdermal therapeutic systems?
The protective overlay maybe mistaken for the side to be applied on the skin patient is properly trained/can also be a lot larger than the actual drug delivery surface
