Influence of ultrasonic dissolution on the stability of cyclophosphamide powder for injection

F. S R Della Cuna, Mariella Mella, Annalisa Lanza, Riccardo Gatti, Anna Maria Goglio

Research output: Contribution to journalArticle

Abstract

Aim. Cyclophosphamide is widely employed as cytotoxic agent both for conventional (2) and high dose (up to 7 g/m2) anticancer therapies. In Italy cyclophosphamide is available in vials containing 500 mg and 1 g of drug generally reconstituted with 25 ml and 50 ml of solvent, respectively (20 mg/ml). Both formulations are inconvenient for routine preparation due to the prolonged handling-time and the high amounts of solvent required for dissolution. Materials and methods. We evaluated the effects of ultrasonic treatment of cyclophosphamide to short the dissolution time and to reduce the amounts of solvent required in comparison with the traditional manual shaking. Commercially available formulations of cyclophosphamide (Endoxan® 500 mg, 1 g vials) were resuspended at 50 mg/ml in sterile water, 0.9% sodium chloride or 5% dextrose and treated for 5 min at 50°C in an ultrasonic bath. The solvent volumes were 10 ml for 500 mg vials and 20 ml for 1 g vials. After complete dissolution (visual inspection), the chemical stability of two concentrations (10 and 50 μg/ml) was determined using the high performance liquid chromatography method with UV detection and nuclear proton magnetic resonance. Results. No significant differences in chemical stability between the solutions obtained from the two different methods were found. Conclusion. Ultrasonic treatment allows the reduction of the amount of solvent to be dissolved and a significant shortening of dissolution time.

Original languageEnglish
Pages (from-to)55-60
Number of pages6
JournalEuropean Journal of Oncology
Volume9
Issue number1
Publication statusPublished - Mar 2004

Fingerprint

Ultrasonics
Powders
Cyclophosphamide
Injections
Cytotoxins
Baths
Sodium Chloride
Italy
Protons
Magnetic Resonance Spectroscopy
Therapeutics
High Pressure Liquid Chromatography
Glucose
Water
Pharmaceutical Preparations

Keywords

  • Cyclophosphamide chemical stability
  • HPLC
  • NMR
  • Ultrasonic dissolution

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Influence of ultrasonic dissolution on the stability of cyclophosphamide powder for injection. / Della Cuna, F. S R; Mella, Mariella; Lanza, Annalisa; Gatti, Riccardo; Goglio, Anna Maria.

In: European Journal of Oncology, Vol. 9, No. 1, 03.2004, p. 55-60.

Research output: Contribution to journalArticle

Della Cuna, F. S R ; Mella, Mariella ; Lanza, Annalisa ; Gatti, Riccardo ; Goglio, Anna Maria. / Influence of ultrasonic dissolution on the stability of cyclophosphamide powder for injection. In: European Journal of Oncology. 2004 ; Vol. 9, No. 1. pp. 55-60.
@article{4a9e8a4175ec4a93931c38b2498e8e11,
title = "Influence of ultrasonic dissolution on the stability of cyclophosphamide powder for injection",
abstract = "Aim. Cyclophosphamide is widely employed as cytotoxic agent both for conventional (2) and high dose (up to 7 g/m2) anticancer therapies. In Italy cyclophosphamide is available in vials containing 500 mg and 1 g of drug generally reconstituted with 25 ml and 50 ml of solvent, respectively (20 mg/ml). Both formulations are inconvenient for routine preparation due to the prolonged handling-time and the high amounts of solvent required for dissolution. Materials and methods. We evaluated the effects of ultrasonic treatment of cyclophosphamide to short the dissolution time and to reduce the amounts of solvent required in comparison with the traditional manual shaking. Commercially available formulations of cyclophosphamide (Endoxan{\circledR} 500 mg, 1 g vials) were resuspended at 50 mg/ml in sterile water, 0.9{\%} sodium chloride or 5{\%} dextrose and treated for 5 min at 50°C in an ultrasonic bath. The solvent volumes were 10 ml for 500 mg vials and 20 ml for 1 g vials. After complete dissolution (visual inspection), the chemical stability of two concentrations (10 and 50 μg/ml) was determined using the high performance liquid chromatography method with UV detection and nuclear proton magnetic resonance. Results. No significant differences in chemical stability between the solutions obtained from the two different methods were found. Conclusion. Ultrasonic treatment allows the reduction of the amount of solvent to be dissolved and a significant shortening of dissolution time.",
keywords = "Cyclophosphamide chemical stability, HPLC, NMR, Ultrasonic dissolution",
author = "{Della Cuna}, {F. S R} and Mariella Mella and Annalisa Lanza and Riccardo Gatti and Goglio, {Anna Maria}",
year = "2004",
month = "3",
language = "English",
volume = "9",
pages = "55--60",
journal = "European Journal of Oncology",
issn = "1128-6598",
publisher = "Mattioli 1885 S.p.A.",
number = "1",

}

TY - JOUR

T1 - Influence of ultrasonic dissolution on the stability of cyclophosphamide powder for injection

AU - Della Cuna, F. S R

AU - Mella, Mariella

AU - Lanza, Annalisa

AU - Gatti, Riccardo

AU - Goglio, Anna Maria

PY - 2004/3

Y1 - 2004/3

N2 - Aim. Cyclophosphamide is widely employed as cytotoxic agent both for conventional (2) and high dose (up to 7 g/m2) anticancer therapies. In Italy cyclophosphamide is available in vials containing 500 mg and 1 g of drug generally reconstituted with 25 ml and 50 ml of solvent, respectively (20 mg/ml). Both formulations are inconvenient for routine preparation due to the prolonged handling-time and the high amounts of solvent required for dissolution. Materials and methods. We evaluated the effects of ultrasonic treatment of cyclophosphamide to short the dissolution time and to reduce the amounts of solvent required in comparison with the traditional manual shaking. Commercially available formulations of cyclophosphamide (Endoxan® 500 mg, 1 g vials) were resuspended at 50 mg/ml in sterile water, 0.9% sodium chloride or 5% dextrose and treated for 5 min at 50°C in an ultrasonic bath. The solvent volumes were 10 ml for 500 mg vials and 20 ml for 1 g vials. After complete dissolution (visual inspection), the chemical stability of two concentrations (10 and 50 μg/ml) was determined using the high performance liquid chromatography method with UV detection and nuclear proton magnetic resonance. Results. No significant differences in chemical stability between the solutions obtained from the two different methods were found. Conclusion. Ultrasonic treatment allows the reduction of the amount of solvent to be dissolved and a significant shortening of dissolution time.

AB - Aim. Cyclophosphamide is widely employed as cytotoxic agent both for conventional (2) and high dose (up to 7 g/m2) anticancer therapies. In Italy cyclophosphamide is available in vials containing 500 mg and 1 g of drug generally reconstituted with 25 ml and 50 ml of solvent, respectively (20 mg/ml). Both formulations are inconvenient for routine preparation due to the prolonged handling-time and the high amounts of solvent required for dissolution. Materials and methods. We evaluated the effects of ultrasonic treatment of cyclophosphamide to short the dissolution time and to reduce the amounts of solvent required in comparison with the traditional manual shaking. Commercially available formulations of cyclophosphamide (Endoxan® 500 mg, 1 g vials) were resuspended at 50 mg/ml in sterile water, 0.9% sodium chloride or 5% dextrose and treated for 5 min at 50°C in an ultrasonic bath. The solvent volumes were 10 ml for 500 mg vials and 20 ml for 1 g vials. After complete dissolution (visual inspection), the chemical stability of two concentrations (10 and 50 μg/ml) was determined using the high performance liquid chromatography method with UV detection and nuclear proton magnetic resonance. Results. No significant differences in chemical stability between the solutions obtained from the two different methods were found. Conclusion. Ultrasonic treatment allows the reduction of the amount of solvent to be dissolved and a significant shortening of dissolution time.

KW - Cyclophosphamide chemical stability

KW - HPLC

KW - NMR

KW - Ultrasonic dissolution

UR - http://www.scopus.com/inward/record.url?scp=2542420803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2542420803&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:2542420803

VL - 9

SP - 55

EP - 60

JO - European Journal of Oncology

JF - European Journal of Oncology

SN - 1128-6598

IS - 1

ER -