Biopharmaceutical implications of excipient variability on drug dissolution from immediate release products
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Biopharmaceutical implications of excipient variability on drug dissolution from immediate release products. / Zarmpi, P.; Flanagan, T.; Meehan, E.; Mann, J.; Ostergaard, J.; Fotaki, N.
In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 154, 2020, p. 195-209.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Biopharmaceutical implications of excipient variability on drug dissolution from immediate release products
AU - Zarmpi, P.
AU - Flanagan, T.
AU - Meehan, E.
AU - Mann, J.
AU - Ostergaard, J.
AU - Fotaki, N.
PY - 2020
Y1 - 2020
N2 - Elucidating the impact of excipient variability on oral product performance in a biopharmaceutical perspective would be beneficial and allow excipient implementation on Quality by Design (QbD) approaches. The current study investigated the impact of varying viscosity of binders (hypromellose (HPMC)) and superdisintegrants (sodium starch glycolate (SSG)) and particle size distribution of lubricants (magnesium stearate (MgSt)) on the in vitro dissolution of a highly and a poorly soluble drug from immediate release formulations. Compendial (pharmacopoeia buffers) and biorelevant (media simulating the gastrointestinal fluids) media and the USP 2 and USP 4 apparatuses were used to assess the exerted excipient effects on drug dissolution. Real-time dissolution UV imaging provided mechanistic insights into disintegration and dissolution of the immediate release formulations. Varying the viscosity type of HPMC or SSG did not significantly affect drug dissolution irrespective of the compound used. Faster drug dissolution was observed when decreasing the particle size of MgSt for the highly soluble drug. The use of real-time dissolution UV Imaging revealed the influential role of excipient variability on tablet disintegration, as for the highly soluble drug, tablets containing high viscosity HPMC or low particle size MgSt disintegrated faster as compared to the control tablets while for the poorly soluble drug, slower tablet disintegration was observed when increasing the viscosity of the HPMC as compared to the control tablets. Changes in drug dissolution when varying excipients may be anticipated if the excipient change has previously affected drug solubility. The use of multivariate data analysis revealed the influential biopharmaceutical factors such as critical excipient types/properties, drug aqueous solubility, medium/hydrodynamic characteristics affecting the impact of excipient variability on in vitro drug dissolution.
AB - Elucidating the impact of excipient variability on oral product performance in a biopharmaceutical perspective would be beneficial and allow excipient implementation on Quality by Design (QbD) approaches. The current study investigated the impact of varying viscosity of binders (hypromellose (HPMC)) and superdisintegrants (sodium starch glycolate (SSG)) and particle size distribution of lubricants (magnesium stearate (MgSt)) on the in vitro dissolution of a highly and a poorly soluble drug from immediate release formulations. Compendial (pharmacopoeia buffers) and biorelevant (media simulating the gastrointestinal fluids) media and the USP 2 and USP 4 apparatuses were used to assess the exerted excipient effects on drug dissolution. Real-time dissolution UV imaging provided mechanistic insights into disintegration and dissolution of the immediate release formulations. Varying the viscosity type of HPMC or SSG did not significantly affect drug dissolution irrespective of the compound used. Faster drug dissolution was observed when decreasing the particle size of MgSt for the highly soluble drug. The use of real-time dissolution UV Imaging revealed the influential role of excipient variability on tablet disintegration, as for the highly soluble drug, tablets containing high viscosity HPMC or low particle size MgSt disintegrated faster as compared to the control tablets while for the poorly soluble drug, slower tablet disintegration was observed when increasing the viscosity of the HPMC as compared to the control tablets. Changes in drug dissolution when varying excipients may be anticipated if the excipient change has previously affected drug solubility. The use of multivariate data analysis revealed the influential biopharmaceutical factors such as critical excipient types/properties, drug aqueous solubility, medium/hydrodynamic characteristics affecting the impact of excipient variability on in vitro drug dissolution.
KW - Excipient variability
KW - HPMC
KW - Sodium starch glycolate
KW - Magnesium stearate
KW - In vitro drug dissolution
KW - Multivariate data analysis
KW - SCREW WET GRANULATION
KW - IN-VITRO
KW - FUNCTIONAL EQUIVALENCE
KW - PHARMACEUTICAL QUALITY
KW - INTRINSIC DISSOLUTION
KW - BIORELEVANT MEDIA
KW - CROSPOVIDONE NF
KW - BEHAVIOR
KW - TABLET
KW - HYDRODYNAMICS
U2 - 10.1016/j.ejpb.2020.07.014
DO - 10.1016/j.ejpb.2020.07.014
M3 - Journal article
C2 - 32681966
VL - 154
SP - 195
EP - 209
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
SN - 0939-6411
ER -
ID: 249303105