title: Formulation and biopharmaceutical evaluation of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets.
abstract: The objective of this study was to prepare and evaluate some physiochemical and biopharmaceutical properties of bitter taste masking microparticles containing azithromycin loaded in dispersible tablets. In the first stage of the study, the bitter taste masking microparticles were prepared by solvent evaporation and spray drying method. When compared to the bitter threshold (32.43µg/ml) of azithromycin (AZI), the microparticles using AZI:Eudragit L100=1:4 and having a size distribution of 45-212µm did significantly mask the bitter taste of AZI. Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H NMR) proved that the taste masking of microparticles resulted from the intermolecular interaction of the amine group in AZI and the carbonyl group in Eudragit L100. Differential scanning calorimeter (DSC) analysis was used to display the amorphous state of AZI in microparticles. Images obtaining from optical microscopy and scanning electron microscopy (SEM) indicated the existence of microparticles in regular cube shape with many layers. In the second stage, dispersible tablets containing microparticles (DTs-MP) were prepared by direct compression technique. Stability study was conducted to screen pH modulators for DTs-MP, and a combination of alkali agents (CaCO3:NaH2PO4, 2:1) was added into DTs-MP to create microenvironment pH of 5.0-6.0 for the tablets. The disintegration time of optimum DTs-MP was 53±5.29s and strongly depended on the kinds of lubricant and diluent. The pharmacokinetic study in the rabbit model using liquid chromatography tandem mass spectrometry showed that the mean relative bioavailability (AUC) and mean maximum concentration (Cmax) of DTs-MP were improved by 2.19 and 2.02 times, respectively, compared to the reference product (Zithromax®, Pfizer).
authors.affiliation: Department of Pharmaceutics, Hanoi University of Pharmacy, Viet Nam. Electronic address: nguyenthachtung@hup.edu.vn.
authors.forename: Nguyen-Thach
authors.initials: NT
authors.lastname: Tung
authors.affiliation: National Institute for Food Control, Viet Nam. Electronic address: sontc@nifc.gov.vn.
authors.forename: Cao-Son
authors.initials: CS
authors.lastname: Tran
authors.affiliation: Department of Pharmaceutics, Hanoi University of Pharmacy, Viet Nam.
authors.forename: Tran-Linh
authors.initials: TL
authors.lastname: Nguyen
authors.affiliation: Department of Pharmaceutics, Hanoi University of Pharmacy, Viet Nam.
authors.forename: Tung
authors.initials: T
authors.lastname: Hoang
authors.affiliation: Department of Pharmaceutics, Hanoi University of Pharmacy, Viet Nam.
authors.forename: Thanh-Dat
authors.initials: TD
authors.lastname: Trinh
authors.affiliation: College of Pharmacy, Thai Binh University, Viet Nam.
authors.forename: Thi-Ngan
authors.initials: TN
authors.lastname: Nguyen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D017963:Azithromycin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D004339:Drug Compounding / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D065569:Gastrointestinal Absorption / Q000187:drug effects / Q000502:physiology; D008863:Microspheres; D011817:Rabbits; D013607:Tablets; D013649:Taste / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D013607:Tablets; D017963:Azithromycin
keywords: Azithromycin; Bioavailability; Bitter taste masking; Dispersible tablets; Microparticles; Stability