A pharmaceutical comparison of different commercially available imiquimod 5% cream products.
BACKGROUND
Alternatives to the innovator product for imiquimod 5% cream are currently marketed in South America and the People's Republic of China.


METHODS
Seven alternative imiquimod 5% cream products were compared with the innovator product using physiochemical tests for cream appearance, pH, drug content and presence of crystals, as well as in vitro release testing of drug using Franz diffusion cells.


RESULTS
In contrast to the innovator product, which had no crystalline imiquimod, significant amounts of suspended crystalline imiquimod were found in six of the seven alternative products. In vitro release rates of imiquimod were significantly slower in these six products compared with the innovator (p<0.001). In vitro release rates of imiquimod were significantly faster than the innovator (p<0.05) for the one alternative product without crystals.


CONCLUSIONS
The clinical relevance of the differences observed is unknown; however, they raise concerns about whether these alternatives are therapeutically equivalent. While a generic topical imiquimod would almost certainly require clinical studies of therapeutic equivalence for approval in countries with more stringent regulatory environment, vigilance is warranted regarding importation of pharmaceutical products labeled as 'identical' in the absence of adequate evaluations.
Harrison
Lester I
LI
3M Company, 3M Drug Delivery Systems Division, 3M Center, Saint Paul, MN 55144, USA. liharrison@mmm.com
Stoesz
Jim D
JD
Battiste
John L
JL
Nelson
Robert J
RJ
Zarraga
Isidro E
IE
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000627:therapeutic use; D000287:Administration, Topical; D000634:Aminoquinolines / Q000737:chemistry* / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004348:Drug Labeling; D004355:Drug Stability; D064420:Drug-Related Side Effects and Adverse Reactions; D016568:Drugs, Generic / Q000737:chemistry*; D006801:Humans; D000077271:Imiquimod; D009824:Ointments; D011336:Probability; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013810:Therapeutic Equivalency
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D016568:Drugs, Generic; D009824:Ointments; D000077271:Imiquimod