Sulfobutyl Ether β-Cyclodextrin (SBE-β-CD) in Eyedrops Improves the Tolerability of a Topically Applied Pilocarpine Prodrug in Rabbits

Abstract

The effects of a novel, modified p-cyclodextrin (SBE4-p-CD; a variably substituted sulfobutyl ether with an average degree of substitution of four) on eye irritation and miotic response of an ophthalmically applied pilocarpine prodrug, 0,0'-dipropionyl-(l,4-xylylene) bispilocarpate, in albino rabbits were studied. Compared to the commercial pilocarpine eyedrop solution (163 mM, equivalent to 3.4% pilocarpine), 12-24 mM pilocarpine prodrug solutions (equivalent to 0.5 -1.0% pilocarpine, respectively) decreased peak miotic intensity (I max ) and increased the time to reach peak (t max ), but did not significantly affect values for the area under the miosis versus time curves (AUC), i.e. 12 -24 mM pilocarpine prodrug appeared to be equivalent to 163 mM pilocarpine. Ocularly applied 12-24 mM pilocarpine prodrug solutions, however, were more irritating than a commercial pilocarpine eyedrop solution. Coadministered SBE4-p-CD significantly decreased the eye irritation of the pilocarpine prodrug solutions. Coadministered SBE4-P-CD did not affect the miotic response of prodrug solution when the molar ratio of SBE4-p-CD to prodrug was low. However, increasing the molar ratio of SBE4-p-CD to prodrug decreased the I max and AUC values. The results show that eye irritation of the pilocarpine prodrug is prevented by levels of SBE4-P-CD that do not affect the apparent ocular absorption of the prodrug.

Cyclodextrins

“…Oral administration of concentrated, high-volume CD-drug combinations to rodents often results in decreased delivery of drug molecules. The same is seen with some ophthalmic products (Järvinen et al, 1994;Järvinen, Järvinen, Urtti, et al, 1995;Jarho et al, 1996). For example, in the case of ophthalmics, an eyedrop volume of 30 to 45 µL is diluted into only 7 to 10 µL of precorneal fluid.…”

Potential Use of 2-Hydroxypropyl-.BETA.-cyclodextrin for Preparation of Orally Disintegrating Tablets Containing dl-.ALPHA.-Tocopheryl Acetate, an Oily Drug

“…14,15) Recently, high functional and bioadaptability of CyD derivatives have been developed to accommodate various applications. [16][17][18] Regarding the application of CyDs to oily drugs, conventional tablets containing CyD complexes with prostaglandin or nitroglycerin are known. 19) Therefore, in the present study, we prepared orally disintegrating tablets containing VE, lactose and b-CyDs as additives, and examined the potential use of b-CyD and 2-hydroxypropyl-b-CyD (HP-b-CyD) as excipients of orally disintegrating tablets containing VE.…”

Novel sulfobutyl ether cyclodextrin gradient leads to highly active liposomal irinotecan formulation

“…In this study, we developed a modified drug‐loading technology to increase the retention of irinotecan, which involved the use of sulfobutylether‐ β ‐cyclodextrin (sbe‐CD) as anions in conjunction with transmembrane triethylammonium (TEA) gradient. Sbe‐CD is one of the most popular beta‐CD derivatives used as a pharmaceutical excipient due to an improved toxicity profile and ability to solubilize poorly water‐soluble drugs [36,37] …”