In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy
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In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy. / Salim, Malinda; Fraser-Miller, Sara J.; Bērziņš, Kārlis; Sutton, Joshua J.; Gordon, Keith C.; Boyd, Ben J.
In: Pharmaceutics, Vol. 15, No. 7, 1968, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy
AU - Salim, Malinda
AU - Fraser-Miller, Sara J.
AU - Bērziņš, Kārlis
AU - Sutton, Joshua J.
AU - Gordon, Keith C.
AU - Boyd, Ben J.
N1 - Funding Information: This work was funded by the Bill and Melinda Gates Foundation (OPP1160404). Funding is also acknowledged by ARC Linkage (project ID LP180101147). Publisher Copyright: © 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion. Upon lipolysis of the digestible components in MC-SNEDDS containing fenofibrate as a model drug, sharp phonon peaks appeared at the low-frequency Raman spectral region (<200 cm−1), indicating the precipitation of fenofibrate in a crystalline form from the formulation. Two multivariate data analysis approaches (principal component analysis and partial least squares discriminant analysis) and one univariate analysis approach (band ratios) were explored to track these spectral changes over time. The low-frequency Raman data produces results in good agreement with in situ small angle X-ray scattering (SAXS) measurements with all data analysis approaches used, whereas the mid-frequency Raman requires the use of PLS-DA to gain similar results. This suggests that LFRS can be used as a complementary, and potentially more accessible, technique to SAXS to determine the kinetics of drug precipitation from lipid-based formulations.
AB - Low-frequency Raman spectroscopy (LFRS) is a valuable tool to detect the solid state of amorphous and crystalline drugs in solid dosage forms and the transformation of drugs between different polymorphic forms. It has also been applied to track the solubilisation of solid drugs as suspensions in milk and infant formula during in vitro digestion. This study reports the use of LFRS as an approach to probe drug precipitation from a lipid-based drug delivery system (medium-chain self-nanoemulsifying drug delivery system, MC-SNEDDS) during in vitro digestion. Upon lipolysis of the digestible components in MC-SNEDDS containing fenofibrate as a model drug, sharp phonon peaks appeared at the low-frequency Raman spectral region (<200 cm−1), indicating the precipitation of fenofibrate in a crystalline form from the formulation. Two multivariate data analysis approaches (principal component analysis and partial least squares discriminant analysis) and one univariate analysis approach (band ratios) were explored to track these spectral changes over time. The low-frequency Raman data produces results in good agreement with in situ small angle X-ray scattering (SAXS) measurements with all data analysis approaches used, whereas the mid-frequency Raman requires the use of PLS-DA to gain similar results. This suggests that LFRS can be used as a complementary, and potentially more accessible, technique to SAXS to determine the kinetics of drug precipitation from lipid-based formulations.
KW - drug
KW - in vitro digestion
KW - lipid-based formulation
KW - low-frequency Raman spectroscopy
KW - precipitation
KW - SNEDDS
U2 - 10.3390/pharmaceutics15071968
DO - 10.3390/pharmaceutics15071968
M3 - Journal article
C2 - 37514154
AN - SCOPUS:85166349885
VL - 15
JO - Pharmaceutics
JF - Pharmaceutics
SN - 1999-4923
IS - 7
M1 - 1968
ER -
ID: 366498903