Influence of 5% dextrose volume on amphotericin B deoxycholate preparation

J Pharm Pharmacol. 2016 Apr;68(4):433-8. doi: 10.1111/jphp.12533. Epub 2016 Mar 14.

Abstract

Objectives: Preparation of amphotericin B deoxycholate (AmB-d) in different volumes of 5% dextrose (D5W) was studied to investigate a interesting phenomenon that AmB-d was easy to bring pipe blockage when diluted in 500 ml but not in 50 ml.

Methods: AmB-d (25 mg/vial) in 50 ml, 250 ml or 500 ml D5W was prepared. Fluids were collected before and after infusion, then were assayed by validated high-performance liquid chromatography (HPLC) method. Light obscuration assay was used to detect the particles in transfusions.

Key findings: pH values of different volumes of D5W were all about 3.7, which was lower than the requirement of AmB-d package insert (pH > 4.2). The number of insoluble particles >10 μm/25 μm in 25 mg/500 ml infusions exceeded China Pharmacopoeia limit. Filters in 25 mg/500 ml infusion set were full of AmB-d after dripping slowly for 6 h, and 331.3 ml solution was left in the bottles and only 11.3% of AmB-d could flow out. Whereas the AmB-d infusion consists of 25 mg/50 ml, 25 mg/250 ml and 50 mg/500 ml could meet with China Pharmacopoeia standards, and they flowed out easily and completely.

Conclusions: In practice, 25 mg/250 ml and 50 mg/500 ml would be more suitable for clinical use, rather than 25 mg/500 ml. We provided a convenient method for AmB-d preparation.

Keywords: 5% dextrose; amphotericin B deoxycholate; high-performance liquid chromatography; preparation; solubility.

Publication types

  • Comparative Study

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / chemistry*
  • Amphotericin B / standards
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemistry*
  • Antifungal Agents / standards
  • Chromatography, High Pressure Liquid
  • Deoxycholic Acid / administration & dosage
  • Deoxycholic Acid / chemistry*
  • Deoxycholic Acid / standards
  • Drug Combinations
  • Drug Compounding
  • Glucose / chemistry*
  • Glucose / standards
  • Hydrogen-Ion Concentration
  • Infusions, Parenteral
  • Particle Size
  • Pharmaceutical Solutions
  • Solubility

Substances

  • Antifungal Agents
  • Drug Combinations
  • Pharmaceutical Solutions
  • Deoxycholic Acid
  • Amphotericin B
  • amphotericin B, deoxycholate drug combination
  • Glucose