Abstract
Objective: The present study emphasizes the synthesis, optimization, and evaluation of ocular in-situ gel for ophthalmic drug delivery against conjunctivitis.
 Methods: Pre-formulation studies on the drug and polymers were carried out, which included the study of various physicochemical properties of the drug and drug-polymer compatibility studies. The 12 different formulations were further pre-optimised by Taguchi method for determining the number of influential factors. Furthermore, the formulation optimization was done by using ‘Box–Behnken’ design (BBD) (Design expert 10 software) for assessing the effect of formulation variables on product characteristics viz. viscosity, gelation temperature (GT), and mean release time (MRT). About 13 suggested runs of the experiment were carried out and formulations were optimised. Finally, three batches of the optimised formulation were prepared and evaluated for in vitro drug release, isotonicity of formulation, anti-microbial potential, ocular irritancy, and accelerated stability testing.
 Results: Pre-formulation study confirmed the purity, solubility, and compatibility of drug measured by λmax, partition coefficient, stability study, and Fourier-transform infrared spectroscopy (FTIR) analysis. Taguchi screening method suggested about 12 different formulations and 3 most prominent influential factors including viscosity, GT, and drug release. 13 different formulations designed based on ‘BBD’ method were further optimised by considering the most influential factors suggested by Taguchi screening. The in vitro evaluation of the optimised formulation gave satisfactory results in terms of drug release, and anti-microbial activity. It was found to be isotonic with no ocular irritancy. Further, the preparation immediately transformed from sol to gel upon administration into cul-de-sac region of the eye due to multi-dimensional approaches utilised for in-situ gel formation namely temperature change Pluronic, ion sensitivity due to Gellan-gum, pH sensitivity because of Carbopol.
 Conclusion: The optimised in-situ gelling ocular drug formulation showed promising potency for ophthalmic drug delivery with no irritancy due to the multifactorial mechanism.
Highlights
In-situ forming formulation is an advanced system of drug delivery in which in-situ phase transition occurs on the surface at the site of application
As desired the prepared formulation was liquid at non-physiological conditions and was transformed to gel form under physiological conditions
Preformulation studies established the authenticity of the drug sample and its compatibility with the polymers used in the formulation
Summary
In-situ forming formulation is an advanced system of drug delivery in which in-situ phase transition occurs on the surface at the site of application. The time required to form gel is significantly large in case of Gellan-gum, which sometimes leads to oozing out of the instilled formulation due to reflex tearing before it can gel. These formulations dependent on the singular mechanism are more susceptible to failure. The different sets of combined polymers in miscellaneous concentration was used to the developed formulation and optimised by design expert software (Design-Expert® 10 software) for utmost release of the drug, apposite viscosity at ocular site and optimised gelation temperature (GT). The ocular irritancy was observed in the rabbit’s eye for 14 d
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