title: 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.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Chu
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.forename: Wei-cong
authors.initials: WC
authors.lastname: Ma
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Fu
authors.forename: Xiao-yue
authors.initials: XY
authors.lastname: Yu
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Zhen-zhen
authors.initials: ZZ
authors.lastname: Wang
authors.forename: Sheng-jun
authors.initials: SJ
authors.lastname: Mao
mesh_terms: D000527:Alprostadil / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D004655:Emulsions; D005079:Excipients; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D000527:Alprostadil