TY - JOUR
T1 - Design and Evaluation of Two-Step Biorelevant Dissolution Methods for Docetaxel Oral Formulations
AU - Shah, Brijesh
AU - Dong, Xiaowei
N1 - Funding Information:
This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM138225 to Dong, X.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.
PY - 2022/7
Y1 - 2022/7
N2 - Dissolution is a pivotal tool for oral formulations. Dissolution could be used to either reduce the risk of product failure through quality control or predict and understand in vivo performance of drug formulations. The latter is always challenging because multiple factors such as selection of media, gastrointestinal components, physiological factors, consideration of fasted and fed state are involved. Previously published dissolution methods such as one-step dissolution in individual simulated gastric fluid, simulated intestinal fluid, or phosphate buffer saline did not signify the realistic gastrointestinal transit effect. Docetaxel (DTX), a poorly water-soluble drug, is commercially available only as injectable dosage forms, and thus many publications studied the development of oral DTX formulations. In our previous report, we developed oral lipid-based DTX granules that showed higher oral absorption in rats compared to DTX powder. However, one-step dissolution in simulated gastric fluid showed no difference between DTX granules and DTX powder. Therefore, the present study aimed to develop new two-step biorelevant dissolution methods for DTX oral formulations. In the study, new two-step biorelevant dissolution methods in fasted or fed states with pancreatin were developed and compared with other previously reported dissolution methods. The new two-step biorelevant dissolution methods successfully discriminated the difference of dissolution between DTX granules and DTX powder, which reflected the in vivo difference of absorption of these two formulations. Moreover, food effects were confirmed for DTX. The new dissolution methods have the potential to be used to predict and understand in vivo performance of oral solid dosage forms. Graphical Abstract: [Figure not available: see fulltext.].
AB - Dissolution is a pivotal tool for oral formulations. Dissolution could be used to either reduce the risk of product failure through quality control or predict and understand in vivo performance of drug formulations. The latter is always challenging because multiple factors such as selection of media, gastrointestinal components, physiological factors, consideration of fasted and fed state are involved. Previously published dissolution methods such as one-step dissolution in individual simulated gastric fluid, simulated intestinal fluid, or phosphate buffer saline did not signify the realistic gastrointestinal transit effect. Docetaxel (DTX), a poorly water-soluble drug, is commercially available only as injectable dosage forms, and thus many publications studied the development of oral DTX formulations. In our previous report, we developed oral lipid-based DTX granules that showed higher oral absorption in rats compared to DTX powder. However, one-step dissolution in simulated gastric fluid showed no difference between DTX granules and DTX powder. Therefore, the present study aimed to develop new two-step biorelevant dissolution methods for DTX oral formulations. In the study, new two-step biorelevant dissolution methods in fasted or fed states with pancreatin were developed and compared with other previously reported dissolution methods. The new two-step biorelevant dissolution methods successfully discriminated the difference of dissolution between DTX granules and DTX powder, which reflected the in vivo difference of absorption of these two formulations. Moreover, food effects were confirmed for DTX. The new dissolution methods have the potential to be used to predict and understand in vivo performance of oral solid dosage forms. Graphical Abstract: [Figure not available: see fulltext.].
KW - biorelevant media
KW - dissolution
KW - docetaxel
KW - oral delivery
KW - poorly water-soluble drugs
UR - http://www.scopus.com/inward/record.url?scp=85128457189&partnerID=8YFLogxK
U2 - 10.1208/s12249-022-02256-2
DO - 10.1208/s12249-022-02256-2
M3 - Article
C2 - 35441281
AN - SCOPUS:85128457189
SN - 1530-9932
VL - 23
JO - AAPS PharmSciTech
JF - AAPS PharmSciTech
IS - 5
M1 - 113
ER -