Development and optimization of ifosfamide nanostructured lipid carriers for oral delivery using response surface methodology

Subramanian Selvamuthukumar,Ramaiyan Velmurugan

doi:10.1007/s13204-015-0434-6

Subramanian Selvamuthukumar, Ramaiyan Velmurugan

Open Access

https://doi.org/10.1007/s13204-015-0434-6

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Journal: Applied Nanoscience	Publication Date: Mar 26, 2015
Citations: 52	License type: CC BY 4.0

Affiliation: Annamalai University

Abstract

The research focuses on the development and optimization of ifosfamide nanostructured lipid carriers for oral delivery with the application of response surface methodology. The objectives of the study were to develop a formulation for ifosfamide to be delivered orally, overcome the instability of the drug in acidic environment during oral administration, to sustain the release, drug leakage during storage and low loading capacity. A modified solvent diffusion method in aqueous system was applied to prepare nanostructured lipid nanoparticles. Hydrophilic polymers such as chitosan and sodium alginate were used as coating materials. Glycerol mono oleate and oleic acid were used as solid and liquid lipid, respectively. Poloxamer is used as stabilizers. The central composite rotatable design consisting of three-factored factorial design with three levels was used in this study. The physiochemical characterization included evaluation of surface morphology, particle size and surface charge of the drug in the delivery system. The in vitro drug release, entrapment and drug loading efficiency and as well as the storage stability were evaluated. The results showed that the optimal formulation was composed of drug/lipid ratio of 1:3, organic/aqueous phase ratio of 1:10 and concentration of surfactant of 1 % w/v. Ifosfamide nanostructured lipid carrier under the optimized conditions gave rise to the entrapment efficiency of 77 %, drug loading of 6.14 %, mean diameter of 223 nm and zeta potential value of −25 mV. Transmission electron microscopy analysis showed spherical particles. The in vitro experiment proved that ifosfamide from the delivery system released gradually over the period of 72 h. Sodium alginate cross-linked chitosan nanostructured lipid carrier demonstrated enhanced stability of ifosfamide, high entrapment efficiency and sustained release.

Highlights

Ifosfamide is one of the widely used antineoplastic drugs belonging to the alkylating agents group
Compared to physical mixture the peak intensities of formulaton is weaker, suggesting that the degree of the crystallinity is lower in the nanoparticle than in the raw material. These results indicate that incorporation of ifosfamide to the lipid matrix leads to less ordered crystals in nanostructured lipid carrier (NLC) and confirms the deduction in differential scanning calorimetric (DSC) analysis
The Ifosfamide NLC was optimized using the central composite rotatable design (CCRD)-RSM by fitting a quadratic model to the response data

Summary

Introduction

Ifosfamide is one of the widely used antineoplastic drugs belonging to the alkylating agents group. Ifosfamide is a white crystalline hygroscopic powder having a melting point of 40 °C. The powder has a water solubility of about 100 mg/ml. Ifosfamide, being susceptible to hydrolytic degradation degrades in acidic media with its rate of degradation depending on the pH of the solution; it is commercially available in dry form and is supplied as sterile packaged dry powder for dissolution in water for injection prior to administration. The low melting point and the hygroscopic nature of ifosfamide make it necessary to fill the powder with great care by accurately controlling both temperature and humidity to achieve a sterile product. Prolonged storage of the dry powder results in sintering and yellowing, which

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