Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Pharmaceutical Compositions And Methods For Producing Low Impurity Concentrations Of The Same

a technology of compositions and pharmaceutical compositions, applied in the field of pharmaceutical compositions, to achieve the effect of reducing or minimizing the level of certain impurities

Inactive Publication Date: 2010-05-06
HOSPIRA +1
View PDF12 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]In particular, the present invention describes pharmaceutical composition having clevidipine as an active ingredient, and having a reduced level of one or more impurities selected from a group consisting of Substance 23, Substance 24, Substance 25 and H168 / 79.
[0016]The fourth aspect of the present invention is a method of treating or alleviating a disease or condition in a subject in need thereof, comprising administering to the subject an effective amount of a pharmaceutical composition having clevidipine or any of its pharmaceutical acceptable salt forms as the active ingredient, wherein the level of impurities is reduced or minimized to no more than 0.2% weight-to-weight of impurity to clevidipine for any of Substance 23, Substance 24, and Substance 25, and no more than 1.5% for H168 / 79 based on a weight-to-weight of impurity to clevidipine. As used herein the disease or condition refers to any disease or condition which may be treated using a selective calcium channel block, such as clevidipine. Examples of such disease or condition include, without limitation, hypertension, such as primary hypertension, secondary hypertension, acute hypertension, chronic hypertension, high blood Pressure, chest pain (angina), migraine, brain aneurysm complications, irregular heartbeats (arrhythmia) and Raynaud's disease.

Problems solved by technology

For example, some impurities arise from the process used in making clevidipine, while others are due to gradual degradation of the active ingredient.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Pharmaceutical Compositions And Methods For Producing Low Impurity Concentrations Of The Same
  • Pharmaceutical Compositions And Methods For Producing Low Impurity Concentrations Of The Same
  • Pharmaceutical Compositions And Methods For Producing Low Impurity Concentrations Of The Same

Examples

Experimental program
Comparison scheme
Effect test

example 1

HPLC Procedure

[0035]Clevidipine assay and related substances were tested at each time point by a stability indicating method. This method is an isocratic, normal phase HPLC method with peak detection at 220 nm wavelength.

Column temperature: 35-40 degrees C.

Injection volume: 20 μl.

Flow rate: 1.0 ml / min.

Run time about 25 minutes.

Mobile phase of Heptane:ethanol (90:10) is employed and used for the assay of clevidipine and the degradation products with the exception of Substance 24.

Condition column with clevidipine mobile phase at 1.0 mL / min for 4 hours.

New column should be conditioned overnight at 0.2 mL / min.

When a degradation product is eluted, column can be washed with filtered ethanol for about 2 hours at 1.0 mL / min, then proceed with equilibration.

Examples of Column: PVA silica column 4.6 mm×150 mm, 5 micron PV12s051546WT or equivalent.

example 2

HPLC Procedure Substance 24

[0036]This method is an isocratic, normal phase HPLC method with peak detection at 220 nm wavelength.

Column temperature: 35-40 degrees C.

Injection volume: 20 μl to 100 μl.

Run time about 60 minutes.

Mobile phase of Heptane:Isopropyl Alcohol (95:5) is employed is used for the assay of Substance 24.

Condition column with Heptane:Isopropyl Alcohol 95:5 mobile phase at 1.0 ml / min until the blank injection baseline is stable. New column should be conditioned overnight at 0.2 mL / min.

Examples of Column: Two PVA silica columns 4.6 mm×150 mm, 5 micron PV12s051546WT or equivalent.

Flow rate 1.0 mL / min.

[0037]Calculation of percent impurity based on total peak area:

impurityPeakArea(100)(totalpeakareaofdegradationproducts+H324 / 38peakarea(clevidipinepeakarea))

[0038]Calculation of percent impurity based on total peak area using H168 / 79 as the impurity example:

H168 / 79PeakArea(100)(totalpeakareaofdegradationproducts+H324 / 38peakarea(clevidipinepeakarea))

[0039]When a standard of...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
temperaturesaaaaaaaaaa
Login to View More

Abstract

A composition having clevidipine as an active ingredient is described. The composition includes clevidipine as an active ingredient and an amount of the impurity H168 / 79 that is no greater than about 1.5%, or where the ratio between clevidipine and H168 / 79 is equal or above 60 to 1.

Description

[0001]This application claims priority from U.S. Provisional Application No. 61 / 085,597 filed on Aug. 1, 2008 and U.S. Provisional Application No. 61 / 093,772 filed on Sep. 3, 2008. The above mentioned applications are incorporated herein by reference.FIELD OF THE INVENTION[0002]The instant invention relates to pharmaceutical compositions, and in particular to compositions of clevidipine having a reduced level of impurities, and a method of maintaining the stability of such pharmaceutical compositions.BACKGROUND OF THE INVENTION[0003]Clevidipine, which is also known as Cleviprex™, is a short-acting, vascular selective calcium antagonist that has been shown to reduce arterial blood pressure with a fast termination of effect due to metabolism by blood and tissue esterases. As an arterial-selective vasodilator, clevidipine reduces peripheral vascular resistance directly, without dilating the venous capacitance bed.[0004]The chemical name of clevidipine is butyroxymethyl methyl 4-(2′,3′-...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/4418G01N30/02
CPCA61K31/519G01N30/02A61K31/4422A61P9/00A61P9/12A61K31/4418A61K31/436
Inventor MOTHERAM, RAJESHWARKRISHNA, GOPALDING, MINFLOOD, KEITHRAMAKRISHNA, KORNEPATI
Owner HOSPIRA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com