Kajian Metode Top Down dalam Pembuatan Nanokristal Obat Antidiabetika Oral

Nina Renata (Prodi Farmasi, Fakultas Farmasi dan Sains, Universitas Islam Bandung, Indonesia)
Fitrianti Darusman (Prodi Farmasi, Fakultas Farmasi dan Sains, Universitas Islam Bandung, Indonesia)
Hanifa Rahma (Prodi Farmasi, Fakultas Farmasi dan Sains, Universitas Islam Bandung, Indonesia)

Bandung Conference Series: Pharmacy
501 - 508

Abstract. Type 2 diabetes mellitus remains one of the most prevalent non-communicable diseases in Indonesia, and most first-line oral antidiabetic agents such as glibenclamide, glimepiride, and gliclazide belong to Biopharmaceutics Classification System (BCS) class II, characterized by poor aqueous solubility and consequently limited and variable oral bioavailability. Nanocrystal technology has emerged as a practical formulation strategy to overcome this limitation by reducing drug particle size to the nanometer range, thereby increasing the surface area available for dissolution. This article aims to review top-down methods used to produce nanocrystals of oral antidiabetic drugs through a literature review approach. Sources were obtained from international scientific databases, including PubMed, ScienceDirect, and MDPI, focusing on publications from the last ten years. The review shows that wet media milling and high-pressure homogenization are the most widely applied top-down techniques, either alone or combined with cocrystallization to form nano-cocrystals. Each method has distinct mechanisms, critical process parameters, and stabilizer requirements that determine the final particle size and dissolution performance. Overall, top-down nanocrystallization offers a scalable and solvent-minimal approach for improving the solubility, dissolution rate, and potential bioavailability of poorly soluble oral antidiabetic drugs. Abstract. Type 2 diabetes mellitus remains one of the most prevalent non-communicable diseases in Indonesia, and most first-line oral antidiabetic agents such as glibenclamide, glimepiride, and gliclazide belong to Biopharmaceutics Classification System (BCS) class II, characterized by poor aqueous solubility and consequently limited and variable oral bioavailability. Nanocrystal technology has emerged as a practical formulation strategy to overcome this limitation by reducing drug particle size to the nanometer range, thereby increasing the surface area available for dissolution. This article aims to review top-down methods used to produce nanocrystals of oral antidiabetic drugs through a literature review approach. Sources were obtained from international scientific databases, including PubMed, ScienceDirect, and MDPI, focusing on publications from the last ten years. The review shows that wet media milling and high-pressure homogenization are the most widely applied top-down techniques, either alone or combined with cocrystallization to form nano-cocrystals. Each method has distinct mechanisms, critical process parameters, and stabilizer requirements that determine the final particle size and dissolution performance. Overall, top-down nanocrystallization offers a scalable and solvent-minimal approach for improving the solubility, dissolution rate, and potential bioavailability of poorly soluble oral antidiabetic drugs. Abstrak. . Diabetes melitus tipe 2 masih menjadi salah satu penyakit tidak menular dengan prevalensi tertinggi di Indonesia, dan sebagian besar obat antidiabetika oral lini pertama seperti glibenklamid, glimepirid, dan gliklazid termasuk ke dalam Biopharmaceutics Classification System (BCS) kelas II yang memiliki kelarutan dalam air rendah sehingga bioavailabilitas oralnya terbatas dan bervariasi. Teknologi nanokristal menjadi salah satu strategi formulasi yang banyak dikembangkan untuk mengatasi keterbatasan tersebut dengan mengecilkan ukuran partikel obat hingga skala nanometer sehingga luas permukaan yang tersedia untuk disolusi meningkat. Artikel ini bertujuan untuk mengkaji metode-metode top-down yang digunakan dalam pembuatan nanokristal obat antidiabetika oral melalui pendekatan studi literatur. Sumber pustaka diperoleh dari basis data ilmiah internasional seperti PubMed, ScienceDirect, dan MDPI dengan fokus pada publikasi sepuluh tahun terakhir. Hasil kajian menunjukkan bahwa wet media milling dan high pressure homogenization merupakan teknik top-down yang paling banyak diterapkan, baik secara tunggal maupun dikombinasikan dengan pendekatan kokristalisasi untuk membentuk nano-kokristal. Setiap metode memiliki mekanisme, parameter proses kritis, dan kebutuhan stabilizer yang berbeda, yang menentukan ukuran partikel akhir serta kinerja disolusinya. Secara keseluruhan, nanokristalisasi top-down menawarkan pendekatan yang scalable dan minim pelarut untuk meningkatkan kelarutan, laju disolusi, dan potensi bioavailabilitas obat antidiabetika oral yang sukar larut.