Sains Malaysiana 53(10)(2024): 3445-3454

http://doi.org/10.17576/jsm-2024-5310-17

Solubility and Dissolutıon Improvement of Paramethoxycinnamic Acid (PMCA) Induced by Cocrystal Formation using Caffeine as a Coformer

(Penambahbaikan Keterlarutan dan Pelarutan Asid Parametoksisinamik (PMCA) Teraruh oleh Pembentukan Kokristal menggunakan Kafein sebagai Koformer)

MELANNY IKA SULISTYOWATY¹, SUCİATİ FİTRݹ, NİNİS YULİATİ^1,2, TAHTA AMRİLLAH³, CHE AZURAHANİM CHE ABDULLAH⁴ & DWİ SETYAWAN^1,*

¹Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya 60115, Indonesia

²Department of Pharmacy Technology, Faculty of Pharmacy, Institut Ilmu Kesehatan Bhakti Wiyata Kediri, Kediri 64114, Indonesia

³Nanotechnology Engineering, Faculty of Advanced Technology and Multidiscipline, Universitas Airlangga, Surabaya 60115, Indonesia

⁴Institute of Nanoscience and Nanotechnology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

Diserahkan: 21 Ogos 2023/Diterima: 13 Ogos 2024

Abstract

Para-methoxy cinnamic acid (pMCA) is a derivative compound of ethyl p-methoxycinnamate that could be obtained in nature. pMCA has excellent pharmacological properties. However, in their application as a drug, pMCA has poor water solubility. In this present research, we try to increase the water solubility of pMCA using the cocrystal formation (cocrystallization) strategy. Here, we use caffeine as a coformer that can interact very well with pMCA via non-covalent bonding and Van der Waals interaction to achieve cocrystal formation. The cocrystal samples were successfully synthesized using various synthesis techniques; physical mixture, solvent evaporation, and microwave radiation methods. It shows that the solubility of the samples synthesized using microwave-assisted and solvent evaporation increases about 3.30 and 3.12 times, respectively, whereas the dissolution rate profile increases 2.50 and 2.39 times, respectively, compared to pure APMS. Our findings explain the importance of the cocrystal formation strategy to enhance the solubility of active material pMCA. This strategy can also be used as a standard formulation of a new drug system with excellent solubility and dissolution which is very important for the pharmaceutical industry.

Keywords: Caffeine; cocrystal; dissolution; drugs; para-methoxy cinnamic acid; solubility

Abstrak

Asid sinamik para-metoksi (pMCA) ialah sebatian terbitan etil p-metoksisinamat yang boleh didapati secara semula jadi. pMCA mempunyai sifat farmakologi yang sangat baik seperti sifat analgesik, anti-radang, anti-diabetes, anti-kanser, hepatopelindung dan neuropelindung. Walau bagaimanapun, dalam penggunaannya sebagai ubat, pMCA mempunyai keterlarutan air yang lemah. Manakala, keterlarutan dadah merupakan aspek penting yang perlu dimiliki oleh sesuatu ubat untuk mencapai kesan yang dikehendaki. Dalam penyelidikan ini, kami cuba meningkatkan keterlarutan air pMCA menggunakan strategi pembentukan kokristal (penghabluran). Di sini, kami menggunakan kafein sebagai koformer yang boleh berinteraksi dengan baik dengan pMCA melalui ikatan bukan kovalen dan interaksi Van der Waals untuk mencapai pembentukan kokristal. Sampel kokristal telah berjaya disintesis menggunakan pelbagai teknik sintesis; campuran fizikal, penyejatan pelarut dan kaedah sinaran gelombang mikro. Semua sampel kokristal mempunyai keterlarutan yang sangat baik berbanding dengan keadaan murni atau pMCA tulen. Sampel yang disediakan menggunakan sinaran gelombang mikro mempunyai keterlarutan yang paling tinggi berbanding sampel yang disediakan menggunakan kaedah campuran fizikal dan penyejatan pelarut. Penemuan kami menerangkan kepentingan strategi pembentukan kokristal untuk meningkatkan keterlarutan bahan aktif pMCA. Strategi ini juga boleh digunakan sebagai formulasi standard sistem ubat baharu dengan keterlarutan dan pembubaran yang sangat baik yang sangat penting untuk industri farmaseutikal.

Kata kunci: Asid sinamik para-metoksi; dadah; kafein; keterlarutan; kokristal; pembubaran

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*Pengarang untuk surat-menyurat; email: dwisetyawan-90@ff.unair.ac.id