Research paper Preparation and in vitro evaluation of lipidic carriers and fillers for inhalation Thami Sebti, Karim Amighi * Laboratory of Pharmaceutics and Biopharmaceutics, Universite ´ Libre de Bruxelles, Brussels, Belgium Received 10 October 2005; accepted in revised form 4 November 2005 Available online 27 December 2005 Abstract The present study relates to compositions of solid lipidic microparticles (SLmP), composed of biocompatible phospholipids and cholesterol, and their use as carriers or as fillers delivering drugs directly to the lungs via a dry powder inhaler (DPI). SLmP were obtained by spray-drying and were formulated as lipidic matrices entrapping budesonide or as physical blends (drug carrier). They were developed in order to improve the delivery of the active drug by the pulmonary route. The SLmP were evaluated for their physical characteristics and in vitro deposition measurements were performed using the Multi-stage Liquid Impinger (MsLI). The Pulmicort Turbuhaler w DPI (AstraZeneca) was used as a comparator product. The SLmP appeared to be spherical low-density material characterized by a smooth surface. The mass median diameters (D(0,5)), and the volume mean diameters (D[4,3]) were tiny and ranged from 1,7 to 3,1 mm and from 2,0 to 3,9 mm, respectively. The SLmP formulations, delivered by the Cyclohaler w inhaler, were found to emit a fine particle dose (FPD) of 93–113 mg, which is very promising comparing to the FPD (68 mg) delivered by the Pulmicort Turbuhaler w . q 2005 Elsevier B.V. All rights reserved. Keywords: Inhalation; Lipid particles; Excipients; Dry powder inhaler; Drug deposition 1. Introduction The pulmonary route presents several advantages in the treatment of respiratory diseases over other administration routes for the same drugs leading to the systemic delivery of such drugs. Drug inhalation enables a rapid and predictable onset of action and induces fewer side effects than adminis- tration by other routes [1]. Three main delivery systems have been devised for the inhalation of aerosolised drugs, namely, pressurised metered- dose inhalers (MDIs), nebulizers, and dry powder inhalers (DPIs). The latter are currently the most convenient alternative to MDIs as they are breath-actuated and do not require the use of any propellants [2,3]. The deposition site in the respiratory tract and the efficiency of inhaled aerosols are critically influenced by the aerodynamic diameter, size distribution, shape and density of particles. For an effective inhalation therapy, inhaled particles should have an aerodynamic diameter between 1 and 5 mm to reach the lower airways [2,4]. Since micronized particles are generally very cohesive and characterized by poor flow properties, drug particles in dry powder formulations are usually blended with coarse and fine carrier particles. This improves particle flow into the inhalation device (capsules) during the filling process, ensures accurate dosage of active ingredients and increases the dispersing properties of cohesive dry particles during emission [5–8]. Furthermore, the carrier particles should be chemically and physically stable and inert to the drug substance and should not exhibit harmful effects, especially on the respiratory tract. Carbohydrates, in particular lactose, are widely used as drug carriers in DPI formulations [9]. Over the last decades, attention from various research groups has focused on the use of solid lipid particles (SLP) as a transport system of considerable interest for pharmaceutical applications. Compared to more ‘classical’ transporters such as liposomes, micelles, or polymeric nanospheres and nanocap- sules, SLP posses numerous advantages, including the possibility of increased drug stability, high drug payload, incorporation of lipophilic and hydrophilic drugs, low to non- existent biotoxicity of the carrier and few problems with European Journal of Pharmaceutics and Biopharmaceutics 63 (2006) 51–58 www.elsevier.com/locate/ejpb 0939-6411/$ - see front matter q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2005.11.003 * Corresponding author. Laboratory of Pharmaceutics and Biopharmaceutics, Universite ´ Libre de Bruxelles, Campus Plaine, CP 207, Boulevard du Triomphe, 1050 Brussels, Belgium. Tel.: C32 2 6505252; fax: C32 2 6505269. E-mail address: kamighi@ulb.ac.be (K. Amighi).