An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

Clive Wilson,Claire Dunn,Mark McAllister,James Mann,Claudia da Costa Mathews,Jesper Østergaard,James Butler,Ibrahim Khadra,Camille Barragat,Gavin Halbert,Henrik Pamelund,Wayne Matthews,Kelly Etherson,Natalie Sanderson,Toshiko Izumi

doi:10.1016/j.ejpb.2020.02.005

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.

Highlights

The most convenient and frequent way of administering drugs is via the oral route [1]
Indomethacin in blank Fasted State Simulated Intestinal Fluid (FaSSIF) was selected as all other sites had data for this active pharmaceutical ingredient (API)/medium combination and there was sufficient quantity of the API to allow a duplicate run including molar extinction coefficient (MEC) to be completed
At site 7 only two compounds were tested in FaSSIF, the rank order was as expected for these compounds based on the grouped rank order

Summary

Introduction

The most convenient and frequent way of administering drugs is via the oral route [1]. Depending upon the drug’s pKa ionisation and solubility will vary and the use of salt forms may result in completely different drug solubilities and dissolution rates in GI tract fluids than in pure water [3,7,8]. Biorelevant media such as FaSSIF (Fasted Stated Simulated Intestinal Fluid) are commonly used to more accurately mimic in vivo conditions, resulting in better predictions overall [9]. These media have frequently been used to mimic human intestinal fluids for greater biorelevance in solubility and dissolution experiments [3,10,11]

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Conclusion