Encapsulation of Commercially Available Losartan for Blinding Purposes Does Not Affect its Bioavailability

Abstract

When developing any new drug for an established therapeutic area, it is important to show that the new drug is as effective as, or superior to, pre-existing therapies. The credibility of comparative studies is dependent on them being carried out in an unbiased fashion. It is generally a prerequisite that such studies are conducted in a double-blind manner, which often involves the use of the doubledummy technique, where matching active and placebo preparations are given in combination.[1] If the matching placebo preparations are not readily available, alternative methods of blinding the study medication have to be considered, for example enclosing active and placebo test medications in capsules to make them identical in appearance.[2] However, it is important to verify that the properties of the original preparation have not been altered by the encapsulation, through in vitro and/or in vivo investigations. Commercially available tablets of the antihypertensive drug losartan[3] were encapsulated for use in a comparative double-blind clinical trial.[4] The in vitro dissolution and chemical stability of the original tablets have previously been found to remain unchanged following encapsulation (data on file). The purpose of the present study was to investigate whether encapsulation affects the bioavailability of losartan. Bioequivalence of the encapsulated and standard (i.e. nonencapsulated) tablets was, therefore, evaluated following single dose administration in healthy volunteers.