Aerodynamic behavior of alginic-atenolol microparticles obtained by spray drying

CESCHAN NE; BUCALÁ V; RAMÍREZ RIGO MV; SMYTH HDC

Rio de Janeiro

Congreso; XVIII Congresso da Federación Farmacéutica Sudamericana (FEFAS)- 8 RioPharma (Congresso da Ciências Farmacêuticas).; 2015

Federación Farmacéutica Sudamericana

IntroductionAtenolol (AT) is an antihypertensive drug with low oral bioavailability due to its poor intestinal absorption. However AT possesses adequate permeability through the inhalatory membrane(1). Based on this evidence, lung targeting could improve AT biopharmaceutical properties if a formulation capable to reach the deep respiratory regions is achieved. In a previous work, crumpled microparticles with wrinkle surfaces composed by alginic acid (AA) and AT were developed by spray drying (SD)(2). The aim of this study is to analyze the aerodynamic behavior of these materials alone or mixed with a carrier using a next generation impactor (NGI).Materials and Methods AT, AA (biocompatible anionic polyelectrolyte) and lactose monohydrate (carrier, 32-90µm) were used. SD processing variables were selected according to Ceschan et al.(2). The air-flow rate was set at 601 or 742L/h. Regular or high performance cyclone were tested. Feed fluid was prepared neutralizing AA carboxylic groups (75%) with AT amino groups in water. Due to pulmonary biocompatibility requirements, the pH the suspensions were adjusted to around 7. In vitro deposition of microparticles without carrier and 1:3 microparticles:lactose mixtures were determined in a RS01 inhaler (Plastiape, Italy) using a NGI at 40 and 58.8L/min. Drug deposition was determined by UV.Results Emitted fraction (EF=86?95 %), fine particle fraction (FPF=15-45%) and respirable fraction (RF=13-42%) were found to be acceptable in some cases for inhalatory administration and matched with typical results reported for marketed products(3). Mass median aerodynamic diameter (MMAD=3.4-4.8µm) was also satisfactory to allow microparticles to reach lung respiratory region. Geometric standard deviation (GSD=1.5-1.9) indicated that particle distribution was narrow. FPF and RF increased when a higher SD air-flow rate or a high performance cyclone was used. This is related with the ability to produce and collect smaller particles respectively. The use of lactose showed little improvement of aerosolization. However, the handling of the formulation was easier. A lower flow rate across the NGI equipment did not result in significant reductions of in vitro performance.ConclusionEvaluated powders demonstrated robust and adequate in vitro deposition behavior for systemic administration of AT by the inhalatory route.