Lyophilized preliposomal formulation of the non-cross-resistant anthracycline annamycin

Effect of surfactant on liposome formation, stability and size

Yiyu Zou, Waldemar Priebe, Roman Perez-Soler

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

We report a method of preparing a submicron and stable liposome formulation of the non-cross-resistant anthracycline annamycin. The lipids were dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG) at a 7:3 molar ratio and the optimal lipid:drug ratio was 50:1 (w/w). The selected formulation was a preliposome lyophilized powder that contained the phospholipids, annamycin, and Tween 20. The liposome suspension was obtained on the day of use by adding normal saline at 37°C (1 ml/mg annamycin) and hand shaking for 1 min. The presence of Tween 20 was essential in shortening the reconstitution step (from > 2 h to 1 min), avoiding the early formation of free drug crystals, and reducing the median particle size by tenfold (from 1.5 μm to 0.15 μm) without destroying the liposome vesicles. At room temperature, the preliposome powder was chemically stable for > 3 months, and the liposome suspension was chemically and physically stable for > 24 h. The in vitro cytotoxicity of the formulation was equivalent to that of the same lipid composition prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the size of liposome suspensions obtained from lyophilized preliposome powders. The formulation described is being used for ongoing clinical trials with liposomal annamycin.

Original languageEnglish (US)
Pages (from-to)103-108
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume39
Issue number1-2
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

Anthracyclines
Surface-Active Agents
Liposomes
Powders
Suspensions
Polysorbates
Lipids
Cytotoxicity
Choline
Particle Size
Pharmaceutical Preparations
Glycerol
Phospholipids
Evaporation
Hand
Particle size
annamycin
Clinical Trials
Crystals
Temperature

Keywords

  • Annamycin
  • Liposome
  • Lyophilization
  • Reconstitution

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

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title = "Lyophilized preliposomal formulation of the non-cross-resistant anthracycline annamycin: Effect of surfactant on liposome formation, stability and size",
abstract = "We report a method of preparing a submicron and stable liposome formulation of the non-cross-resistant anthracycline annamycin. The lipids were dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG) at a 7:3 molar ratio and the optimal lipid:drug ratio was 50:1 (w/w). The selected formulation was a preliposome lyophilized powder that contained the phospholipids, annamycin, and Tween 20. The liposome suspension was obtained on the day of use by adding normal saline at 37°C (1 ml/mg annamycin) and hand shaking for 1 min. The presence of Tween 20 was essential in shortening the reconstitution step (from > 2 h to 1 min), avoiding the early formation of free drug crystals, and reducing the median particle size by tenfold (from 1.5 μm to 0.15 μm) without destroying the liposome vesicles. At room temperature, the preliposome powder was chemically stable for > 3 months, and the liposome suspension was chemically and physically stable for > 24 h. The in vitro cytotoxicity of the formulation was equivalent to that of the same lipid composition prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the size of liposome suspensions obtained from lyophilized preliposome powders. The formulation described is being used for ongoing clinical trials with liposomal annamycin.",
keywords = "Annamycin, Liposome, Lyophilization, Reconstitution",
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T1 - Lyophilized preliposomal formulation of the non-cross-resistant anthracycline annamycin

T2 - Effect of surfactant on liposome formation, stability and size

AU - Zou, Yiyu

AU - Priebe, Waldemar

AU - Perez-Soler, Roman

PY - 1996

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N2 - We report a method of preparing a submicron and stable liposome formulation of the non-cross-resistant anthracycline annamycin. The lipids were dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG) at a 7:3 molar ratio and the optimal lipid:drug ratio was 50:1 (w/w). The selected formulation was a preliposome lyophilized powder that contained the phospholipids, annamycin, and Tween 20. The liposome suspension was obtained on the day of use by adding normal saline at 37°C (1 ml/mg annamycin) and hand shaking for 1 min. The presence of Tween 20 was essential in shortening the reconstitution step (from > 2 h to 1 min), avoiding the early formation of free drug crystals, and reducing the median particle size by tenfold (from 1.5 μm to 0.15 μm) without destroying the liposome vesicles. At room temperature, the preliposome powder was chemically stable for > 3 months, and the liposome suspension was chemically and physically stable for > 24 h. The in vitro cytotoxicity of the formulation was equivalent to that of the same lipid composition prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the size of liposome suspensions obtained from lyophilized preliposome powders. The formulation described is being used for ongoing clinical trials with liposomal annamycin.

AB - We report a method of preparing a submicron and stable liposome formulation of the non-cross-resistant anthracycline annamycin. The lipids were dimyristoylphosphatidyl choline (DMPC) and dimyristoylphosphatidyl glycerol (DMPG) at a 7:3 molar ratio and the optimal lipid:drug ratio was 50:1 (w/w). The selected formulation was a preliposome lyophilized powder that contained the phospholipids, annamycin, and Tween 20. The liposome suspension was obtained on the day of use by adding normal saline at 37°C (1 ml/mg annamycin) and hand shaking for 1 min. The presence of Tween 20 was essential in shortening the reconstitution step (from > 2 h to 1 min), avoiding the early formation of free drug crystals, and reducing the median particle size by tenfold (from 1.5 μm to 0.15 μm) without destroying the liposome vesicles. At room temperature, the preliposome powder was chemically stable for > 3 months, and the liposome suspension was chemically and physically stable for > 24 h. The in vitro cytotoxicity of the formulation was equivalent to that of the same lipid composition prepared by the standard evaporation method. The results of the study indicate that small amounts of surfactant may be used to enhance the reconstitution step and reduce the size of liposome suspensions obtained from lyophilized preliposome powders. The formulation described is being used for ongoing clinical trials with liposomal annamycin.

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