Microemulsion based intranasal delivery system for treatment of insomnia

Figures & data

Table 1.  Composition and Characterization of Diazepam, Lorazepam and Alprazolam Microemulsions^*.

Abbreviation	Formulation	O (%)	S (%)	CoS (%)	Co-solvent (%)	AQ (%)	Drug Content (%)	Globule Size (nm)	Zeta Potential (mV)	%Transmittance
DME	Diazepam Microemulsion	10	26.3	13.7	10	40	97.77	95.2	−0.209	99.03
LME	Lorazepam Microemulsion	10	26.3	13.7	10	40	98.31	141.7	−2.205	98.28
AME	Alprazolam Microemulsion	10	26.3	13.7	10	40	98.44	106.7	−0.111	99.25

^*O-oil phase (Capmul MCM); S-Surfactant (Tween 80); CoS-Co-surfactant (Captex 200P), Co-solvent (ethanol) and AQ-Aqueous Phase (distilled water).Microemulsions (DME, LME, AME) contain diazepam 15 mg/mL, lorazepam 6.2 mg/mL and alprazolam 1.6 mg/mL respectively.

Table 2.  Sleep pattern of Diazepam formulations (Misra et al).

	Control	DME	DMME	DS	DT
Onset of sleep (min)**	60 ± 10.0	10.5 ± 0.5	8.76 ± 0.40	18.33 ± 0.90	32.33 ± 2.88
RR (10 min)	+ve	+ve	−ve	+ve	+ve
RR (20 min)	+ve	−ve	N.C.^*	+ve	+ve
RR (30 min)	+ve	N.C.	N.C.	−ve	+ve
RR (40 min)	+ve	N.C.	N.C.	N.C.	−ve
SR (15 min)	+ve	−ve	−ve	+ve	+ve
SR (30 min)	+ve	N.C.	N.C.	−ve	+ve
SR (45 min)	+ve	N.C.	N.C.	N.C.	−ve
Duration of sleep (hr)^**	1.13 ± 0.16	6.6 ± 0.36	7.1 ± 0.17	5.66 ± 0.33	6.6 ± 0.36

^*N.C.-Not Checked as the sedation was confirmed.

^**Mean ± SD (n=3)

Figure 1.  The nasal mucosa treated with (A) PBS pH 6.4, (B) Blank microemulsion, and (C) Isopropyl alcohol.

Table 3.  Sleep pattern with various Lorazepam formulations.

	Control	LME	LMME	LS	LT
Onset of sleep (min)^**	47.66 ± 2.51	9.6 ± 0.65	6.65 ± 0.73	14.26 ± 0.74	29.33 ± 2.08
RR (10 min)	+ve	+ve	−ve	+ve	+ve
RR (20 min)	+ve	−ve	N.C.^*	−ve	+ve
RR (30 min)	+ve	N.C.	N.C.	N.C.	+ve
RR (40 min)	+ve	N.C.	N.C.	N.C.	−ve
SR (15 min)	+ve	−ve	−ve	+ve	+ve
SR (30 min)	+ve	N.C.	N.C.	−ve	+ve
SR (45 min)	+ve	N.C.	N.C.	N.C.	−ve
Duration of sleep (hr)^**	0.67 ± 0.03	6.5 ± 0.50	7.13 ± 0.16	5.76 ± 0.61	6.6 ± 0.36

^*N.C.-Not Checked as the sedation was confirmed.

^**Mean ± SD (n=3).

Table 4.  Sleep induction pattern with various Alprazolam formulations.

	Control	AME	AMME	AS	AT
Onset of sleep (min)^**	57.66 ± 32.50	11.60 ± 0.65	7.00 ± 1.00	15.26 ± 0.74	33.43 ± 3.86
RR (10 min)	+ve	+ve	−ve	+ve	+ve
RR (20 min)	+ve	−ve	N.C.^*	−ve	+ve
RR (30 min)	+ve	N.C.	N.C.	N.C.	+ve
RR (40min)	+ve	N.C.	N.C.	N.C.	−ve
SR (15min)	+ve	−ve	−ve	+ve	+ve
SR (30min)	+ve	N.C.	N.C.	−ve	+ve
SR (45min)	+ve	N.C.	N.C.	N.C.	−ve
Duration of sleep (hr)^**	1.50 ± 0.50	6.16 ± 0.29	6.76 ± 0.50	5.66 ± 0.35	6.63 ± 0.35

^*N.C.-Not Checked as the sedation was confirmed.

^**Mean ± SD (n=3).