Biocompatible hydrogels for the controlled delivery of anti-hypertensive agent: development, characterization and in vitro evaluation

Figures & data

Figure 1. The graphical representation of different crosslinking methods.

Figure 2. Chemical structure of captopril.

Table 1. Feed composition of different formulations of Ge/PVP based hydrogels.

Sample codes	Ge/100 g solution	PVP/100 g solution	Ge/PVP (Wt %)	GA/100 g of Ge/PVP (Wt. %)	GA/100 g solution
S1	14.5	3.0	82.85/17.15	3.8	2.660
S2	16.5	3.0	84.61/15.39	3.8	2.964
S3	19.0	3.0	86.36/13.46	3.8	3.344
S4	16.5	3.5	82.50/17.50	3.8	3.040
S5	16.5	4.0	80.48/19.52	3.8	3.116
S6	16.5	4.5	78.57/21.43	3.8	3.192
S7	16.5	3.0	84.61/15.39	3.5	2.730
S8	16.5	3.0	84.61/15.39	4.0	3.120
S9	16.5	3.0	84.61/15.39	4.2	3.276

Figure 3. Presumptive chemical structure of Ge/PVP based hydrogels.

Figure 4. The schematic representation of acid base reactions in corresponding buffer media.

Table 2. Amount of captopril loaded in different samples of GE/PVP hydrogels.

Sample codes	Amount of captopril loaded (g/g of dry gel)
	By swelling	By extraction
S4	0.0562	0.0490
S5	0.0611	0.060
S6	0.0694	0.672
S7	0.0546	0.0517
S8	0.0518	0.0462
S9	0.0492	0.0424

Table 3. % Release of captopril from different samples of Ge/PVP hydrogels.

Sample codes	pH 1.2	pH 6.5	pH 7.5
S1	75.31	52.37	61.72
S2	76.57	53.21	59.16
S3	79.12	54.03	64.97
S7	77.42	56.24	65.54
S8	73.65	49.42	59.63
S9	72.24	47.05	58.82

Figure 5. Equilibrium swelling ratio of Ge/PVP hydrogels with different concentrations of Ge using glutaraldehyde (GA) as crosslinking agent in solutions of different pH; pH 1.2 (□), pH 5.5 (●), pH 6.5 (♦) and pH 7.5 (▲).The data present the mean ± standard deviation of n = 3 individual readings.

Figure 6. Equilibrium swelling ratio of Ge/PVP hydrogels having varying concentrations of PVP (3.5, 4 and 4.5 g) using GA as crosslinking agent (3.8 wt% of Ge and PVP) in solutions of different pH; pH 1.2 (□), pH 5.5 (●), pH 6.5 (♦) and pH 7.5 (▲).The data present the mean ± standard deviation of n = 3 individual readings.

Figure 7. Equilibrium swelling ratio of Ge/PVP hydrogels having varying concentrations GA as crosslinking agent (3.5 wt%, 4 wt% and 4.2 wt% of Ge and PVP) in solutions of different pH; pH 1.2 (□), pH 5.5 (●), pH 6.5 (♦) and pH 7.5 (▲).

Figure 8. Cumulative % release of captopril from Ge/PVP hydrogels (A) Effect of variable concentration of Ge on % drug release in solution of different pH values (B) Effect of crosslinking agent concentration on % drug release in solution of different pH values. The data present the mean ± standard deviation of n = 3 individual readings.

Table 4. Gel fraction of different formulation of Ge/PVP hydrogels.

Sample codes	Ge/PVP ratio	Degree of crosslinking GA (wt%)	Gel fraction (%)
S1	82.85/17.15	3.8	80.21
S2	84.61/15.39	3.8	84.14
S3	86.36/13.46	3.8	84.77
S4	82.50/17.50	3.8	83.53
S5	80.48/19.52	3.8	83.77
S6	78.57/21.43	3.8	84.09
S7	84.61/15.39	3.5	82.79
S8	84.61/15.39	4.0	85.00
S9	84.61/15.39	4.2	88.63

Figure 9. Effect of processing variables on gel fraction of Ge/PVP hydrogels (A) Ge Concentration (B) PVP Concentration (C) GA Concentration, The data present the mean ± standard deviation of n = 3 individual readings.

Table 5. Porosity of different formulations of Ge/PVP hydrogels.

Sample codes	Ge/ PVP ratio	Degree of crosslinking GA (wt %)	Porosity (%)
S1	82.85/17.15	3.8	28.84
S2	84.61/15.39	3.8	34.99
S3	86.36/13.46	3.8	38.53
S4	82.50/17.50	3.8	18.11
S5	80.48/19.52	3.8	23.34
S6	78.57/21.43	3.8	25.74
S7	84.61/15.39	3.5	31.01
S8	84.61/15.39	4.0	26.22
S9	84.61/15.39	4.2	21.87

Figure 10. Effect of processing variables on porosity of Ge/PVP hydrogels (A) Ge concentration (B) PVP concentration (C) GA concentration. The data present the mean ± standard deviation of n = 3 individual readings.

Table 6. Flory-Huggins network parameters of Ge/PVP hydrogels.

Sample codes	V2,s	Χ	M c	M r	q	D (cm²/s)
S1	0.046433	−0.61261	5713.655	93.60281	59.82581	0.259520
S2	0.056222	−0.61237	6129.121	92.95433	64.59157	0.196683
S3	0.054342	−0.61169	6139.349	92.42910	65.00799	0.180310
S4	0.051952	−0.61433	4526.779	96.37461	46.97837	0.249044
S5	0.049411	−0.51359	4710.133	97.46823	48.45973	0.230588
S6	0.048882	−0.61341	5442.316	98.42065	55.59944	0.229931
S7	0.045461	−0.61217	5570.246	95.78332	57.22161	0.235711
S8	0.051231	−0.61433	4234.568	97.08011	42.98879	0.292192
S9	0.053444	−0.61490	4184.892	99.50739	42.03866	0.321289

Table 7. Effect of Ge concentration on drug release kinetics of Ge/PVP hydrogels in different pH solutions using GA as crosslinker (3.8 wt% of Ge and Pec).

Sample codes	Ge contents (%)	pH	Zero order Kinetic		First order Kinetics		Higuchi Model
			K 0 (h ^−1)	r	K 1 (h ^−1)	r	K 2 (h ^−1)	r
S1	14.5	1.2	6.021	0.992	0.1175	0.987	0.257	0.979
		6.5	4.619	0.981	0.0877	0.990	0.201	0.970
		7.5	5.203	0.981	0.0697	0.992	0.225	0.971
S2	16.5	1.2	6.194	0.994	0.1207	0.961	0.261	0.953
		6.5	4.888	0.998	0.0689	0.987	0.198	0.958
		7.5	5.124	0.993	0.0791	0.985	0.209	0.963
S3	19.0	1.2	6.484	0.997	0.1251	0.968	0.265	0.966
		6.5	4.576	0.995	0.0654	0.986	0.183	0.957
		7.5	5.616	0.996	0.0912	0.988	0.226	0.971

Table 8. Effect of Ge concentration on drug release mechanism of Ge/PVP hydrogels in different pH solutions using GA as crosslinker (3.8 wt% of Ge and Pec).

Sample codes	Ge content (%)	pH	Release exponent (n)	r	Order of release
S1	14.5	1.2	0.695	0.989	Non-fickian
		6.5	0.906	0.994	Non-fickian
		7.5	0.751	0.982	Non-fickian
S2	16.5	1.2	0.709	0.976	Non-fickian
		6.5	0.999	0.996	Non-fickian
		7.5	0.742	0.988	Non-fickian
S3	19.0	1.2	0.732	0.989	Non-fickian
		6.5	0.671	0.966	Non-fickian
		7.5	0.726	0.985	Non-fickian

Table 9. Effect of concentration of crosslinker (GA) on drug release kinetics of Ge/PVP hydrogels in different pH solutions.

Sample codes	GA contents (%)	pH	Zero order kinetic		First order kinetics		Higuchi model
			K 0 (h ^−1)	r	K 1 (h ^−1)	r	K 2 (h ^−1)	r
S7	3.5	1.2	6.321	0.985	0.1302	0.983	0.272	0.974
		6.5	5.251	0.989	0.0789	0.980	0.221	0.949
		7.5	5.629	0.973	0.1021	0.989	0.247	0.973
S8	4.0	1.2	6.019	0.994	0.1131	0.980	0.256	0.970
		6.5	4.811	0.988	0.0667	0.988	0.197	0.968
		7.5	5.158	0.996	0.0994	0.987	0.210	0.967
S9	4.2	1.2	6.045	0.984	0.1129	0.990	0.262	0.981
		6.5	4.818	0.988	0.0651	0.981	0.195	0.946
		7.5	5.402	0.995	0.0819	0.982	0.220	0.961

Table 10. Effect of concentration of crosslinker (GA) on drug release mechanism of Ge/PVP hydrogels in different pH solutions.

Sample codes	GA contents (%)	pH	Release exponent (n)	r	Order of release
S7	3.5	1.2	0.706	0.991	Non-fickian
		6.5	0.993	0.994	Non-fickian
		7.5	0.776	0.989	Non-fickian
S8	4.0	1.2	0.739	0.989	Non-fickian
		6.5	0.998	0.895	Non-fickian
		7.5	0.778	0.991	Non-fickian
S9	4.2	1.2	0.798	0.997	Non-fickian
		6.5	0.999	0.997	Non-fickian
		7.5	0.917	0.995	Non-fickian

Figure 11. FT-IR spectra of (A) Gelatin (B) PVP (C) Unloaded hydrogel sample (D) Loaded hydrogel sample (E) Captopril.

Figure 12. XRD spectra of (A) drug loaded Ge/PVP hydrogel sample (B) unloaded Ge/PVP hydrogel sample.

Figure 13. SEM analysis of Surface morphology of Ge/PVP hydrogel (A) Unloaded sample (B) loaded sample (C) Cross-sectional morphology of Unloaded Ge/PVP hydrogel sample (D) loaded Ge/PVP hydrogel sample.