Sustained Ocular Drug Delivery from a Temperature and pH Triggered Novel In Situ Gel System

Figures & data

TABLE 1 Combinations of chitosan/ Pluronic F-127 studied

Formulation (% w/v)	Pluronic F-127 (% w/v)	Chitosan	Gelling capacity
1	14	0.5	+++
2	14	0.25	+++
3	11	0.5	+++
4	11	0.25	+++
5	9	0.5	+++
6	9	0.25	+++
7	7	0.5	++
8	7	0.25	+

TABLE 2 Ingredients of the developed in situ gel formulation

Ingredients	Concentration (w/v)
Timolol maleate	0.25%
Pluronic F-127	9.0%
Chitosan	0.25%
NaCl	q.s.
Methylparaben	0.1%
Water (q.s.)	100%

TABLE 3 Physicochemical properties of the developed in situ gel formulation

Parameter	Inference
Clarity	Clear solution
pH	6.0–6.2
Osmolarity	298–308 mOsmol
Gelation pH	6.9–7.0
Gelation temperature	35–37°C
Viscosity (at 25°C and pH 6.0–6.2)	87 ± 6 cps
Viscosity (at 37°C and pH 7.2–7.4)	2973 ± 110 cps

Values are expressed as mean ± S.D. (n = 6).

TABLE 4 Scoring chart for HET-CAM test

Effect	Scores	Inference
No visible hemorrhage	0	Non irritant
Just visible membrane discoloration	1	Mild irritant
Structures are covered partially due to membrane discoloration or hemorrhage	2	Moderately irritant
Structures are covered totally due to membrane discoloration or hemorrhages	3	Severe irritant

FIG. 1 In vitro release drug release profile from developed in situ gel system. Values are expressed as mean ± S.D. (n = 6)

FIG. 2 In vitro drug transcorneal permeation profile from different formulations. Values are expressed as mean ± S.D. (n = 6)

TABLE 5 Recorded scores in HET-CAM test

	Scores time (in minutes)
Formulation	0	5	15	30	60	120	240	480	1440
In situ gelling sytem
Egg 1	0	0	0	0	0	1	1	1	1
Egg 2	0	0	0	0	0	0	0	1	1
Egg 3	0	0	0	0	0	0	0	0	0
Mean	0	0	0	0	0	0.33	0.33	0.67	0.67
Normal saline control
Egg 1	0	0	0	0	0	0	0	0	0
Egg 2	0	0	0	0	0	0	0	0	0
Egg 3	0	0	0	0	0	0	0	0	0
Mean	0	0	0	0	0	0	0	0	0

FIG. 3 Dynamic scintigraphic images of rabbit's eye up to 20 min after administration of (a) plain drug solution and (b) developed in situ gel system.

FIG. 4 Time-activity curve shows precorneal drainage of various formulations.

FIG. 5 Static whole body image after 2 h administration of (a) plain drug solution and (b) developed in situ gel system.