Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride

Abstract

Abstract. Dilutable nanoemulsions are potent drug delivery vehicles for ophthalmic use due to their numerous advantages as sustained effect and high ability of drug penetration into the deeper layers of the ocular structure and the aqueous humor. The aim of this article was to formulate the antiglaucoma drug dorzolamide hydrochloride as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Thirty-six systems consisting of different oils, surfactants, and cosurfactants were prepared and their pseudoternary-phase diagrams were constructed by water titration method. Seventeen dorzolamide hydrochloride nanoemulsions were prepared and evaluated for their physicochemical and drug release properties. These nanoemulsions showed acceptable physicochemical properties and exhibited slow drug release. Draize rabbit eye irritation test and histological examination were carried out for those preparations exhibiting superior properties and revealed that they were nonirritant. Biological evaluation of dorzolamide hydrochloride nanoemulsions on normotensive albino rabbits indicated that these products had higher therapeutic efficacy, faster onset of action, and prolonged effect relative to either drug solution or the market product. Formulation of dorzolamide hydrochloride in a nanoemulsion form offers, thus, a more intensive treatment of glaucoma, a decrease in the number of applications per day, and a better patient compliance compared to conventional eye drops.

Ocular emulsions and dry eye: a case study of a non-biological complex drug product delivered to a complex organ to treat a complex disease

“…Allergan did not conduct in vitro drug release testing on these emulsions as currently no in vitro release test exists for RESTASIS ® , and none has been established or validated for an ophthalmic emulsion. Common methods proposed in the literature [20][21][22] for testing in vitro drug release for disperse systems, such as sample and separate technique, membrane diffusion technique (dialysis sac or diffusion cells), and continuous fl ow-through technique are not applicable to RESTASIS ® due to a variety of reasons, such as: (a) complex nature of the emulsion; (b) poor solubility of cyclosporine in relevant dissolution media; (c) diffi culties in separating dissolved/released cyclosporine from micellar or oil solubilized portion; (d) similarity of molecular weights of cyclosporine with other excipients in the formulation; and (e) lack of evidence to show correlation of in vitro drug release testing to clinical performance as it cannot simulate the complex drug release and delivery to receiving compartments. In a publication [23] by Rahman et al, 2014, the researchers were unable to use in vitro drug diffusion to discriminate cyclosporine emulsions manufactured utilizing different processes -even when these emulsions showed signifi cant differences in other parameters, such as globule size and viscosity.…”

Improved Corneal Toxicity and Permeability of Tranilast by the Preparation of Ophthalmic Formulations Containing Its Nanoparticles

“…However, the frequent administration of drugs can cause corneal damage as well as undesirable side effects resulting from the systemic absorption of drugs through the nasolacrimal duct 4,5 . Therefore, it is very important to increase the effectiveness of drugs by enhancing their bioavailability 6 . In order to overcome these problems and increase ocular drug bioavailability, several strategies including the preparation of viscous solutions, micro/ nanoparticles and hydrogels have been developed and in-vestigated 1, 4, 7 10 .…”

Development of Curcumin Based Ophthalmic Formulation

“…Systems with low viscosity allow good tolerance with little blinking pain. In contrast, systems with enhanced viscosity, although less tolerant, induce an increase in ocular contact time by reducing the drainage rate and, as a consequence, improve bioavailability .Viscosity of eye drops is required to be not higher than 20.0 cps (Ammar et al, 2009).…”