PMID- 38408708
OWN - NLM
STAT- In-Process
LR  - 20240424
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 196
DP  - 2024 May 1
TI  - Development and characterization of solid lipid-based formulations (sLBFs) of 
      ritonavir utilizing a lipolysis and permeation assay.
PG  - 106732
LID - S0928-0987(24)00043-5 [pii]
LID - 10.1016/j.ejps.2024.106732 [doi]
AB  - As a high number of active pharmaceutical ingredients (APIs) under development 
      belong to BCS classes II and IV, the need for improving bioavailability is 
      critical. A powerful approach is the use of lipid-based formulations (LBFs) that 
      usually consist of a combination of liquid lipids, cosolvents, and surfactants. 
      In this study, ritonavir loaded solid LBFs (sLBFs) were prepared using solid 
      lipid excipients to investigate whether sLBFs are also capable of improving 
      solubility and permeability. Additionally, the influence of polymeric 
      precipitation inhibitors (PVP-VA and HPMC-AS) on lipolysis triggered 
      supersaturation and precipitation was investigated. One step intestinal digestion 
      and bicompartmental permeation studies using an artificial lecithin-in-dodecane 
      (LiDo) membrane were performed for each formulation. All formulations presented 
      significantly higher solubility (5 to >20-fold higher) during lipolysis and 
      permeation studies compared to pure ritonavir. In the combined 
      lipolysis-permeation studies, the formulated ritonavir concentration increased 
      15-fold in the donor compartment and the flux increased up to 71 % as compared to 
      non-formulated ritonavir. The formulation with the highest surfactant 
      concentration showed significantly higher ritonavir solubility compared to the 
      formulation with the highest amount of lipids. However, the precipitation rates 
      were comparable. The addition of precipitation inhibitors did not influence the 
      lipolytic process and showed no significant benefit over the initial formulations 
      with regards to precipitation. While all tested sLBFs increased the permeation 
      rate, no statistically significant difference was noted between the formulations 
      regardless of composition. To conclude, the different release profiles of the 
      formulations were not correlated to the resulting flux through a permeation 
      membrane, further supporting the importance of making use of combined 
      lipolysis-permeation assays when exploring LBFs.
CI  - Copyright (c) 2024. Published by Elsevier B.V.
FAU - Schulzen, Arne
AU  - Schulzen A
AD  - Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, 
      Universitatsstrasse 1, DE-40225, Dusseldorf, Germany.
FAU - Andreadis, Ioannis I
AU  - Andreadis II
AD  - Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23, Uppsala, 
      Sweden; Laboratory of Pharmaceutical Technology, Department of Pharmacy, Faculty 
      of Health Sciences, Aristotle University of Thessaloniki, GR-54124, Thessaloniki, 
      Greece.
FAU - Bergstrom, Christel A S
AU  - Bergstrom CAS
AD  - Department of Pharmacy, Uppsala University, P.O. Box 580, SE-751 23, Uppsala, 
      Sweden; The Swedish Drug Delivery Center, Department of Pharmacy, Uppsala 
      University, P.O. Box 580, SE-751 23, Uppsala, Sweden.
FAU - Quodbach, Julian
AU  - Quodbach J
AD  - Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, 
      Universitatsstrasse 1, DE-40225, Dusseldorf, Germany; Department of Pharmacy, 
      Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3584 CG 
      Utrecht, the Netherlands. Electronic address: j.h.j.quodbach@uu.nl.
LA  - eng
PT  - Journal Article
DEP - 20240224
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
SB  - IM
OTO - NOTNLM
OT  - Flux
OT  - Lipolysis
OT  - Permeation
OT  - Precipitation
OT  - Solid lipid-based formulations
OT  - Solubilization
OT  - Supersaturation
COIS- Declaration of competing interest Ioannis I. Andreadis is currently an employee 
      of AstraZeneca PLC. Christel A. S. Bergstrom is founder of the company Enphasys 
      AB, which holds the patent for the ENA device.
EDAT- 2024/02/27 00:42
MHDA- 2024/02/27 00:42
CRDT- 2024/02/26 19:18
PHST- 2023/12/19 00:00 [received]
PHST- 2024/02/22 00:00 [revised]
PHST- 2024/02/22 00:00 [accepted]
PHST- 2024/02/27 00:42 [pubmed]
PHST- 2024/02/27 00:42 [medline]
PHST- 2024/02/26 19:18 [entrez]
AID - S0928-0987(24)00043-5 [pii]
AID - 10.1016/j.ejps.2024.106732 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2024 May 1;196:106732. doi: 10.1016/j.ejps.2024.106732. Epub 
      2024 Feb 24.