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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