Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery

Abstract

The objective of the present study is to evaluate the utility of melt-cast, topical, ocular inserts for delivery of drugs with different physicochemical properties. The model drugs tested include indomethacin (IN), ciprofloxacin Hydrochloride (CIP) and prednisolone sodium phosphate (PSP). Melt-cast method was used to fabricate ophthalmic inserts. Poly (ethylene oxide) N10, a semi-crystalline thermoplastic polymer (PE0 N10; Mol.wt: 100 kDa) was used as the matrix forming material. Polymeric insert units (4 × 2 × 0.2 mm) with a 10% w/w drug load were tested for in vitro release, transmembrane permeability and in vivo ocular tissue distribution. Marketed ophthalmic solutions were used as control solutions. Drug content in all the formulations ranged between 93 –102% of the theoretical value. Transmembrane flux of IN, PSP and CIP were enhanced by ~3.5-folds, ~3.6-folds and ~2.9-folds, respectively, from the polymeric inserts when compared to the control formulations, post 3 h. Moreover, ocular inserts generated significantly higher drug levels in all the ocular tissues, including the retina-choroid, when compared to their control formulations. The melt-cast ophthalmic inserts show promise as an effective noninvasive ocular drug delivery platform, which will be highly beneficial in the intervention and treatment of a wide variety of ocular complications.

<p>Ocular Inserts of Voriconazole-Loaded Proniosomal Gels: Formulation, Evaluation and Microbiological Studies</p>

“…3 Alongside various protective ocular barriers such as; lacrimation, reflux blinking and nasolacrimal drainage, short pre-corneal residence and deprived corneal penetrability are the vital dynamics responsible for reducing the bioavailability (<5%) of instilled conventional ophthalmic preparations. 4,5 Various nano-strategies such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), polymeric nanoparticles, micelles, nanoemulsions, liposomes besides noisomes and phospholipid have been succeeded in improving the transcorneal drug penetrability. 6,7 In ophthalmic vesicular drug delivery systems comprising liposomes and noisomes, mutual enhancement of the bioavailability as well as drug accumulation is manifested via encapsulation of the drug in lipid vesicles allowing its penetration across cell membrane and therefore, prolonging the extent of action at the corneal surface.…”

“…Alongside various protective ocular barriers such as; lacrimation, reflux blinking and nasolacrimal drainage, short pre-corneal residence and deprived corneal penetrability are the vital dynamics responsible for reducing the bioavailability (<5%) of instilled conventional ophthalmic preparations. 4 , 5 …”

Gellan Gum BasedSol-to-GelTransforming System of Natamycin Transfersomes Improves Topical Ocular Delivery

“…Rapid clearance from the precorneal space and limited corneal permeability of the drugs from conventional dosage forms are responsible for low ocular bioavailability (,5%) (Urtti, 2006;Ali and Byrne, 2008;Huang et al, 2018). Several formulation strategies such as ocular hydrogels, topical ocular inserts, and ointments have demonstrated increased drug residence in the cul-de-sac (Fathi et al, 2015;Jain et al, 2016;Adelli et al, 2017;Balguri et al, 2017). Lately, in situ hydrogels have been demonstrated to enhance the precorneal residence of topically instilled pharmaceutical compounds, and thereby increase the ocular bioavailability (Mundada and Avari, 2009;Sheshala et al, 2015).…”

Recent Advances in Topical Nano drug-delivery Systems for the Anterior Ocular Segment

“…Thus, formulations that settle in the conjunctival sac, and is not easily dispersed across the ocular surface, may utilize the conjunctival-scleral pathway more efficiently. Some recent publications using topical films/inserts seem to utilize this route of entry into the deeper ocular tissues from the surface [36].…”