Preparation of Ibuprofen Microparticles by Antisolvent Precipitation Crystallization Technique: Characterization, Formulation, and In Vitro Performance

Afrina Afrose; Edward T White; Tony Howes; Graeme George; Abdur Rashid; Llew Rintoul; Nazrul Islam

doi:10.1016/j.xphs.2018.07.030

Preparation of Ibuprofen Microparticles by Antisolvent Precipitation Crystallization Technique: Characterization, Formulation, and In Vitro Performance

J Pharm Sci. 2018 Dec;107(12):3060-3069. doi: 10.1016/j.xphs.2018.07.030. Epub 2018 Aug 9.

Authors

Afrina Afrose¹, Edward T White², Tony Howes², Graeme George³, Abdur Rashid⁴, Llew Rintoul⁵, Nazrul Islam⁶

Affiliations

¹ Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
² School of Chemical Engineering, The University of Queensland, Brisbane, Queensland, Australia.
³ Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.
⁴ Department of Pharmaceutics, School of Pharmacy, King Khalid University, Guraiger, Abha 62529, Kingdom of Saudi Arabia.
⁵ School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.
⁶ Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: nazrul.islam@qut.edu.au.

PMID: 30098991
DOI: 10.1016/j.xphs.2018.07.030

Abstract

This study demonstrates the preparation and characterization of ibuprofen (IBP) microparticles with some excipients by a controlled crystallization technique with improved dissolution performance. Using the optimum concentrations pluronic F127, hydroxypropyl methyl cellulose, D-mannitol, and l-leucine in aqueous ethanol, the IBP microparticles were prepared. The dissolution tests were performed in phosphate buffer saline using a United States Pharmacopoeia dissolution tester at 37°C. The Raman spectroscopy was used to investigate the interactions and distribution of the IBP with the additives in the microcrystals. The prepared IBP microparticles showed higher dissolution compared to that of the smaller sized original IBP particles. The Raman data revealed that the excipients with a large number of hydroxyl groups distributed around the IBP particle in the crystal enhanced the dissolution of the drug by increasing the drug-solvent interaction presumably through hydrogen bonding. The Raman mapping technique gave an insight into the enhanced dissolution behavior of the prepared IBP microparticles, and such information will be useful for developing pharmaceutical formulations of hydrophobic drugs. The controlled crystallization was a useful technique to prepare complex crystals of IBP microparticles along with other additives to achieve the enhanced dissolution profile.

Keywords: Raman mapping; crystallinity; dissolution; excipients; ibuprofen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemistry*
Chemical Precipitation
Crystallization / methods*
Drug Compounding / methods*
Excipients / chemistry
Freeze Drying
Hypromellose Derivatives / chemistry
Ibuprofen / chemistry*
Leucine / chemistry
Mannitol / chemistry
Particle Size
Poloxamer / chemistry
Solubility
Solvents / chemistry
Spectrum Analysis, Raman

Substances

Anti-Inflammatory Agents, Non-Steroidal
Excipients
Solvents
Poloxamer
Hypromellose Derivatives
Mannitol
Leucine
Ibuprofen