Formulation and in vivo assessment of terconazole-loaded polymeric mixed micelles enriched with Cremophor EL as dual functioning mediator for augmenting physical stability and skin delivery

Figures & data

Table 1. Experimental runs, independent variables, and measured responses of the 2³ full factorial experimental design of PMMs.

PMM formulations	X1: weight ratio of total Pluronics to drug	X2: Weight ratio of Pluronic P123 to Pluronic F127	X3: percent of Cremophor EL in aqueous medium	Y1: MIE^a (%)	Y2: micellar size^a (nm)	Y3: PDI^a	Y4: ZP^a (mV)
F 1	20	2	5	69.24 ± 8.12	27.99 ± 5.17	0.43 ± 0.42	− 7.65 ± 0.03
F 2	20	2	10	72.03 ± 6.66	72.35 ± 24.82	0.25 ± 0.04	− 5.69 ± 0.72
F 3	20	4	5	69.15 ± 1.33	90.55 ± 11.74	0.24 ± 0.09	− 5.11 ± 0.60
F 4	20	4	10	75.55 ± 10.39	162.42 ± 15.87	0.32 ± 0.05	−10.10 ± 1.70
F 5	40	2	5	51.87 ± 12.44	30.12 ± 4.88	0.57 ± 0.02	−10.46 ± 1.90
F 6	40	2	10	42.03 ± 6.89	97.29 ± 8.08	0.34 ± 0.07	− 6.35 ± 1.13
F 7	40	4	5	92.98 ± 0.4	33.23 ± 8.00	0.16 ± 0.00	− 9.65 ± 0.64
F 8	40	4	10	69.61 ± 7.35	25.40 ± 8.92	0.20 ± 0.05	− 4.59 ± 0.22
PMMs without Cremophor EL	40	4	0	92.98 ± 0.40	48.23 ± 15.07	0.16 ± 0.00	− 9.65 ± 0.64

^a Data are represented as mean ± standard deviation (n = 3).

PPMs: polymeric mixed micelles; MIE: micellar incorporation efficiency percent; PDI: polydispersity index; ZP: zeta potential.

Figure 1. 3-D plot model graphs demonstrating the effect of factors; X₁: weight ratio of total Pluronics to drug, X₂: weight ratio of Pluronic P123 to Pluronic F127, and X₃: percent of Cremophor EL in aqueous medium on micellar incorporation efficiency percent (MIE%) (a and b) and mean micellar size (c and d).

Figure 2. Transmission electron micrograph of the optimal PMMs formulation (F7).

Figure 3. (a) Cumulative amount of TCZ permeated per unit area across skin via optimal PMMs formulation (F7) compared to PMMs lacking Cremophor EL and TCZ suspension. (b) Cumulative amount of TCZ deposited per unit area in the skin via optimal PMMs formulation (F7) compared to TCZ suspension.

Table 2. Parameters obtained from ex vivo studies for the optimal PMMs (F7), PMMs lacking Cremophor EL, and TCZ suspension.

Formulation	Flux at 8 h (J max) (µg/cm^2/h)^a	Amount of drug deposited in the skin after 8 h (µg/cm^2)^a	Local accumulation efficiency (LAE)^a
TCZ suspension	0.92 ± 0.05	3.20 ± 0.13	0.44 ± 0.10
Optimal PMMs (F7)	32.40 ± 1.46	1012.16 ± 38.46	3.9 ± 0.24
PMMs without Cremophor EL	15.32 ± 0.93	264.25 ± 12.52	2.15 ± 0.17

^a Each value represents mean ± standard deviation (n = 3).

Figure 4. Photomicrographs showing histopathological sections (hematoxylin and eosin stained) of (a) normal untreated rat skin and (b) rat skin treated with optimal PMMs formulation (F7).