Design, formulation and evaluation of carboxy methyl tamarind based in situ gelling ophthalmic drug delivery system of dorzolamide hydrochloride

Introduction: A major problem in ocular therapeutics is the attainment of optimum drug concentration at the site of action, which is compromised mainly due to precorneal loss resulting in only a small fraction of the drugs being absorbed. The effective dose administered may be altered by increasing the retention time of medication into the eye by using in situ gel forming polymeric systems. Materials and Methods: In the present investigation, an attempt has been made to design, formulate, and evaluate in situ gelling-based ophthalmic drug delivery system dorzolamide hydrochloride to enhance the precorneal retention and to improve the ocular bioavailability. In situ gel formulations are designed using carboxy methyl tamarind, a polysaccharide, was used with other natural polymers such as xanthan gum, gellan gum, and sodium alginate. The in situ gel formulations were characterized for physicochemical characters, namely physical appearance, pH measurement, gelling capacity, drug content estimation, rheological study, effect of sterilization on the viscosity, in vitro diffusion study mucoadhesive strength, sterility testing, preservative efficacy testing, isotonicity testing, and ocular irritation testing. Results and Discussion: The developed formulations exhibited sustained release of drug from formulations over a 9 h period, thus increased residence time of the drug. Effect of sterilization was studied to check the rigors of sterilization on the viscosity of the formulations. In the study, two optimized formulations were selected on the basis of ability to form good gelling with increased viscosity with a slow and prolong in vitro drug release pattern. The formulations were found to be nonirritating with no ocular damage or abnormal clinical signs observed. Conclusion: Therefore, the developed ophthalmic in situ gel by virtue of its prolonged corneal residence time and sustained drug release could be considered a viable alternative to the conventional eye drops formulation in achieving enhanced bioavailability

Formulation and Evaluation of a Novel In Situ Gum Based Ophthalmic Drug Delivery System of Linezolid

Abstract A major problem in ocular therapeutics is the attainment of optimal drug concentration at the site of action, which is compromised mainly due to precorneal loss resulting in only a small fraction of the drug being ocularly absorbed [1]. The effective dose administered may be altered by increasing the retention time of medication into the eye by using in situ gel forming systems. The aim of the present investigation is to prepare and evaluate novel in situ gum based ophthalmic drug delivery system of linezolid. Hydroxypropyl guar (HPG) and xanthum (XG) were used as gum with the combination of hydroxyethyl cellulose (HEC), carbopol (CP), and sodium alginate as viscosity enhancing agents. Suitable concentrations of buffering agents were used to adjust the pH to 7.4. All the formulations were sterilized in an autoclave at 121°C for 15mins. The formulations were evaluated for clarity, pH measurement, gelling capacity, drug content estimation, rheological study, in vitro diffusion study, antibacterial activity, isotonicity testing, eye irritation testing. The developed formulations exhibited sustained release of drug from formulation over a period of 6hr thus increasing residence time of the drug. The optimized formulations were tested for eye irritation on albino rabbit (male) using the Draize test protocol with crossover studies. The formulations were found to be non-irritating with no ocular damage or abnormal clinical signs to the cornea, iris or conjunctiva observed. Thus these in situ gelling systems containing gums may be a valuable alternative to the conventional systems

Design, formulation, and evaluation of in situ gelling ophthalmic drug delivery system comprising anionic and nonionic polymers

Background: The significant problem in the ocular drug delivery is the attainment of optimal drug concentration at the site of action. Development of therapeutic agents that require repeated long-term administration is a driver for the sustained release drug delivery systems, to result in less frequent dosing, and less invasive techniques. Therefore, to overcome the anatomical barriers and ocular bioavailability constrains, a novel drug delivery system in situ gels have been developed. Materials and Methods: The in situ gelling system comprises gellan gum, an anionic polymer responsible for the ionic gelation. Methylcellulose a nonionic polymer contributes for the viscosity and gels at the body temperature. The formulation was characterized for clarity, appearance, pH, gelation time, drug content estimation, rheological evaluation, effect of sterilization on the viscosity, in vitro diffusion study, isotonicity testing, and ocular irritation testing. Results and Discussion: The developed formulations exhibited sustained release of drug over 8 h thereby increasing residence time of the drug. Sterilization caused no effect on viscosity of the formulation. Optimized formulation was selected on the bases of ability to form instant gel and with increased viscosity of gel with a slow and prolonged in vitro drug release pattern. The optimized formulation was found to be nonirritating with no ocular damage or abnormal clinical signs to the cornea, iris, and conjunctiva. Conclusion: Hence, the developed ophthalmic in situ gel by virtue of its prolonged corneal residence time and sustained drug release could be considered a viable alternative to the conventional eye drops in achieving enhanced bioavailability