Effect of co-solvents on the characteristics of enkephalin microcapsules

Abstract

The objective of this project was to study the effect of the presence of co-solvents with dichloromethane on the properties of leu-enkephalin microcapsules. Six co-solvents, including ethyl acetate, methanol, ethanol, acetone, isopropanol and acetonitrile, at three concentrations of 5%, 10% and 20% (v/v), respectively, of dichloromethane were selected for this study. The resulting microcapsules were evaluated for morphology and particle size, surface area, thermal characteristics and efficiency of encapsulation. The analysis of particle size distribution showed bi- and tri-modal distribution of the microcapsules. The median particle size of the microcapsules was between 17 microm and 57 microm. All microcapsules were smaller than 90 microm. Approximately 10% of the microcapsules were smaller than 500 nm. In general, the microcapsules prepared with co-solvents showed relatively smaller median size. The microcapsules were spherical in shape. DSC analysis of the microcapsules showed that there were no significant differences in the glass transition temperatures. There were significant changes in the efficiency of encapsulation due to the addition of co-solvents. Substitution with 20% methanol resulted in 40% increase in the efficiency of encapsulation (12% vs. 17%). Furthermore, substitution with 20% ethyl acetate, isopropanol, or acetonitrile, reduced the efficiency of encapsulation to as low as 6%.

Effect of solvent type on preparation of ethyl cellulose microparticles by solvent evaporation method with double emulsion system using focused beam reflectance measurement

“…Additionally, organic solvents miscible with water such as methanol and ethanol are frequently used as co‐solvents. They are used to dissolve a drug that is not totally soluble in the solvent in the dispersed phase . Additionally, the physical properties of a solvent would affect the optical properties or opacity level of obtained microparticles.…”

Effect of ethanol as a processing co-solvent on the PLGA microsphere characteristics

“…Co-solvents have been reported to affect the rate of the organic phase partitioning into the external aqueous phase and thus influence the physicochemical properties and release kinetics of PLGA microspheres (Al-Maaieh and Flanagan, 2001;Bodmeier and McGinity, 1988;Graves et al, 2005;Mandal, 1999). Water miscible co-solvents have been used to increase the encapsulation efficiency of hydrophilic drugs when microspheres are prepared by the o/w emulsion-solvent evaporation/extraction method.…”

Solvent Type Effect on Preparation of Ethyl Cellulose Microparticles

“…Dalam pembuatan mikropartikel dengan teknik penguapan pelarut, laju pengerasan mikropartikel merupakan faktor penting dalam mempengaruhi perilaku pelepasan obat [22][23][24] . Pengerasan droplet atau tetesan emulsi yang sangat lambat akan menyebabkan difusi zat obat dari droplet dan efisiensi enkapsulasi menjadi rendah [25][26][27][28] . Laju pengerasan mikropartikel selama proses penguapan pelarut dipengaruhi kelarutan polimer dalam pelarut organik dan kelarutan pelarut organik dalam air, yang pada gilirannya mempengaruhi sifat mikropartikel seperti ukuran partikel, jumlah obat yang di enkapsulasi, porositas matriks, residu pelarut dan pelepasan awal obat [25][26] .…”

“…Pengerasan droplet atau tetesan emulsi yang sangat lambat akan menyebabkan difusi zat obat dari droplet dan efisiensi enkapsulasi menjadi rendah [25][26][27][28] . Laju pengerasan mikropartikel selama proses penguapan pelarut dipengaruhi kelarutan polimer dalam pelarut organik dan kelarutan pelarut organik dalam air, yang pada gilirannya mempengaruhi sifat mikropartikel seperti ukuran partikel, jumlah obat yang di enkapsulasi, porositas matriks, residu pelarut dan pelepasan awal obat [25][26] . Berbagai jenis pelarut dengan sifat fisik yang berbeda (seperti miscibility, kelarutan, volatilitas, titik didih, reaktivitas, viskositas, dll) telah digunakan untuk membuat mikropartikel.…”

“…Berbagai jenis pelarut dengan sifat fisik yang berbeda (seperti miscibility, kelarutan, volatilitas, titik didih, reaktivitas, viskositas, dll) telah digunakan untuk membuat mikropartikel. Sebelumnya kloroform sering digunakan, namun karena toksisitas dan tekanan uap yang rendah, secara bertahap diganti dengan diklorometana 25 . Diklorometana adalah pelarut yang paling umum digunakan untuk enkapsulasi menggunakan teknik penguapan pelarut karena volatilitas yang tinggi, titik didih rendah dan immiscibility tinggi dengan air [29][30][31][32] .…”