This is a randomized, multi-center, double-blind, placebo-controlled, multi-dose, parallel-group study. Approximately 300 subjects (150 per group) 16 years of age and older with a current (within 24 hours from Visit 1) Grade I or II ankle sprain, and who meet all eligibility criteria, will be randomized into the study and will receive either the active treatment (SST-0225 ibuprofen cream), or matching placebo. Subjects will apply an amount equivalent to a 4 inch line of investigational product to the affected ankle approximately every 4-6 hours. At Visit 1 two doses will be applied at the site. All subsequent doses of the investigational product will be applied every 4 to 6 hours with a total of 4 doses in a 24 hour period. Duration of treatment with the investigational product is 7 days.