PMID- 34487937
OWN - NLM
STAT- MEDLINE
DCOM- 20211109
LR  - 20211109
IS  - 1095-7103 (Electronic)
IS  - 0021-9797 (Linking)
VI  - 606
IP  - Pt 2
DP  - 2022 Jan 15
TI  - Concentration and composition dependent aggregation of Pluronic- and 
      Poly-(2-oxazolin)-Efavirenz formulations in biorelevant media.
PG  - 1179-1192
LID - S0021-9797(21)01268-6 [pii]
LID - 10.1016/j.jcis.2021.08.040 [doi]
AB  - Many drugs and drug candidates are poorly water-soluble. Intestinal fluids play 
      an important role in their solubilization. However, the interactions of 
      intestinal fluids with polymer excipients, drugs and their formulations are not 
      fully understood. Here, diffusion ordered spectroscopy (DOSY) and nuclear 
      Overhauser effect spectroscopy (NOESY), complemented by cryo-TEM were employed to 
      address this. Efavirenz (EFV) as model drug, the triblock copolymers Pluronic(R) 
      F-127 (PF127) and poly(2-oxazoline) based pMeOx-b-pPrOzi-b-pMeOx (pOx/pOzi) and 
      their respective formulations were studied in simulated fed-state intestinal 
      fluid (FeSSIF). For the individual polymers, the bile interfering nature of PF127 
      was confirmed and pure pOx/pOzi was newly classified as non-interfering. A 
      different and more complex behaviour was however observed if EFV was involved. 
      PF127/EFV formulations in FeSSIF showed concentration dependent aggregation with 
      separate colloids at low formulation concentrations, a merging of individual 
      particles at the solubility limit of EFV in FeSSIF and joint aggregates above 
      this concentration. In the case of pOx/pOzi/EFV formulations, coincident 
      diffusion coefficients for pOx/pOzi, lipids and EFV indicate joint aggregates 
      across the studied concentration range. This demonstrates that separate 
      evaluation of polymers and drugs in biorelevant media is not sufficient and their 
      mixtures need to be studied to learn about concentration and composition 
      dependent behaviour.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Endres, Sebastian
AU  - Endres S
AD  - Institute of Organic Chemistry, University of Wurzburg, Am Hubland, Wurzburg 
      97074, Germany.
FAU - Karaev, Emil
AU  - Karaev E
AD  - Institute of Organic Chemistry, University of Wurzburg, Am Hubland, Wurzburg 
      97074, Germany.
FAU - Hanio, Simon
AU  - Hanio S
AD  - Institute of Pharmacy and Food Chemistry, University of Wurzburg, Am Hubland, 
      Wurzburg 97074, Germany.
FAU - Schlauersbach, Jonas
AU  - Schlauersbach J
AD  - Institute of Pharmacy and Food Chemistry, University of Wurzburg, Am Hubland, 
      Wurzburg 97074, Germany.
FAU - Kraft, Christian
AU  - Kraft C
AD  - Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, 
      University of Wurzburg, Wurzburg 97080, Germany.
FAU - Rasmussen, Tim
AU  - Rasmussen T
AD  - Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, 
      University of Wurzburg, Wurzburg 97080, Germany; Biocenter, University of 
      Wurzburg, Wurzburg 97074, Germany.
FAU - Luxenhofer, Robert
AU  - Luxenhofer R
AD  - Soft Matter Chemistry, Department of Chemistry, Helsinki University, Helsinki 
      00014, Finland.
FAU - Bottcher, Bettina
AU  - Bottcher B
AD  - Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, 
      University of Wurzburg, Wurzburg 97080, Germany; Biocenter, University of 
      Wurzburg, Wurzburg 97074, Germany.
FAU - Meinel, Lorenz
AU  - Meinel L
AD  - Institute of Pharmacy and Food Chemistry, University of Wurzburg, Am Hubland, 
      Wurzburg 97074, Germany; Helmholtz Institute for RNA-based Infection Biology 
      (HIRI), Wuerzburg DE-97070, Germany.
FAU - Poppler, Ann-Christin
AU  - Poppler AC
AD  - Institute of Organic Chemistry, University of Wurzburg, Am Hubland, Wurzburg 
      97074, Germany. Electronic address: ann-christin.poeppler@uni-wuerzburg.de.
LA  - eng
PT  - Journal Article
DEP - 20210810
PL  - United States
TA  - J Colloid Interface Sci
JT  - Journal of colloid and interface science
JID - 0043125
RN  - 0 (Alkynes)
RN  - 0 (Benzoxazines)
RN  - 0 (Cyclopropanes)
RN  - 0 (Excipients)
RN  - 106392-12-5 (Poloxamer)
RN  - JE6H2O27P8 (efavirenz)
SB  - IM
MH  - Alkynes
MH  - *Benzoxazines
MH  - Cyclopropanes
MH  - Excipients
MH  - *Poloxamer
MH  - Solubility
OTO - NOTNLM
OT  - Bile colloids
OT  - Concentation dependent interaction
OT  - DOSY
OT  - Drug-Polymer Formulations
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/09/07 06:00
MHDA- 2021/11/10 06:00
CRDT- 2021/09/06 20:14
PHST- 2021/05/29 00:00 [received]
PHST- 2021/07/26 00:00 [revised]
PHST- 2021/08/07 00:00 [accepted]
PHST- 2021/09/07 06:00 [pubmed]
PHST- 2021/11/10 06:00 [medline]
PHST- 2021/09/06 20:14 [entrez]
AID - S0021-9797(21)01268-6 [pii]
AID - 10.1016/j.jcis.2021.08.040 [doi]
PST - ppublish
SO  - J Colloid Interface Sci. 2022 Jan 15;606(Pt 2):1179-1192. doi: 
      10.1016/j.jcis.2021.08.040. Epub 2021 Aug 10.