An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution

Etherson, Kelly and Dunn, Claire and Matthews, Wayne and Pamelund, Henrik and Barragat, Camille and Sanderson, Natalie and Izumi, Toshiko and da Costa Mathews, Claudia and Halbert, Gavin and Wilson, Clive and McAllister, Mark and Mann, James and Østergaard, Jesper and Butler, James and Khadra, Ibrahim (2020) An interlaboratory investigation of intrinsic dissolution rate determination using surface dissolution. European Journal of Pharmaceutics and Biopharmaceutics, 150. pp. 24-32. ISSN 0939-6411 (https://doi.org/10.1016/j.ejpb.2020.02.005)

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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.

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