Using Colorimetric Techniques and Capability Analysis to Develop Standard Placebo Tablets for Clinical Studies

Solid dosage forms used in clinical trials are often accompanied by matching placebos that are used to blind the innovator product. In this article, the authors describe a study that was successfully used to develop standard placebo tablets to match active tablets manufactured using the so-called material-sparing paradigm. We outline the experimental procedures and results and propose the formulation and process for implementing the standard placebo concept in clinical programs. We look at several factors including tablet thickness, hardness, composition, color, and surface characteristics. The study evaluates formulations containing microcrystalline cellulose/lactose (MCC/lactose) and microcrystalline cellulose/dicalcium phosphate (MCC/DCP) each in 1:1 and 2:1 ratios. Tablets weighing 100 and 500 mg with the respective thickness of 0.123 ± 0.01 and 0.222 ± 0.02 in. were found to be appropriate for the study. The WIE-313 color index for the lactose-containing tablets was found to be distinguishable from the tablets with DCP. However, the 1:1 MCC/lactose formulations show no significant difference in appearance from the 2:1 MCC/lactose formulation. The same is true for the two MCC/DCP formulations. The conclusions regarding formulation and ratio effects are consistent for samples analyzed from the two sites studied. Finally, hardness and friability data suggest that formulations containing the higher levels of MCC are more robust. We conclude that the 2:1 MCC/lactose and 2:1 MCC/DCP formulations will effectively blind a majority of the active tablets produced using the material-sparing paradigm. Maintaining a clinical supply inventory of standard placebo blend and tablets should dramatically improve manufacturing lead time and efficiency by reducing the additional personnel, equipment, and scheduling constraints that result from the high placebo demands.