The structural, morphological and thermal properties of grafted pH-sensitive interpenetrating highly porous polymeric composites of sodium alginate/acrylic acid copolymers for controlled delivery of diclofenac potassium

Figures & data

Figure 1. Molecular structure of diclofenac potassium.

Table 1. Formulation sheet of NaAlg/AA hydrogels.

Samples codes	NaAlg/100 g of solution	Acrylic acid/100 g of solution	AA/NaAlg (wt% ratio)	EGDMA/100 g of solution	EGDMA wt% of AA
S1	1.7	30	94.60/5.40	0.12	0.4
S2	2.1	30	93.45/6.55	0.12	0.4
S3	2.5	30	92.30/7.70	0.12	0.4
A1	2.1	26	91.95/8.05	0.12	0.4
A2	2.1	32	93.84/6.16	0.12	0.4
A3	2.1	38	94.47/5.53	0.12	0.4
E1	2.1	30	93.45/6.55	0.09	0.3
E2	2.1	30	93.45/6.55	0.15	0.5
E3	2.1	30	93.45/6.55	0.18	0.6

Figure 2. Presumptive structure of cross-linked NaAlg/AA hydrogels.

Table 2. Dynamic (q) and equilibrium swelling (Eq) ratios of NaAlg/AA hydrogels.

Sample no	pH 1.2		pH 5.5		pH 6.5		pH 7.5
	q	Eq	q	Eq	Q	Eq	q	Eq
S1	2.32	5.03	10.53	55.17	11.88	78.84	13.50	84.19
S2	2.45	5.25	11.06	59.36	12.24	79.49	13.42	86.43
S3	2.52	5.41	11.40	64.40	12.59	86.21	13.86	90.43
A1	2.54	5.81	12.14	75.59	13.066	89.89	13.71	95.12
A2	2.29	4.76	10.06	49.23	10.90	69.27	12.02	81.12
A3	2.01	4.15	8.96	46.28	10.35	58.47	11.27	72.58
E1	2.33	4.93	8.89	60.18	9.75	67.96	10.67	78.50
E2	2.31	4.77	8.71	54.70	9.20	59.27	9.70	68.22
E3	2.03	4.66	8.47	50.48	8.96	52.35	9.40	66.91

Table 3. Amount of diclofenac potassium loaded and released (%) in different formulation of NaAlg/AA hydrogels.

Sample codes	Amount of diclofenac potassium Loaded (g/g of dry gel)			Amount of diclofenac potassium released (%) (pH of the solution)
	By swelling	By weight	By extraction	1.2	5.5	7.5
A1	0.362	0.365	0.358	15.61	56.57	79.48
A2	0.319	0.311	0.305	14.15	54.66	75.21
A3	0.289	0.281	0.273	13.40	51.20	73.09
E1	0.294	0.286	0.283	16.35	57.56	82.79
E2	0.227	0.229	0.220	11.88	52.92	75.36
E3	0.201	0.197	0.206	10.26	51.11	73.42

Figure 3. Dynamic swelling ratio (q) of NaAlg/AA hydrogels with different concentrations of AA (26, 32 and 38 g) using EGDMA as crosslinking agent (0.4 wt%) in solution of different pH in 0.05 M USP phosphate buffer.

Figure 4. Release of diclofenac potassium from NaAlg/AA hydrogels using different concentrations of AA (26, 32 and 38 g) at various pH values in 0.05 M USP phosphate buffer.

Figure 5. Dynamic swelling ratio (q) of NaAlg/AA hydrogels with different concentrations of NaAlg (1.5, 2 and 2.5 g) using EGDMA as crosslinking agent (0.4 wt%) in solution of different pH in 0.05 M USP phosphate buffer.

Figure 6. Dynamic swelling ratio (q) of NaAlg/AA hydrogels with different concentrations of EGDMA (0.3, 0.5 and 0.6 wt%) as crosslinking agent in solution of different pH in 0.05 M USP phosphate buffer.

Figure 7. Release of diclofenac potassium from NaAlg/AA hydrogels using different concentrations of EGDMA as crosslinking agent (0.3, 0.5 and 0.6 various pH values in 0.05 M USP phosphate buffer.

Table 4. Flory–Huggins network parameter of NaAlg/AA hydrogels.

Samples codes	v2,s	χ	Mc	Mr	q	D (cm²/sec)
S1	0.247735	−0.60176	72.12	79.30	0.909	0.381591
S2	0.22126	−0.58865	108.78	81.43	1.33	0.348889
S3	0.238343	−0.59703	87.60	83.49	1.049	0.327951
A1	0.199746	−0.57847	121.99	80.36	1.15	0.208936
A2	0.213217	−0.5848	100.33	78.48	1.27	0.31077
A3	0.22872	−0.59228	101.54	77.83	1.43	0.558354
E1	0.210174	−0.58336	138.27	79.20	1.39	0.395282
E2	0.219274	−0.5877	113.81	79.42	1.43	0.309341
E3	0.222695	−0.58935	110.99	79.53	1.74	0.325175

Table 5. Effect of reaction variables on gel fraction and porosity.

Sample codes	Degree of crosslinking EGDMA (wt%)	Gel fraction (%)	Porosity (%)	p-Value
S1	0.4	92.66	24.31	0.005
S2	0.4	91.98	26.08	0.05
S3	0.4	91.31	29.86	0.05
A1	0.4	92.83	22.14	0.005
A2	0.4	93.85	25.07	0.005
A3	0.4	95.20	27.35	0.05
E1	0.3	90.36	27.11	0.005
E2	0.5	91.17	23.97	0.005
E3	0.6	93.33	22.82	0.005

Figure 8. Effect of variable concentration on gel fraction (a) NaAlg concentration (b) Acrylic acid concentration and (c) EGDMA concentration.

Figure 9. Effect of variable concentrations on porosity % (a) NaAlg concentration (b) Acrylic acid concentration and (c) EGDMA concentration.

Table 6. Effect of different concentration of acrylic acid on drug release kinetics of NaAlg/AA hydrogels in solutions of different pH values using EGDMA as crosslinking agent (0.4% of AA).

Sample codes	AA contents	pH	Zero order kinetic		First order kinetics		Higuchi model
			K0 (h − 1)	r	K0 (h − 1)	r	K0 (h − 1)	r
A1	26	1.2	1.283	0.998	0.014	0.997	0.054	0.987
		5.5	4.027	0.991	0.066	0.974	0.171	0.964
		7.5	5.648	0.997	0.115	0.956	0.240	0.970
A2	32	1.2	1.204	0.997	0.013	0.995	0.050	0.951
		5.5	3.710	0.983	0.053	0.957	0.157	0.951
		7.5	0.523	0.993	0.088	0.961	0.221	0.957
A3	38	1.2	1.148	0.992	0.012	0.986	0.044	0.969
		5.5	3.572	0.987	0.051	0.974	0.153	0.964
		7.5	5.075	0.991	0.093	0.947	0.214	0.954

Table 7. Effect of degree of crosslinking on drug release kinetics of NaAlg/AA hydrogels in solutions of different pH values.

Sample codes	EGDMA contents (%)	pH	Zero order kinetic		First order kinetics		Higuchi model
			K0 (h − 1)	r	K0 (h − 1)	r	K0 (h − 1)	r
E1	0.3	1.2	1.340	0.997	0.014	0.995	0.245	0.968
		5.5	4.04	0.990	0.061	0.973	0.172	0.971
		7.5	5.075	0.991	0.093	0.947	0.214	0.954
E2	0.5	1.2	1.102	0.975	0.011	0.946	0.041	0.839
		5.5	3.780	0.991	0.054	0.975	0.160	0.959
		7.5	5.265	0.994	0.100	0.952	0.223	0.952
E3	0.6	1.2	0.983	0.970	0.009	0.966	0.038	0.883
		5.5	5.166	0.983	0.050	0.970	0.152	0.958
		7.5	5.166	0.993	0.095	0.958	0.219	0.964

Table 8. Effect of different concentration of acrylic acid on drug release mechanism of NaAlg/AA hydrogels in solutions of different pH values using EGDMA as crosslinking agent (0.4% of acrylic acid).

Sample codes	AA content	pH	Release exponent (n)	r	Order of release
A1	26	1.2	0.808	0.998	Non-fickian
		5.5	0.650	0.992	Non-fickian
		7.5	0.589	0.986	Non-fickian
A2	32	1.2	0.957	0.993	Non-fickian
		5.5	0.629	0.992	Non-fickian
		7.5	0.581	0.980	Non-fickian
A3	38	1.2	0.898	0.992	Non-fickian
		5.5	0.651	0.991	Non-fickian
		7.5	0.582	0.980	Non-fickian

Table 9. Effect of degree of crosslinking on drug release mechanism of NaAlg/AA hydrogels in solutions of different pH values.

Sample codes	EGDMA content (%)	pH	Release exponent (n)	r	Order of release
E1	0.3	1.2	0.823	0.989	Non-fickian
		5.5	0.632	0.988	Non-fickian
		7.5	0.573	0.983	Non-fickian
E2	0.5	1.2	0.675	0.734	Non-fickian
		5.5	0.664	0.986	Non-fickian
		7.5	0.595	0.984	Non-fickian
E3	0.6	1.2	0.802	0.983	Non-fickian
		5.5	0.598	0.970	Non-fickian
		7.5	0.650	0.986	Non-fickian

Figure 10. FTIR spectra of (a) acrylic acid (b) sodium alginate (c) diclofenac potassium (d) unloaded hydrogel and (e) loaded hydrogel.

Figure 11. DSC spectra of pure drug (diclofenac potassium), loaded NaAlg/AA hydrogel and unloaded NaAlg/AA hydrogel.

Figure 12. XRD pattern of loaded and unloaded NaAlg/AA hydrogel.

Figure 13. SEM micrographs of NaAlg/AA hydrogels (a) Surface morphology of unloaded hydrogel (b) Surface morphology of loaded hydrogel (c, e) Cross sectional morphology of unloaded hydrogel and (d, f) Cross sectional morphology of loaded hydrogel at various resolutions.