An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

Abstract

The purpose of this study was to conduct an interlaboratory ring-study, with six partners (academic and industrial), investigating the measurement of intrinsic dissolution rate (IDR) using surface dissolution imaging (SDI) equipment. Measurement of IDR is important in pharmaceutical research as it provides characterising information on drugs and their formulations. This work allowed us to assess the SDI's interlaboratory performance for measuring IDR using a defined standard operating procedure (see supporting information) and six drugs assigned as low (tadalafil, bromocriptine mesylate), medium (carvedilol, indomethacin) and high (ibuprofen, valsartan) solubility compounds. Fasted State Simulated Intestinal Fluid (FaSSIF) and blank FaSSIF (without sodium taurocholate and lecithin) (pH 6.5) were used as media. Using the standardised protocol an IDR value was obtained for all compounds and the results show that the overall IDR rank order matched the solubility rank order. Interlaboratory variability was also examined and it was observed that the variability for lower solubility compounds was higher, coefficient of variation > 50%, than for intermediate and high solubility compounds, with the exception of indomethacin in FaSSIF medium. Inter laboratory variability is a useful descriptor for understanding the robustness of the protocol and the system variability. On comparison to another published small-scale IDR study the rank ordering with respect to dissolution rate is identical except for the high solubility compounds. This results indicates that the SDI robustly measures IDR however, no recommendation on the use of one small scale method over the other is made.

An investigation of drug compact topography as relates to intrinsic dissolution rates determined by dissolution imaging

“…The apparent larger variation in the PAR IDR determination is largely skewed by the inflated IDR determination for the 0.25 kN experiments. Similar levels of variation have been reported using the Sirius SDI dissolution imaging system, a predecessor of the instrument applied in the current study (10), and the μDISS Profiler™ (9). Etherson et al reported in an inter-laboratory small-scale dissolution study that the relative standard deviation (expressed as a percentage) of IDR values varied from 33-130 % using 6 compounds (n = 6), and FaSSIF and blank FaSSIF as the dissolution media across seven sites (10).…”

“…Similar levels of variation have been reported using the Sirius SDI dissolution imaging system, a predecessor of the instrument applied in the current study (10), and the μDISS Profiler™ (9). Etherson et al reported in an inter-laboratory small-scale dissolution study that the relative standard deviation (expressed as a percentage) of IDR values varied from 33-130 % using 6 compounds (n = 6), and FaSSIF and blank FaSSIF as the dissolution media across seven sites (10). For IBU, there was a large variation in the absolute measured IDR values from the two generation of the SDI equipment.…”

“…In the context of the BCS solubility classification, highly soluble APIs have been suggested to possess intrinsic dissolution rates above 0.1 mg min −1 cm −2 , whereas rates below this limit would often be attributed to APIs with a low BCS solubility classification (8). Albeit a seemingly simple parameter, the determination of intrinsic dissolution rates remains challenging (9,10). Intrinsic dissolution rate (IDR), the rate of dissolution adjusted for the surface area of a compound (e.g., µg/min/cm 2 ), is measured while controlling the surface area available for dissolution and applying sink conditions (5,9).…”

Application of UV dissolution imaging to pharmaceutical systems

“…Intrinsic dissolution rate (IDR) is defined as the rate of mass transfer per a unit area which is exposed to dissolution media (130). Throughout an experiment, the IDR surface area should be kept constant, and the use of a constant flow of dissolution media (in the case of UV dissolution imaging) applied to maintain sink conditions.…”

Methodological Considerations in Development of UV Imaging for Characterization of Intra-Tumoral Injectables Using cAMP as a Model Substance

“…Hydrogel matrixes have been used together with UV imaging to determine drug diffusion [ 19 ] and drug release from different vehicles into hydrogels [ 11 , 20 , 21 ]. UV imaging has been used to characterize dissolution behavior, including determination of intrinsic dissolution rates for active pharmaceutical ingredients [ 22 , 23 ]. UV imaging has also found use in characterizing the performance of injectable formulations [ 15 , 18 ].…”