In-vitro and in-vivo respiratory deposition of a developed metered dose inhaler formulation of an anti-migraine drug.

Enhancement of zolmitriptan bioavailability through development of micronized zolmitriptan pressurized metered dose inhaler (MDI) as an alternative to its traditional drug delivery systems. A reversed phase HPLC method for zolmitriptan determination was developed and evaluated. Micronized zolmitriptan MDI formulations were prepared using two different propellants. The prepared formulations were evaluated for mean shot weight, drug content, and leakage rate in addition to in-vitro deposition using next generation impactor where mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle dose, fine particle fraction (FPF), emitted dose (ED), and dispersibility were determined. The selected formulation was evaluated for in-vivo bronchial absorption in rats. The physicochemical characters of the prepared formulations were found to be dependent mainly on the vapor pressure of the used propellant. MDI formulation prepared with HFA 134a propellant was found to have the lowest MMAD (3.47 ± 0.65) with GSD of 2.3 ± 0.4. It also had the highest FPF (41.9), ED (89.26 ± 2.35) with dispersibility of 46.9%. This formulation, when applied to rats, resulted in faster Tmax (27 ± 5 min) with higher Cmax (1236 ± 116 ng/mL) and AUC(0-12) (3375 ± 482 ng/mL·h) over the oral tablet. Its relative bioavailability was 72.7% which was 1.25 times higher than the oral tablet relative bioavailability. Zolmitriptan MDI formulation was developed using micronized zolmitriptan powder without further modification or particle engineering. The developed formulation using HFA 134a propellant could be favorable alternative, with enhanced bioavailability, to zolmitriptan oral tablet for acute migraine treatment.

The microbial contamination of pressurised metered-dose inhalers anonymously sourced from the South-East Queensland Australia community population.

OBJECTIVES: To provide preliminary evidence regarding the presence, identity and level of microbial contamination of metered-dose inhalers sourced from the community. To correlate the level of microbial colonisation to the visible presence of debris on the interior and exterior surface of the device mouthpiece. METHODS: In this exploratory study, 45 post-use de-identified pressurised metered-dose inhalers were collected from the South-East Queensland Australian community. Prior to swabbing, the presence of visible debris on the internal and external surfaces of the mouthpiece was recorded for each device. Swabs taken from external and inner surfaces of the mouthpiece of each device were streaked onto standard growth media for colony counts. Individual colonies were selected and enriched then streaked onto a range of differential and chromogenic media for differential identification. KEY FINDINGS: A total of 36 post-use pressurised metered dose inhalers (80%) were shown to be colonised by microbes relative to unused devices (P=0.01). Devices were primarily colonised by common respiratory flora, including Staphylococcus, Streptococcus and Haemophilus species. Of greatest concern was the positive identification of methicillin-resistant Staphylococcus aureus (18%) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (7%), Pseudomonas aerugonisa (2%) and Candida species (9%). The level of internal microbial contamination appeared to correlate to the presence of visible debris on the inside of the inhaler mouthpiece (P=0.06) but not external debris (P=0.59) while external contamination was not associated with internal (P=0.99) or external debris (P=0.63). CONCLUSIONS: These preliminary data suggest that pressurised metered dose inhalers are potential reservoirs for bacteria. While this study was not aimed at determining the impact that contaminated pressurised metered-dose inhalers may have on the user, future research is being conducted to address the implications of these findings and the consequences they may have for the population of users.

The influence of inhaled corticosteroids and spacer devices on the growth of respiratory pathogenic microorganisms.

BACKGROUND: Guidelines advise weekly cleansing of spacers, with one of the reasons being to prevent the spacers from becoming colonized with respiratory pathogens. Earlier work in clinical settings showed conflicting results. METHODS: Common respiratory pathogens and Candida albicans were applied on Petri dishes with and without inhaled corticosteroids and in 3 brands of spacer devices, with and without inhaled corticosteroids. Growth was measured. RESULTS: After 24 hours, Staphylococcus aureus grew in 7 of 18 spacers (39%); Pseudomonas aeruginosa grew in 12 out of 18 spacers (67%); and C albicans survived in 5 of 18 spacers (28%). Microorganisms survived on Petri dishes with fluticasone and beclomethasone but not when budesonide was applied. One out of 30 metal Nebuhalers (3%) was colonized after 24 hours, whereas of 30 Volumatics 8 (27%) and Aerochambers, 17 (57%) still had viable microorganisms. Application of inhaled steroids did not affect growth in the spacers. CONCLUSION: The colonization of metal spacers is lower than of spacers made of polycarbonate or polyethylene. C albicans can survive in spacers. The survival of microorganisms in spacers is not influenced by inhaled corticosteroids.

Effect of mouthpiece washing on aerosol performance of CFC-free Ventolin.

The prescribing information for chlorofluorocarbon (CFC)-free salbutamol metered-dose inhalers carries a strongly-worded instruction to wash the mouthpiece weekly, but patients rarely carry this out. This study investigated the effect of washing/not washing the mouthpiece on CFC-free Ventolin aerosol performance. Twelve CFC-free Ventolin inhalers were actuated two puffs four times/day, and assessed by unit dose sampler and cascade impactor on Days 1, 7, 8, 14, 15, 21, and 22 ("throughlife," i.e., over the entire content of the inhaler). The mouthpieces of six inhalers were washed after the last actuation on Days 7, 14, and 21. A single priming maneuver, as recommended by the manufacturer, was sufficient for fine particle mass. There were no significant through-life differences in delivered dose between washed and unwashed inhalers. Without washing, fine particle mass fell from 47 microg to 33 microg (Friedman p=0.002). Fine particle mass increased significantly after washing (median change + 11.2 microg, p=0.019 cf. unwashed). Large particle mass showed no significant through-life trend for washed or unwashed inhalers, but was significantly reduced after washing (p=0.04 cf. unwashed). This study shows a progressive through-life reduction in fine particle mass from CFC-free Ventolin inhalers, which is prevented by weekly mouthpiece washing. However, in view of the steep bronchodilator dose-response curve for salbutamol, further studies are needed to determine whether such device care is clinically necessary.

Lack of awareness of need to clean CFC-free metered-dose inhalers.

BACKGROUND: Chlorofluorocarbon (CFC)-free metered-dose inhalers (MDIs) were introduced into Australia in 1999. Device care instructions were modified (e.g., CFC-free salbutamol inhalers to be washed weekly), but this information was not communicated directly to health care professionals. OBJECTIVE: This pilot study aimed to assess the level of awareness of device care protocols for CFC-free MDIs by patients and their pharmacists. SETTING AND DESIGN: Purchasers of CFC-free MDIs were recruited from four community pharmacies. They were interviewed regarding information sources, knowledge of propellant change, and awareness of and adherence to device care protocols. The dispensing pharmacists were interviewed for knowledge of CFC-free device care. The primary outcome variable was awareness of the relevant device care protocol. RESULTS: Thirty-nine patients were interviewed. Most patients (77%) were aware of the change to CFC-free propellant. Only nine patients (23%) were aware of the need to wash the device holder, and four patients (10% of total) complied with the specified protocol. One of the ten dispensing pharmacists could describe correct device care protocols for the CFC-free MDIs. CONCLUSIONS: Although most patients are aware that MDIs are now CFC-free, there is a low level of awareness of the device care required for these inhalers, and a very low rate of compliance with recommended practice. Although the clinical impact of failing to wash the device holder is unclear, this added instruction may have substantial implications for patient satisfaction and medication delivery. Pharmaceutical manufacturers need to highlight to health care professionals any clinically important changes in device care instructions, so that appropriate information may be passed on to patients.