Formulation development of celecoxib-cyclodextrin suspensions for ophthalmic delivery

Abstract

Celecoxib (CCB), a nonsteroidal anti-inflammatory drug (NSAID), could be beneficial in the treatment of age-related macular degeneration (AMD) and diabetic retinopathy (DR) through the inhibition of COX-2 enzyme. Currently, the several methods can deliver drugs to the back of the eye. i.e., oral, intravitreal injection, subconjunctival injection and topical. Among routes of administration, topical eye drop is non-invasive method and local effects. However, due to low aqueous solubility of CCB, it hampers ocular bioavailability. Thus, the aim of this study was to develop topical eye drop suspensions containing cyclodextrin (CD) and polymer delivering to the posterior segment of the eye. CDs, the solubilizer, i.e., alpha-CD, beta-CD, gamma-CD, HP-beta-CD and RM-beta-CD and mucoadhesive polymers i.e., hydroxypropylmethylcellulose (HPMC) chitosan and hyaluronic acid (HA) were used. The phase solubility profiles and CCB/CD complex characteristics were investigated. RM-beta-CD exhibited the greatest solubilizer among CDs tested. HPMC was the potential polymer to form ternary complex with CCB/RM-beta-CD which gave 11-folds complexation efficiency higher than that of its binary complex. The aggregate size of ternary complexes in solution were found in the range of 250 - 350 nm which could solubilize themselves resulting in increasing CCB solubility. The data obtained from FT-IR, DSC, PXRD and 1H-NMR indicated that there were interaction of CCB with CD as inclusion complex. The CCB eye drops formulations were prepared by unheated and heating method (sonication at the temperature of 70oC for 1 hour). The physicochemical and chemical characterizations, mucoadhesive properties and in-vitro permeation were determined. The physicochemical properties i.e., appearance, pH, osmolality and viscosity were in acceptable range. The particle sizes below 10 µm indicated possibly no irritation to the eye. The formulation containing HA showed the excellent mucoadhesive properties. The increasing of % CCB content in most cases by heat resulting in higher flux permeation through semipermeable membrane and through simulated artificial vitreous humor, especially the formulation containing RM-beta-CD and HA (0.5% w/v). Therefore, it may be a promising candidate as topical formulation which can deliver CCB to the posterior segment of eye to treat AMD and DR.