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Fig 1.

Chemical structure of DCN [1].

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Table 1.

I-Optimal factorial design used to optimize solid dispersion systems of DCN.

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Table 2.

Experimental runs, formulation variables, measured responses of the I-Optimal factorial design and similarity factor.

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Table 3.

Modeling parameters of DCN.

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Fig 2.

DSC compatability studies of plain drug (a), PVP K25 (b), PVP K90 (c), PEG 4000 (d), PEG 8000 (e), PM of drug and PVP K25 (f), PM of drug and PVP K90 (g), PM of drug and PEG 4000 (h) and PM of drug and PEG 8000 (i).

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Fig 3.

FTIR compatability studies of plain drug (a), PVP K25 (b), PVP K90 (c), PEG 4000 (d), PEG 8000 (e), PM of drug and PVP K25 (f), PM of drug and PVP K90 (g), PM of drug and PEG 4000 (h) and PM of drug and PEG 8000 (i).

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Fig 4.

In-vitro dissolution profiles of DCN-SD containing different D:P ratios of PVP K25, compared to plain DCN.

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Fig 5.

In-vitro dissolution profiles of DCN-SD containing different D:P ratios of PVP K90, compared to plain DCN.

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Fig 6.

In-vitro dissolution profiles of DCN-SD containing different D:P ratios of PEG 4000, compared to plain DCN.

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Fig 7.

In-vitro dissolution profiles of DCN-SD containing different D:P ratios of PEG 8000, compared to plain DCN.

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Fig 8.

Line plots for the effect of formulation variables on DC %.

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Fig 9.

Line plots for the effect of D:P ratio on DE (15 min) % (a), DE (60 min) % (b) and MDT (c).

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Fig 10.

Line plots for the effect of polymer type on DE (15 min) % (a), DE (60 min) % (b) and MDT (c).

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Table 4.

Fitting results of dissolution profiles data of plain DCN and SD systems to distinguished models.

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Table 5.

Statistical parameters for selection of the best fit model of the measured responses.

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Fig 11.

In-vitro dissolution profile of DCN from the optimized SD compared to plain DCN in phosphate buffer (pH 6.8).

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Fig 12.

DSC thermograms of drug powder (a) and optimized SD (b).

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Fig 13.

Powder X-ray diffraction spectra of drug powder (a) and optimized SD (b).

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Fig 14.

Scanning electron micrographs of pure DCN (a) and the optimized SD (b).

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Table 6.

Comparison of PBPK-simulated model and reported DCN pharmacokinetic parameters following a single oral dose (50 mg) in healthy adults and geriatrics.

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Fig 15.

Physiologically based pharmacokinetic (PBPK) model–simulated DCN plasma concentration-time curves following oral administration of optimized SD and plain DCN in healthy adults and geriatrics.

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