Transdermal Medications
Transdermal is a delivery system designed to allow for the penetration of a medication through the skin.
Introduction
There are some potential advantages of transdermal over oral medications.
- Negligible systemic effect
- Lowers adverse drug interactions
- Direct delivery to pain receptors, potentially at higher concentrations
- Minimal abuse and addiction
- Avoid first-pass effect and reduces organ toxicity
- Reduces opioid tolerance
- Rapid termination and likely to produce fewer side effects
- Combining multiple medications in a single product
Absorption is affected by
- Skin type: from best absorption to worst is genitals > head/neck > trunk > arm > leg
- Age: Skin is more permeable in the very young and elderly.
Bases
Skin has an aqueous environment in the dermis along with a lipid rich environment in the stratum corneum. This poses a challenge for transdermal delivery of medications.
The challenge was initially solved through the development of Pluronic Lethicin Organogel (PLO). This compound has a hydrophilic base called pluronic and a lipophilic base called lethicin isopropyl palmitate. This combination was mixed together (along with the drug) under pressure producing an ointment with both lipophilic and hydrophilic properties with drug micelles that are able to penetrate through this skin. This was the gold standard for many years but had downsides. It was very tacky and greasy, and if it got too cold it would split.
Later the base Lipoderm was developed which was superior in many respects. This is a creamer base than PLO and so is cosmetically more acceptable. It does not separate and has less chance of sensitivity. Compared to PLO lipoderm significantly increased skin penetration and retention, sometimes up to three times as effective as PLO. It can be further modified for example by adding pentylene glycol which enhances permeation slightly.
Prescribing
The following is an example for the prescribing of a compounded product for neuropathic pain:
API (anaesthetic) %
API (anticonvulsant) %
API (hypotensive) %
API (muscle relaxant)%
Transdermal Base (Example: Lipoderm)
Drug Options for Compounding
Agents can be mixed together to allow for the targeting of multiple receptors.
- Ketamine: High potency NMDA antagonist with minimal absorption
- NSAIDs: Diclofenac (up to 10% compared to 2% OTC), ibuprofen, ketoprofen (up to 20%).
- Amitriptyline: Serotonin and noradrenaline reuptake inhibitor. It can be effective for itch and is synergistic with other agents.
- Lidocaine: Prevents depolarisation of nerves through interaction of sodium channels
- Baclofen: A GABA B agonist
- Gabapentin: GABA receptor agonist
- Gualphensen: skeletal muscle relaxant. It is also an expectorant.
- Clonidine: alpha receptor agonist, decreases sympathetic flow and suppresses the release of Na in sympathetic nerves
- Menthol/camphor: counter irritants
- Loperamide: mu receptor agonist can be exchanged for morphine.
