Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies

Figures & data

Table 1. Composition of the different prepared ketoconazole-loaded proniosomal gels.

Formula	Span20	Span60	Span65	Span80	Tween80	Brij35	Brij72	Brij92	Pluronic (F68)	Pluronic (L121)	Lecithin
F1	500 mg
F2	250 mg										250 mg
F3		500 mg
F4		250 mg									250 mg
F5			500 mg
F6			250 mg								250 mg
F7				500 mg
F8				250 mg							250 mg
F9					500 mg
F10					250 mg						250 mg
F11						500 mg
F12						250 mg					250 mg
F13							500 mg
F14							250 mg				250 mg
F15								500 mg
F16								250 mg			250 mg
F17									500 mg
F18									250 mg		250 mg
F19										500 mg
F20										250mg	250 mg

Table 2. Physical evaluation of the prepared ketoconazole-loaded proniosomal gels.

Formula	%Drug entrapped ± S.D	Z-average (d.nm)±S.D	PDI ± S.D
F1	57.90 ± 2.90	1322 ± 82	0.09 ± 0.00
F2	87.10 ± 1.19	590.80 ± 34	0.14 ± 0.06
F3	85.20 ± 1.67	855 ± 57	0.49 ± 0.13
F4	86.60 ± 1.80	535.20 ± 28	0.15 ± 0.08
F5	83.80 ± 2.30	339 ± 19	0.61 ± 0.18
F6	93.00 ± 1.10	559.10 ± 22	0.60 ± 0.20
F7	47.00 ± 1.25	2695 ± 98	0.61 ± 0.10
F8	79.50 ± 3.10	413.60 ± 24	0.11 ± 0.03
F9	37.50 ± 1.15	97.56 ± 12	0.37 ± 0.11
F10	49.50 ± 2.34	140.60 ± 10	0.21 ± 0.09
F11	40.60 ± 1.55	4432 ± 105	1 ± 0.42
F12	49.90 ± 1.25	452.70 ± 63	0.49 ± 0.11
F13	60.60 ± 1.21	2271 ± 79	1 ± 0.37
F14	74.90 ± 0.65	550 ± 72	1 ± 0.50
F15	62.90 ± 2.25	1096 ± 89	1 ± 0.39
F16	72.70 ± 2.96	1140 ± 99	0.34 ± 0.13
F17	41.60 ± 1.31	1961 ± 88	0.87 ± 0.29
F18	51.70 ± 2.96	805 ± 63	0.36 ± 0.09
F19	51.40 ± 3.85	663.40 ± 92	0.77 ± 0.34
F20	70.70 ± 2.70	510.30 ± 49	0.62 ± 0.23

Figure 1. In vitro release profile of the different prepared KET-loaded proniosomal gel formulae prepared with: (A) Spans (B) Tween 80 (C) Brijs (D) Pluronics.

Figure 2. In vitro release of the different prepared KET-loaded proniosomal gel formulae at Q 2 h and Q 8 h.

Figure 3. In vitro corneal permeation of the selected KET-loaded proniosomal gel formulae.

Table 3. Permeability parameters of the selected ketoconazole-loaded proniosomal gels.

Formula	Permeability coefficient (cm^2/h)	Steady-state flux (mcg/cm^2hr)	Correlation coefficient (R)
F2	0.000244	2.44	0.993
F3	0.0002009	2.009	0.99
F4	2.36 × 10^−5	0.236	0.91
F5	3.18 × 10^−6	0.0318	0.88
F6	6.39 × 10^−6	0.0639	0.924

Figure 4. Concentration-time curve of KET-proniosomal gel formula (F2) and KET-SP in aqueous humor of albino rabbits.

Table 4. Pharmacokinetic parameters of ketoconazole after topical administration of KET-Gel optimum formula and KET-SP rabbit's eye.

Pharmacokinetic parameters	KET-Gel (F2)	KET-SP
Cmax (mcg/ml)	18.8 ± 1.23	0.896 ± 0.052
Tmax median tmax (h)^a	4	2
AUC 0–8 (mcg.h/mL)	60.1 ± 3.04	3.15 ± 0.27
AUC 0–∞ (mcg.h/mL)	62.48 ± 3.56	3.18 ± 0.25
K (h^−1)	0.625 ± 0.045	0.682 ± 0.251
T1/2 (h)	1.1 ± 0.07	1.01 ± 0.264
MRT (h)	3.88 ± 0.1	2.5 ± 0.0305