Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique

Figures & data

Figure 1. Risperidone chemical formula.

Table 1. Composition and pre-compression characterization of risperidone liquisolid formulae.

Formula	Vehicle type	LDC^a	Lf	Q	q	Dis^b	Unit dose weight (mg)	Angle of repose	Ci%	Hausner ratio
F1	Transcutol HP	10	0.243	165	8.25	17.325	192.48	32.22	17.84	1.21
F2		20		83	4.15	8.715	96.82	31.16	19.16	1.19
F3		30		55	2.75	5.775	64.16	31.62	18.18	1.18
F4	Labrasol	10	0.202	198	9.9	20.76	230.64	30.12	17.67	1.17
F5		20		99	4.95	10.395	115.49	29.86	16.16	1.19
F6		30		66	3.3	6.93	76.994	30.25	16.87	1.16
F7	PEG 400	10	0.104	385	19.25	40.425	449.12	31.12	20.01	1.12
F8		20		193	9.65	20.265	225.14	31.24	18.79	1.14
F9		30		128	6.4	13.44	149.32	32.11	18.89	1.17
F10	Tween 80	10	0.142	282	14.1	29.61	328.97	30.35	18.13	1.20
F11		20		141	7.05	14.805	164.43	31.63	18.87	1.18
F12		30		94	4.7	9.87	109.66	32.15	17.82	1.19
F13	Labrasol/Labrafil (1:1)	10	0.151	265	13.25	27.825	309.14	30.75	18.92	1.17
F14		20		133	6.65	13.965	155.15	31.41	19.37	1.17
F15		30		89	4.45	9.345	103.82	31.82	19.41	1.16

^aLiquid drug concentration.

^b Disintegrant amount (mg).

Table 2. Post-compression characterization of risperidone liquisolid formulation tablets.

Formula name	Average weight (mg) ± SD	Thickness (cm)	Diameter (cm)	Content uniformity (%) ± S.D	Friability (%)	Hardness (N)	Disintegration time (s)
F1	194.12 ± 0.661	0.15	0.6	98.39 ± 0.869	0.63	58	47
F2	94.97 ± 0.499	0.12	0.2	97.96 ± 0.991	0.69	55	42
F3	66.27 ± 0.211	0.11	0.2	100.75 ± 0.844	0.77	46	35
F4	232.31 ± 0.816	0.25	0.6	99.08 ± 0.261	0.67	56	42
F5	113.69 ± 1.039	0.13	0.2	97.89 ± 0.844	0.69	54	44
F6	77.11 ± 0.133	0.11	0.2	98.39 ± 0.587	0.72	49	40
F7	450.72 ± 0.731	0.22	0.8	98.99 ± 0.992	0.52	68	53
F8	223.21 ± 0.829	0.25	0.6	100.41 ± 1.340	0.64	58	45
F9	151.41 ± 0.654	0.13	0.6	101.69 ± 0.261	0.71	52	42
F10	329.17 ± 0.961	0.20	0.8	99.31 ± 0.844	0.59	64	52
F11	165.51 ± 1.071	0.13	0.6	100.71 ± 1.340	0.73	49	38
F12	112.16 ± 0.370	0.13	0.2	97.92 ± 0.869	0.71	49	40
F13	308.29 ± 1.129	0.18	0.8	99.28 ± 0.991	0.61	60	49
F14	156.33 ± 0.397	0.13	0.6	99.19 ± 0.519	0.69	56	44
F15	102.82 ± 0.157	0.12	0.2	98.72 ± 1.340	0.73	48	37

Figure 2. Dissolution data of risperidone from different prepared liquisolid tablet formulae in comparison to plain drug and conventional tablets.

Table 3. One way ANOVA test of dissolution data.

	Sum of squares	df	Mean square	F	Sig.
Between groups	39 658.936	16	2478.684	2.261	0.006
Within groups	149 081.813	136	1096.190
Total	188 740.749	152

Figure 3. Graphical presentation of post hoc statistical analysis of dissolution data.

Figure 4. Solid state characterization of risperidone liquisolid formula (F13) using A) DSC, B) IR and C) XRD.

Figure 5. Mean plasma concentration time curve of risperidone liquisolid formula (F13) and conventional tablet in rabbits.

Table 4. Mean pharmacokinetic parameters of risperidone liquisolid formula (F13) and conventional tablet in rabbits.

Parameter	F13	Commercial tablet
Cpmax	137.518 ± 23.2	38.673 ± 4.61
Tmax	1 ± 0.215	1 ± 0.199
AUC0–48	1213.111 ± 85.39	276.984 ± 14.72
AUC0–∞	1441.711 ± 93.88	321.011 ± 19.81
K	0.0619 ± 0.0192	0.10545 ± 0.0843
T1/2	7.556 ± 0.421	6.619 ± 0.311

Table 5. Confidence intervals of the statistically calculated mean differences of risperidone pharmacokinetic parameters.

Parameter	p value	Mean difference	Confidence interval
Cpmax	<0.001	98.845	94.074–103.616
Tmax		0.9364	0.504–1.369
AUC0–48		936.127	880.497–991.757
AUC0–∞		1120.966	1049.192–1192.206
K		−0.0136	− (0.0201–0.007)