Formulation and optimization of duloxetine hydrochloride buccal films: in vitro and in vivo evaluation

Figures & data

Table 1. Composition of DH buccoadhesive films.

Formula code	HPMC % (w/v)	PVA % (w/v)	PG % (w/w)	H2O (ml)
F1	1%	_	10%	15
F2	2%	_	10%	15
F3	_	4%	10%	15
F4	_	6%	10%	15
F5	1%	4%	10%	15
F6	2%	4%	10%	15
F7	1%	6%	10%	15
F8	2%	6%	10%	15
F9	1%	_	30%	15
F10	2%	_	30%	15
F11	_	4%	30%	15
F12	_	6%	30%	15
F13	1%	4%	30%	15
F14	2%	6%	30%	15
F15	1%	4%	30%	15
F16	2%	4%	30%	15

Table 2. The physicochemical parameters of the prepared DH buccoadhesive films.

	Thickness (mm)	Weight (mg)	% Drug content	pH	Max. Swelling index (%)	Mucoadhesion force (N)	Kinetic parameters of the release data ofDH films
	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	Mean ± SD	K	n	R^2
F1	0.2 ± 0.0047	10.78 ± 0.226	98.73 ± 1.22	7.21 ± 0.034	143.84 ± 4.37	0.138 ± 0.002	0.049	0.77	0.993
F2	0.28 ± 0.0082	12.42 ± 0.286	98.51 ± 0.97	7.16 ± 0.02	218.35 ± 6.12	0.252 ± 0.003	0.030	0.901	0.973
F3	0.24 ± 0.0047	24.61 ± 0.308	98.93 ± 1.63	7.01 ± 0.07	49 ± 1.28	0.111 ± 0.001	0.219	0.424	0.991
F4	0.26 ± 0.0024	29.25 ± 0.359	99.14 ± 0.75	7.28 ± 0.05	34.83 ± 1.94	0.09 ± 0.002	0.163	0.564	0.998
F5	0.59 ± 0.0082	26.46 ± 0.393	98.82 ± 1.27	6.99 ± 0.03	27.36 ± 1.16	0.137 ± 0.003	0.092	0.508	0.978
F6	0.66 ± 0.0047	35.32 ± 0.357	99.12 ± 0.97	7.02 ± 0.06	22.51 ± 1.64	0.125 ± 0.003	0.115	0.495	0.905
F7	0.67 ± 0.0082	52.19 ± 0.531	98.98 ± 0.66	7.24 ± 0.01	30.58 ± 2.01	0.174 ± 0.003	0.058	0.519	0.995
F8	0.72 ± 0.0082	65.88 ± 0.196	99.11 ± 0.95	7.17 ± 0.02	28.76 ± 1.88	0.149 ± 0.002	0.090	0.493	0.976
F9	0.14 ± 0.0082	16.84 ± 0.481	99.16 ± 1,73	6.62 ± 0.08	135.42 ± 5.49	0.123 ± 0.001	0.077	0.749	0.998
F10	0.27 + 0.0082	19.69 ± 0.194	98.89 ± 1.96	6.86 ± 0.03	152.37 ± 6.03	0.238 ± 0.003	0.130	0.562	0.965
F11	0.21 + 0.0047	25.77 ± 0.350	98.78 ± 2.15	6.97 ± 0.03	45.28 ± 1.47	0.08 ± 0.003	0.051	0.86	0.995
F12	0.32 + 0.0216	29.95 ± 0.371	99.32 ± 1.48	7.27 ± 0.06	31.84 ± 1.21	0.075 ± 0.002	0.402	0.24	0.927
F13	0.56 + 0.0125	29.66 ± 0.460	98.78 ± 2.41	6.60 ± 0.04	25.68 ± 1.33	0.118 ± 0.003	0.044	0.832	0.955
F14	1.04 + 0.017	37.07v0.384	98.69 ± 2.33	6.21 ± 0.04	22.37 ± 1.19	0.106 ± 0.005	0.051	0.878	0.998
F15	0.77 + 0.0047	53.97 ± 0.252	99.15 ± 1.78	6.92 ± 0.03	27.58 ± 1.65	0.157 ± 0.004	0.162	0.491	0.958
F16	1.12 + 0.0094	66.94 ± 0.894	98.74 ± 2.11	6.97 ± 0.05	25.39 ± 1.78	0.133 ± 0.002	0.244	0.409	0.997

Figure 1. Release profiles of DH films prepared with (A) 10% PG (F1–F8) and (B) 30% PG (F9–F16).

Table 3. Weights and percentage drug content of the selected films (F2) stored at 40  ^°C temperature and 75% relative humidity compared to freshly prepared films.

Time (months)		0	1	2	3	6
Weight (mg) Mean ± SD	Fresh	13.42 ± 0.29	13.33 ± 0.36	13.21 ± 0.29	13.09 ± 0.371	13.01 ± 0.42
	Stored	13.47 ± 0.33	13.36 ± 0.26	13.26 ± 0.25	13.19 ± 0.24	13.11 ± 0.19
Drug Content (%) Mean ± SD	Fresh	104.46 ± 0.34	104.26 ± 0.75	103.93 ± 1.04	103.84 ± 0.59	104.02 ± 0.69
	Stored	104.06 ± 0.14	103.57 ± 0.38	102.73 ± 0.20	102.4 ± 0.44	102.58 ± 0.41

Figure 2. Release profile of DH from the freshly prepared and stored F2 films in SSF (pH 6.8).

Figure 3. Mean plasma concentration–time profiles of DH after oral administration of Cymbalta^® capsules and buccal administration of F2 films to human volunteers.

Table 4. Pharmacokinetic parameters of DH following the oral administration of Cymbalta^® capsules and buccal administration of F2 (Mean ± SD).

Pharmacokinetic parameter	Cymbalta^® 30 mg capsule	F2 films
Cmax (ng/ml)	54.10 ± 33.83	89.33 ± 34.21
Tmax (h)	5.67 ± 1.86	3.5 ± 0.84
AUC0–t (ng h/ml)	518.5 ± 333.32	1536.8 ± 931.45
AUC0–∞ (ng h/ml)	535.09 ± 337.01	1646.17 ± 1043.7
MRT (h)	20.99 ± 4.8	22.36 ± 4.32
K (1/h)	0.05 ± 0.01	0.05 ± 0.01
Relative bioavailability (%)	–	296.39