Comparative physicochemical, anti-inflammatory, and analgesic activity assay of synthesized chromium and nickel complexes of indomethacin

Figures & data

Table 1. FT-IR wave number bands (n) of indomethacin and its metal complexes

I	InCr	InNi	Comment
Wave length(1,000–600) cm^−1
840.01, 925.85	838.08, 926.81	836.16, 918.13	C–C stretch
657.74, 753.22	754.18	658.7, 756.11	C–Cl stretch
925.85	926.81	918.13	Carboxyl OH bending
Wave length(1,820–1,660) cm^−1
1,691.6	1,679.06	1,680.03	Carbonyl group
1,717.64	–	–	C=O conjugation of –COOH
Wave length (3,425–2,400) cm^−1
2,831.55	2,837.34	2,843.12	C-H stretching
2,915.46, 2,927.03, 2,965.61	2,927.99	2,934.74	OH conjugation of –COOH
-	3,403.45	3,406.35	Presence of coordinated H2O

Abbreviations: I = indomethacin, InCr = chromium-indomethacin complex, InNi = nickel-indomethacin complex and n = wave number of maximum absorption peaks in reciprocal centimeters.

Table 2. Absorbance (in chloroform) found in UV–Visible spectrum of indomethacin and its complexes

Compound	λmax (nm)	Absorbance
I	318	0.747
InCr	320	0.369
InNi	319	0.352

Abbreviations: I = indomethacin, InCr = chromium-indomethacin complex, InNi = nickel-indomethacin complex.

Figure 1. Comparison of DSC curves of indomethacin and its complexes.

Table 3. pH-solubility profile of parent indomethacin and its chromium and nickel complex

pH	Solubility (mg/ml)
	In	InCr	InNi
2	0.082	0.328	0.042
3	0.29	0.174	0.051
4	0.101	0.411	0.242
5	0.49	0.603	1.067
6	0.312	0.282	0.53
7	0.912	0.369	0.647

Abbreviations: In = indomethacin, InCr = chromium-indomethacin complex and InNi = nickel-indomethacin complex.

Table 4. Dissolution profile of parent indomethacin and its chromium and nickel complex at different time

Time (min)	% of drug release
	In	InCr	InNi
10	3.9	4.6	12.3
20	8.3	5.6	23.6
30	12.8	5.7	24.6
40	17.3	7.3	28.6
50	21	7.8	30.9
60	24	9	33.3

Abbreviations: In = indomethacin, InCr = chromium-indomethacin complex and InNi = nickel indomethacin complex.

Table 5. Peripheral analgesic activities of metal complexes of indomethacin

Sample code	Number of writhing (Mean ± S. E. M.)	% inhibition of writhing
Control	36.4 ± 1.503	–
In (sd)	23.6 ± 1.327*	35.16
InCr (sd)	21.8 ± 1.772*	40.11
InNi (sd)	20.4 ± 1.03**	43.96
In (dd)	13 ± 1.703**	64.29
InCr (dd)	12.2 ± 0.86	66.48
InNi (dd)	12 ± 0.447	67.03

Notes: Values are presented as mean ± S.E.M., where n = 5; In = indomethacin, InCr = chromium-indomethacin complex, InNi = nickel-indomethacin complex, sd = single dose (10 mg/kg) and dd = double dose (20 mg/kg).

^* Significant level at p < 0.05 compared to control group.

^** Significant level at p < 0.01 compared to control group.

Table 6. Central analgesic activity of metal complexes of indomethacin

Samples	Reaction time (Mean ± S. E. M.) (% time elongation of tail flicking)
	30 min	60 min	90 min	120 min
Morphine	15.4 ± 0.483 (110.95%)	12.68 ± 0.399 (95.08%)	12.08 ± 0.563***(91.75%)	10.2 ± 0.361** (64.52%)
In (sd)	10.8 ± 0.63** (47.95%)	10.6 ± 0.534*** (63.08%)	9.76 ± 0.498** (54.92%)	9.62 ± 0.532** (55.16%)
InCr (sd)	11.24 ± 0.812** (53.97%)	10.8 ± 0.762** (66.15%)	9.92 ± 0.499** (57.46%)	9.78 ± 0.637 (57.74%)
InNi (sd)	10.94 ± 0.366*** (49.86%)	10.8 ± 0.348 (66.15%)	9.94 ± 0.406** (57.78%)	9.78 ± 0.392** (57.74%)
In (dd)	11.1 ± 0.962* (52.05%)	11.9 ± 0.871*** (83.08%)	11.84 ± 0.878*** (87.94%)	9.6 ± 0.507** (54.84%)
InCr (dd)	12 ± 0.909** (64.38%)	11.96 ± 0.43 (84%)	11.56 ± 0.849** (83.49%)	9.32 ± 0.532* (50.32%)
InNi (dd)	11.72 ± 0.719** (60.55%)	12.48 ± 0.566*** (92%)	11.8 ± 0.676** (87.30%)	9.7 ± 0.507* (56.45%)

Notes: Values are presented as mean ± S.E.M., where n = 5; In = indomethacin, InCr = chromium-indomethacin complex, InNi = nickel-indomethacin complex, sd = single dose (10 mg/kg) and dd = double dose (20 mg/kg).

^* Significant level at p < 0.05 compared to control group.

^** Significant level at p < 0.01 compared to control group.

^*** Significant level at p < 0.001 compared to control group.

Table 7. Anti-inflammatory activity of metal complexes of indomethacin

Group	Dose (mg/kg)	Paw volume ± SEM (% inhibition of edema)
		1 h	2 h	3 h	4 h
Control	–	0.9 ± 0.0084	1.156 ± 0.0614	1.218 ± 0.0479	1.334 ± 0.0674
In	100	0.84 ± 0.0089** (23.02%)	0.84 ± 0.013*** (61.81%)	0.868 ± 0.0149*** (61.05%)	0.928 ± 0.0159*** (58.89%)
InCr	15	0.79 ± 0.0116*** (25.4%)	0.738 ± 0.0146*** (73.23%)	0.818 ± 0.0296*** (62.11%)	0.866 ± 0.0236*** (61.52%)
InNi	15	0.808 ± 0.0108*** (29.37%)	0.74 ± 0.0141** (78.35%)	0.822 ± 0.0309*** (66.32%)	0.884 ± 0.032*** (62.97%)

Notes: Values are presented as mean ± S.E.M., where n = 5; In = indomethacin, InCr = chromium-indomethacin complex and InNi = nickel-indomethacin complex.

^** Significant level at p < 0.01 compared to control group.

^*** Significant level at p < 0.001 compared to control group.