PENINGKATAN KELARUTAN ETIL p-METOKSISINAMAT DENGAN PEMBENTUKAN KOKRISTAL MENGGUNAKAN METODE SOLVENT EVAPORATION DAN KOFORMER UREA

Abstract

Etil p-metoksisinamat (EPMS) merupakan isolat dengan persentase terbesar pada kencur (Kampferia galanga), tetapi sifatnya yang sukar larut air menyebabkan keterbatasan pada disolusi dan bioavailabilitas. Bioavailabilitas yang terbatas mengakibatkan aktivitas farmakologi yang rendah. Untuk mengatasi permasalahan tersebut, kelarutan EPMS dalam air perlu ditingkatkan. Penelitian ini bertujuan untuk meningkatkan kelarutan EPMS melalui pembentukan kokristal menggunakan metode solvent evaporation dan koformer urea. EPMS dan urea dengan perbandingan 1:1, 1:2, 1:3, dan 2:1 dilarutkan dalam etanol kemudian diuapkan. Kokristal EPMS-urea yang diperoleh dikarakterisasi menggunakan mikroskop digital, High Performance Liquid Chromatography (HPLC), spektrofotometer Fourier Transform Infrared (FT-IR), Powder X-Ray diffraction (PXRD), dan uji kelarutan di dalam air. Hasil penelitian menunjukkan kokristal EPMS-urea terbentuk akibat terjadinya ikatan hidrogen dan mengalami penurunan ukuran partikel, penurunan kristalinitas, dan peningkatan kelarutan. Kadar EPMS dalam sistem kokristal sebesar 91 -106%.

Review: Potency of Amide Derivates as Co-Crystal Formers and Its Impact on the Physicochemical of Active Pharmaceutical Ingredients

“…Coformer is an excipient with a small molecular weight that is required in small amounts in the formation of co-crystals because the ratio of coformer and drug in forming co-crystals uses a stoichiometric ratio. Stoichiometric ratios are used in forming co-crystals because co-crystals require molecular interactions in the process of their formation, such as hydrogen bonds and van der Waals bonds (Rachmaniar et al, 2020). In general, the ratio between API and coformer is 1:1, 1:2, or vice versa.…”

“…Ethyl p-methoxycinnamate (EPMS) is less soluble in water, causing limitations in its dissolution and bioavailability. With the formation of hydrogen bonds in the EPMS-urea co-crystal, there is a decrease in particle size, a decrease in crystallinity, and an increase in solubility in water (1.6 times that of pure EMPS) (Rachmaniar et al, 2020). The use of co-crystal formers of amide derivates and their effects on the physicochemical properties of active pharmaceutical ingredients can be seen in Table II.…”

“…The solubility of EMPS is 1.6 times higher than that of pure EMPS solvent. Solvent Evaporations (Rachmaniar et al, 2020)…”