Study of Co-crystal Preparation Methods for Oral Antidiabetic Drugs
Keywords:
Co-crystal, Oral Antidiabetic Drugs, Co-crystal SynthesisAbstract
Abstract. Diabetes mellitus is a metabolic disease with increasing prevalence, while some oral antidiabetic drugs still have limitations in terms of solubility, dissolution rate, and low bioavailability. One approach to overcome these problems is the formation of co-crystals, namely multicomponent crystal systems formed through noncovalent interactions between active substances and coformers. This article aims to review various methods for preparing co-crystals for oral antidiabetic drugs and their characteristics. The study was conducted using a literature review method of scientific articles obtained through Google Scholar, ScienceDirect, PubMed, and ResearchGate. Data were analyzed narratively to measure the mechanisms, advantages, limitations, and potential applications of each method. The results of the study indicate that solvent evaporation, antisolvent, cooling crystallization, slurry, spray drying, neat milling, and liquid-assisted grinding methods have different characteristics in producing co-crystals. The selection of an effective method influences the success of co-crystal formation and increases the solubility, dissolution rate, stability, and bioavailability of oral antidiabetic drugs. Therefore, the selection of synthesis method needs to be adjusted to the characteristics of the active substance and the purpose of developing pharmaceutical preparations.
Abstrak. Diabetes melitus merupakan penyakit metabolik dengan prevalensi yang terus meningkat, sedangkan beberapa obat antidiabetik oral masih memiliki keterbatasan berupa kelarutan, laju disolusi, dan bioavailabilitas yang rendah. Salah satu pendekatan untuk mengatasi permasalahan tersebut adalah pembentukan ko-kristal, yaitu sistem kristal multikomponen yang terbentuk melalui interaksi nonkovalen antara zat aktif dan koformer. Artikel ini bertujuan mengkaji berbagai metode pembuatan ko-kristal pada obat antidiabetik oral serta karakteristiknya. Penelitian dilakukan menggunakan metode literature review terhadap artikel ilmiah yang diperoleh melalui Google Scholar, ScienceDirect, PubMed, dan ResearchGate. Data dianalisis secara naratif untuk membandingkan mekanisme, keunggulan, keterbatasan, dan potensi penerapan setiap metode. Hasil kajian menunjukkan bahwa metode solvent evaporation, anti-solvent, cooling crystallization, slurry, spray drying, neat grinding, dan liquid-assisted grinding memiliki karakteristik yang bereda dalam menghasilkan ko-kristal. Pemilihan metode yang tepat berpengaruh terhadap keberhasilan pembentukan ko-kristal serta peningkatan kelarutan, laju disolusi, stabilitas, dan biovailabilitas obat antidiabetic oral. Oleh karena itu, pemilihan metode sintesis perlu disesuaikan dengan karakteristik zat aktif dan tujuan pengembangan sediaan farmasi.
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