Compounding for Pain Managment

Mina Bashta. R.Ph.
Skycare Pharmacy
Skycare Compounding Labs
540 Davis drive, unit 1,2
Newmarket, Ontario L3Y 2P3
Tel      (844) 727-4276
Fax      (844)-727-4277

1,000 words

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Compounding for Pain Managment


by Mina Bashta, R.Ph.


Major categories of pain


Inflammatory – Response to tissue damage that potentiates pain

Soft tissue – pressure ulcers, burns

Nociceptive – CNS and peripheral afferent pathways modulated via spinal cord

Somatic – aching, constant, localized (musculoskeletal)

Visceral – sharp, crescendo/decrescendo (cholecystitis, renal    stones, intestinal obstruction, MI)

Neuropathic – ischemia, destruction or encroachment of nerve by  disease or tumor

Paroxysmal – shooting or shock-like pain on a background of burning, aching sensation

Cost of chronic pain

Quality of life


Physical functioning

Ability to perform activities of daily living



Psychological Morbidity





Sleep disturbances

Loss of self?esteem

Social Consequences


Marital/family relations

Intimacy/sexual activity

Social isolation

Socioeconomic Consequences


Healthcare costs


Lost workdays


The Transdermal route:


Skin:is the bodies largest organ

Permeable membrane

Patient preference



Why use the Transdermal route?


Oral route not desirable or not available

Inability to swallow (Mucositis or dysphagia)


Drug Interactions

Can be used to obtain a localized or a systemic effect

Lower systemic absorption when choosing to apply for a local effect

Drug concentration at the site of administration can be 30 fold higher than with an oral dose

Decreased potential for systemic side effects when targeting specific areas with a transdermal

Allows multimodal approach[1]


Drawbacks of Transdermal route:


Possible irritation at application site

Drying of the skin with transdermal products

Variations in the stratum corneum barrier may lead to variable absorption and may require adding penetration enhancers

Need to concentrate dosage form to accommodate therapeutic response[2]



Factors for drug absorption


Transcutaneous flow of compounds across the stratum corneum is directly proportional to the concentration gradient & therefore can be attributed to passive diffusion.          

As surface area ?? & thickness of epidermis ??, the rate of transdermal flux ??

The underlying epidermal layers & the dermis area are an aqueous environment

Highly hydrophilic drugs will absorb poorly through the stratum corneum but better in the aqueous layers of the epidermis

Highly lipophilic drugs will absorb better through the stratum corneum but slowed when they reach the aqueous layers of epidermis


Choosing the best vehicle:


For compounds used exclusively for the treatment of a skin condition, passive diffusion into the superficial epidermis could be sufficient

Vehicle such as Glaxal Base or Petrolatum (Vaseline®)

For a drug to be delivered to the general circulation, the drug / vehicle must maintain affinity for both aqueous and lipid environments to absorb effectively

Vehicles such as PLO or Lipoderm® (Gold Standard)




NMDA Antagonists / Glutamate Antagonist







 Magnesium Chloride





Issues surrounding the use of Ketamine


Dependence, hallucinations, out of body experiences

History of abuse since the seventies

Side effects include Anxiety, chest pain, palpitations, agitation, Rhabdomyolysis (muscle tissue breakdown), Urinary tract complications, renal impairment, dilated common bile duct, abnormal liver function.


Mechanism of action


NMDA / Ca++ channel blocker

Blocks a cascade of of intracellular events that inhibit the hyper excitability of the spinal cord neurons.


Use / Function


General Anesthetic

Neuropathic pain of various origins, including postherpetic neuralgia, complex regional pain syndrome, cancer pain, orofacial pain, and phantom limb pain.

Effective in treating painful neuropathy when other traditional methods have failed

Post-operative pain and other post-traumatic pain

Control of pain during dressing changes


Strength in transdermal cream


3%?30% Ketamine (alone or in combination)


Strength in topical spray


3?5% Ketamine (alone or in combination)

Strength in intranasal soultion


10?15% Ketamine / lidocaine 2?4%,

1 spray bilaterally PRN (0.1ml per spray,10?15mg)

Strength in Oral dosing


35?50mg TID as a baseline

AMPA Antagonist





Valproic Acid




Mechanism of action


AMPA-Na+ channel blockers

Voltage Regulated Na+ & Ca++ Blockade


Use / Function


Chronic/ Neuropathic Pain

Helpful in burning, stabbing pains, feelings of electric shock

Topical could be used to wean patients off oral dosing

Great for trigger points

Indicated usage is for epileptic seizure control

Off label use neuropathic pain

Widely prescribed orally


Side effects at normal oral doses






Weight gain



Transdermal application


Localized tissue concentration

Minimal systemic side effects, sedation and ataxia nonexistent

Start at 6% and titrate to patient response to 10%, used 12% very successfully

No conversion factors















Bioavailability of transdermal NSAID reported to be generally less than 5 –15 % in sites with lower absorption 


Mechanism of action


Blockade of Cox-1 and Cox-2 enzymes, these enzymes play a key role in making prostaglandins.

Decrease prostaglandin production ? less swelling and less pain


Uses / Function


Controlling inflammatory conditions such as RA, OA, tennis elbow, Soft Tissue Inflammation, Plantar Fasciitis

Effective for pain in acute injuries


Strength in transdermal cream


Ketoprofen 5 – 20%

Diclofenac 2 – 10%

Piroxicam 1 – 5%

DMSO 3 – 10%

Flurbiprofen 10%

Ibuprofen 5 – 30%

Indomethacin 5 – 20%

Naproxen 10 – 20%




Other APIs



Strengh in trasndermal cream: 2 – 10% (little benefit going beyond that)

Tri-cyclic anti?depressant

Oral side effects:


Dry mouth

Sexual dysfunction

Off label as neuropathic pain and sleep modifier (orally)




Strength in trasndermal cream: 2?15%

Ca channel blocker, vasodilator ? great for increasing blood flow in conditions that are secondary to poor circulation such as diabetic neuropathy

Beneficial in both dermatome and trigger point creams




Strength in trasndermal cream: 2?5%

Irreversible alpha?agonist

increased blood flow




Strength in trasndermal cream: 0.1 – 0.3%

Alpha?2 Agonists

Beneficial in neuropathic pain 

Anti-hypertensive effects start showing at 0.4% and above


Lidocaine, Tetracaine, Bupivacaine


AMPA?Na Channel blocker anesthetic


Opioids – strength in transdermal cream;


Morphine 1% (10mg/Gm)

Hydromorphone 0.3% (3mg/Gm)

Loperamide 2?7% (20?70mg/Gm)

[1] Reference: Sawynok J. Topical analgesics in neuropathic pain. Curr Pharm Des 2005; 11(23):2995?3004

[2] Reference: Heir, Gary DMD, et al. IJPC 2004; 8:337-343