The effect of a modified β-cyclodextrin, SBE4-β-CD, on the aqueous stability and ocular absorption of pilocarpine

Kristiina Järvinen Department of Pharmaceutical Chemistry and Center for Drug Delivery Research, The University of Kansas, Lawrence, KS, USA; Department of Pharmaceutical Technology, The University of Kuopio, Kansas City, KS, USA

Tomi Järvinen Department of Pharmaceutical Chemistry and Center for Drug Delivery Research, The University of Kansas, Lawrence, KS, USA; Department of Chemistry, The University of Kuopio, Finland

Diane O. Thompson Department of Pharmaceutical Chemistry and Center for Drug Delivery Research, The University of Kansas, Lawrence, KS, USA; CyDex, L.C., Kansas City, KS, USA

Valentino J. Stella Department of Pharmaceutical Chemistry and Center for Drug Delivery Research, The University of Kansas, Lawrence, KS, USA; CyDex, L.C., Kansas City, KS, USA

Abstract

In the present study, the effects of a novel, modified β-cyclodextrin derivative (SBE4-β-CD; a variably substituted sulfobutyl ether of β-cyclodextrin with an average degree of substitution of four) on the aqueous stability of pilocarpine and on its ocular absorption in albino rabbits were studied. For stability reasons, commercial pilocarpine eyedrops are formulated at pH 4–5, a pH range where pilocarpine (pK_a ⌣ 7) is almost completely ionized. As shown in the present and past studies, increasing the pH of the pilocarpine solution from 4.5 to 7.0 increases the ocular absorption of pilocarpine. SBE4-β-CD increased the aqueous stability of pilocarpine (0.36 mM) at pH 7.0 (4°C, projected values from Arrhenius data at 25°C, 37°C and 50°C); in the absence of SBE4-β-CD, t_90% was 236 days. In the presence of 1 mM and 25 mM of SBE4-β-CD, t_90% was 382 days and 2054 days, respectively, suggesting that indeed, pilocarpine does interact with SBE4-β-CD.

SBE4-β-CD did not damage the corneal epithelium in vitro and was well-tolerated by the rabbit eye in vivo Coadministered SBE4-β-CD did not significantly affect the miotic response of pilocarpine solutions at pH values of 4.5 or 7.0 when the molar ratio of SBE4-β-CD to pilocarpine was between 0.2:1–7:1. The effect of the Coadministered SBE4-β-CD on the miotic response of pilocarpine solutions was also compared to that of 2-hydroxy-propyl-β-cyclodextrin (HP-β-CD) which has recently been suggested to increase ocular bioavailability of pilocarpine in rabbits. Our studies could not confirm the earlier observations. Curr. Eye Res. 13: 897–905, 1994.

Key Words:

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.