Optimization cocrystal formation of furosemide with malic acid coformer using neat grinding method to improve solubility and dissolution

Agus Siswanto; Riski Oktaviana Saputri; Uqie Shabrina Hasyyati

doi:10.35814/jifi.v24i2.2140

Authors

Agus Siswanto Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Jl. K.H. Ahmad Dahlan 53142, Indonesia
Riski Oktaviana Saputri Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Jl. K.H. Ahmad Dahlan 53142, Indonesia
Uqie Shabrina Hasyyati Faculty of Pharmacy, Universitas Muhammadiyah Purwokerto, Jl. K.H. Ahmad Dahlan 53142, Indonesia

DOI:

https://doi.org/10.35814/jifi.v24i2.2140

Keywords:

cocrystal, dissolution, furosemide, malic acid, neat grinding

Abstract

Furosemide is a Biopharmaceutical Classification System (BCS) IV class diuretic. Its bioavailability is limited because of poor solubility. The present study aims to evaluate the cocrystallization of furosemide with malic acid as a coformer by neat grinding for improving solubility. The objective was to find the best ratio of furosemide to malic acid for cocrystal production. Optimization was carried out by Simplex Lattice Design (SLD) in Design-Expert 13.0 software with furosemide (A) and malic acid (B) as variables in concentrations of 1 molar (low) to 2 molar (high) for eight experimental trials. The optimum formulation was identified by numerical analysis of solubility and dissolution (Q60) data. Results showed that the formation of furosemide–malic acid cocrystals by neat grinding improved solubility and dissolving rate. The optimal molar ratio of furosemide:malic acid was 1.339:1.661 with the desirability value of 0.965. The optimized capsule formulation complied with the required physical properties and dissolution release parameters.

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