Topiramate Compositions and Methods of Making and Using the Same

a technology of sulfoalkyl ether and composition, which is applied in the field of compositions comprising topiramate and sulfoalkyl ether cyclodextrin, can solve the problems that the oral composition of topiramate may not be appropriate, and achieve the effect of blocking absorption

Inactive Publication Date: 2009-09-24
RGT UNIV OF MINNESOTA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]As described herein, compositions suitable for injectable administration that include topiramate and a cyclodextrin have been developed. These injectable compositions are useful, e.g., for treating patient populations for which oral compositions of topiramate are not appropriate. For example, oral compositions of topiramate may not be appropriate because a patient may be too young, unable to swallow, undergoing GI surgery, incapacitated, or have a disorder that blocks absorption. Further, injectable compositions of topiramate would be useful for treating conditions where patients need to rapidly attain an increased concentration of topiramate. These injectable compositions also provide a more controlled dosing than do oral compositions.

Problems solved by technology

For example, oral compositions of topiramate may not be appropriate because a patient may be too young, unable to swallow, undergoing GI surgery, incapacitated, or have a disorder that blocks absorption.

Method used

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  • Topiramate Compositions and Methods of Making and Using the Same
  • Topiramate Compositions and Methods of Making and Using the Same
  • Topiramate Compositions and Methods of Making and Using the Same

Examples

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example 1

Topiramate Phase Solubility Study

[0099]A phase solubility study was conducted with the cyclodextrin CAPTISOL® and topiramate to evaluate the extent of solubilization of the drug by the derivatized cyclodextrin. An HPLC method was modified from the literature and shown to be linear over the range of interest. Chromatograms from injection of two of the topiramate standards are shown in FIGS. 1 and 2.

[0100]Results of the solubility study are illustrated in FIGS. 3 and 4 and show that topiramate is well solubilized by the cyclodextrin CAPTISOL® in water. Type A-linear phase solubility is observed and a binding constant of 71 M−1 was calculated from the equation: K1:1=slope / S0(1-slope), where S0 is the intrinsic solubility of the drug and “slope” is the slope of the molar plot of drug solubility versus cyclodextrin content. The magnitude of the calculated binding constant is low due to the drug being reasonably soluble in water in the absence of cyclodextrin (intrinsic solubility of 7.86...

example 2

Preparation and Verification of [13C]6-Topiramate

[0110]Isotopically labeled topiramate ([13C]6-TPM) was synthesized by Isotech Laboratories, Inc. Quantitative identification of the stable-isotope topiramate was performed by Isotech Laboratories, Inc. using 1H-NMR, 13C-NMR, and mass spectrometry. The [13C]6-TPM was then to the University of Minnesota for further quantitative analysis by liquid chromatography / mass spectrometry (LC / MS).

[0111]The LC / MS procedure was as follows: 25 mg [13C]6-TPM was weighed on a Cahn electrobalance, transferred into a 2 dram vial, and dissolved in 2.5 mL of 10% w / v CAPTISOL® aqueous solution. The 10% w / v CAPTISOL® aqueous solution was prepared by weighing 10 g of CAPTISOL® (adjusted for water content) and dissolving it in 100 mL of water. Reference unlabeled topiramate (obtained from Sigma-Aldrich Co. or Toronto Research Chemicals, Inc.) was prepared in an identical fashion. Separation of topiramate was performed using reverse phase chromatography, and d...

example 3

Formulation of [13C]6-TPM with Sulfoalkyl Ether Cyclodextrin

[0113]The stable-isotope topiramate was sent in sealed containers from University of Minnesota to the Pharmaceutical Service Division, College of Pharmacy, University of Iowa, Iowa City, 10 52242, for formulation into a parenteral solution suitable for administration into humans.

[0114]The stable-isotope topiramate was formulated with CAPTISOL® for intravenous administration. The resulting composition contained 1% w / v topiramate and 10% w / v CAPTISOL®. The manufacturing procedure was as follows:[0115]1) 200 g of CAPTISOL® (adjusted for water content) was dissolved in 2.0 L of deionized sterile water to generate a 10% w / v CAPTISOL® solution;[0116]2) 20 g of [13C]6-TPM was added to the 10% w / v CAPTISOL® solution;[0117]3) The solution was stirred for 24 hours at room temperature;[0118]4) Ampoules were sterilized in preparation for filling;[0119]5) All equipment to be used was prepared and sterilized;[0120]6) The solution was tra...

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Abstract

The present invention is directed to compositions comprising topiramate and a sulfoalkyl ether cyclodextrin, and methods of making and using the same.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation-In-Part of U.S. application Ser. No. 11 / 855,642, filed Sep. 14, 2007, which claims the benefit of the filing date of U.S. application No. 60 / 844,875, filed Sep. 15, 2006, each of which is herein incorporated by reference in its entirety.STATEMENT OF GOVERNMENT RIGHTS[0002]Work related to this patent document was funded in part by the U.S. government (NIH Grant NS-16308-26). The government may have certain rights in this patent document.BACKGROUND OF THE INVENTION[0003]1. Field of the Invention[0004]The present invention is related to compositions comprising topiramate and a sulfoalkyl ether cyclodextrin, methods of making the compositions, and methods of treating subjects in need thereof.[0005]2. Background Art[0006]Topiramate (2,3:4,5-di-O-isopropylidene-β-D-fructopyranose sulfamate, C12H21NO8S, molecular weight 339.36) is a sulfamate-substituted monosaccharide, related to fructose, and is an anticonvul...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/35A61P25/00
CPCA61K31/357A61K31/724A61K2300/00A61P25/00A61K9/0019A61K47/40
Inventor CLOYD, JAMES C.
Owner RGT UNIV OF MINNESOTA
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