Determination of intrinsic dissolution rate using miniaturized rotating and stationary disk systems

Abstract

The objective of this study was to assess the feasibility and reliability of using miniaturized disk dissolution apparatus for intrinsic dissolution rate (IDR) measurement in the early drug discovery process when bulk drug supply is very limited. The two apparatus, a miniaturized rotating disk system (mRDS) and a miniaturized stationary disk system (mSDS), were evaluated using chloramphenicol as a model drug with sample sizes of 3-10 mg. Wood's rotating disk system (wRDS) was used as control with a sample size of 150 mg. The effect of various experimental parameters on IDR was studied on the two miniaturized apparatus. While compression force, disk distance, dissolution volume, and drug loading did not have significant effects on IDR measured by mRDS, dissolution volume and disk distance showed significant effects by mSDS. When all experimental parameters were held constant, the stationary system generated significantly higher IDRs compared with the two rotating systems (mRDS and wRDS). The mRDS yielded IDR values comparable to those by wRDS at 25 rpm (a slower rotation speed). These study results indicate that both miniaturized systems produce reliable IDR measurements with a small quantity of material, which provides a desirable advantage over other methods (e.g., wRDS, solubility measurement) in the early drug discovery phase.