This study reports the release properties of the poorly water-soluble drug hydrocortisone, antibacterial agent triclosan, and the water-soluble anti-aging compounds salicylic acid and ascorbic acid from gels, creams, and ointments, alone or combined with triclosan. Drug release was measured with the flow-through, Franz, and Enhancer cell release testing methods. For the 3 methods, a cellulose acetate membrane soaked in lipophilic oleic acid and dissolution mediums composed of a phosphate buffer pH 5.8 or a 50% ethanol: buffer mixture gave more constant and less variable release profiles (similarity factors, f2, above 50). Comparison of the release rates of hydrocortisone, salicylic acid, ascorbic acid, and triclosan from creams and gels showed that the rates measured with the flow-through cells were significantly slower (p < 0.01) than those measured with the Franz and Enhancer cells. In all 3 systems, hydrophilic compounds released faster in the buffer solution and from the gels. Less water-soluble compounds and lipophilic compounds released faster in the hydro-alcohol mixture and from creams and ointments. The disadvantages of the flow-through cells were difficult operation and small sample sizes which caused variable results. The advantages of the Enhancer cells were that they used the basic USP dissolution apparatus and had a larger volume range making it easier to adapt the system for studying the release of products containing low concentrations of active ingredients or ingredients that are difficult to analyze.