Loading effect on particle size measurements by inertial sampling of albuterol metered dose inhalers.

PURPOSE: The purpose of this study is to investigate the albuterol loading effect on particle size measurements by studying the effect of the amount of albuterol delivered, the number of puffs used, and the sampling techniques used in particle size measurement. METHODS: Particle size distribution profiles for different albuterol loadings were evaluated using an 8-stage cascade impactor and a sensitive HPLC electrochemical assay method. A commercial albuterol MDI (Proventil) and other specially prepared albuterol MDIs were used in the study. RESULTS: As the amount of albuterol was increased, either by increasing the number of puffs or the amount delivered per puff, the measured MMAD increased. This increase was more prominent in some formulations (Proventil) than others. Further, albuterol particles previously deposited on the valve and/or actuator didn't play a role in the observed multi-puff/loading effect. CONCLUSIONS: The collection of the least amount of aerosol in a cascade impactor provides a better estimate of MMAD, as it minimizes modifications of the collection surfaces.

Stability of sterile aqueous lidocaine hydrochloride and epinephrine injections submitted by U.S. hospitals.

The stability of lidocaine hydrochloride and epinephrine injections that had been stored in hospital pharmacies across the United States was studied. Through a voluntary drug stability program, the Food and Drug Administration selected 220 samples (representing four manufacturers) from hospital pharmacies representing an adequate cross section of the country. The samples were analyzed for strength, identification, pH, and physical condition. Six samples failed to meet USP requirements for strength of epinephrine, but all six of these samples had passed the expiration dates. Of the 62 samples that were analyzed for the presence of the d-isomer of epinephrine, approximately 95% had less than 5% d-isomer present. Only one sample had greater than 10% d-isomer present, and this sample had a low epinephrine content (26%) and had passed the expiration date. Lidocaine hydrochloride and epinephrine injections appear to be stable after storage under actual marketplace conditions.

Stability of sterile aqueous epinephrine injections submitted by U.S. hospitals.

The stability of sterile aqueous epinephrine injections stored in hospital pharmacies across the United States was studied. Through a voluntary drug stability program, FDA selected 254 samples of epinephrine injection submitted by hospital pharmacies. The samples were analyzed for strength, identification, d-isomer content, related impurities, pH, total acidity, and physical condition. Of the 254 samples tested, 23 samples did not meet USP requirements for epinephrine strength. Four of these samples were still within their expiration dates and seven had no expiration dates, indicating they were manufactured before 1975. An additional 19 samples did not meet USP requirements for total acidity. Some samples were found to be racemic; it appears that the racemic mixture originates from using d,l-epinephrine as the starting material rather than from racemization during shelf-life. Epinephrine injections obtained from hospital pharmacies appear to be stable within their expiration dates.

High-performance liquid chromatographic determination of d-/l-epinephrine enantiomer ratio in lidocaine-epinephrine local anesthetics.

A procedure for the determination of the ratio of d- to l-epinephrine in lidocaine-epinephrine local anesthetics is described. Epinephrine was isolated via Sep-Pak cartridges and derivatized with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate; the d- and l-chiral derivatives were separated and measured by high-performance liquid chromatography. About 70 samples of various dosage forms and concentrations from four manufacturers were successfully analyzed by the method.

Analysis of USP epinephrine injections for potency, impurities, degradation products, and d-enantiomer by liquid chromatography, using ultraviolet and electrochemical detectors.

A liquid chromatographic (LC) method was adapted for the determination of epinephrine and related impurities in intravenous and cardiac injections; ultraviolet (UV) and electrochemical detectors (EC) were used in series. Epinephrine was determined and related impurities, i.e., adrenalone, epinephrine sulfonic acid, and norepinephrine, were detected directly in a small portion of the injection solution. Diastereoisomers of the epinephrine enantiomers were prepared by derivatization and determined by LC with a UV detector. The recovery of epinephrine added to epinephrine injection was 100%. The recovery of d-enantiomer from a d, l mixture was 100%. Impurities at levels less than 1% were easily detected. The LC method with UV detection is faster and more convenient than the USP XX method. In addition, impurities can be detected in the same portion of sample. The procedure is stability-indicating.