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

Formulations of cyclophosphamide liquid concentrate

a technology of cyclophosphamide and liquid concentrate, which is applied in the direction of phosphorous compound active ingredients, drug compositions, biocides, etc., can solve the problems of deterioration, material with prolonged dissolution time and decreased potency, and reduce stability during manufacturing, so as to improve solubility characteristics and enhance appearance

Inactive Publication Date: 2015-11-12
AUROMEDICS PHARMA LLC
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent aims to create liquid cyclophosphamide containing compositions that have better solubility and appearance, while keeping the potency suitable for a pharmaceutical form.

Problems solved by technology

The monohydrate form is preferred for pharmaceutical processing, since the anhydrous form readily picks up water to form the monohydrate when exposed to a relative humidity of about 20-30% or higher at about 25° C. While the monohydrate is stable, nonetheless, under dry conditions (e.g. a relative humidity of about 20% or less) the monohydrate begins to lose this water of hydration which can reduce stability during manufacturing.
During processing and / or storage of the currently available dry powder formulation, the product can acquire a glassy and / or sticky nature resulting in an undesirable material with prolonged dissolution times and decreased potency.
This deterioration is more pronounced as storage time is extended or if the upper limit of the storage temperature range is exceeded.
This study concluded that warming vials of cyclophosphamide in order to facilitate dissolution after adding an aqueous vehicle could decrease the potency of the final injectable product.
In summary, these stability limitations and dissolution difficulties can often result in clinical usage of sub-potent cyclophosphamide solutions.

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
  • Formulations of cyclophosphamide liquid concentrate

Examples

Experimental program
Comparison scheme
Effect test

example 2

[0032]Since cyclophosphamide is essentially a highly water soluble drug and Alam et al in U.S. Pat. No. 4,879,286, tested low drug concentrations, the expectation was that organic solvents would limit the solubility attainable with acceptable parenteral solvents.

[0033]In this example, studies were initiated to determine the solubility of cyclophosphamide monohydrate in pharmaceutically acceptable solvents such as propylene glycol, polyethylene glycol and ethanol. It was surprisingly found that the solubility of cyclophosphamide monohydrate was in excess of 500 mg / ml in each of these solvents. The advantage of making a 500 mg / ml solution is that when diluted to achieve the desired 20 mg / ml solution of cyclophosphamide, suitable for intravenous administration, the organic solvent concentration in the admixture is less than about 3% which is a safe level to administer intravenously.

[0034]Since these solvents provided more than adequate solubility, the stability of the solutions contain...

examples 4-8

[0041]A test of stability at a different concentrations and different size of the vial was conducted to observe any evaporative loss of ethanol. The stability data presented in Table 8.

TABLE 8ExampleStorage% CPPNo.CPP / CAmg / vialconditionNMRHPLC4375 / 4.52 g / 100 cc25° C.3 M90.688.3vial6 M78.978.815° C.6 M96.795.5 5° C.3 M99.499.76 M99.399.15500 / 6.02 g / 10 cc25° C.3 M87.886.7vial6 M74.574.715° C.6 M95.795.4 5° C.3 M99.3100.56 M98.698.66200 / 2.41 g / 50 cc25° C.3 M95.896.8(1 g)vial6 M88.489.615° C.6 M97.797.2 5° C.3 M99.799.46 M99.6100.2200 / 2.4500 mg / 25 cc25° C.6 M88.288.2(500 mg)vial15° C.6 M98.098.8 5° C.6 M99.599.47200 / 6.0500 mg / 25 cc25° C.3 M95.696.7vial6 M87.586.6 5° C.3 M99.9101.56 M99.7100.58375 / 6.01 g / 50 cc25° C.3 M92.393.5vial6 M79.881.5 5° C.3 M99.4101.16 M99.3100.6

[0042]No weight loss, due to evaporation of ethanol, was observed in any of the stoppered vials at all storage conditions and time points.

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
concentrationaaaaaaaaaa
concentrationaaaaaaaaaa
concentrationaaaaaaaaaa
Login to View More

Abstract

Cyclophosphamide containing compositions preferably in the form of solutions having extended stability are disclosed. The compositions contain cyclophosphamide, ethanol and an ethanol soluble acidifying agent such as citric acid. Ready to dilute or ready to use cyclophosphamide containing composition of the invention maintain high levels cyclophosphamide content after about 18 or 24 months at a temperature of about 5° C.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority from U.S. Provisional Application No. 61 / 991,247 filed May 9, 2014, the contents of which are incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention is directed to improved cyclophosphamide formulations and methods of making the same.BACKGROUND OF THE INVENTION[0003]Cyclophosphamide is the generic name for 2-[bis(2-chloroethyl)amino]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide monohydrate, a widely used antineoplastic drug chemically related to the nitrogen mustards. Cyclophosphamide is one example of a group of cyclic phosphoric acid ester amides which were disclosed and claimed in U.S. Pat. No. 3,018,302 granted Jan. 23, 1962 to H. Arnold et al. Cyclophosphamide is sold under the proprietary name CYTOXAN. ENDOXAN and NEOSAR are other proprietary names for similar pharmaceutical formulations of cyclophosphamide. The commercial cyclophosphamide product is a steri...

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): A61K31/664A61K47/12A61K47/10
CPCA61K31/664A61K47/12A61K47/10A61K9/0019A61K9/08A61K31/675A61P35/00A61K47/20
Inventor PALEPU, NAGESH R.BUXTON, PHILIP CHRISTOPHER
Owner AUROMEDICS PHARMA LLC
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