Formulation optimization of prostaglandin E₁-loaded lipid emulsion: Enhanced stability and reduced biodegradation

Abstract

The purpose of this study is to develop a new formulation for prostaglandin E₁ (PGE₁)-loaded lipid emulsion (Lipo-PGE₁) with improved stability and reduced biodegradation. High-pressure homogenization was used to prepare the Lipo-PGE₁, and high-performance liquid chromatography and accelerated test were used to evaluate its physicochemical stability. A tissue homogenate incubation test was firstly established and validated to assess its biodegradation. The factors influencing the stability of Lipo-PGE₁, including oil phase, emulsifier, pH value, and drug concentration were systematically investigated. The optimized formulation consisting of poloxamer188 1.5% (w/v), egg lecithin 0.5% (w/v), soybean oil 10.0% (w/v), oleic acid 0.24% (w/v), and glycerol 2.2% (w/v), with the pH value at 4.0, was defined and characterized. When compared with the currently available commercial product of Lipo-PGE₁, the degradation percentage of this optimized Lipo-PGE₁ reduced by 47.1% after sterilization, the drug remaining percentage increased by 13.9% after storage at 4°C over 6 months. Also, a significant reduction in biodegradation of the optimized Lipo-PGE₁ in comparison with the commercial Lipo-PGE₁ was observed by a tissue homogenate incubation test. Overall, we provided a novel formulation for Lipo-PGE₁ with a better physicochemical stability and a less biodegradation than the currently available commercial product of Lipo-PGE₁, indicating its potential superiority in clinical application.

Keywords::

• Prostaglandin E₁
• lipid emulsion
• formulation
• stability
• biodegradation

Acknowledgments

The authors thank Dr. Benjamin Lee for reviewing this manuscript.

Declaration of interest

This work was supported by the grants from National Natural Science Foundation of China (No. 30772668), Doctoral Fund of Ministry of Education of China (No. 20070610050), and National Scientific and Technological Major Special Project of China—“Key New Drugs Creation and Manufacturing” (No. 2009ZX09310-002 and No. 2009ZX09503-020).

The authors report no declaration of interest.