Abstract
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® 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.
Highlights
Diacerein (DCN) is chemically known as 4,5—diacetyloxy—9,10 dihydro-9, 10-dioxo2-anthracenecarboxylic acid having the chemical structure shown in “Fig 1” [1]
The obtained results are coherently enrolled to establish an in-vivo correlation (IVIVC) via implementing Physiologically based pharmacokinetic (PBPK) modeling in order to predict the oral bio-performance of this BCS Biopharmaceutics Classification System (II) active pharmaceutical ingredients (APIs) and confirm the bioavailability enhancement of the optimized solid dispersions (SD) compared to plain DCN
It is concluded that all solid dispersion systems prepared using different hydrophilic polymers, succeeded in enhancing DCN dissolution properties
Summary
Diacerein (DCN) is chemically known as 4,5—diacetyloxy—9,10 dihydro-9, 10-dioxo2-anthracenecarboxylic acid having the chemical structure shown in “Fig 1” [1]. The potential benefits of DCN exist in being a successful alternative to NSAIDs with the advantage of excluding gastric side effects [5] It acquires disease modifying properties [6] (pro-anabolic/chondro-protective effects), which are highly beneficial in this chondro-destructive disease [7]. DCN belongs to Biopharmaceutics Classification System, class II (BCS II) active pharmaceutical ingredients (APIs) It is poorly soluble, with reported aqueous solubility of 3.197 mg/mL [8]. It suffers from poor dissolution properties, reduced oral absorption [5] and lowered bioavailability equal to 35–56% [9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
