Combining lipid based drug delivery and amorphous solid dispersions for improved oral drug absorption of a poorly water-soluble drug
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Combining lipid based drug delivery and amorphous solid dispersions for improved oral drug absorption of a poorly water-soluble drug. / Nora, Georgia-Ioanna; Venkatasubramanian, Ramakrishnan; Strindberg, Sophie; Siqueira-Jørgensen, Scheyla Daniela; Pagano, Livia; Romanski, Francis S.; Swarnakar, Nitin K.; Rades, Thomas; Müllertz, Anette.
In: Journal of Controlled Release, Vol. 349, 2022, p. 206-212.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Combining lipid based drug delivery and amorphous solid dispersions for improved oral drug absorption of a poorly water-soluble drug
AU - Nora, Georgia-Ioanna
AU - Venkatasubramanian, Ramakrishnan
AU - Strindberg, Sophie
AU - Siqueira-Jørgensen, Scheyla Daniela
AU - Pagano, Livia
AU - Romanski, Francis S.
AU - Swarnakar, Nitin K.
AU - Rades, Thomas
AU - Müllertz, Anette
N1 - Publisher Copyright: © 2022 The Authors
PY - 2022
Y1 - 2022
N2 - Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (Seq) in the SNEDDS (superSNEDDS, 250% of Seq). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of Seq), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% Seq in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48 h to 1 month under ambient conditions. The PK study in rats displayed significantly higher Cmax and AUC0-7h (3-fold increase) and faster Tmax for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.
AB - Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (Seq) in the SNEDDS (superSNEDDS, 250% of Seq). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of Seq), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% Seq in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48 h to 1 month under ambient conditions. The PK study in rats displayed significantly higher Cmax and AUC0-7h (3-fold increase) and faster Tmax for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.
KW - Amorphous solid dispersion (ASD)
KW - In vitro lipolysis
KW - Pharmacokinetic studies
KW - Self-nanoemusifying drug delivery systems (SNEDDS)
KW - Supersaturated SNEDDS (superSNEDDS)
KW - Supersaturation
U2 - 10.1016/j.jconrel.2022.06.057
DO - 10.1016/j.jconrel.2022.06.057
M3 - Journal article
C2 - 35787914
AN - SCOPUS:85133786934
VL - 349
SP - 206
EP - 212
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -
ID: 314962500