Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3) cells

Figures & data

Figure 1 Powder X-ray diffraction patterns of (A) zinc oxide, (B) CETN, and (C) cetirizine.

Abbreviation: CETN, cetirizine nanocomposite.

Figure 2 Structure of cetirizine at different pH (A–C) and molecular structure model of cetirizine intercalated between the interlayer of ZLH (D).

Abbreviation: ZLH, zinc-layered hydroxide.

Table 1 Fourier transform infrared assignment for cetirizine and CETN^21,29

Assignments	Cetirizine	CETN
ν (O–H)	3432 for O–H in carboxylic group	3424 in the layer; H2O
ν (CHar)	3044–3023	–
ν (CH2)	2984–2949	2958–2817
ν (OH) dimmer	2628, 2505 and 2379	–
ν (NH^+) cyclic	2217	–
ν (COOH)	1740	–
ν (φ. parasubst)	1601	1602
ν (φ. monosubst)	1496, 1077 and 758	1488
ν (C–Cl)	1457	1453
ν (C–O) in carboxylic group	1435, 1383, 1356 and 1319	–
δ (O–H)	1284, 1274, 1263 and 1242	–
δ (CH2 CH2O CH2)	1185	1130
2 adj φ	846 and 809	853 and 804
ν (CH monosubst)	758	758
Zn–O and Zn–OH	–	503
νas(COO^−)	–	1602
νs(COO^−)	–	1408

Abbreviations: adj, adjacent; CETN, cetirizine nanocomposite; monosubst, monosubstitution; parasubst, parasubstitution.

Figure 3 Fourier transform infrared spectra of (A) cetirizine and (B) the cetirizine nanocomposite.

Figure 4 Thermogravimetric and differential thermogravimetric analyses of (A) cetirizine and (B) the cetirizine nanocomposite.

Table 2 Physico-chemical properties of zinc oxide and the cetirizine nanocomposite (CETN)

Sample	C (%)	H (%)	N (%)	Zn (% w/w)	Anion (% w/w)	BET surface area m^2/g	BJH pore volume cm^3/g	BJH average pore diameter Å
ZnO	–	–	–	(80.3)	–	6	0.01	111
CETN	32.1	4.1	3.5	32.3b	49.4a (47.3c)	24	0.71	96

Notes: Value in the parentheses is a theoretical value.

a Estimated from carbon, hydrogen, nitrogen and sulfur analysis data;

b estimated from atomic absorption spectroscopy analysis;

c estimated from UV.

Abbreviations: BET, Brunauer, Emmett, and Teller method; BJH, Barrett–Joyner–Halenda method; ZnO, zinc oxide; CETN, cetirizine nanocomposites.

Figure 5 Adsorption-desorption isotherms for zinc oxide and CETN (A) and Barret–Joyner–Halenda method pore size distribution for zinc oxide and CETN (B).

Abbreviation: CETN, cetirizine nanocomposite.

Figure 6 Field emission scanning electron microscope image of zinc oxide (A and B) and the cetirizine nanocomposite (C and D).

Figure 7 (I) Release profiles of cetirizine from the cetirizine nanocomposite at pH 7.4 (A) and pH 4.8 (B) up to 5 hours; (II) release profiles of cetirizine up to 83 hours.

Note: Inset shows the release profiles of cetirizine from its physical mixture of cetirizine with zinc layered hydroxide at pH 7.4 (C) and pH 4.8 (D).

Table 3 Correlation coefficient (R²), rate constant (k), and half time (t_1/2) obtained by fitting the data of the release of cetirizine from the cetirizine nanocomposite (CETN) into phosphate buffer solution at pH 7.4 and pH 4.8

Aqueous solution	Saturation release (%)	R^2			Pseudo-second order
		Pseudo-first order	Pseudo-second order	Parabolic diffusion	Rate constant, k (g/mg · h)	t1/2 (h)
pH 7.4	96	0.7867	0.9967	0.7555	0.003	3.80
pH 4.8	97	0.8277	0.9994	0.5391	0.008	1.36

Figure 8 Fitting of the data of cetirizine released from the cetirizine nanocomposite into various solutions to the first-, pseudo-second order kinetics and parabolic diffusion model for pH 7.4 (A–C) and pH 4.8 (D–F).

Table 4 Viability of normal Chang liver cells after 24 hours’ treatment with zinc-layered hydroxide (ZLH) and cetirizine nanocomposite (CETN)

Concentrations (μg/mL)	Viability (%)
	ZLH	CETN
0.00	100.0	100.0
7.81	102.9	99.4
15.62	99.4	98.9
31.25	97.7	95.9
62.5	91.8	91.8
125	87.1	81.9
250	69.0	64.3
500	63.7	58.5
1000	23.4	22.2

Figure 9 Trypan Blue assays of normal Chang liver cells after 24 hours of treatment with zinc-layered hydroxide (ZLH) and cetirizine nanocomposite (CETN).

Table 5 Inhibition percentage of histamine release in rat basophilic leukemia cells by free cetirizine, the cetirizine nanocomposite (CETN), zinc-layered hydroxide (ZLH), and cetirizine intercalated into CETN

Concentration (ng/mL)	Inhibition (%)
	Cetirizine	ZLH	CETN	Cetirizine in CETN*
1000	80.0	22.5	83.8	–
500	73.7	16.2	77.3	67.6
250	58.1	15.3	66.5	62.0
125	50.2	4.0	57.2	62.5
62.5	29.0	1.2	40.8	56.0
31.25	19.3	0.6	30.6	40.2
15.63	8.5	−1.1	11.7	31.7

Note:

* Inhibition (%) by intercalated cetirizine into CETN = (inhibition by CETN at 1000 ng/mL – inhibition by ZLH at 500 ng/mL), because the loading of cetirizine into CETN is 49.4%.

Figure 10A–C Histamine release response of rat basophilic leukemia cells treated at different concentrations of cetirizine, cetirizine nanocomposite, and zinc-layered hydroxide.

Figure 11 Percentage inhibition of histamine release into rat basophilic leukemia cells at different concentrations of cetirizine (CET), cetirizine nanocomposite (CETN), and zinc-layered hydroxide (ZLH).

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