Novel ionically crosslinked acrylamide-grafted poly(vinyl alcohol)/sodium alginate/sodium carboxymethyl cellulose pH-sensitive microspheres for delivery of Alzheimer's drug donepezil hydrochloride: Preparation and optimization of release conditions

Figures & data

Figure 1. Possible grafting reaction of AAm onto PVA.

Table I. Elemental analysis, AAm % of PVA-g-PAAm, grafting efficiency (%), intrinsic viscosity, and viscosity average molar mass of polymers.

Polymer	Reaction time (h)	% N	% C	% H	AAm % of PVA-g-PAAm	Grafting efficiency (%)	[η]
PVA-g-PAAm	3	6.76	51.32	8.17	34.32	99.8	1.1268	69,641
PVA	–	–	–	–	–	–	0.9266	50,266

Figure 2. (I) FTIR results of PVA (A), PVA-g-PAAm (B); (II) FTIR results of NaAlg (A), NaCMC (B), PVA (C), DP (D), empty microspheres (E), DP-loaded microspheres (F).

Figure 3. (I) DSC thermograms of PVA (A), PVA-g-PAAm (B); (II) DSC thermograms of DP (A), DP-loaded microspheres (B), and empty microspheres (C).

Figure 4. XRD diffractograms of DP (A), empty microspheres (B), DP-loaded microspheres (C).

Figure 5. SEM photographs of empty PVA-g-PAAm/NaAlg/NaCMC microsphere (C_8,0)x5000 (A), DP-loaded PVA-g-PAAm/NaAlg/NaCMC microsphere (C₈)x4500 (B).

Table II. Preparation conditions, entrapment efficiency (%), microsphere yield (%), and microsphere size (μm) of the DP-loaded microspheres.

Code	Crosslinker type	PVA-g-PAAm /NaAlg/ NaCMC (w/w/w)	Crosslinker concentration (%) (w/v)	Crosslinking time (min)	Drug/polymer ratio (w/w)	Entrapment efficiency (%)	Microsphere yield (%)	Microspheres size (μm)
D1	AlCl3	1/2/1	7.0	30	1/4	20.27 ± 1.42	99.13 ± 1.49	97.50 ± 2.50
E1	ZnCl2	1/2/1	7.0	30	1/4	23.31 ± 1.32	81.04 ± 4.24	80.11 ± 1.83
F1	CaCl2	1/2/1	7.0	30	1/4	40.39 ± 3.13	72.89 ± 2.49	68.02 ± 0.53
G1	GA	1/2/1	7.0	30	1/4	26.08 ± 0.67	50.65 ± 1.90	123.53 ± 0.40
C1	FeCl3	1/2/1	7.0	30	1/4	84.77 ± 1.20	76.05 ± 2.81	88.33 ± 1.52
C2	FeCl3	2/2/1	7.0	30	1/4	74.39 ± 2.24	71.65 ± 1.07	88.61 ± 1.27
C3	FeCl3	3/2/1	7.0	30	1/4	75.38 ± 0.56	69.53 ± 1.02	42.92 ± 1.19
C4	FeCl3	1/2/1	3.0	30	1/4	73.72 ± 1.73	66.93 ± 2.21	58.33 ± 2.88
C5	FeCl3	1/2/1	5.0	30	1/4	82.40 ± 3.89	74.28 ± 3.99	76.33 ± 1.52
C6	FeCl3	1/2/1	10.0	30	1/4	86.46 ± 3.96	> 100	73.33 ± 3.33
C7	FeCl3	1/2/1	7.0	15	1/4	75.68 ± 0.34	67.83 ± 1.40	94.17 ± 2.20
C8	FeCl3	1/2/1	7.0	60	1/4	69.61 ± 0.88	58.21 ± 0.41	57.64 ± 3.23
C9	FeCl3	1/2/1	7.0	30	1/2	36.64 ± 3.60	50.28 ± 0.25	90.83 ± 3.53
C10	FeCl3	1/2/1	7.0	30	1/8	98.74 ± 2.31	88.82 ± 0.66	85.83 ± 3.81

Figure 6. Effect of crosslinker type on the DP release. PVA-g-PAAm/NaAlg/NaCMC: 1/2/1, d/p: 1/4, exposure time to crosslinker: 30 min, concentration of crosslinker: 7%.

Table III. ESD of the empty microspheres.

Code	Water	pH 1.2	pH 6.8	pH 7.4
C1,0	24.72 ± 0.59	61.99 ± 0.75	477.22 ± 2.95	718.39 ± 5.57
E1,0	61.33 ± 0.31	45.73 ± 0.49	299.44 ± 4.56	440.61 ± 1.04
F1,0	152.33 ± 4.51	91.07 ± 0.17	eroded	eroded
G1,0	24.73 ± 2.36	19.84 ± 3.17	38.31 ± 2.87	48.91 ± 1.57
C2,0	57.29 ± 2.98	201.16 ± 1.20	712.13 ± 1.32	862.33 ± 1.52
C3.0	71.10 ± 0.70	219.53 ± 1.80	747.4 ± 1.44	896.69 ± 1.23
C4,0	29.02 ± 1.70	66.49 ± 3.24	782.67 ± 2.82	716.66 ± 7.32
C5,0	26.87 ± 0.63	65.40 ± 1.55	762.03 ± 1.65	712.03 ± 2.84
C6,0	22.55 ± 1.02	60.48 ± 1.93	352.83 ± 1.71	525.21 ± 1.20
C7,0	156.43 ± 1.69	357.40 ± 1.44	492.53 ± 2.33	856.96 ± 6.37
C8,0	35.68 ± 2.18	62.92 ± 3.60	328.02 ± 2.07	495.84 ± 0.89

Figure 7. Effect of PVA-g-PAAm/NaAlg/NaCMC ratio on the DP release. d/p: 1/4, exposure time to FeCl₃: 30 min, concentration of FeCl₃: 7%.

Figure 8. (I) Effect of FeCl₃ concentration on DP release. PVA-g-PAAm/NaAlg/NaCMC ratio: 1/2/1, d/p: 1/4, exposure time: 30 min; (II) Effect of exposure time to FeCl₃ on DP release. PVA-g-PAAm/NaAlg/NaCMC ratio: 1/2/1, d/p: 1/4, concentration of FeCl₃: 7%.

Figure 9. Effect of d/p ratio on DP release. PVA-g-PAAm/NaAlg/NaCMC ratio: 1/2/1, concentration of FeCl₃: 7%, exposure time to FeCl₃: 30 min.

Table IV. D, k, n, r values calculated from Eqs. (6) and (7).

Code	D × 10^12 (cm^2/s)	k (min^− n)	n	r	Diffusion mechanism
C1	2.67	0.1380	0.682	0.9732	Anomalous transport
D1	2.07	0.1325	0.437	0.9262	Fickian transport
E1	2.38	0.0848	0.706	0.9911	Anomalous transport
F1	1.50	0.0960	0.626	0.9792	Anomalous transport
G1	0.02	0.0013	0.950	0.9831	Anomalous transport
C2	2.87	0.1173	0.663	0.9790	Anomalous transport
C3	30.39	0.1453	0.845	0.9987	Anomalous transport
C4	3.28	0.1356	0.869	0.9992	Anomalous transport
C5	3.24	0.1349	0.729	0.9838	Anomalous transport
C6	1.72	0.1754	0.544	0.9426	Anomalous transport
C7	4.54	0.1235	0.766	0.9896	Anomalous transport
C8	0.07	0.0138	1.086	0.9790	Case II
C9	3.48	0.0329	1.005	0.9986	Case II
C10	1.64	0.0021	1.685	0.9804	Case II