title: A mixed solvent system for preparation of spherically agglomerated crystals of ascorbic acid.
abstract: The objective of this research was to develop a novel solvent system to prepare spherically agglomerated crystals (SAC) of ascorbic acid with improved flowability for direct compression. A spherical agglomeration method was developed by selecting the mixed solvents (n-butyl and ethyl acetate) as a poor solvent and the process was further optimized by using triangular phase diagram and particle vision measurement. Physiochemical properties of SAC were characterized and compared with original drug crystals. It showed that amount of poor solvent, ratio of solvent mixture, and drug concentration are critical for preparation of SAC with desirable properties. The solid state of SAC was same as original crystals according to DSC, XRD, and FT-IR results. There was no significant difference in solubility and dissolution rate of drug between SAC and original crystals. The flowability and packability of SAC as well as the tensile strength and elastic recovery of tablets made from SAC were all significantly improved when compared with original crystals and tablets from crystals. It is concluded that the present method was suitable to prepare SAC of ascorbic acid for direct compression.
authors.affiliation: a Laboratory of Pharmaceutical Crystal Engineering & Technology , School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors.forename: Fuzheng
authors.initials: F
authors.lastname: Ren
authors.affiliation: a Laboratory of Pharmaceutical Crystal Engineering & Technology , School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a Laboratory of Pharmaceutical Crystal Engineering & Technology , School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Laboratory of Pharmaceutical Crystal Engineering & Technology , School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Fu
authors.affiliation: a Laboratory of Pharmaceutical Crystal Engineering & Technology , School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors.forename: Qiufang
authors.initials: Q
authors.lastname: Jing
authors.affiliation: a Laboratory of Pharmaceutical Crystal Engineering & Technology , School of Pharmacy, East China University of Science and Technology , Shanghai , China.
authors.forename: Guobin
authors.initials: G
authors.lastname: Ren
mesh_terms: D001205:Ascorbic Acid; D003460:Crystallization; D010316:Particle Size; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D012997:Solvents; D001205:Ascorbic Acid
keywords: Ascorbic acid; binary mixed solvent; micromeritic properties; spherical crystallization