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. 2017 Jul 4:12:4733-4745.
doi: 10.2147/IJN.S139706. eCollection 2017.

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

Ahmed N Allam  1 , Sherif I Hamdallah  1 , Ossama Y Abdallah  1
Affiliations

Chitosan-coated diacerein nanosuspensions as a platform for enhancing bioavailability and lowering side effects: preparation, characterization, and ex vivo/in vivo evaluation

Ahmed N Allam et al. Int J Nanomedicine. .

Abstract

Nanodrug delivery systems have been widely reviewed for their use in several drug formulations to improve bioavailability, sustain effect, and decrease side effects of many candidate drugs. The objective of this study was to evaluate the potential of chitosan (CS)-coated nanosuspensions to enhance bioavailability and reduce the diarrheal side effect of diacerein (DCN) after oral administration. DCN nanosuspensions (DNS) were prepared by sonoprecipitation technique using different stabilizers at three different concentrations. The selected DNS with optimum particle size (PS), polydispersity index (PDI), and Zeta potential (ZP) was coated with three different concentrations of CS-coated DNS (CS-DNS) and screened. In vitro dissolution was performed for the selected lyophilized formulae and compared with DCN powder in addition to the assessment of drug crystallinity via scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. Ex vivo drug permeability using noneverted rat intestine, intraluminal content, and mucoadhesion evaluation was studied for nominated formulae in comparison to DCN suspension. Moreover, in vivo study, pharmacokinetic parameters, and evaluation of diarrheal potential were conducted after oral administration of selected formulae. Polyvinyl pyrrolidone (PVP)-stabilized DNS showed a significant increase (P≤0.05) in PS and PDI as the stabilizer concentration increased. PVP-stabilized DNS with the lowest CS concentration was protected from aggregation by lyophilization with mannitol. A remarked enhancement in dissolution parameters was observed in the nanocrystals' formulae. Morphological examination and X-ray diffraction confirmed drug crystallinity. The intermediate permeation parameters of CS-DNS-F10, lowest rhein-to-DCN ratio in intraluminal content along with the highest percentage of mucoadhesive, could serve as a sustaining profile of coated formula. CS-DNS-F10 showed a significantly higher Cmax of 0.74±0.15 µg/mL at a delayed Tmax of 3.60±0.55 hours with a relative bioavailability of 172.1% compared to DCN suspension. CS-coated nanosuspensions could serve as promising revenue to enhance bioavailability and reduce the diarrheal side effect of DCN after oral administration.

Keywords: chitosan; diacerein; nanosuspension; permeability; pharmacokinetics; side effects.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Effect of lyophilization on the particle size (A) and polydispersity index (B) of formulae DNS-F7 and CS-DNS-F10 with and without mannitol. Abbreviations: CS-DNS, chitosan-coated DNS; DNS, diacerein nanosuspension.
Figure 2
Figure 2
Diffusion profile (A) and dissolution parameters (B) for DCN suspension, DNS-F7, and CS-DNS-F10 in orthophosphate buffer at pH 6.8 (n=3). Abbreviations: CS-DNS, chitosan-coated DNS; DCN, diacerein; DNS, DCN nanosuspension; MDT, mean dissolution time; %DE, % diffusion efficiency; %PD120, percent diffused in 120 minutes.
Figure 3
Figure 3
DSC of DNS-F7 and CS-DNS-F10. Abbreviations: CS-DNS, chitosan-coated DNS; DCN, diacerein; DSC, differential scanning calorimetry; DNS, DCN nanosuspension; PM, physical mixture; PVP, polyvinyl pyrrolidone.
Figure 4
Figure 4
Powder X-ray powder diffraction (A) and scanning electron microscopy (B) of DNS-F7 and CS-DNS-F10. Abbreviations: CS-DNS, chitosan-coated DNS; DCN, diacerein; DNS, DCN nanosuspension; PM, physical mixture; PVP, polyvinyl pyrrolidone.
Figure 5
Figure 5
Permeation profile (A) and different permeation parameters (B) of DCN suspension, DNS-F7, and CS-DNS-F10 through noneverted rat intestine in the mixture of Krebs–Ringer phosphate buffer saline pH 7.4 and isopropyl alcohol (7:3, v/v) at 37°C for 2 hours (n=3). Abbreviations: CS-DNS, chitosan-coated DNS; DCN, diacerein; DNS, DCN nanosuspension.
Figure 6
Figure 6
Plasma concentration–time curve of DCN suspension, DNS-F7, and CS-DNS-F10 after oral dose of 15 g/kg of rat for 24 hours (n=5). Abbreviations: CS-DNS, chitosan-coated DNS; DCN, diacerein; DNS, DCN nanosuspension.
Figure 7
Figure 7
Diarrheal score for different formulae with a dose of 50 mg/kg for 5 successive days. Abbreviations: CS-DNS, chitosan-coated DNS; DCN, diacerein; DNS, DCN nanosuspension.
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References

    1. Onakpoya IJ, Heneghan CJ, Aronson JK. Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Med. 2016;14:10. - PMC - PubMed
    1. Mahajan A, Singh K, Tandon VR, Kumar S, Kumar H. Diacerein: a new symptomatic slow acting drug for osteoarthritis. J Med Educ Res. 2006;8:173–175.
    1. Kongtharvonskul J, Anothaisintawee T, McEvoy M, Attia J, Woratanarat P, Thakkinstian A. Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis knee: a systematic review and network meta-analysis. Eur J Med Res. 2015;20:24. - PMC - PubMed
    1. Panova E, Jones G. Benefit and risk assessment of diacerein in the treatment of osteoarthritis. Drug Saf. 2015;38(3):245–252. - PubMed
    1. Pavelka K, Bruyere O, Cooper C, Kanis J, Leeb B, Maheu E. Diacerein: benefits, risks and place in the management of osteoarthritis. An opinion-based report from the ESCEO. Drugs Aging. 2016;33(2):75–85. - PMC - PubMed

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