Factors affecting the stability and performance of ipratropium bromide; fenoterol hydrobromide pressurized-metered dose inhalers. 2013

Jenjira Ninbovorl, and Somchai Sawatdee, and Teerapol Srichana
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90112, Thailand.

The aim of the study was to investigate the factors affecting the stability and performance of ipratropium bromide and fenoterol hydrobromide in a pressurized-metered dose inhaler (pMDI). A factorial design was applied to investigate the effects of three parameters (propellant, water, and ethanol) on the performance of 27 designed formulations of a solution-based pMDI. The formulations that contained a hydrofluoroalkane (HFA) propellant lower than 72% v/v and an ethanol concentration higher than 27% v/v remained as clear solutions. Nine formulations that contained the HFA propellant higher than 74% v/v precipitated. The results indicated that it was not only the HFA propellant content of the formulations that was related to the formulation instability but also ethanol content. Only six formulations from the 18 formulations, that did not precipitate, produced drug contents that were within the acceptable range (80-120%). These six formulations generated aerosols with mass median aerodynamic diameters (MMAD) of approximately 2 μm with a fine particle fraction (FPF; particle size, <6.4 μm) between 45% and 52%. The MMAD and FPF did not change significantly after 6 months of storage (P > 0.05).

UI MeSH Term Description Entries
D009241 Ipratropium A muscarinic antagonist structurally related to ATROPINE but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic. N-Isopropylatropine,(endo,syn)-(+-)-3-(3-Hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-8-azoniabicyclo(3.2.1)octane,Atrovent,Ipratropium Bromide,Ipratropium Bromide Anhydrous,Ipratropium Bromide Monohydrate,Ipratropium Bromide, (endo,anti)-Isomer,Ipratropium Bromide, (exo,syn)-Isomer,Ipratropium Bromide, endo-Isomer,Itrop,Sch-1000,Sch-1178,N Isopropylatropine,Sch 1000,Sch 1178,Sch1000,Sch1178
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D001993 Bronchodilator Agents Agents that cause an increase in the expansion of a bronchus or bronchial tubes. Bronchial-Dilating Agents,Bronchodilator,Bronchodilator Agent,Broncholytic Agent,Bronchodilator Effect,Bronchodilator Effects,Bronchodilators,Broncholytic Agents,Broncholytic Effect,Broncholytic Effects,Agent, Bronchodilator,Agent, Broncholytic,Agents, Bronchial-Dilating,Agents, Bronchodilator,Agents, Broncholytic,Bronchial Dilating Agents,Effect, Bronchodilator,Effect, Broncholytic,Effects, Bronchodilator,Effects, Broncholytic
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D004356 Drug Storage The process of keeping pharmaceutical products in an appropriate location. Drug Storages,Storage, Drug,Storages, Drug
D004867 Equipment Design Methods and patterns of fabricating machines and related hardware. Design, Equipment,Device Design,Medical Device Design,Design, Medical Device,Designs, Medical Device,Device Design, Medical,Device Designs, Medical,Medical Device Designs,Design, Device,Designs, Device,Designs, Equipment,Device Designs,Equipment Designs
D005280 Fenoterol A synthetic adrenergic beta-2 agonist that is used as a bronchodilator and tocolytic. Berotec,Berotek,Fenoterol Hydrobromide,Fenoterol Hydrochloride,Partusisten,Phenoterol,Th-1165a,p-Hydroxyphenyl-orciprenaline,p-Hydroxyphenylorciprenaline,Hydrochloride, Fenoterol,Th 1165a,Th1165a,p Hydroxyphenyl orciprenaline,p Hydroxyphenylorciprenaline
D005617 Chlorofluorocarbons, Methane A group of methane-based halogenated hydrocarbons containing one or more fluorine and chlorine atoms. Fluorocarbon Aerosols,Fluorocarbon Propellants,Chlorofluoromethanes,Aerosols, Fluorocarbon,Methane Chlorofluorocarbons,Propellants, Fluorocarbon
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations

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