PMID- 33471832
OWN - NLM
STAT- MEDLINE
DCOM- 20210609
LR  - 20220331
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 1
DP  - 2021
TI  - Preparation of solid dispersion systems for enhanced dissolution of poorly water 
      soluble diacerein: In-vitro evaluation, optimization and physiologically based 
      pharmacokinetic modeling.
PG  - e0245482
LID - 10.1371/journal.pone.0245482 [doi]
LID - e0245482
AB  - Diacerein (DCN), a BCS II compound, suffers from poor aqueous solubility and 
      limited bioavailability. Solid dispersion systems (SD) of DCN were prepared by 
      solvent evaporation, using hydrophilic polymers. In-vitro dissolution studies 
      were performed and dissolution parameters were evaluated. I-Optimal factorial 
      design was employed to study the effect of formulation variables (drug:polymer 
      ratio and polymer type) on the measured responses including; drug content (DC) 
      (%), dissolution efficiency at 15 min (DE (15 min)%) and 60 min (DE (60 min)%) 
      and mean dissolution time (MDT) (min). The optimized SD was selected, prepared 
      and evaluated, allowing 10.83 and 3.42 fold increase in DE (15 min)%, DE (60 
      min)%, respectively and 6.07 decrease in MDT, compared to plain drug. DSC, XRD 
      analysis and SEM micrographs confirmed complete amorphization of DCN within the 
      optimized SD. Physiologically based pharmacokinetic (PBPK) modeling was employed 
      to predict PK parameters of DCN in middle aged healthy adults and geriatrics. 
      Simcyp(R) software established in-vivo plasma concentration time curves of the 
      optimized SD, compared to plain DCN. Relative bioavailability of the optimized SD 
      compared to plain drug was 229.52% and 262.02% in healthy adults and geriatrics, 
      respectively. Our study reports the utility of PBPK modeling for formulation 
      development of BCS II APIs, via predicting their oral bio-performance.
FAU - Fouad, Shahinaze A
AU  - Fouad SA
AUID- ORCID: 0000-0001-8980-4619
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Ahram Canadian University, 6th 
      of October City, Giza, Egypt.
FAU - Malaak, Fady A
AU  - Malaak FA
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Ahram Canadian University, 6th 
      of October City, Giza, Egypt.
FAU - El-Nabarawi, Mohamed A
AU  - El-Nabarawi MA
AD  - Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo 
      University, Cairo, Egypt.
FAU - Abu Zeid, Khalid
AU  - Abu Zeid K
AD  - Department of Pharmaceutics, Faculty of Pharmacy, Ahram Canadian University, 6th 
      of October City, Giza, Egypt.
FAU - Ghoneim, Amira M
AU  - Ghoneim AM
AUID- ORCID: 0000-0003-2963-2135
AD  - Department of Pharmaceutics and Pharmaceutical Technology, Faculty of 
      Pharmaceutical Sciences and Pharmaceutical Industries, Future University in 
      Egypt, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20210120
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anthraquinones)
RN  - 059QF0KO0R (Water)
RN  - 4HU6J11EL5 (diacerein)
SB  - IM
MH  - Anthraquinones/*chemistry/*pharmacokinetics
MH  - Models, Biological
MH  - Solubility
MH  - Water/*chemistry
PMC - PMC7816977
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/01/21 06:00
MHDA- 2021/06/10 06:00
PMCR- 2021/01/20
CRDT- 2021/01/20 17:10
PHST- 2020/08/20 00:00 [received]
PHST- 2021/01/02 00:00 [accepted]
PHST- 2021/01/20 17:10 [entrez]
PHST- 2021/01/21 06:00 [pubmed]
PHST- 2021/06/10 06:00 [medline]
PHST- 2021/01/20 00:00 [pmc-release]
AID - PONE-D-20-25781 [pii]
AID - 10.1371/journal.pone.0245482 [doi]
PST - epublish
SO  - PLoS One. 2021 Jan 20;16(1):e0245482. doi: 10.1371/journal.pone.0245482. 
      eCollection 2021.