The Use of Radio-Labeled Drug in Early Dosage form Development to Provide a Relation Between Physical Dosage form Characteristics and Bioavailability

A chemical compound in early drug development was used in its radio-labeled form to provide a relation to the physical dosage form characteristics and bioavailability. The ¹⁴C-labeled compound, a dibenzthiepin acetic acid derivative, was recrystallized in the same manner as the cold compound. A procedure was developed such that the crystal type and size obtained was similar to that of the cold compound. The photomicrographs and specific surface area of both cold and ¹⁴C-1abeled material were equivalent. Capsules, prepared with both cold and ¹⁴C-labeled material, were demonstrated to have equivalent in vitro dissolution profiles.

The capsules containing the ¹⁴C-labeled material were found to be well absorbed when administered to cynomolgus monkeys. Assuming the monkey is a good absorption model for man, this study provided a preliminary assessment of the bioavailability of the compound in man. It also established preliminary control parameters for the raw material and the dissolution of the capsules. These controls would then be used for monitoring capsules intended for early clinical studies.