Long-term sustained release Poly(lactic-co-glycolic acid) microspheres of asenapine maleate with improved bioavailability for chronic neuropsychiatric diseases

Figures & data

Table 1. The variables and ranges used in the experimental study.^a.

Cp (mg/mL)	Rd/p	CE (wt%)	SE (r/min)	TE (min)	Ro/w	SEva (r/min)	TEva (min)
75–200	1:10–1:1	0.50–2.00	400–700	5–20	1:5–1:20	200–400	5–7

^aC_p: polymer concentration; R_d/p: the ratio of drug to polymer; C_E: emulsifier concentration; S_E: emulsification speed; T_E: emulsification time; R_o/w: the ratio of oil to water; S_Eva: evaporation speed; T_Eva, evaporation time.

Table 2. Summary of ASM-PLGA microspheres prepared by different techniques.

Types	Encapsulation efficiency (%)	Drug loading (%)	Particle size (μm)	Span
ASM-PLGA-ESE	80.06	13.29	50.61	0.88
ASM-PLGA-SPG	91.36	15.23	66.07	0.66
ASM-PLGA-M	96.91	16.16	45.02	0.17

Table 3. The variables and ranges used in the experimental study^a.

Cp (mg/mL)	Rd/p	CE (wt%)	P (KPa)	V (mL)	S (r/min)
25–75	1:10 to 1:2	0.50–2.00	4–12	2.5–7.5	200–400

^aC_p: polymer concentration; R_d/p: the ratio of drug to polymer; C_E: emulsifier concentration; P: extraction pressure; V: Fill volume; S: stirring speed.

Scheme 1. Schematic of the synthetic approach for the PLGA microspheres. PVA, poly (vinyl alcohol); ASM, asenapine maleate; PLGA, poly (lactic-co-glycolic acid).

Table 4. The variables and ranges used in the experimental study^a.

Cp (mg/mL)	CE (wt%)	Sd (μL/min)	Sc (μL/min)
25–100	0.50–2.00	5–15	50–250

^aC_p: polymer concentration; C_E: emulsifier concentration; S_d: speed of dispersed phase; S_c: speed of continuous phase.

Figure 1. The SEM images of (A) ASM-PLGA-ESE, (B) ASM-PLGA-SPG, (C) ASM-PLGA-M.

Figure 2. (A) XRD diffractograms and (B) DSC thermograms of ASM, PLGA, as well as ASM-PLGA microspheres.

Figure 3. ASM accumulated release from different PLGA microspheres in vitro.

Figure 4. The degradation process of ASM-PLGA-M obtained by SEM images.

Figure 5. Plasma concentration-time curve of ASM-PLGA-M microspheres following intramuscular administration in beagles.

Table 5. The pharmacokinetic parameters of ASM-PLGA-M.

Parameter	1	2	3	Mean ± SD
AUC0-∞ (ng·mL^-1·d)	418.67	354.18	375.09	406.13 ± 26.86
MRT0-∞ (d)	15.01	13.16	13.88	14.02 ± 0.76
Cmax (ng·mL^-1)	58.53	42.68	35.58	45.60 ± 9.59
Tmax (d)	1	1	1	1