The aim of this work is to explore the possibilities of using hydroxyapatite microspheres (HAP-MS) and polymer coated HAP-MS as the vehicles for the sustained release of small molecular drugs. The adsorption/desorption behaviors of model drug, doxycycline hydrochloride (Dox.HCI), on HAP-MS were systemically studied. Drug loaded HAP-MS was encapsulated by biodegradable PLGA using S/O/W emulsion-solvent evaporation method, and the in vitro drug release was tested. The adsorption kinetics of Dox.HCI onto HAP-MS fitted well to Freundlich model at lower drug concentrations, but when the HAP-MS was incubated in concentrated drug solutions higher than a critical concentration, precipitation of drug from solutions occurred. Rapid desorption or release of Dox.HCI from HAP-MS was observed. While, the release profile of Dox.HCI from PLGA coated microspheres showed steady slow drug release lasted for at least 7 days without obvious burst release. PLGA coated HAP-MS may provide a novel, injectable carrier for loading and long-period sustained release of small molecular, water-soluble drugs. (C) 2009 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.