Particle engineering/different film approaches for earlier absorption of meloxicam

Figures & data

Table 1. Composition of different Mel intraoral fast disintegrating films.

Formula	Polymer	HPMC (mg)	PVA (mg)	HEC (mg)	Aspartame (mg)	PG (ml)	Citric acid (mg)	Water to (ml)
G0	HPMC E5	200	–	–	30	0.1	20	10
G1	HPMC E5	100	–	–	30	0.1	20	10
G2	HPMC E5	200	–	–	30	0.1	20	10
G3	HPMC E15	100	–	–	30	0.1	20	10
G4	HPMC E15	200	–	–	30	0.1	20	10
G5	HEC	–	–	100	30	0.1	20	10
G6	HEC	–	–	200	30	0.1	20	10
G7	PVA	–	100	–	30	0.1	20	10
G8	PVA	–	200	–	30	0.1	20	10
G9	HPMC E5 + PVA	50	50	–	30	0.1	20	10
G10	HEC+ PVA	–	50	50	30	0.1	20	10
G11	HPMC E 15+PVA	50	50	–	30	0.1	20	10

The dose of Mel was kept at 15 mg/4 cm² film (an amount of Mel SCA equivalent to15 mg of Mel in all formulae except G0 which contains a dose of raw meloxicam equivalent to 15 mg).

Table 2. Composition of different Mel edible films.

Formula	Polymer	HPMC (mg)	SCA (g)	Raw Mel (g)	Glycerol (g)	Water to (ml)
G12	HPMC E5	500	0.25	–	0.5	10
G13	HPMC E15	500	0.25	–	0.5	10
G14	HPMC E5	500	–	0.25	0.5	10
G15	HPMC E15	500	–	0.25	0.5	10

The dose of Mel was kept at 15 mg/4 cm² film.

Figure 1. X-Ray diffractograms (A) and DSC patterns (B) of Mel spherical crystalline agglomerate (SCA).

Table 3. Physicochemical and mechanical characteristics of the prepared Mel films.

Formula	% Drug content^a	Thickness (mm)^a	Surface pH^b	DT ^b (s)	TS (N/cm^2)^b	%E (cm %)^b	EM
G0	97.28 ± 1.23	0.122 ± 0.02	6.51 ± 0.12	25 ± 1.52	1.54 ± 0.15	73.34 ± 3.52	2.47 ± 0.32
G2	97.80 ± 1.44	0.120 ± 0.02	6.47 ± 0.134	23 ± 2.08	1.38 ± 0.14	75.4 ± 3.29	2.54 ± 0.25
G3	99.04 ± 1.53	0.125 ± 0.02	6.74 ± 0.152	19 ± 2.50	2.55 ± 0. 29	95.7 ± 2.42	1.64 ± 0.15
G4	97.52 ± 1.44	0.175 ± 0.03	6.89 ± 0.121	34.67 ± 3.10	3.43 ± 0. 24	83.42 ± 5.32	3.25 ± 0.31
G5	97.66 ± 0.92	0.130 ± 0.03	6.25 ± 0.154	27 ± 3.05	1.35 ± 0. 27	72.4 ± 4.25	2.76 ± 0.27
G6	97.75 ± 0.36	0.225 ± 0.05	6.65 ± 0.111	39 ± 2.51	2.44 ± 0. 15	67.85 ± 3.63	3.84 ± 0.29
G7	97.32 ± 0.64	0.240 ± 0.03	6.70 ± 0.178	66 ± 5.13	8.23 ± 0.75	38.4 ± 2.25	20.55 ± 1.34
G8	98.37 ± 1.65	0.275 ± 0.02	6.76 ± 0.153	94 ± 8.21	12.23 ± 1.13	42.5 ± 1.5	26.87 ± 2.14
G9	97.54 ± 1.12	0.23 ± 0.02	6.67 ± 0.174	38 ± 3.60	4.52 ± 0. 23	70.54 ± 3.15	4.63 ± 0.58
G10	97.15 ± 0.75	0.215 ± 0.03	6.81 ± 0.12	55 ± 2.65	3.25 ± 0. 12	61.5 ± 2.29	5.35 ± 0.37
G11	96.76 ± 0.55	0.250 ± 0.02	6.72 ± 0.128	43 ± 3.50	4.87 ± 0. 33	65.7 ± 4.15	5.64 ± 0.44
G12	98.20 ± 1.54	0.225 ± 0.25	–	–	13.84 ± 1.22	46.88 ± 4.24	7.15 ± 0.77
G13	97.50 ± 1.34	0.235 ± 0.27	–	–	15.38 ± 1.04	35.4 ± 3.25	10.23 ± 1.04
G14	97.72 ± 1.43	0.234 ± 0.17	–	–	14.87 ± 1.34	44.32 ± 5.21	8.75 ± 0.57
G15	96.84 ± 1.43	0.241 ± 0.19	–	–	16.54 ± 1.12	33.43 ± 4.35	10.66 ± 1.23

DT = disintegration time, TS = tensile strength, %E = percent elongation, EM = modulus of elasticity.

^aValues are expressed as mean ± SD; n = 5.

^bValues are expressed as mean ± SD; n = 3.

Figure 2. Dissolution profiles of Mel edible films in SGF pH 1.2 (A) and SSF pH 6.8 (B).Statistically significant differences are indicated as *p < 0.05.

Figure 3. Dissolution profiles of Mel fast disintegrating films in SSF pH 6.8. Statistically significant differences are indicated as *p < 0.05.

Figure 4. Chromatogram of Mel (RT = 5.526) and piroxicam internal standard (RT = 3.359) in plasma.

Figure 5. Mel plasma concentration-time profiles after administration of Mobic® tablets, G3 fast disintegrating film and G12 edible film.

Table 4. Mean pharmacokinetic parameters of Mel following administration of different formulae.

Parameter	Mobic® Tablet ± SD	G3 ± SD	G12 ± SD	p G3/Tab	p G12/Tab	p G3/G12
Cmax (µg/ml)	0.89 ± 0.02	1.23 ± 0.026	1.03 ± 0.076	***	*	**
Tmax (h)	4.67 ± 1.15	1.67 ± 0.29	2.67 ± 0.58	**	*	ns
t(1/2) (h)	8.66 ± 0.51	5.76 ± 0.48	6.80 ± 0.4	***	**	*
Kel (h^–1)	0.08 ± 0.005	0.12 ± 0.011	0.102 ± 0.006	***	**	*
AUC (µg h/ml)
(0–0.5)	0.016 ± 0.0012	0.1425 ± 0.013	0.0625 ± 0.013	***	**	***
(0–4)	1.702 ± 0.08	3.66 ± 0.17	2.705 ± 0.06	***	***	***
(0–24)	9.135 ± 0.91	12.33 ± 0.89	9.95 ± 1.14	**	ns	*
% Relative bioavailability	–	136	109	–	–	–

ns, not significant; Tab, Mobic® Tablet.

Statistically significant difference between groups is indicated as *p < 0.05; **p ≤ 0.01 and ***p ≤ 0.001.