Solubility, stability, physicochemical characteristics and in vitro ocular tissue permeability of hesperidin: a natural bioflavonoid.
OBJECTIVE
Hesperidin holds potential in treating age-related macular degeneration, cataract and diabetic retinopathy. The aim of this study, constituting the first step towards efficient ocular delivery of hesperidin, was to determine its physicochemical properties and in vitro ocular tissue permeability.


METHODS
pH dependent aqueous solubility and stability were investigated following standard protocols. Permeability of hesperidin across excised rabbit cornea, sclera, and sclera plus retinal pigmented epithelium (RPE) was determined using a side-bi-side diffusion apparatus.


RESULTS
Hesperidin demonstrated poor, pH independent, aqueous solubility. Solubility improved dramatically in the presence of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and the results supported 1:1 complex formation. Solutions were stable in the pH and temperature (25, 40 degrees C) conditions tested, except for samples stored at pH 9. Transcorneal permeability in the apical-basal and basal-apical directions was 1.11 +/- 0.86 x 10(-6) and 1.16 +/- 0.05 x 10(-6) cm/s, respectively. The scleral tissue was more permeable (10.2 +/- 2.1 x 10(-6) cm/s). However, permeability across sclera/choroid/RPE in the sclera to retina and retina to sclera direction was 0.82 +/- 0.69 x 10(-6), 1.52 +/- 0.78 x 10(-6) cm/s, respectively, demonstrating the barrier properties of the RPE.


CONCLUSIONS
Our results suggest that stable ophthalmic solutions of hesperidin can be prepared and that hesperidin can efficiently permeate across the corneal tissue. Further investigation into its penetration into the back-of-the eye ocular tissues is warranted.
Majumdar
Soumyajit
S
Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, 111 Faser Hall, University, Mississippi 38677, USA. majumso@olemiss.edu
Srirangam
Ramesh
R
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D003315:Cornea / Q000378:metabolism*; D004355:Drug Stability; D005128:Eye Diseases / Q000188:drug therapy; D006569:Hesperidin / Q000737:chemistry* / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009883:Ophthalmic Solutions; D010539:Permeability; D011817:Rabbits; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012590:Sclera / Q000378:metabolism*; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
D009883:Ophthalmic Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D006569:Hesperidin