Ketoprofen mesoporous silica nanoparticles SBA-15 hard gelatin capsules: preparation and in vitro/in vivo characterization

Figures & data

Table 1. Composition of the hard gelatin capsule blend.

Formula	Ingredients (mg)
F#1	SBA-15-KP	Aerosil	Mg stearate	Microcrystalline cellulose	Crosscarmellose sodium	SLS*
	91.7	0.18	0.91	27.53	4.58	1.83

*Sodium lauryl sulfate.

Table 2. Composition of different tested groups.

Group	Treatment	Composition
I	Control	Distilled water
II	Carrier	0.1% SBA-15
III	Standard reference	Ketofan® capsule content
IV	Prepared formula (F#1)	SBA-15-KP + Aerosil + Mg Stearate + Avicel 101+ Ac-Di-Sol + SLS

Figure 1. TGA charts of ketoprofen, SBA-15 and SBA-15-KP.

Table 3. Quantification of the amount of KP loaded into SBA-15 by TGA and extraction.

	TGA				Extraction
Sample	Weight loss below 100 °C (%)	Total weight loss (%)	Weight loss of KP (mg/g)	Weight loss of KP (wt%)	Amount of KP extracted (mg/g)	Amount of KP extracted (wt%)	Average KP loaded (wt%)
SBA-15	3.59	3.59		-	-	-	-
SBA-15-KP	3.04	57.36	543.2	54.32	544.8	54.48 ± 0.1	54.40 ± 0.1

Figure 2. HRTEM images of SBA-15 (left image) and SBA-15-KP (right image).

Figure 3. SAXRD patterns of Ketoprofen, SBA-15 and SBA-15-KP.

Table 4. Structural and textural parameters of free and loaded SBA-15.

Material	Specific surface area (m^2/g)	Total pore volume (cc/g)	Pore diameter (nm)	Cell* parameter ao (nm)	Pore diameter distribution ranges (nm)
SBA-15	780	0.83	6.24	10.96	5.1–7.0
SBA-15-KP	340	0.18	5.45	10.99	4.2–5.8

*The distance from centers of two adjacent pores.

Figure 4. X-ray diffractogram of Ketoprofen, SBA-15 and SBA-15-KP.

Figure 5. DSC thermograms of Ketoprofen, SBA-15 and SBA-15-KP.

Figure 6. FT-IR Spectra of Ketoprofen, SBA-15 and SBA-15-KP.

Figure 7. Adsorption/desorption isotherms of SBA-15 and SBA-15-KP.

Figure 8. Dissolution profile of Ketoprofen and SBA-15-KP.

Table 5. Release mechanism of KP from SBA-15.

Release models	Kinetic parameters	Free KP	Loaded KP
First order	R^2	0.995	0.961
	AIC	29.53	50.88
	k1(min^−1)	0.005	0.127
	t1/2 (min)	135.22	5.46
Higuchi	R^2	0.861	0.231
	AIC	66.75	100.03
	kH (min^−1/2)	3.59	11.9
	t1/2 (min)	193.91	17.64
Korsmeyer–Peppas	R^2	0.994	0.782
	AIC	33.03	70.19
	n value	0.91	0.14
	KKP (min^−n)	0.611	53.054
	t1/2 (min)	126.31	0.65
Weibull	R^2	0.997	0.994
	AIC	27.06	39.83
	α	248.26	2.48
	Td (min)	184.81	7.05
	β	1.05	0.57
	t1/2 (min)	130.86	4.75

Figure 10. Pore size distribution of SBA-15 and SBA-15-KP.

Table 6. Ant-inflammatory activity results.

	Control		Carrier		Ketofan®		Formula (F#1)
Hours	Mean % change in edema (volume ± S.D^a)	% Inhibition	Mean % change in edema (volume ± S.D)	% Inhibition	Mean % change in edema (volume ± S.D)	% Inhibition	Mean % Change in edema (volume ± S.D)	% Inhibition
1/2	48.9 ± 6.1	–	46.8 ± 5.7	4.3	27.1 ± 4.4	44.5	7.1 ± 2.4^b	85.4
1	70.9 ± 8.5	–	70.0 ± 5.2	1.2	32.0 ± 5.4	52	12.4 ± 2.6^b	82.5
2	83.2 ± 9.8	–	78.3 ± 5.0	5.8	32.1 ± 5.1	62.4	28.1 ± 1.7	66.2
3	95.4 ± 9.6	–	88.8 ± 8.4	6.9	45.5 ± 7.6	52.3	32.2 ± 3.8	66.2
4	96.7 ± 12.4	–	90.2 ± 7.7	6.7	43.2 ± 10.5	57.5	40.2 ± 7.6	58.4
5	103.9 ± 14.8	–	99.9 ± 3.5	3.8	50.5 ± 7.4	48.4	40.6 ± 6.3	59

^aStandard deviation.

^bVery highly significant.

Table 7. Central analgesic activity results.

	Control	Carrier	Ketofan®	Formula F#1
Minutes	Mean R.T^a ± S.D^b	Mean R.T ± S.D	Mean R.T ± S.D	Mean R.T ± S.D
0 (Baseline)	4.0 ± 0.6	4.0 ± 0.6	4.0 ± 0.3	3.8 ± 0.4
30	3.4 ± 0.7	3.1 ± 0.5	5.8 ± 0.3	11.9 ± 0.8^c
60	3.8 ± 0.5	3.8 ± 1.5	8.3 ± 1.0	11.4 ± 0.7^c
90	3.6 ± 0.5	3.7 ± 0.7	9.2 ± 0.7	11.4 ± 1.0^c
120	3.6 ± 0.7	3.9 ± 1.1	9.9 ± 1.1	10.5 ± 0.9

^aReaction time.

^bStandard deviation.

^cVery highly significant.

Figure 9. Dssolution profile of SBA-15-KP and F#1.