Stimuli-sensitive hydrogels: a novel ophthalmic drug delivery system.
BACKGROUND
Stimuli-sensitive hydrogels are three-dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids on stimulation, such as pH, temperature and ionic change.


OBJECTIVE
To develop hydrogels that are sensitive to stimuli, i.e. pH, in the cul-de-sac of the eye for providing a prolonged effect and increased bioavailability with reduction in frequency of administration.


METHODS
Hydrogels were formulated by using timolol maleate as the model drug, polyacrylic acid as the gelling agents, hydroxyl ethyl cellulose as the viscolizer and sodium chloride as the isotonic agent. Stirring of ingredients in pH 4 phosphate buffer at high speed was carried out. The dynamic dialysis technique was used for drug release studies. In vivo study for reduction in intraocular pressure was carried out by using albino rabbits.


METHODS
Drug release studies data were used for statistical analysis in first-order plots, Higuchi plots and Peppas exponential plots. Student t-test was performed for in vivo study.


RESULTS
Viscosity of the hydrogel increases from 3.84 cps to 9.54 cps due to change in pH 4 to pH 7.4. The slope value of the Peppas equation was found to be 0.3081, 0.3743 and 0.2964. Up to 80% of drug was released in an 8 h drug release study. Sterile hydrogels with no ocular irritation were obtained.


CONCLUSIONS
Hydrogels show increase in viscosity due to change in pH. Hydrogels were therapeutically effacious, stable, non-irritant and showed Fickian diffusion. In vivo results clearly show a prolonged reduction in intraocular pressure, which was helpful for reduction in the frequency of administration.
Singh
Vinod
V
Department of Pharmaceutics & Pharmacology, SBS PG Institute of Biomedical Sciences and Research, Dehradun, Uttarakhand, India. vinod.panipat@gmail.com
Bushetti
S S
SS
Appala
Raju
R
Shareef
Adil
A
Imam
Syed S
SS
Singh
Mamta
M
D000818:Animals; D016503:Drug Delivery Systems; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D013999:Timolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014783:Viscosity
D020100:Hydrogels; D009883:Ophthalmic Solutions; D013999:Timolol