Bile salt/phospholipid mixed micelle precursor pellets prepared by fluid-bed coating

Figures & data

Figure 1 The ternary phase diagram of the SDC/phospholipids/water solutions.

Abbreviation: SDC, sodium deoxycholate.

Table 1 The fitted results of the Boltzmann equation and the CMC of the mixed micelles in different solutions

Solution	A1	A2	x0 (CMC)	X^2	r^2
Water	1.668	1.126	0.0406	0.0002	0.9951
1% PVP	1.495	1.171	0.0952	0.0001	0.9897
1% PEG	1.844	1.142	0.0457	0.0005	0.9905
1% HPMC	1.579	1.051	0.0996	0.0003	0.9936

Note: Boltzmann equation: $y=\left(A_1-A_2\right)/\left(1+e^{\left(x-x_0\right)/\Delta x}\right)+A_2$.³³

Abbreviations: A₁ the upper limits of the sigmoid; A₂, the lower limits of the sigmoid; CMC, critical micelle concentration; HPMC, hydroxypropyl methyl cellulose; PEG, polyethylene glycol; PVP, polyvinyl pyrrolidone.

Figure 2 Effects of HPMC (A), PVP (B), and PEG (C) on the solubilizing ability of MMs to FB (37°C, n = 3).

Abbreviations: FB, fenofibrate; HPMC, hydroxypropyl methyl cellulose; MMs, mixed micelles; PVP, polyvinyl pyrrolidone; PEG, polyethylene glycol.

Figure 3 Plots of pyrene in a 1:3 ratio versus concentration of MMs in 1% HPMC, PVP, and PEG aqueous solutions.

Abbreviations:I, fluorescence intensity; HPMC, hydroxypropyl methyl cellulose; MM, mixed micelle; PVP, polyvinyl pyrrolidone; PEG, polyethylene glycol.

Figure 4 SEM photographs of the surface (A–C, ×50) and cross-section (D–F, ×200 of A–C, respectively) of the preMM pellets prepared with FB:PEG:micellar carrier = 1:1.5:1.5 (A and D), 1:1:2 (B and E) and 1:0:3 (C and F), respectively.

Abbreviations: FB, fenofibrate; MM, mixed micelle; PEG, polyethylene glycol; SEM, scanning electron microscopy.

Figure 5 Particle size distribution for original (A) and reconstituted (B) MMs.

Abbreviations: Diam, diameter; MMs, mixed micelles; S.Dev, standard deviation.

Figure 6 Redispersion profiles of preMM pellets with different FB:PEG:micellar carrier weight ratios (values displayed in brackets) and dissolution of FB from physical mixture, solid dispersion pellets (FB:PEG = 1:3) and Lipanthyl® (Laboratoires Fournier SA, Dijon, France).

Abbreviations: PM, physical mixture; FB, fenofibrate; MM, mixed micelle; PEG, polyethylene glycol.

Figure 7 X-ray powder diffraction patterns of FB, PEG, physical mixture, solid dispersion (FB:PEG = 1:3) and preMMs with different FB:PEG:micellar carrier weight ratios.

Abbreviations: FB, fenofibrate; MMs, mixed micelles; PEG, polyethylene glycol.

Table 2 The main pharmacokinetic parameters of preMM pellets (FB:PEG:micellar carrier = 1:1.5:1.5), solid dispersion pellets (FB:PEG = 1/3) and Lipanthyl® (Laboratoires Fournier SA, Dijon, France), after a single dose

Parameters	PreMM pellets	Solid dispersion	Lipanthyl®
Cmax(μg/mL)	0.874 ± 0.395	0.662 ± 0.222	0.397 ± 0.162
tmax (hours)	1.438 ± 0.427	1.125 ± 0.250	1.063 ± 0.239
A∪C0–t (μg/mL ⋅ hour)	4.123 ± 2.263	2.837 ± 1.459	1.451 ± 0.394
A∪C0–∞ (μg/mL ⋅ hour)	7.200 ± 5.347	5.755 ± 4.104	2.033 ± 1.200
Fr(%)	100	145	284

Abbreviations: A∪C_0–t, area under the curve to the last measurable concentration; A∪C_0–∞, area under the curve extrapolated to infinity; C_max, maximum concentration; FB, fenofibrate; MM, mixed micelle; PEG, polyethylene glycol; T_max, time of maximum concentration.

Figure 8 Mean plasma FB acid concentration-time curves in beagle dogs after oral administration of preMM pellets (FB:PEG:micellar carrier = 1:1.5:1.5), solid dispersions pellets (FB:PEG = 1:3) and Lipanthyl® (Laboratoires Fournier SA, Dijon, France) (n = 6).

Abbreviations: FB, fenofibrate; MM, mixed micelle; PEG, polyethylene glycol.

LuYTangNQiJWuWPhase solubility behavior of hydrophilic polymer/cyclodextrin/lansoprazole ternary system studied at high polymer concentration and by response surface methodologyPharm Dev Technol201217223624121067338

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