pH-sensitive interpenetrating polymer network microspheres of poly(vinyl alcohol) and carboxymethyl cellulose for controlled release of the nonsteroidal anti-inflammatory drug ketorolac tromethamine

Figures & data

Figure 1. Structure of KT.

Figure 2. Schematic representation of the synthesis of IPN polymers.

Table I. Formulation codes, results of percentage entrapment efficiency, and yield of the microspheres.

Formulation code	Polymer ratio (NaCMC/PVA) (w/w)	Drug/Polymer ratio (w/w)	Exposure time to crosslinking agent (minutes)	% Entrapment efficiency	% Yield
A1	1/1	1/8	30	8	92
A2	1/2	1/8	30	6	62
A3	1/4	1/8	30	5	51
A4	1/6	1/8	30	4	55
A5	1/8	1/8	30	2	67
B1	1/8	1/8	45	10	64
C1	1/8	1/1	30	30	22
C2	1/8	½	30	31	30
C3	1/8	1/4	30	32	26
C4	1/8	1/6	30	34	72

Figure 3. FTIR spectrum of (a) pristine PVA, (b) pristine NaCMC, and (c) KT-loaded NaCMC/PVA microspheres (drug/polymer ratio: 1/8 (w/w), polymer/polymer ratio: 1/1 (w/w)).

Figure 4. FTIR spectrum of (a) KT-loaded microspheres (drug/polymer ratio: 1/8 (w/w), polymer/polymer ratio: 1/1 (w/w)), (b) pristine KT, and (c) placebo NaCMC/PVA microspheres (polymer/polymer ratio: 1/1 (w/w)).

Figure 5. DSC thermograms of (a) pristine KT, (b) KT-loaded NaCMC/PVA microspheres (drug/polymer ratio: 1/8 (w/w), polymer/polymer ratio: 1/1 (w/w)), and (c) placebo NaCMC/PVA microspheres (polymer/polymer ratio: 1/1 (w/w)).

Figure 6. Scanning electron micrographs of KT-loaded IPN microspheres (a) 4000 magnification, and (b) 8000 magnification.

Figure 7. X-RD pattern of (a) KT-loaded microspheres, and (b) placebo microspheres.

Figure 8. Effect of the NaCMC/PVA ratio on KT release (*):1/1, (x):1/2, (▲):1/4, (■):1/6, (♦):1/8, (drug/polymer ratio:1/8, concentration of GA:0.66 M, exposure time to GA:30 min.).

Figure 9. Effect of the drug/polymer ratio on KT release (*):1/8, (x):1/6, (▲):1/4, (■):1/2, (♦):1/1, (NaCMC/PVA ratio:1/1, concentration of GA:0.66 M, exposure time to GA:30 min.).

Figure 10. Effect of the exposure time on KT release (♦): 30 min., (■): 45 min. (NaCMC/PVA ratio: 1/1, drug/polymer ratio:1/8, concentration of GA:0.66 M).

Table II. Results of swelling study of empty IPN microspheres.

NaCMC/PVA ratio	pH = 1.2	pH = 6.8	pH = 7.4
1/1	110.23 ± 4.46	128.10 ± 1.85	142. ± 2.08
1/2	86.79 ± 1.24	91.94 ± 3.51	108.05 ± 1.74
1/4	65.82 ± 4.41	78.53 ± 3.97	92.76 ± 4.90
1/6	45.71 ± 4.46	61.84 ± 1.85	73.68 ± 2.08
1/8	20.14 ± 1.24	49.12 ± 3.51	62.10 ± 1.74

Table III. Results of k, n and r calculated with equation (3).

Formulation code	k	n	r	Diffusion mechanism
A1	0.0743	0.131	0.925	Fickian transport
A2	0.0884	0.178	0.910	Fickian transport
A3	0.2055	0.089	0.894	Fickian transport
A4	0.1862	0.139	0.940	Fickian transport
A5	0.218	0.059	0.846	Fickian transport
B1	0.232	0.106	0.893	Fickian transport
C1	0.368	0.140	0.925	Fickian transport
C2	0.518	0.068	0.938	Fickian transport
C3	0.344	0.116	0.946	Fickian transport