title: Coamorphous Loratadine-Citric Acid System with Enhanced Physical Stability and Bioavailability.
abstract: Coamorphous systems using citric acid as a small molecular excipient were studied for improving physical stability and bioavailability of loratadine, a BCS class II drug with low water solubility and high permeability. Coamorphous loratadine-citric acid systems were prepared by solvent evaporation technique and characterized by differential scanning calorimetry, X-ray powder diffraction, and Fourier transform infrared spectroscopy. Solid-state analysis proofed that coamorphous loratadine-citric acid system (1:1) was amorphous and homogeneous, had a higher Tgover amorphous loratadine, and the intermolecular hydrogen bond interactions between loratadine and citric acid exist. The solubility and dissolution of coamorphous loratadine-citric acid system (1:1) were found to be significantly greater than those of crystalline and amorphous form. The pharmacokinetic study in rats proved that coamorphous loratadine-citric acid system (1:1) could significantly improve absorption and bioavailability of loratadine. Coamorphous loratadine-citric acid system (1:1) showed excellently physical stability over a period of 3 months at 25°C under 0% RH and 25°C under 60% RH conditions. The improved stability of coamorphous loratadine-citric acid system (1:1) could be related to an elevated Tgover amorphous form and the intermolecular hydrogen bond interactions between loratadine and citric acid. These studies demonstrate that the developed coamorphous loratadine-citric acid system might be a promising oral formulation for improving solubility and bioavailability of loratadine.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China.
authors.forename: Ruimiao
authors.initials: R
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Chang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Shaanxi Province, Xi'an, 710061, China. agzeng@mail.xjtu.edu.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001682:Biological Availability; D019343:Citric Acid / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D017336:Loratadine / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
chemical_list: D005079:Excipients; D019343:Citric Acid; D017336:Loratadine
keywords: bioavailability; coamorphous loratadine-citric acid systems; loratadine; physical stability