PRE-FORMULATION STUDY ON 5-FLUOROURACIL AND CERTAIN LIPIDS FOR SOLID LIPID NANOPARTICLES PREPARATION

Mona M Elkhatib,Ali S Al-Badrawy,Suzan A Abdelrazek,Amir I Ali

doi:10.22159/ijap.2022v14i2.43491

Mona M Elkhatib, Ali S Al-Badrawy + Show 2 more

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https://doi.org/10.22159/ijap.2022v14i2.43491

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Abstract

Objective: The study's objective involved compatibility studies to investigate the possible interactions between 5-fluorouracil (5-FU) and four different lipids, and the most appropriate lipid was chosen. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier Transform Infrared spectroscopy (FT-IR) are used for the compatibility study between 5-FU and several excipients as cholesterol, compritol®, stearic acid, and glycerol monostearate (GMS). Methods: The physical mixture between 5-FU and each lipid was made by mixing of a certain amount of drug with the same amount of lipid. Drug lipid blended mixtures were made by solvent evaporation casting method. 5-FU alone, physical mixture and blended mixture were measured using Differential scanning calorimetry (DSC) to investigate melting peak of drug and effect of each lipid on this melting point, X-ray diffraction (XRD) to observe the crystalline or amorphous state of drug and Fourier Transform Infrared (FT-IR) to determine any chemical interaction between drug and these lipids by observing any shift happened to characteristic peaks related to the drug. Results: 5-FU Tm (280.04 °C) peak appeared in drug-lipid physical mixtures with minor changes in position while this peak disappeared in 5-FU-compritol® and 5-FU-cholesterol blended mixture, indicating that the drug is molecular dispersed. XRD result showed that the crystalline structure of 5-FU was present in physical mixtures with four lipids, while in the 5-FU-compritol® blended mixture, the crystalline state of the drug was disappeared, confirming the DSC result. The FT-IR spectrum of the 5-FU-physical mixtures with four lipids showed that all characteristic peaks of the drug appeared with minor changes. In the case of 5-FU-blended mixtures with mentioned lipids, no chemical interaction occurred between the drug and mentioned lipids except in the drug-stearic acid blended mixture, the N-H peak at 3136.25 cm-1 was disappeared due to amide ester formation. Conclusion: The most appropriate lipids suitable for the preparation of 5-FU solid lipid nanoparticles were GMS and cholesterol.

Highlights

MethodsThe physical mixture between 5-FU and each lipid was made by mixing of a certain amount of drug with the same amount of lipid
The Fourier Transform Infrared spectroscopy (FT-IR) spectrum of the 5-FU-physical mixtures with four lipids showed that all characteristic peaks of the drug appeared with minor changes
Differential scanning calorimetry (DSC) measurements were performed on 5-FU in pure form, 5-FU-physical mixtures with four lipids, and 5-FU blended mixtures with four lipids

Summary

Methods

The physical mixture was made by mixing in a mortar with a pestle for 5 min. Drug-lipid blended mixture was prepared by the simple solvent evaporation casting method [17]. The prepared solutions (drug and melted lipids) were poured into glass agar dishes and dried at room temperature for 48 h [18]. The enthalpy scale was done on the drug alone, physical mixtures, and blended mixtures. Infrared spectra of the drug, physical mixture and blended mixtures at functional group region (4000-400 cm-1) were measured. Discs were prepared by mixing the sample with a small amount of KBr and compressing the high-pressure mixture [22]. The powder samples (physical mixture or blended mixture) were gently mixed with 300 mg of potassium bromide powder compressed into discs at a force using a manual tablet presser. All samples were taken in triplicate and the data presented were the average of the three measurements [17]

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CONCLUSION