The intrinsic dissolution rate (IDR, µg/min/cm2) that is a dissolution rate adjusted for the surface area of the compound and the dissolution rate both describes how fast the compound is released from the crystal lattice into solution. Quantitative/kinetic solubility information obtained from IDR and dissolution rate measurements, especially as a function of pH, may determine the extent of regulatory concern about the different solid forms.
IDR is an intrinsic property that is suitable to assess in a number of situations, for example during salt selections, when exploring the impact of polymorph changes on dissolution, and when investigating to what extent micronisation may overcome hurdles such as dissolution-limited absorption.
- Evaluation of the drug solubility in accordance with the biopharmaceutical classification system (BCS)
- Comparison of different forms/salts/cocrystals of the same compound (is a higher dissolution rate obtained by changing salt?)
- Setting specifications for particles sizes
- Development of dissolution methods
For Material Experts:
Instrument and measuring principle
The intrinsic dissolution rate is defined as the rate of dissolution of a pure pharmaceutical active ingredient when the surface area, stirring speed, pH and ionic strength of the dissolution medium is kept constant. I.e. the surface area of the compound is well defined in contrast to in a dissolution rate measurement. Thus, it is measured as the release of API from a tablet with a flat and well-defined surface area into an aqueous solution at a given pH value.
|Instrument||Vankel VK8000 Dissolution Sampling Station with Woods apparatus (tablet diameter 0.5 cm)|
|USP/Ph. Eur.||<1087> / 2.9.29 Intrinsic Dissolution (non-GMP)|
|Sample amount||30-50 mg|
|Stirring rates||50 or 100 RPM|
|Result||Reported as curve and IDR (mg/cm2/min)|
Bergström CA, Box K, Holm R, Matthews W, McAllister M, Müllertz A, Rades T, Schäfer KJ, Teleki A (2019 ) Biorelevant intrinsic dissolution profiling in early drug development: Fundamental, methodological, and industrial aspects. Eur J Pharm Biopharm 139:101-14.
Issa MG, Ferraz HG (2011) Intrinsic dissolution as a tool for evaluating drug solubility in accordance with the biopharmaceutics classification system. Dissolut Technol 18(3):6-13.
Lawrence XY, Carlin AS, Amidon GL, Hussain AS (2004) Feasibility studies of utilising disk intrinsic dissolution rate to classify drugs. International journal of pharmaceutics 270(1-2):221-7.
Löbmann K, Flouda K, Qiu D, Tsolakou T, Wang W, Rades T (2014) The influence of pressure on the intrinsic dissolution rate of amorphous indomethacin. Pharmaceutics. Sep;6(3):481-93.
Shevchenko A, Bimbo LM, Miroshnyk I, Haarala J, Jelínková K, Syrjänen K, van Veen B, Kiesvaara J, Santos HA, Yliruusi J (2012) A new cocrystal and salts of itraconazole: Comparison of solid-state properties, stability and dissolution behavior. Int J Pharm 436(1-2):403-9
Tenho M, Aaltonen J, Heinänen P, Peltonen L, Lehto VP (2007) Effect of texture on the intrinsic dissolution behaviour of acetylsalicylic acid and tolbutamide compacts. J Appl Cryst 40(5):857-64.
Tseng YC, Patel M, Zhao Y (2014) Determination of intrinsic dissolution rate using miniaturised rotating and stationary disk systems. Dissolut Technol 21(2): 24-29