Optimization of freeze-dried nanoparticles of ginkgolide B by central composite design-response surface methodology and their in vitro release studies
10.7501/j.issn.0253-2670.2019.22.009
- Author:
Lu-Jia ZHU
1
Author Information
1. College of Pharmacy, Zhejiang Chinese Medical University
- Publication Type:Journal Article
- Keywords:
Central composite design-response surface methodology;
Ginkgolide B;
In vitro release;
Nanoparticles;
Polymer;
Polysaccharide;
Preparation technology
- From:
Chinese Traditional and Herbal Drugs
2019;50(22):5439-5447
- CountryChina
- Language:Chinese
-
Abstract:
Objective: In order to solve the problem of ginkgolide B (GB) for preparing the intravenous injection dosage form, such as it’s low solubility, rapid elimination in vivo and poor stability in long-term storage, a novel biodegradable polysaccharide polymer was used as a carrier to encapsulate GB into nanoparticles with sustained-release profile, which then was freeze dried for keep its stability. Methods: GB nanoparticles (GB-NP) were prepared by coacervation method with hydrophilicity polymer. The Design-Expert 8.0 software was applied for experimental design. The formulation was finalized by investigating the concentration of GB, the mass ratio of GB to polymer, and the pH of the polymer solution with size and polydispersity indexas the evaluation parameters. The optimum formulation and technique were selected by response surface method. Then the nanoparticle suspension was further freeze dried and in vitro release behavior was tested in PBS containing 30% ethanol. Results: The optimum prescription conditions were as follows: the concentration of GB was 1.5 mg/mL, the ratio of GB mass to polymer mass was 0.1 and the polymer solution pH was set at 5.0. The entrapment efficiency was (99.64 ± 0.45)% with the drug loading ratio of (9.04 ± 0.04)%. Average particle size of GB-NP was (192.8 ± 2.8) nm with a preferable PDI of 0.18 ± 0.03. The freeze-drying conditions were described as follows: using 1% mannitol as freeze- drying supporting agent, the solution of GB-NP was pre-frozen for 12 h at −80 ℃ and dried for 24 h at −40 ℃. The release behavior of free GB was rapid with the cumulative release rate reaching (64.74 ± 3.95)% during the first hour, while the cumulative release rate of GB in nanoparticles was (36.90 ± 1.41)% during the first hour. Conclusion: The GB-NP using this special biodegradable polysaccharide polymer can improve GB’s dissolution behavior in water and make GB sustained release in vitro, which is beneficial for preparing GB’s intravenous injection dosage form.
