Abstract
The goal of this study was to develop and characterize an ion-activated in situ gel-forming estradiol (E2) solution eye drops intended for the prevention of age-related cataracts. Accordingly, in situ gelling eye drops were made using gellan gum as an ion-activated gel-forming polymer, polysorbate-80 as drug solubilizing agent, mannitol as tonicity agent, and combination of potassium sorbate and edetate disodium dihydrate (EDTA) as preservatives. The formulations were tested for the following characteristics: pH, clarity, osmolality, antimicrobial efficacy, rheological behavior, and in vitro drug release. Stability of the formulation was also monitored for 6 months at multiple storage conditions per ICH Q1A (R2) guidelines. The solution eye drops resulted in an in-situ phase change to gel-state when mixed with simulated tear fluid (STF). The gel structure formation was confirmed by viscoelastic measurements. Drug release from the gel followed non-fickian mechanism with 80% of drug released in 8 hr. The formulations were found to be clear, isotonic with suitable pH and viscoelastic behavior and stable at accelerated and long-term storage conditions for 6 months. In vitro results suggest that the developed formulation is suitable for further investigation in animal models to elucidate the ability of estrogen to prevent and delay cataracts.
Highlights
A cataract is defined as a clouding of the eye’s natural lens
Potassium sorbate and edetate disodium dihydrate (EDTA) were chosen as preservatives in the formulation as they were found to be compatible with other excipients in the formulation
EDTA binds to the essential minerals in the microbial cytoskeleton and disorganizes its assembly, thereby, enhancing the permeability of potassium sorbate resulting in a synergistic antimicrobial effect
Summary
The lens focuses the incident light on the retina to activate photoreceptors and cause vision. Due to the clouding of lens, the incident light is scattered causing blurred vision [1]. Among the 285 million who are visually impaired globally, 33% (about 95 million) of the cases are due to cataract [2, 3]. It occurs more frequently in older population (> 50 years old). In the US alone, the Center for Disease Control (CDC) estimated that 15 million Americans aged 65 years or older have a cataract in one or both eyes. By 2020, the estimated number of people aged 40 or older with cataracts is expected
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