OBJECTIVE

To demonstrate the process by which a placebo formulation was designed for an oral solid dose product that would be dispensed to the patient as a fast-dissolve tablet.  The tablet is added to water and the resulting solution is dosed as a antibiotic mouthwash.   Placebo matching was required not only for the tablet but also for the solution which the patient took.

BACKGROUND

Clinical studies on solid dose products may require a placebo that is devoid of an active pharmaceutical ingredient.  The placebo, in the case of a tablet, should possess the same shape and color compared to the active product.  This presents a challenge to the formulator because many active pharmaceutical ingredients (API’s) are colored.  Active and placebo are often film-coated with a non-functional coating that renders the two tablets virtually indistinguishable to patient and clinician alike.

In this case study, API (X) was an insoluble compound with a yellow-green color and targeted as a fast dissolve tablet for oral solution dosing.  Its solubility in solution was aided by a buffer system that adjusted the pH upward, where the API possessed greater solubility.  Because the tablet was required to dissolve in [buffered] water in 30 seconds or less, the feasibility of using a film-coat to blind the active from placebo was not considered.  The primary approach centered on the use of FD&C lakes to color the tablet (dry) and the use of FD&C dyes to color the resulting solution.  The interactive effect of the FD&C dye on the dry tablet as well as the effect of FD&C lakes on the solution were considered.

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