PENINGKATAN SIFAT FISIKOKIMIA KELARUTAN DAN DISOLUSI RAMIPRIL DENGAN KRISTAL MULTIKOMPONEN MENGGUNAKAN KOFORMER GOLONGAN ASAM KARBOKSILAT
DOI:
https://doi.org/10.36423/pharmacoscript.v8i1.2040Keywords:
Ramipril, Kristal multikomponen, Kelarutan, DisolusiAbstract
Salah satu tantangan utama pengembangan obat saat ini adalah kelarutan yang buruk, karena diperkirakan 40% dari semua obat yang baru dikembangkan memiliki kelarutan dan permeabilitas yang buruk. Akibatnya, kandidat baru yang memasuki jalur pengembangan obat gagal karena sifat biofarmasi yang tidak optimal. Ramipril termasuk ke dalam BCS kelas II dengan nilai pKa 5,2 dan memiliki kelarutan air yang buruk dengan nilai bioavailabilitas yang rendah yaitu 28%. Absorbsi ramipril setelah pemberian oral yaitu 50%-60%. Keterbatasan sifat fisikokimia yang dimiliki ramipril dapat diatasi dengan modifikasi kristal salah satunya dengan pembentukkan kristal multikomponen menggunakan teknik kokristalisasi. Pendekatan dalam memperbaiki sifat fisikokimia ramipril dengan konteks kelarutan dan disolusi masih jarang dilakukan, sehingga dengan teknik kokristalisasi dalam modifikasi kristal ramipril menjadi suatu novelty dalam penelitian ini. Pendekatan dengan kristal multikomponen bertujuan untuk meningkatkan sifat fisikokimia ramipril seperti kelarutan dan disolusi. Metode yang digunakan dalam preparasi kristal multikomponen dengan teknik kokristalisasi yaitu liquid assisted grinding menggunakan koformer golongan asam karboksilat seperti asam tartrat dengan perbandingan 1:1. Hasil penelitian menunjukkan bahwa kelarutan kristal multikomponen ramipril 4,35 mg/10 mL dan ramipril murni 1,69 mg/10 mL dalam aquadest. Kristal multikomponen ramipril terdisolusi 73,27% dan ramipril murni 51,74% selama 60 menit menggunakan media aquadest. Modifikasi kristal ramipril menggunakan teknik kristal multikomponen menggunakan metode liquid assisted grinding memberikan dampak perubahan sifat fisikokimia dalam meningkatkan kelarutan dan laju disolusi.
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