Pemilihan Jenis Koformer dan Metode Preparasi dalam Sistem Penghantaran Sediaan Ko-Amorf

Ko-amorf adalah suatu sistem multikomponen padat yang mengandung zat aktif dan molekul dengan berat molekul rendah lainnya (koformer) yang dapat berupa eksipien atau zat aktif yang relevan secara farmakologis. Formulasi ko-amorf yang dibuat dengan metode preparasi dan jenis koformer yang berbeda dapat menghasilkan perbedaan yang signifikan dalam stabilitas fisik dan profil disolusi suatu bentuk ko-amorf. Tujuan penulisan dari artikel review ini adalah untuk menggali informasi lebih dalam tentang sistem ko-amorf, klasifikasi ko-amorf, karakterisasi ko-amorf serta pengaruh jenis koformer dan metode preparasi ko-amorf terhadap pembentukan ko-amorf. Artikel review ini disusun dengan literature search melalui PubMed, MDPI dan Science Direct dengan memasukkan kata kunci co-amorphous, co-amorphous formulations, co-amorphous stabilizers, co-amorphous drug formulations. Dari review ini ditemukan terdapat beberapa jenis koformer yang dapat digunakan untuk pembentukan ko-amorf yaitu dapat berupa zat aktif yang relevan secara farmakologis dan eksipien seperti diantaranya yaitu asam amino, asam karboksilat, asam tanat, quercetin, sakarin dan nikotinamid. Dan untuk metode preparasi ko-amorf yang dapat digunakan diantaranya yaitu ball milling, cryomilling, melt quenching/ quench cooling, hot melt extrusion, solvent evaporation, spray drying, freeze drying hingga teknologi seperti supercritical antisolvent dan microwave technique. Keberhasilan pembentukan ko-amorf ditentukan diantaranya oleh pemilihan jenis koformer yang melibatkan berbagai sifat yang perlu dipertimbangkan, seperti Tg, potensial ikatan hidrogen, ketercampuran/ miscibility, atau perilaku kristalisasi. Sifat zat aktif dan eksipien seperti stabilitas termal, suhu leleh dan kecenderungan kristalisasi zat aktif dan eksipien, menjadi faktor yang perlu diperhatikan dalam pemilihan metode preparasi ko-amorf.

Formation of Polymer-Carbon Nanotube Composites by Two-Step Supercritical Fluid Treatment

An approach for polymer-carbon nanotube (CNT) composite preparation is proposed based on a two-step supercritical fluid treatment. The first step, rapid expansion of a suspension (RESS) of CNTs in supercritical carbon dioxide, is used to de-bundle CNTs in order to simplify their mixing with polymer in solution. The ability of RESS pre-treatment to de-bundle CNTs and to cause significant bulk volume expansion is demonstrated. The second step is the formation of polymer-CNT composite from solution via supercritical antisolvent (SAS) precipitation. SAS treatment allows avoiding CNT agglomeration during transition from a solution into solid state due to the high speed of phase transition. The combination of these two supercritical fluid methods allowed obtaining a polycarbonate-multiwalled carbon nanotube composite with tensile strength two times higher compared to the initial polymer and enhanced elasticity.

Supercritical Antisolvent Fractionation of Antioxidant Compounds from Salvia officinalis

The increasing interest towards greener antioxidants obtained via natural sources and more sustainable processes encourages the development of new theoretical and experimental methods in the field of those compounds. Two advanced separation methods using supercritical CO2 are applied to obtain valuable antioxidants from Salvia officinalis, and a first approximation to a QSAR model relating molecular structure with antioxidant activity is explored in order to be used, in the future, as a guide for the preselection of compounds of interest in these processes. Separation experiments through antisolvent fractionation with supercritical CO2 were designed using a Response Surface Methodology to study the effect of pressure and CO2 flow rate on both mass yields and capability to obtain fractions enriched in three antioxidant compounds: chlorogenic acid, caffeic acid and rosmarinic acid which were tracked using HPLC PDA. Rosmarinic acid was completely retained in the precipitation vessel while chlorogenic and caffeic acids, though distributed between the two separated fractions, had a major presence in the precipitation vessel too. The conditions predicted for an optimal overall yield and enrichment were 148 bar and 10 g/min. Although a training dataset including much more compounds than those now considered can be recommended, descriptors calculated from the σ-profiles provided by COSMO-RS model seem to be adequate for estimating the antioxidant activity of pure compounds through QSAR.

Assessment of amentoflavone loaded sub-micron particle preparation using supercritical antisolvent for its antitumor activity

Introduction: The amentoflavone (AMF) loaded polymeric sub-micron particles were prepared using supercritical antisolvent (SAS) technology with the aim of improving the anticancer activity of AMF. Materials and Methods: Zein and phospholipid mixtures composed of hydrogenated phosphatidylcholine (HPC) and egg lecithin (EPC) were used as carrier materials and, the effects of carrier composition on the product morphology and drug release behavior were investigated. When the mass ratio of Zein/HPC/EPC was 7/2/1, the AMF loaded particles were spherical shape and sub-micron sized around 400 nm, with a drug load of 4.3±0.3 w% and entrapment efficacy of 87.8±1.8%. The in vitro drug release assay showed that adding EPC in the wall materials could improve the dispersion stability of the released AMF in an aqueous medium, and the introduction of HPC could accelerate the drug release speed. Results: MTT assay demonstrated that AMF-loaded micron particles have an improved inhibitory effect on A375 cells, whose IC50 was 37.39μg/ml, compared with that of free AMF(130.2μg/ml). Conclusion: It proved that the AMF loaded sub-micron particles prepared by SAS were a prospective strategy to improve the antitumor activity of AMF, and possibly promote the clinical use of AMF preparations.