The in vitro evaluation of polyethylene glycol esters of hydrocortisone 21-succinate as ocular prodrugs

• Published in: International journal of pharmaceutics Vol. 182; no. 1; pp. 79 - 92
• Main Authors: Foroutan, S.M., Watson, D.G.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.05.1999; Elsevier
• Subjects: Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Chromatography, High Pressure Liquid; Cornea - enzymology; Cornea - metabolism; Corneal and scleral penetration; Corneal enzymes; Esterases - metabolism; Esters - chemistry; Esters - pharmacokinetics; General pharmacology; Hydrocortisone; Hydrocortisone - analogs & derivatives; Hydrocortisone - chemistry; Hydrocortisone - pharmacokinetics; In Vitro Techniques; Liver - enzymology; Medical sciences; Ophthalmic Solutions; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene glycol esters; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacokinetics; Prodrug; Prodrugs - chemistry; Prodrugs - pharmacokinetics; Sclera - metabolism; Sheep; Surface activity; Surface Tension; Swine; Corneal enzymes; Corneal and scleral penetration; Prodrug; Hydrocortisone; Polyethylene glycol esters; Surface activity; Cornea; Lipophily; Esterases; Ethylene oxide polymer; Eye; Ester; Absorption; Diffusion; Ungulata; Sclera; Corticosteroid; Enzyme; Steroid hormone; Chain length; Antiinflammatory agent; Permeation; In vitro; Hydrolysis; Vertebrata; Mammalia; Hydrolases; Sheep; Absorption enhancer; Artiodactyla
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(99)00059-9

The rate of hydrolysis of polyethylene glycol esters of hydrocortisone 21-succinate (H-PEGs) by a commercial esterase and by enzymes from ovine cornea was studied. Both the commercial esterase and the corneal enzymes rapidly hydrolysed the H-PEGs. Both lipophilicity and the PEG chain length had an influence on the rate of enzymatic hydrolysis, a significant decrease in enzymatic hydrolysis rate being associated with an increase in the polymer chain length. The in vitro penetration of H-PEGs across ovine cornea and sclera was assessed. In corneal penetration studies no prodrug was detected in the receiver phase while in the sclera penetration study both drug and prodrug were detected. Results from in vitro corneal and scleral absorption studies showed that the use of H-PEG400 increased the rate at which hydrocortisone diffused through excised ovine cornea compared to the use of hydrocortisone itself, particularly when the donor phase was removed after 15 min in order to mimic the situation in vivo. In addition, H-PEG200, H-PEG400, H-PEG600, H-PEG900 and H-PEG2000 gave a significant increase in the rate of diffusion of hydrocortisone+H-PEG through the sclera compared to hydrocortisone itself. Our results on ovine eye show that the rate of diffusion of hydrocortisone across the sclera is about six times higher than that in cornea and for the H-PEGs the scleral diffusion was 10–100 times higher than that observed in the cornea.