pH responsive alginate polymeric rafts for controlled drug release by using box behnken response surface design

Figures & data

Table 1. Independent and dependent variables and constrains in box-behnken design.

Variables	Level			Constrains
	−1	0	+1
Independent
X1 Sodium alginate (%)	10	25	40	In the range
X2 HPMC K100M (%)	6	10	14	In the range
X3 Sodium bicarbonate (%)	20	30	40	In the range
Dependent
Y2% drug release at 2 h (%)				20–40
Y4% drug release at 4 h (%)				40–60
Y8% drug release at 8 h (%)				80–100

Table 2. Composition of alginate raft forming tablets.

Formulation code	PSS (mg)	Sodium alginate (mg)	HPMC K100M (mg)	Sodium bicarbonate (mg)	Citric acid (mg)	Calcium carbonate (mg)	Total weight (mg)
AR1	40	40	56	120	60	84	400
AR2	40	100	40	120	60	40	400
AR3	40	160	40	100	50	10	400
AR4	40	40	40	80	40	160	400
AR5	40	100	40	120	60	40	400
AR6	40	120	56	100	50	34	400
AR7	40	100	24	80	40	116	400
AR8	40	140	24	120	60	16	400
AR9	40	160	40	80	40	40	400
AR10	40	100	24	140	70	26	400
AR11	40	40	24	120	60	116	400
AR12	40	100	40	120	60	40	400
AR13	40	80	56	140	70	14	400
AR14	40	40	40	160	80	40	400
AR15	40	100	56	80	40	84	400

Table 3. Observed responses for alginate rafts forming tablets (n = 6).

Formulation code	Independent variables			Dependent variables
	X1 (%)	X2 (%)	X3 (%)	Y2 (%)	Y4 (%)	Y8 (%)
AR1	10	14	30	24.54 ± 0.011	49.11 ± 0.023	79.78 ± 0.091
AR2	25	10	30	35.43 ± 0.023	60.98 ± 0.982	95.67 ± 0.095
AR3	40	10	25	31.12 ± 0.123	53.89 ± 0.312	90.12 ± 0.011
AR4	10	10	20	41.23 ± 0.093	64.65 ± 0.256	93.11 ± 0.034
AR5	25	10	30	36.87 ± 0.034	59.92 ± 0.095	95.23 ± 0.711
AR6	30	14	25	30.99 ± 0.081	57.78 ± 0.367	79.12 ± 0.098
AR7	25	6	20	47.76 ± 0.456	72.21 ± 0.087	92.68 ± 0.458
AR8	35	6	30	47.34 ± 0.125	75.29 ± 0.087	94.01 ± 0.059
AR9	40	10	20	36.50 ± 0.087	58.89 ± 0.054	98.32 ± 0.911
AR10	25	6	35	44.42 ± 0.056	71.12 ± 0.178	95.32 ± 0.081
AR11	10	6	30	45.67 ± 0.049	68.34 ± 0.034	95.67 ± 0.487
AR12	25	10	30	34.44 ± 0.086	64.55 ± 0.031	94.42 ± 0.043
AR13	20	14	35	25.65 ± 0.056	46.65 ± 0.012	79.35 ± 0.045
AR14	10	10	40	33.99 ± 0.014	58.87 ± 0.054	94.45 ± 0.123
AR15	25	14	20	21.53 ± 0.987	46.55 ± 0.654	81.98 ± 0.014

Figure 1. 3D response surface graph showing effects of sodium alginate (X₁), HPMC K100M (X₂) and sodium bicarbonate (X₃) on (A) % drug release at 2 h (Y₂), (B) % drug release at 4 h (Y₄) and (C) % drug release at 8 h (Y₈).

Table 4. Disintegration time of tablets and strength, weight, volume and thickness of raft (n = 6).

Formulation code	Disintegration time (s)	Raft strength (g)	Raft weight (g)	Raft volume (ml)	Raft thickness (cm)
AR1	54	3.19 ± 0.067	1.39 ± 0.012	5.5 ± 0.15	3.5 ± 0.045
AR2	63	5.29 ± 0.039	1.84 ± 0.010	7.2 ± 0.05	4.5 ± 0.216
AR3	57	7.31 ± 0.012	2.10 ± 0.029	8.9 ± 0.05	5.5 ± 0.136
AR4	55	3.10 ± 0.097	1.32 ± 0.011	5.7 ± 0.25	3.9 ± 0.048
AR5	67	5.20 ± 0.013	1.85 ± 0.010	7.5 ± 0.15	4.7 ± 0.193
AR6	65	7.30 ± 0.067	2.20 ± 0.013	8.4 ± 0.35	5.6 ± 0.085
AR7	64	5.59 ± 0.019	1.79 ± 0.011	7.3 ± 0.25	4.7 ± 0.212
AR8	63	7.32 ± 0.047	2.00 ± 0.015	8.7 ± 0.15	5.5 ± 0.110
AR9	64	7.11 ± 0.010	2.19 ± 0.010	8.8 ± 0.05	5.8 ± 0.245
AR10	57	5.10 ± 0.062	1.80 ± 0.034	7.0 ± 0.45	4.3 ± 0.021
AR11	53	3.11 ± 0.069	1.23 ± 0.011	5.9 ± 0.85	3.8 ± 0.125
AR12	57	5.78 ± 0.067	1.79 ± 0.032	7.9 ± 0.14	4.9 ± 0.211
AR13	54	5.61 ± 0.076	1.90 ± 0.021	7.8 ± 0.25	4.7 ± 0.745
AR14	53	3.15 ± 0.013	1.11 ± 0.012	5.5 ± 0.15	3.4 ± 0.236
AR15	59	5.36 ± 0.063	1.92 ± 0.056	7.6 ± 0.15	4.6 ± 0.045

Table 5. Buffering capacity, neutralizing capacity, resilience, FLT and TFT of raft forming tablets (n = 6).

Formulation code	pH After 4 min	pH After 20 min	Buffering capacity (meq)	Neutralizing capacity (meq)	Raft resilience (min)	FLT (s)	TFT (h)
AR1	4.1	5.4	11.5 ± 1.01	6.9 ± 0.57	>480	51	>8
AR2	4.2	5.5	11.0 ± 1.04	5.5 ± 0.49	>480	52	>8
AR3	5.5	6.7	15.7 ± 1.05	7.5 ± 0.31	>480	51	>8
AR4	3.5	4.2	10.3 ± 1.81	6.8 ± 0.55	>480	54	>8
AR5	4.6	5.6	13.9 ± 1.07	7.6 ± 0.10	>480	52	>8
AR6	4.4	5.2	11.5 ± 1.05	5.7 ± 0.49	>480	49	>8
AR7	3.2	4.6	10.6 ± 1.91	6.8 ± 0.23	>480	48	>8
AR8	4.2	5.8	12.5 ± 1.41	6.7 ± 0.26	>480	50	>8
AR9	3.8	4.9	11.2 ± 1.01	6.5 ± 0.56	>480	55	>8
AR10	5.7	6.9	14.7 ± 1.05	7.6 ± 0.12	>480	54	>8
AR11	4.1	5.0	10.90 ± 1.30	4.9 ± 0.49	>480	49	>8
AR12	4.6	5.2	13.69 ± 1.04	7.8 ± 0.16	>480	56	>8
AR13	5.0	6.3	12.10 ± 1.10	6.9 ± 0.59	>480	51	>8
AR14	5.3	6.5	10.20 ± 1.31	5.8 ± 0.49	>480	53	>8
AR15	3.4	4.3	12.70 ± 1.21	7.0 ± 0.34	>480	50	>8

Figure 2. Drug release profile of pantoprazole sodium sesquihydrate from alginate rafts (n = 6).

Figure 3. FTIR spectra of (A) PSS, (B) sodium alginate, (C) HPMC K100M and (D) alginate raft of optimized formulation AR9.

Figure 4. DSC thermograms of (A) PSS, (B) sodium alginate, (C) HPMC K100M and (D) tablet of optimized formulation AR9 and (E) alginate raft of optimized formulation AR9.

Figure 5. XRD of (A) PSS, (B) sodium alginate, (C) HPMC K100M and (D) tablet of optimized formulation AR9 and (E) alginate raft of optimized formulation AR9.