Biodegradable Ocular Inserts for Sustained Delivery of Brimonidine Tartarate: Preparation and In Vitro/In Vivo Evaluation

Abstract

The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. Therefore, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglaucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K-90 (PVP K-90) as film-forming polymer blended with different viscosity grades of bioadhesive polymers namely hydroxypropyl methycellulose, carbopol, sodium alginate, and chitosan. The prepared ocular inserts were evaluated for various physicochemical parameters, swelling behavior, and in vitro release patterns. Sodium alginate-based ocular inserts revealed the most sustainment in drug release (99% at 6 h), so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The obtained in vitro release results for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP K-90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure (IOP) lowering effect when inserted in albino rabbits eyes showed superior sustainment effect compared with that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one-side-coated ocular insert showed more IOP lowering effect compared with that of its non-coated or dual-side-coated counterpart.

Ophthalmic Drug Dosage Forms: Characterisation and Research Methods

“…In specified time intervals, inserts are taken out, dried with filter paper, and weighed once more. The procedure is repeated until the moment when mass growth is not observed anymore [21, 78, 85]. The degree to which the liquid is taken up, called the swelling index, is calculated from the formula $\begin{array}{c}\text{Swelling index}=\left[\frac{\left(W_t-W_{\mathrm{0}}\right)}{W_{\mathrm{0}}}\right]\times \mathrm{100},\end{array}$ where W 0 is the initial sample weight and W t is the sample weight at t time [21].…”

Assessment of alkoxylphenacyl-based polycarbonates as a potential platform for controlled delivery of a model anti-glaucoma drug

“…The sustained release could be attributed to multifaceted mechanisms involving combination of hydrolytic degradation and micropore formation/growth that most likely resulted in microchannels within the microfilm matrix. Overall, the potential of AP-PCL microfilms to achieve prolonged release of BRT is attractive for a chronic ocular disorder like glaucoma as reported in earlier studies (20)(21)(22). Ongoing studies in our laboratory are considering the effects of various parameters on drug release from AP-PCL microfilms, these include: AP-PCL copolymer composition, drug loading, and microfilm preparation method.…”

Chitosan Mucoadhesive Buccal Films: Effect of Different Casting Solvents on Their Physicochemical Properties

“…Besides, swelling of the polymer is necessary for initiating mucoadhesion [15]. The swelling index of medicated mucoadhesive films was determined using two aqueous vehicles; namely, distilled water and simulated saliva solution (2.38g NaR 2RHPOR4R, 0.19g KHR 2RPOR4R and 8g NaCl/liter of distilled water adjusted with phosphoric acid to pH 6.8±0.05) [16].…”