Effect of Conventional and Ultrasound-Assisted Recrystallisation of Mefenamic Acid Crystal
Abstract
Mefenamic acid is classified as a Biopharmaceutical Classification System (BCS) Class II drug. Crystallisation techniques can significantly influence the critical properties of mefenamic acid crystals, an essential consideration in the pharmaceutical industry. This study investigates the effect of recrystallisation on the morphology and particle size of mefenamic acid crystals using ethyl acetate as the solvent. Recrystallisation was conducted using both conventional and ultrasonic-assisted methods. The yield was calculated, and characterization was performed to determine the crystal properties, shape, and particle size using polarized microscopy, X-ray Diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR). The results showed that conventional recrystallisation yielded 25.078%, while ultrasonic-assisted recrystallisation at 50 W, 60 W, 70 W, and 80 W yielded 43.47%, 47.71%, 51.90%, and 50.20%, respectively. Skewness and kurtosis values for the average crystal length and width indicated a normal distribution. XRD analysis revealed that the diffraction peak intensity of conventionally recrystallised crystals became narrow. In contrast, the diffraction peak intensity of ultrasonically assisted crystals broadened. FTIR results demonstrated that the recrystallisation process did not alter the fundamental chemical structure of mefenamic acid. Recrystallisation methods influence crystal shape and size, with ultrasonic-assisted techniques producing crystals of smaller average size than those obtained through conventional methods.
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References
Suksaeree J, Siripornpinyo P, Chaiprasit S. Formulation, Characterization, and In Vitro Evaluation of Transdermal Patches for Inhibiting Crystallization of Mefenamic Acid. Journal of Drug Delivery. 2017(1):1–7. Crossref
SeethaLekshmi S, Row TNG. Conformational Polymorphism in a Non-steroidal Anti-inflammatory Drug, Mefenamic Acid. Crystal Growth & Design. 2012;12:4283–4289. Crossref
Indra I, Fauzi A, Aryani R. Karakterisasi dan Uji Disolusi Aspirin Hasil Rekristalisasi Penguap Pelarut. Jurnal Sains Farmasi & Klinis. 2019;6(2):164–170. Crossref
Iyer SR, Gogate PR. Ultrasound Assisted Crystallization of Mefenamic Acid: Effect of Operating Parameters and Comparison with Conventional Approach. Ultrasonics Sonochemistry. 2017(34):896–903. Crossref
Cunha VRR, Izumi CMS, Petersen PAD, Magalhães A, Temperini MLA, Petrilli HM, et al. Mefenamic Acid Anti-Inflammatory Drug: Probing Its Polymorphs by Vibrational (IR and Raman) and Solid-State NMR Spectroscopies. J Phys Chem B. 2014;118(16):4333–4344. Crossref
Li WG, Wang XD, Huang YH, Kuang DB. Ultrasound-Assisted Crystallization Enables Large-Area Perovskite Quasi-Monocrystalline Film for High-Sensitive X-ray Detection and Imaging. Advanced Materials. 2023;35(31):31–35. Crossref
Kim HN, Suslick KS. The Effects of Ultrasound on Crystals: Sonocrystallization and Sonofragmentation. Crystals. 2018;8(7):1–20. Crossref
Rahima AA, Dewi EN. Simulasi Pengaruh Reflux Ratio pada Proses Pemurnian Etil Asetat dengan Distilasi Ekstraktif Menggunakan Chemcad. J Chemurg. 2020;4(1):6–11. Crossref
Shah H, Jain A, Laghate G, Prabhudesai D. Pharmaceutical Excipients. Remingt Sci Pract Pharm. 2021;633–643. Crossref
Indra I, Rahman R, Yulianti R. Karakterisasi Karbamazepin Hasil Rekristalisasi Berbagai Pelarut Organik dengan Metode Slow Evaporation. J Farm dan Ilmu Kefarmasian Indones. 2021;8(3):227–234. Crossref
Bunaciu AA, Udristioiu EG, Aboul-Enein HY. X-Ray Diffraction: Instrumentation and Applications. Critical Reviews in Analytical Chemistry. 2015;45(4):289–299. Crossref
Khairunisa LF, Widyasanti A, Nurjanah S. Kajian Pengaruh Kecepatan Pengadukan terhadap Rendemen dan Mutu Kristal Patchouli Alcohol dengan Metode Cooling Crystallization. J Keteknikan Pertan Trop dan Biosist. 2019;7(1):55–66. Crossref
Xiang L, Fu M, Wang T, Wang D, Xv H, Miao W, et al. Application and Development of Ultrasound in Industrial Crystallization. Ultrason Sonochem. 2024;111(167062):1–26. Crossref
Zhang B, Ådnebergli I, Stefanidis GD, Van Gerven T. Effects of Ultrasound on Reactive Crystallization and Particle Properties of an Aromatic Amine in Batch and Continuous Modes. Ultrason Sonochem. 2024;111(107121):1–11. Crossref
Mudalip SKA, Sezali NA, Bakar MRA. Effect of Ultrasonic Waves on Polymorphism and Crystal Size Distributions of Mefenamic Acid. In: IOP Conference Series: Materials Science and Engineering. 2020. 1–8. Crossref
Sabnis SS, Singh SD, Gogate PR. Improvements in Azithromycin Recrystallization using Ultrasound for Size Reduction. Ultrason Sonochem. 2022;83:105922–105926. Crossref
Bahanan R. Pengaruh Waktu Sonokimia terhadap Ukuran Kristal Kalsium Karbonat (CaCO3). UIN Syarif Hidayatullah, Jakarta; 2010.
Azis A. Belajar Statistik dengan SPSS dan Manual. Jakarta: Lingkaran Matematika; 2015. 6-15.
Rojsitthisak P, Khunthon S, Noomun K, Limpanart S. Response Surface Method to Optimize the Preparation of Carboxymethyl Cellulose from Corn Peel Agricultural Waste. ScienceAsia. 2017;43(1):8–14. Crossref
Mudalip SKA, Bakar MRA, Jamal P, Adam F, Che Man R, Sulaiman SZ, et al. Effects of Solvents on Polymorphism and Shape of Mefenamic Acid Crystals. MATEC Web Conf. 2018;150:1–5. Crossref
Kresnamurti A, Izazi F, Camelia D. Standarisasi dan Analisis FTIR Ekstrak Etanol 70% Bulu Babi (Echinometra mathaei) dari Sabang, Nanggroe Aceh Darussalam. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2022;9(1):1–8. Crossref
Guntarti A, Sholehah K, Irna N, Fistianingrum W. Penentuan Parameter Non Spesifik Ekstrak Etanol Kulit Buah Manggis (Garcinia mangostana) pada Variasi Asal Daerah. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2015;2(5):202–207.
Tripathi D, Sharma DK, Sahoo J. Analytical Applications of Mefenamic Acid by Hydrotrope Approach: Titrimetric Estimation and Ultraviolet Method Validation. Asian Journal of Pharmaceutical and Clinical Research. 2021;14(7):40-44. Crossref
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