Malaysian Journal of Analytical Sciences Vol 24 No 3 (2020): 363 - 372

 

 

 

 

PHASE BEHAVIOUR STUDY ON MEDIUM-CHAIN TRIGLYCERIDE/ SURFACTANT/WATER SYSTEMS CONTAINING GEMCITABINE USING PHASE INVERSION COMPOSITION TECHNIQUE

 

(Kajian Tingkah Laku Fasa Bagi Sistem Trigliserida Rantaian Sederhana/Surfaktan/Air yang Mengandungi Gemcitabine dengan Menggunakan Teknik Komposisi Penyongsangan Fasa)

 

Nadiatul Atiqah Wahgiman, Norazlinaliza Salim*, Mohd Basyaruddin Abdul Rahman

 

Integrated Chemical BioPhysics Research, Faculty of Science,

University Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

 

*Corresponding author:  azlinalizas@upm.edu.my

 

 

Received: 20 November 2019; Accepted: 21 April 2020; Published:  9 June 2020

 

 

Abstract

In this study, the phase behavior of medium-chain triglyceride (MCT)/surfactant/water containing gemcitabine (GEM) was investigated. Ternary phase diagrams (TPD) were constructed with different surfactants (Span 20, Span 60, Span 80, Tween 80) and a mixture of surfactant (Tween 80:Span 80, at ratio 1:1). Two observations were recorded, isotropic and multilayer regions. The isotropic region was classified as a transparent, translucent or homogeneous mixture, while the multilayer region was classified as an opaque, milky or heterogeneous mixture. From the ternary phase diagrams constructed, it showed that MCT/(Tween 80: Span 80, ratio 1:1)/ GEM in deionized water system gave the largest isotropic region with the minimum usage of mixed surfactant, where 25% area of the isotropic region was formed with 1% of the usage of surfactant. The composition of F1 (selection based on the ternary phase diagram) was 0.02 % w/w of GEM, 19.98 % w/w of deionized water, 5.00 % w/w of Tween 80:Span 80 at ratio 1:1 and 75 % w/w of MCT. Nanoemulsion formulation was prepared by low energy emulsification method (i.e. phase inversion composition (PIC) technique). As the formulation was prepared in large scale with PIC technique, sodium chloride solution (0.1 M NaCl solution) was added to form a stable formulation as stabilizer. Effect of different volume of NaCl solution (0.5, 1.0 and 1.5 mL) added into formulation was investigated. The results showed that the particle size increased as the amount of NaCl increased, the effect of the amount of NaCl solution is significant towards particles size on F1. The F1 was stable in normal storage condition as it remained a homogeneous formulation against centrifugation test and it was also stable in storage stability test at different temperature (4, 25 and 45 °C) within three months.

 

Keywords:  gemcitabine, nanoemulsion, ternary phase diagram

 

Abstrak

Dalam kajian ini, sifat fasa pada trigliserida rantaian sederhana (MCT)/surfaktan/air yang mengandungi GEM telah dikaji. Gambar rajah fasa ternari (TPD) telah dibina dengan surfaktan yang berbeza (Span 20, Span 60, Span 80, Tween 80) dan campuran surfaktan (Tween 80:Span 80, pada nisbah 1:1). Dua pemerhatian telah direkodkan, rantau isotropik dan pelbagai lapis. Rantau isotropik telah diklasifikasikan sebagai telus, lut atau campuran homogen, manakala rantau pelbagai lapisan telah diklasifikasikan sebagai legap, seperti susu atau campuran heterogen. Daripada gambar rajah fasa ternari yang telah dibina, ianya menunjukkan yang sistem MCT/(Tween 80: Span 80, pada nisbah 1:1)/ GEM dalam air ternyahion telah memberi rantau isotropik yang paling tinggi dengan penggunaan campuran surfaktan yang minimum, di mana 25% keluasan rantau isotropik telah terhasil dengan 1% penggunaan surfaktan. Komposisi F1 (pilihan berdasarkan pada gambar rajah fasa ternari) ialah 0.02% w/w daripada GEM, 19.98% w/w daripada air ternyahion, 5.00% w/w daripada Tween 80:Span 80, pada nisbah 1:1 dan 75% w/w daripada MCT. Formulasi nanoemulsi telah dihasilkan dengan pengemulsi yang rendah tenaga (fasa penyongsangan (PIC). Formulasi yang dihasilkan dalam skala yang besar dengan teknik PIC, natrium klorida (0.1M larutan NaCl) telah ditambah untuk menghasilkan formulasi yang stabil sebagai penstabil. Kesan tiga isipadu larutan NaCl yang berbeza (0.5, 1.0 dan 1.5 mL) telah ditambah dalam formulasi dan dikaji. Keputusan menunjukkan peningkatan saiz zarah apabila jumlah NaCl meningkat, jumlah larutan NaCl memberi kesan yang signifikan terhadap saiz zarah F1. F1 adalah stabil di dalam penyimpanan keadaan biasa apabila ianya kekal homogen ketika diuji dengan ujian emparan dan stabil dalam ujian penyimpanan  kestabilan pada suhu yang berbeza (4, 25 dan 45 °C) selama 3 bulan.

 

Kata kunci:  gemcitabine, nanoemulsi, gambar rajah fasa ternari

 

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