title: A theoretical-empirical analysis on the initial dissolution rate of drugs from polydispersed particles.
abstract: The purpose of this work is to clarify the relationship of mean particle size to the dissolution rate of polydispersed particles for Biopharmaceutical Classification System (BCS) Class II drugs. An equation for the initial dissolution rate of polydispersed particles relative to mean particle diameter was theoretically derived from the Noyes-Whitney equation assuming spherical particles and sink conditions. To verify the relationship of dissolution to the mean particle diameters, the dissolution rates of 6 types of hypothetically-generated log-normal polydispersed particles and 3 different sized particles of aprepitant, a designated BCS class II drug, were compared with known mean diameters calculated according to surface area-weighted mean diameter (D(3,2), commonly referred to as the Sauter mean diameter), length-weighted mean diameter (D(3,1)) and number-weighted mean diameter (D(3,0)). The results confirmed that the initial dissolution rates of polydispersed particles reflect the mean diameter and correlated best with the reciprocal of D(3,2) at the start of dissolution, in accord with our theoretical conclusions. The particle size required for sufficient dissolution of aprepitant was also investigated by examining the relationship between D(3,2) and oral absorption predicted using a physiological-based model.
authors.affiliation: Discovery Platform Technology Department, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. takanorus@chugai-pharm.co.jp
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Takano
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takata
authors.forename: Koji
authors.initials: K
authors.lastname: Shiraki
authors.forename: Shoichi
authors.initials: S
authors.lastname: Higo
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D002626:Chemistry, Pharmaceutical; D036262:Empirical Research; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations