Methods of stabilizing azithromycin

a stabilizing method and azithromycin technology, applied in the field of packaging azithromycin, can solve the problems of erythromycin a, is susceptible to degradation, is unstable, etc., and achieves the effect of improving the stability of azithromycin

Inactive Publication Date: 2008-06-26
TEVA PHARM USA INC
View PDF12 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010] In some embodiments, the invention encompasses methods for packaging azithromycin which show improved stability of azithromycin upon storage.

Problems solved by technology

Macrolide antibiotics of the erythromycin class, such as erythromycin A, are known to be unstable in an acidic environment and are inactivated by gastric acids.
Azithromycin is subject to degradation that may occur during manufacture and / or storage.
For example, azithromycin is susceptible to degradation if exposed to elevated temperatures and / or air during manufacturing processes, processes that include formulation of the pharmaceutical dosage form.
The susceptibility of azithromycin to degradation may lead to deviation of the drug product from regulatory purity requirements even prior to the product reaching the patient.
In addition, once formulated, azithromycin tends to degrade under normal storage conditions, which may result in the presence of unacceptable levels of impurities at the time of administration.

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
  • Methods of stabilizing azithromycin
  • Methods of stabilizing azithromycin
  • Methods of stabilizing azithromycin

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0073] Several azithromycin samples were analyzed using HPLC to determine the level of impurities within each sample. The analytical conditions of the HPLC were column of 150×4.6 mm; packing material of Kromasil KR 100-5C18, 5Φ; and an eluent of 40% 0.05 M K2HPO4 adjusted to a pH of 8.2 and 60% acetonitrile. The flow rate was 0.9 ml / min; the detector set at 210 nm; and column temperature of 30° C. The samples were injected into the HPLC and run for over 35 min. The impurities were determined by their relative retention times (RRT) as compared to azithromycin and were reported as a weight percent (versus azithromycin) of the total composition. Additional impurities found in the samples were reported under “other RRT” as a weight percent of the azithromycin content. The results of the analytical tests is summarized in Table A. Table A demonstrates a finding of the main azithromycin degradation products where azithromycin batches have been stored under uncontrolled temperature conditio...

example 2

Storage Testing

[0074] Three samples of azithromycin were separately packaged in a standard polyethylene bag, and then the polyethylene bags containing azithromycin were separately packaged into aluminum bags with silica gel. The stored azithromycin was submitted to stability programs either long term or accelerated to determine the effect upon azithromycin stability and the production of degradation products. The longer term stability program comprised submitting the sample to a temperature of about 25° C.±2° C. at a relative humidity of 60%±5%. The accelerated program comprised submitting the sample to a temperature of about 40° C.±2° C. at a relative humidity of 75%+5%. The samples were analyzed at regular intervals to determine the impurity profiles as assayed by HPLC using the technique described in Example 1. The water content was determined by Karl Fischer methodology; and the ethanol content was determined by gas chromatography. The results of these tests are summarized in T...

example 3

Azithromycin Stability as a Function of Storage Temperature

[0076] Samples of azithromycin were placed in storage bags and each batch sample was analyzed after storage at a variety of temperatures using the analytical techniques as described in Example 1. Each batch was packaged in a polyethylene bag and subsequently, each bag was packaged in an aluminum bag with silica gel. Table D summarizes the effects of storage temperature on the production of azithromycin degradation products. The results demonstrate that storing azithromycin at low temperatures (+5° C.) leads to inhibition of the production of degradation products.

TABLE DAzithromycin Stability as a Function of Storage TemperatureAZTTimeRRT (%)OtherTotalBatch(months)T° C.0.260.340.370.80RRT %%Batch00.070.030.1No. 432-80.070.120.060.060.120.33250.360.410.260.320.411.5Batch00.070.030.1No. 532-80.100.150.070.080.150.43250.440.620.390.430.621.9Batch00.130.070.040.130.2No. 632-80.070.170.110.030.170.43250.390.570.320.340.571.8

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
timeaaaaaaaaaa
temperaturesaaaaaaaaaa
Login to view more

Abstract

A method of packaging of azithromycin which provides improved stability of azithromycin upon storage. Additionally, compositions and methods of stabilizing azithromycin compositions are described. Stabilized azithromycin compositions comprise an intimate admixture of azithromycin and a stabilizing-effective amount of an antioxidant to improve the resistance of the azithromycin to degradation. Coprecipitation or co-milling of azithromycin and an antioxidant are particularly preferred means of achieving an intimate admixture. Pharmaceutical formulations comprising a stabilized azithromycin composition and methods of making such formulations are also described.

Description

RELATED APPLICATIONS [0001] This application is a continuation in part of U.S. application Ser. No. 10 / 782,047, filed Feb. 19, 2004, which claims the benefit of priority to U.S. provisional application Ser. No. 60 / 448,946, filed Feb. 19, 2003, herein incorporated by reference. This application is also a continuation in part of U.S. application Ser. No. 10 / 936,075, filed Sep. 7, 2004, which is a continuation of U.S. application Ser. No. 10 / 822,773, filed Apr. 13, 2004, which is a continuation of U.S. application Ser. No. 10 / 247,097, filed Oct. 18, 2002, which claims the benefit of priority to U.S. provisional application Ser. Nos. 60 / 336,346, filed Oct. 18, 2001; 60 / 331,931, filed Nov. 21, 2001; and 60 / 341,295, filed Dec. 17, 2001, herein incorporated by reference.FIELD OF THE INVENTION [0002] The invention encompasses methods of packaging azithromycin to prevent the degradation of azithromycin upon storage. The invention also relates to stabilized azithromycin compositions, methods ...

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): B65D85/84
CPCA61K9/2009A61K9/2054A61K9/2027A61K9/2013
Inventor PESACHOVICH, MICHAELISAACS, SARAHSINGER, CLAUDESCHWARTZ, EDUARDBERGER, EDITTENENGAUZER, RUTHSCHWARZ, JOSEPHHRAKOVSKY, JULIALESSEN, TANIAKHONDO, LEVMATHIVANAN, MATHI
Owner TEVA PHARM USA INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap