A novel sustained release drug–resin complex-based microbeads of ciprofloxacin HCl

Figures & data

Table 1. Ratio of sodium polystyrene sulfonate resin to drug for drug–resin complex.

S. No.	Assigned code	Drug–resin
1	DRC-A	1:1
2	DRC-B	1:1.5
3	DRC-C	1:2
4	DRC-D	1:3
5	DRC-E	1:4

DRC, drug–resin complex.

Table 2. Batch specification of beads.

Batch	Code	DRC:polymer	Polymer ratio (alginate:pectin)	Drug:polymer
Batch-I	NRB1	–	2.5:2.5	1:1
	BDRC-A1	1:1	2.5:2.5	–
	BDRC-B1	1:1	3:2	–
	BDRC-C1	1:1	4:1	–
	BDRC-D1	1:1	1:4	–
	BDRC-E1	1:1	2:3	–
Batch-II	NRB2	–	2.5:2.5	0.5:1
	BDRC-A2	0.5:1	2.5:2.5	–
	BDRC-B2	0.5:1	3:2	–
	BDRC-C2	0.5:1	4:1	–
	BDRC-D2	0.5:1	1:4	–
	BDRC-E2	0.5:1	2:3	–

DRC, drug–resin complex; NRB, non-resin beads; BDRC, beads containing drug–resin complex.

Figure 1. Schematic diagram of chemical reaction for drug resin complex.

Figure 2. Schematic diagram of preparation of bead by an ionotropic gelation method.

Figure 3. Light microscopic photographs at 10×. (A) CFN, (B) SPS resin, (C) Drug–resin complex and (D) microbead.

Table 3. Micromeritic studies of the prepared formulations.

Batch	Formulation code	Particle size (mm)	Tapped density (g/cm^3)	True density (g/cm^3)	Compressibility index (%)	Porosity (%)	Yield (%)	Drug entrapment efficiency (%)
Batch-I	NRB1	1.13 ± 0.13	1.19 ± 0.48	1.43 ± 0.28	12.04 ± 0.19	16.67 ± 0.51	91.90 ± 1.03	76.24 ± 1.02
	BDRC-A1	1.35 ± 0.09	1.04 ± 0.52	1.28 ± 0.49	13.06 ± 0.78	18.80 ± 0.25	93.50 ± 1.12	78.83 ± 1.36
	BDRC-B1	1.31 ± 0.11	1.09 ± 0.61	1.35 ± 0.58	12.34 ± 0.64	19.61 ± 0.59	95.70 ± 1.02	79.74 ± 0.65
	BDRC-C1	1.20 ± 0.12	1.25 ± 0.37	1.47 ± 0.29	11.00 ± 0.27	14.97 ± 0.32	97.50 ± 1.34	80.74 ± 1.25
	BDRC-D1	1.45 ± 0.08	1.14 ± 0.49	1.61 ± 0.64	13.63 ± 0.27	29.53 ± 0.41	90.60 ± 1.27	71.55 ± 1.18
	BDRC-E1	1.39 ± 0.09	1.06 ± 0.57	1.25 ± 0.31	10.63 ± 0.26	14.96 ± 0.57	89.20 ± 1.17	74.97 ± 1.11
Batch-II	NRB2	1.12 ± 0.12	1.11 ± 0.46	1.31 ± 0.31	12.77 ± 0.19	15.64 ± 0.57	89.13 ± 1.12	77.02 ± 1.36
	BDRC-A2	1.32 ± 0.07	1.16 ± 0.57	1.39 ± 0.57	12.90 ± 0.69	16.29 ± 0.31	93.73 ± 1.09	78.43 ± 1.16
	BDRC-B2	1.30 ± 0.14	1.06 ± 0.63	1.47 ± 0.48	13.89 ± 0.54	27.69 ± 0.49	94.17 ± 1.36	79.38 ± 1.48
	BDRC-C2	1.19 ± 0.11	1.16 ± 0.47	1.35 ± 0.71	14.90 ± 0.69	14.01 ± 0.62	96.10 ± 1.19	80.78 ± 0.99
	BDRC-D2	1.43 ± 0.08	1.22 ± 0.39	1.51 ± 0.64	12.07 ± 0.59	19.55 ± 0.41	92.80 ± 1.28	72.39 ± 1.69
	BDRC-E2	1.34 ± 0.13	1.09 ± 0.29	1.25 ± 0.38	11.63 ± 0.46	13.12 ± 0.47	90.53 ± 1.06	73.45 ± 1.04

DRC, drug–resin complex; NRB, non-resin beads; BDRC, beads contain drug–resin complex. Data are the average of values (mean ± SD) (n = 3).

Figure 4. DSC thermograms of (A) CFN, (B) Tulsion 344 resin, (C) drug–resin complex (DRC-A).

Figure 5. IR spectra of (A) CFN, (B) Tulsion 344 and (C) drug–resin complex.

Figure 6. Swelling properties of various formulations (Batch-I). NRB, non-resin beads; BDRC, Beads contain drug–resin complex.

Figure 7. Swelling properties of various formulations (Batch-II). NRB, non-resin beads; BDRC, beads contain drug–resin complex.

Figure 8. In vitro drug release profile of CFN from various formulations (Batch-I). NRB, non-resin beads; BDRC, beads contain drug–resin complex; CIFRAN, marketed formulation of CFN. Values are mean ± SD (n = 3).

Figure 9. In vitro drug release profile of CFN from various formulations (Batch-II). NRB, non-resin beads; BDRC, beads contain drug–resin complex; CIFRAN, marketed formulation of CFN. Values are mean ± SD (n = 3).

Table 4. One-way ANOVA (Dunnett multiple comparison) test for in vitro drug release of CFN in GI fluid.

Comparison	Mean difference	q	p Value
CIFRAN vs. BDRC-A1	48.335	6.708**	p < 0.01
CIFRAN vs. BDRC-B1	51.276	7.116**	p < 0.01
CIFRAN vs. BDRC-C1	54.043	7.500**	p < 0.01
CIFRAN vs. BDRC-D1	42.779	5.936**	p < 0.01
CIFRAN vs. BDRC-E1	45.273	6.283**	p < 0.01

CIFRAN, marketed formulation of CFN; BDRC, beads containing drug–resin complex. ANOVA indicates analysis of variance; q, parameter obtained with p when performing ANOVA;

**very significant.

Table 5. One-way ANOVA (Dunnett multiple comparison) test for in vitro drug release of CFN in GI fluid.

Comparison	Mean difference	q	p Value
CIFRAN vs. BDRC-A2	49.096	6.872**	p < 0.01
CIFRAN vs. BDRC-B2	50.722	7.100**	p < 0.01
CIFRAN vs. BDRC-C2	54.012	7.560**	p < 0.01
CIFRAN vs. BDRC-D2	43.047	6.025**	p < 0.01
CIFRAN vs. BDRC-E2	45.686	6.395**	p < 0.01

CIFRAN, marketed formulation of CFN; BDRC, beads containing drug–resin complex. ANOVA indicates analysis of variance; q, parameter obtained with p when performing ANOVA;

**very significant.

Table 6. Release kinetics of formulation (Batch-I and Batch-II).

	Zero order	First order	Higuchi matrix	Korsemeyer– Peppas		Hixson– Crowell
	Formulation code	r^2	r^2	r^2	r^2	n	r^2
NRB1	0.9947	0.8858	0.9546	0.9862	0.2177	0.9066
BDRC-A1	0.9809	0.9277	0.9166	0.9968	0.288	0.8983
BDRC-B1	0.9837	0.9443	0.9212	0.9934	0.3055	0.9042
BDRC-C1	0.9857	0.9568	0.8252	0.9936	0.3232	0.9080
BDRC-D1	0.9874	0.9578	0.9489	0.9941	0.2749	0.9436
BDRC-E1	0.9906	0.9509	0.9415	0.9919	0.2838	0.9388
NRB2	0.9957	0.8951	0.9537	0.9883	0.2252	0.9151
BDRC-A2	0.9787	0.9274	0.9105	0.9979	0.2933	0.8989
BDRC-B2	0.9790	0.9347	0.9121	0.9971	0.2972	0.8902
BDRC-C2	0.9858	0.9522	0.9296	0.9905	0.304	0.9001
BDRC-D2	0.9866	0.9544	0.9438	0.9898	0.2603	0.9055
BDRC-E2	0.9909	0.9494	0.9399	0.9915	0.2644	0.9140

NRB, non-resin beads; BDRC, beads contain drug–resin complex. r², correlation coefficient.