New analytical techniques to facilitate preformulation screening in propellant systems.
The objective of these studies was to investigate the applicability of an online direct inject HPLC method for the preformulation screening of pharmaceutical agents in pressurized metered dose inhalers (MDIs). The technique was initially utilized for the solubility determination of solid solutes. This study explores the extension of the online direct inject method for the evaluation of drug stability in propellant systems as well as for the analysis of MDI vials crimped with metered valves. Through-life content analysis confirmed that a single vial may be repeatedly sampled, thus facilitating the stability evaluation of a single unit over time. The method was successfully used for evaluating the stability of a model drug, as a function of several different formulation configurations, with minimal sample numbers. Additionally, studies determined that after modifications were made to the injection coupler, the technique was also feasible for use with 50 and 100 microL metered valves, however further modifications are necessary for 25 microL valves.
Mogalian
Erik
E
College of Pharmacy, University of Arizona, Tucson, AZ, USA. mogalian@pharmacy.arizona.edu
Kuehl
Philip J
PJ
Myrdal
Paul B
PB
D000280:Administration, Inhalation; D000335:Aerosol Propellants / Q000008:administration & dosage / Q000737:chemistry*; D000336:Aerosols; D001507:Beclomethasone / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation; D004339:Drug Compounding; D004355:Drug Stability; D004867:Equipment Design; D000431:Ethanol / Q000737:chemistry; D005240:Feasibility Studies; D006588:Hexanones / Q000008:administration & dosage / Q000737:chemistry*; D036501:Metered Dose Inhalers; D011312:Pressure; D015203:Reproducibility of Results; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013696:Temperature; D014867:Water / Q000737:chemistry
D000335:Aerosol Propellants; D000336:Aerosols; D006588:Hexanones; D014867:Water; D000431:Ethanol; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one; D001507:Beclomethasone