Ultrahigh verapamil-loaded controlled release polymeric beads using superamphiphobic substrate: D-optimal statistical design, in vitro and in vivo performance

Figures & data

Table 1. Composition of VP-loaded polymeric beads adopting D-optimal design with their resultant dependent variables.

System Number	A: Polymer Type	B: Eudragit RS100 content (% w/w)^a	C: Drug load (mg)	EE %± SD (% w/w)	Q 3hr ± SD (% w/w)	Q 6hr ± SD (% w/w)	Q 12hr ± SD (%w/w)
S1	PLGA 5004	0.00	109.40	98.02 ± 0.40	21.68 ± 11.40	31.72 ± 15.24	42.58 ± 15.10
S2		0.00	109.40	98.95 ± 0.14	17.50 ± 07.66	25.59 ± 09.60	37.53 ± 12.36
S3		10.41	40.00	93.41 ± 0.13	04.78 ± 01.11	04.79 ± 03.73	11.35 ± 02.62
S4		12.50	97.66	97.61 ± 0.03	20.18 ± 09.47	29.72 ± 12.76	40.27 ± 15.52
S5		14.57	160.00	98.11 ± 0.38	36.50 ± 12.04	49.36 ± 13.82	60.80 ± 12.13
S6		14.57	160.00	97.16 ± 0.42	46.64 ± 12.75	59.94 ± 15.11	73.07 ± 16.42
S7		21.88	40.00	92.94 ± 1.85	19.70 ± 03.84	19.27 ± 01.20	28.11 ± 00.56
S8		25.00	90.53	92.31 ± 1.79	42.15 ± 10.87	52.46 ± 10.09	64.72 ± 07.38
S9	PLGA 5010	0.00	40.00	96.68 ± 0.34	00.65 ± 00.58	02.73 ± 01.11	05.46 ± 05.59
S10		0.00	160.00	99.19 ± 0.03	32.14 ± 17.12	47.04 ± 21.13	65.35 ± 19.67
S11		0.00	160.00	99.30 ± 0.38	29.16 ± 05.70	44.27 ± 07.21	58.37 ± 05.89
S12		12.50	66.43	98.15 ± 0.40	06.65 ± 02.04	13.08 ± 03.55	21.98 ± 05.12
S13		12.50	130.10	98.88 ± 0.06	23.35 ± 00.52	35.93 ± 05.94	54.66 ± 09.53
S14		25.00	40.00	96.36 ± 0.32	22.35 ± 05.88	17.03 ± 02.26	27.39 ± 00.00
S15		25.00	160.00	97.29 ± 0.98	36.53 ± 05.86	55.62 ± 06.59	74.79 ± 05.97
S16	PCL	0.00	40.00	96.59 ± 0.31	39.25 ± 00.69	46.62 ± 00.73	61.08 ± 05.22
S17		0.00	40.00	96.30 ± 1.87	34.20 ± 00.39	37.56 ± 07.38	53.82 ± 08.97
S18		0.00	160.00	98.35 ± 0.06	52.79 ± 00.36	65.50 ± 00.80	75.36 ± 01.26
S19		0.00	160.00	98.94 ± 0.34	50.08 ± 04.94	61.01 ± 06.45	73.69 ± 06.89
S20		12.50	100.00	97.82 ± 0.64	47.79 ± 02.14	60.67 ± 01.68	69.65 ± 02.02
S21		23.05	59.82	97.50 ± 0.67	50.32 ± 05.24	59.42 ± 03.73	71.37 ± 03.54
S22		25.00	160.00	98.86 ± 0.08	72.69 ± 03.06	86.94 ± 05.99	95.90 ± 02.58

^aPercent out of total polymer weight (150 mg).

Figure 1. SEM images showing (A) the prepared superamphiphobic substrate with micro-length hierarchical structure at different magnification powers (800, 3000, and 6000 x, respectively) and (B) the optimized VP-loaded PCL based bead system (“OS”) with different magnification powers (120× and 1000×).

Figure 2. (A) Contact angles and percentages of the trapped air for different liquids on the superamphiphobic treated aluminum surface compared to the contact angles of the untreated surface; While (B) optical images of contact angles for water (B1), olive oil (B2), and the optimized VP-loaded PCL based solution (B3).

Figure 3. Line plot presenting the effect of the variables on: entrapment efficiency (EE%): Effect of (A) main polymer type, (B) Eudragit RS100 content, (C) drug load, and (D) two factor interaction between polymer type and Eudragit RS100 content. In-vitro release (Q12hr): Effect of (E) main polymer type, (F) Eudragit RS100 content, and (G) drug load.

Figure 4. (A) Release profiles of VP from the optimized system (“OS”) compared to the market product (Isoptin^®); while (B) shows the FTIR spectrum of pure VP (B1), PCL (B2), drug free PCL beads (B3), and optimized VP-loaded PCL beads (B4).

Figure 5. Mean VP plasma concentration- time curve and mean pharmacokinetic parameters of VP following oral administration of Isoptin^® and VP-loaded PCL beads (“OS”) filled capsules to six albino rabbits.