Table 1 summarizes patient characteristics and their treatment responses. A total of 11 patients of 13 completed the study. Two of the 11 patients reported minimal improvement. The other nine patients reported at least 50% reduction on the pain scale after two weeks. During both of 2-week follow up, no patient dropped out due to adverse effects or lack of efficacy. All of the patients reported using no more than four pumps a day. Each pump is equivalent to 1 mL of the 2% diclofenac in microemulsion solution. The remaining volume in the bottles were assessed to ensure that patients were not exceeding seven pumps a day.
Topical NSAIDs are used as an alternative to oral NSAID for mild to moderate musculoskeletal pain to provide localized drug delivery with equal efficacy but minimizing systemic adverse effects. The maximum recommended daily dose should not exceed 320 mg of diclofenac per site.5 For lower extremities, the daily dose should not exceed 160 mg of diclofenac to each affected joint and for upper extremities, the maximum daily dose is 80 mg of diclofenac.4 Table 2 summarizes estimated absorption in milligram (mg) for each concentration used topically.
In Canada, pharmacies are permitted to provide non-commercially available concentrations of diclofenac in any semisolid base. The common prescription concentrations are compounded in PLO as semisolid base. There is limited published information about the efficacy or toxicity of diclofenac in PLO gel.7,8 One study compared diclofenac 2% in PLO gel with placebo for mild to moderate osteoarthritis of the knee.8 The study, however, did not use a standardized pain assessment score to evaluate the pain response. The authors concluded that diclofenac in PLO gel provided therapeutic values in treating mild to moderate osteoarthritis of the knee.
Microemulsion transdermal drug delivery formulations are thermodynamically stable, and have superior bioavailability and better penetration of lipophilic and hydrophilic drug into the dermis.9,10 A study in healthy volunteers showed that microemulsion was tolerated well.11 In an in-vitro study, it was shown that the diclofenac in PLO gel or currently commercially available products released about 50% less of the active drugs compared to the microemulsion formulation (40% vs 80%).12 In this study, 2% diclofenac in microemulsion foam provided adequate pain control for the patients. Each 50 ml bottle has a total of 1 g diclofenac. Each 1 ml pump of the diclofenac 2% in microemulsion provides 6 mg of diclofenac. At maximum the dose of seven pumps a day, the total daily diclofenac is 42 mg for each site which was significantly below the 320 mg a day recommendation.
This is the first observational study to assess the clinical effects and adverse events using diclofenac powder in microemulsion in the treatment of musculoskeletal pain. Due to the small sample size, the before and after pain intensity statistical tests could not be used to provide meaningful results. Prior to enrolling in the study, five of the 11 patients had used either diclofenac 10% in PLO gel or diclofenac 1.5% or 2.32% alcohol based or Emulgelâ without adequate relief. All of these patients, however, reported at least 50% reduction in the visual analogue score from baseline after using diclofenac 2% in microemulsion foam. Patient number 8 reported no response to the diclofenac microemulsion foam. The pain severity could be associated with the patient’s severe back pain. Patients number 7 and 10 with severe pain were given the topical formulation because they both have renal insufficiency and they would be at risk of renal function deterioration if given oral NSAID. Patient number 11 was awaiting knee replacement surgery and preferred not to take oral NSAID. Most notable comments from the patients were that the microemulsion foam is less messy and the absorption was almost instantaneous which resulted in quicker onset of action. No adverse event was reported by the patients in the study.
Diclofenac 2% in microemulsion foam appears to be effective in the treatment of mild to moderate musculoskeletal pain either as a single agent or an adjuvant agent. It was well tolerated.
LIMITATIONS
This is an observational study and the sample size is small. Although a majority of patients had positive response, a higher strength was trialed on the two patients who reported inadequate response.