HS-GC-FID method for quantification of HFA-152a in cell culture media, and plasma from a range of species and regulatory compliant validations.

Introduction: 1,1-Difluoroethane (HFA-152a) is being developed as an alternative propellant in pressurized metered dose inhalers (pMDIs). As a part of the regulatory development pathway, pharmacology, toxicology and clinical studies have been conducted with inhaled HFA-152a. These studies require fit for purpose regulatory compliant (GxP validated) methods for quantification of HFA-152a from blood.

Respiratory Tract Deposition of HFA-Beclomethasone and HFA-Fluticasone in Asthmatic Patients.

Background: The asthmatic patient's respiratory tract deposition of HFA fluticasone (Flovent HFA(™)) has not been established. There is a known large particle size difference with another commercial inhaled HFA steroid (QVAR(™)). This study compared the 2D and 3D respiratory tract deposition of each inhaled steroid.

Nasal Deposition of HFA-Beclomethasone, Aqueous Fluticasone Propionate and Aqueous Mometasone Furoate in Allergic Rhinitis Patients.

Background: The deposition of nasal aerosols from both aqueous formulations and propellant-based formulations has only minimally been described in rhinitis patients. This study quantified the regional nasal deposition of QNASL(™) (HFA-beclomethasone, nasal aerosol), Flonase(™) (fluticasone propionate, nasal spray) and Nasonex(™) (mometasone furoate monohydrate, nasal spray).

Methods: This study was an open label, crossover study in nine patients with allergic rhinitis.

Biologic comparison of inhaled insulin formulations: Exubera™ and novel spray-dried engineered particles of dextran-10.

Inhaled peptides and proteins have promise for respiratory and systemic disease treatment. Engineered spray-dried powder formulations have been shown to stabilize peptides and proteins and optimize aerosol properties for pulmonary delivery. The current study was undertaken to investigate the in vitro and in vivo inhalation performance of a model spray-dried powder of insulin and dextran 10 in comparison to Exubera™.

Characterization of respiratory deposition of fluticasone-salmeterol hydrofluoroalkane-134a and hydrofluoroalkane-134a beclomethasone in asthmatic patients.

Background: Fixed combination fluticasone-salmeterol is the most used anti-inflammatory asthma treatment in North America, yet no studies report the actual respiratory tract dose or the distribution of drug within the lungs. Inflammation due to asthma affects all airways of the lungs, both large and small. Inhaled steroid delivery to airways results from a range of drug particle sizes, with emphasis on smaller drug particles capable of reaching the peripheral airways.

A pilot study to assess lung deposition of HFA-beclomethasone and CFC-beclomethasone from a pressurized metered dose inhaler with and without add-on spacers and using varying breathhold times.

Background: The study objective of this pilot study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP; QVAR™) and CFC-beclomethasone dipropionate (CFC-BDP; Becloforte™) with and without the add-on spacers, Aerochamber™, and Volumatic™. The smaller particles of HFA-BDP were presumed to produce greater lung deposition using spacers, with and without a delay [i.e.

Particle size of inhaled corticosteroids: does it matter?

A question with respect to asthma therapy revolves around the issue of whether better efficacy occurs with an ultrafine-particle inhaled corticosteroid because of better lung deposition into the distal airways. This article reviews particle size and delivery devices of different steroids, clinical outcomes of small- versus large-particle steroids, and the issue of pharmacoeconomics.

Inhaled insulin is associated with prolonged enhancement of glucose disposal in muscle and liver in the canine.

Diabetic patients treated with inhaled insulin exhibit reduced fasting plasma glucose levels. In dogs, insulin action in muscle is enhanced for as long as 3 h after insulin inhalation. This study was designed to determine whether this effect lasts for a prolonged duration such that it could explain the effect observed in diabetic patients.

Inhalation aspects of therapeutic aerosols.

The pulmonary route of drug delivery can provide an excellent alternative to other routes both for local lung disease as well as systemic delivery. The year 2006 marks the 50th year since the invention of metered dose inhalers, yet inhalation is a very much underutilized route of delivery, possibly because inhalation drug development is perceived as being too difficult and expensive. However with proper knowledge these purported difficulties can be overcome.

Inhalation of human insulin (exubera) augments the efficiency of muscle glucose uptake in vivo.

This study assessed the site of increased glucose uptake resulting from insulin inhalation, quantified its effect under steady-state glucose concentrations, and identified the time to onset of effect. Human insulin was administered to 13 beagles via inhalation (Exubera [insulin human (rDNA origin)] Inhalation Powder; n = 7) or infusion into the inferior vena cava (Humulin R; n = 6) using an algorithm to match plasma insulin levels and kinetics for both groups. Somatostatin and glucagon were infused.

Inhalation of human insulin is associated with improved insulin action compared with subcutaneous injection and endogenous secretion in dogs.

This study compared the effects of endogenous (portal) insulin secretion versus peripheral insulin administration with subcutaneous or inhaled human insulin [INH; Exubera, insulin human (rDNA origin) inhalation powder] on glucose disposal in fasted dogs. In the control group, glucose was infused into the portal vein (Endo; n = 6). In two other groups, glucose was infused portally, whereas insulin was administered peripherally by inhalation (n = 13) or s.

Two-dimensional and three-dimensional imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers.

Drug deposition is an important factor that contributes to safety and efficacy outcomes of inhaled steroid therapy. Ciclesonide is a nonhalogenated, inhaled corticosteroid under investigation for the treatment of asthma. Therefore, this study was performed to assess lung deposition of ciclesonide.

Alternative propellant aerosol delivery systems.

The year 2006 represents the 50th anniversary of the pressurized metered dose inhaler. With most technologies, 50 years represents a significant time span for technology evolution and modification, but with propellant-driven metered dose inhalers, the pace of change has been relatively slow. We are now in the era of alternative propellant aerosol delivery systems, but at this 50-year juncture, what are the characteristics of these systems and what are the prospects for future advances? This review will consider alternative propellant aerosol delivery systems broadly from their inception through future opportunities and challenges.

Influence of particle size and patient dosing technique on lung deposition of HFA-beclomethasone from a metered dose inhaler.

The objective of this study was to determine the lung delivery of HFA-134a-beclomethasone dipropionate (HFA-BDP) from a breath-activated inhaler (QVAR Autohaler) compared with proper and improper press and breathe (QVAR P&B) metered dose inhaler (MDI) technique. The hypothesis was that that the smaller particles of BDP from HFA-BDP would stay suspended longer in the inspiratory air of patients and thus reduce the deleterious effects of inhaler discoordination. The study was an open label, four period, cross-over design.

The CFC to HFA transition and its impact on pulmonary drug development.

The terms of the Montreal Protocol have eliminated chlorofluorocarbons (CFCs) and other ozone-depleting agents from commercial use, with the exemption of their use as propellants in metered-dose inhalers. Two new propellants have been approved for CFC substitutes: hydrofluoroalkane (HFA)-134a and HFA-227. An extensive safety program was conducted by the International Pharmaceutical Aerosol Consortium for Toxicity Testing (IPACT studies I and II), which found that the HFAs were as safe as or safer than the CFCs.

Inhalation of insulin (Exubera) is associated with augmented disposal of portally infused glucose in dogs.

The results of the present study, using the conscious beagle dog, demonstrate that inhaled insulin (INH; Exubera) provides better glycemic control during an intraportal glucose load than identical insulin levels induced by insulin (Humulin) infusion into the inferior vena cava (IVC). In the INH group (n = 13), portal glucose infusion caused arterial plasma glucose to rise transiently (152 +/- 9 mg/dl), before it returned to baseline (65 min) for the next 2 h. Net hepatic glucose uptake was minimal, whereas nonhepatic uptake rose to 12.

Inhalation of insulin in dogs: assessment of insulin levels and comparison to subcutaneous injection.

Pulmonary insulin delivery is being developed as a more acceptable alternative to conventional subcutaneous administration. In 15 healthy Beagle dogs (average weight 9.3 kg), we compared insulin distribution in arterial, deep venous, and hepatic portal circulation.

Lung deposition of hydrofluoroalkane-134a beclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone : a cross-over study in healthy volunteers.

Study Objectives: To compare the lung deposition of radiolabeled hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) with chlorofluorocarbon fluticasone propionate (CFC-FP) and chlorofluorocarbon beclomethasone (CFC-BDP).

Design: Six-day, open-label, nonrandomized, crossover study.

Setting: Clinical research laboratory.