Efficient Evaluation of In Vivo Performance in Human for Generic Formulation by Novel Dissolution-Absorption
Motoki Onishi1,2, Kozo Tagawa3, Maiko Jiko1
1Medical Analysis Research Department, Pharmaceutical Research & Technology Division, Towa Pharmaceutical Co., Ltd, Kyoto Research Park KISTIC #202, 134, Chudoji Minami-machi, Shimogyo-ku, Kyoto, Japan.
Purpose:
The pharmaceutical bioequivalence of generic medicines must be confirmed with corresponding original drugs. Although the in vitro dissolution tests are required, results of the mandatory in vitro study do not necessarily reflect the in vivo performance after oral administration. Then, we have tried to develop the novel "Dissolution-Absorption Prediction (DAP) workflow" to evaluate the in vivo performance of generic medicines.
Methods:
The DAP workflow consists of an "In vitro two-cell connected dissolution (TCCD) system" mimicking the changes in the luminal pH associated with gastrointestinal transit of medicines, "Evaluation of pharmacokinetics of active pharmaceutical ingredient (API)" and "Prediction of plasma concentration-time profile". TCCD system-evaluated dissolution kinetics of APIs from generic formulations and pharmacokinetic parameters based on human data regarding the original drugs were used to calculate the plasma concentration-time profiles of APIs after the oral administration of generic medicines.
Results:
The mandatory in vitro dissolution tests indicated that the dissolution properties of valsartan (BCS class II) and fexofenadine (BCS class III/IV) in generic formulations did not coincide with those in the corresponding original formulations. The TCCD system provided the very similar dissolution kinetics for the generic and original formulations for the two APIs. Plasma concentration-time profiles evaluated utilizing the dissolution profiles obtained by the TCCD system were in good agreement with the observed profiles for both the generic and original formulations for each API.
Conclusions:
The DAP workflow would be valuable for estimating the in vivo performance of generic formulation and deducing their bioequivalence with the original formulation.
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