Sains Malaysiana 49(10)(2020): 2513-2525

http://dx.doi.org/10.17576/jsm-2020-4910-17

Formulation of Metformin-Loaded Alginate Microspheres by Ionotropic Gelation-Aerosolization Technique

(Formulasi Mikrosfera Alginat Muatan-Metformin oleh Pengegelan Ionotropik- Kaedah Aerosol)

DEWI MELANI HARIYADI¹*, YASHWANT PATHAK^1,2, ESTI HENDRADI¹, TRISTIANA ERAWATI¹, IZZATUL HIDAYAH¹ & ELIZABETH SANTOS¹

¹Pharmaceutics Department, Faculty of Pharmacy, Universitas Airlangga, 60286, Indonesia

²College of Pharmacy, University of South Florida, 33612, United States of America

Received: 26 December 2019/Accepted: 18 April 2020

ABSTRACT

Metformin hydrochloric acid (HCl)-loaded alginate microspheres prepared using aerosolization method were subsequently evaluated for their physico-chemical characteristics in terms of particle size, morphology, drug loading, entrapment efficiency, yield and in vitro release. A two factorial Design of Experiment (DoE) was used to study the influence of polymer alginate and cross-linker calcium chloride (CaCl₂) concentrations on microparticle characteristics. The results indicated that all microspheres were spherical in shape, while their particle size was less than 5 µm, although this increased with the intensification of alginate and CaCl₂ concentrations. Encapsulation efficiency, loading, and yield were all enhanced by increasing alginate concentration and, conversely, decreasing CaCl₂ concentration. The highest encapsulation efficiency, loading, and yield were 40, 31, and 73%, respectively, produced by a formula containing 1.75% alginate and 3% CaCl₂. The drug release of Metformin-loaded microparticles in HCl pH 1.2 ranged from 22 to 28% during a two-hour period, while further drug release of PBS pH 7.4 increased from 67 to 95% over ten hours. The total amount of drug released during a 12-h period increased by reducing alginate concentration. Furthermore, a kinetic study of the dissolution data confirmed the prevalence of a diffusion-controlled mechanism or Higuchi pattern of drug release.

Keywords: Aerosolization; alginate microspheres; design of experiment; metformin

ABSTRAK

Mikrosfera alginat muatan-metformin asid hidroklorik (HCl) yang disediakan menggunakan kaedah aerosol telah dinilai untuk ciri fizikal-kimia berdasarkan saiz zarah, morfologi, muatan ubat, kecekapan pemerangkapan, kadar hasil dan pelepasan in vitro. Dua reka bentuk uji kaji (DoE) faktoran digunakan untuk mengkaji pengaruh alginat polimer dan kepekatan penghubung silang kalsium klorida (CaCl₂) pada ciri mikrozarah. Keputusan kajian menunjukkan bahawa kesemua mikrosfera mempunyai bentuk sfera, manakala saiz zarah kurang daripada 5 µm, walaupun ia meningkat dengan pengamatan alginat dan kepekatan CaCl₂. Kecekapan pengapsulan, muatan, kadar hasil kesemuanya dipertingkat dengan peningkatan kepekatan alginat dan sebaliknya penurunan kepekatan CaCl₂. Kecekapan pengkapsulan, muatan dan kadar hasil tertinggi masing-masing adalah 40,31 dan 73%, dihasilkan dengan formula yang mengandungi alginat 1.75% dan CaCl₂ 3%. Perlepasan ubat mikrozarah muatan-metformin dalam HCl pH 1.2 berjulat antara 22 sehingga 28% ketika tempoh dua jam, manakala perlepasan ubat daripada PBS pH 7.4 meningkat daripada 67 sehingga 95% dalam masa 10 jam. Jumlah keseluruhan  perlepasan ubat ketika tempoh 12 jam meningkat dengan penurunan kepekatan alginat. Selain itu, kajian kinetik berkenaan data perlarutan memperakui prevalens mekanisme terkawal-penyerapan atau pola Higuchi perlepasan ubat.

Kata kunci: Aerosol; metformin; mikrosfera alginat; reka bentuk uji kaji

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*Corresponding author; email: dewi-m-h@ff.unair.ac.id