Hydrofluoroalkane Research Articles

Nanoparticle-Stabilized Colloids in Compressible Hydrofluoroalkanes

In this work, we show that nanoparticles (NPs) dispersed in compressible hydrofluoroalkanes (HFAs) at small volume fractions are capable of stabilizing micrometer-sized particle colloids, which otherwise flocculate due to strong van der Waals forces. Water-soluble, biodegradable NPs with a chitosan (CS) core, grafted with highly HFA-philic moieties, can be readily dispersed in the low dielectric HFAs and are capable of imparting stability to a wide range of therapeutic particles having different chemistries (polar or hydrophobic; small and large molecular weight, including peptides and proteins) and morphologies (micronized crystals or amorphous). These NP systems thus serve as a broadly applicable platform for the noninvasive delivery of therapeutics to and through the lungs using propellant-based, portable inhalers, and are also of potential relevance in other industries where HFAs are employed as solvents or propellants. This concept may also be applicable to other compressible solvents.

Systemic bioavailability of hydrofluoroalkane formulations containing fluticasone propionate and salmeterol

Systemic bioavailability of hydrofluoroalkane formulations containing fluticasone propionate and salmeterol

Pharmacokinetic Evaluation of BDP HFA Nasal Aerosol and BDP HFA Inhalation Aerosol in Healthy Subjects

RATIONALE: The purpose of this study was to compare the pharmacokinetic (PK) profiles of beclomethasone dipropionate (BDP) and beclomethasone-17-monopropionate (17-BMP; the active metabolite of BDP) after nasal or oral administration of BDP hydrofluoroalkane (HFA).

Comparative lung bioavailability of fluticasone/salmeterol via a breath-actuated spacer and conventional plastic spacers

This study compares the in vivo relative lung bioavailability of Hydrofluoroalkane (HFA) Seretide delivered via unprimed and unwashed Aerochamber Plus (AP) or Volumatic (VM) spacers, a integrated breath-actuated vortex Synchro-Breathe (SB) device and an Evohaler pMDI (EH) device using adrenal suppression and early fall in serum potassium (K) as surrogates for respirable dose. Seventeen healthy volunteers completed this randomised double-blind, double-dummy crossover study. Single doses of placebo/Seretide 250 (total dose ex valve fluticasone 2000 mcg/salmeterol 200 mcg) were administered via the devices. Overnight urinary cortisol/creatinine (OUCC) and serum K were measured at baseline and after each dose. Significant suppression of OUCC and K occurred from baseline with the SB, AP and VM but not with the EH devices. The geometric mean fold suppression (95% confidence interval, p) was: EH, 1.59 (0.80-3.14, p=0.40); AP, 4.26 (3.01-6.02, p<0.001); VM, 3.11 (1.99-4.78, p<0. 001); SB, 3.29 (2.04-5.24, p<0.001). For K, the arithmetic mean fall (mmol/l) (95% confidence interval; p) was: EH, -0.10 (-0.25-0.05, p=0.18); AP, -0.23 (-0.41 to -0.04, p=0.02); VM, -0.22 (-0.44 to -0.01, p=0.04); SB, -0.28 (-0.42 to -0.13, p=0.001). The breath-actuated SB device was comparable to 'out of the box' small and large volume spacers and produced similar improvements in relative systemic lung bioavailability for fluticasone and salmeterol.

Plume temperature emitted from metered dose inhalers

The temperature of the drug cloud emitted from a pressurised metered dose inhaler (pMDI) may result in patient discomfort and inconsistent or non-existent dose delivery to the lungs. The effects of variations in formulation (drug, propellant, co-solvent content) and device hardware (metering volume, actuator orifice diameter, add-on devices) upon the temperature of pMDI plumes, expressed as replicate mean minimum values (MMPT), collected into a pharmacopoeial dose unit sampling apparatus (DUSA), have been investigated. Ten commercially available and two development products, including chlorofluorocarbon (CFC) suspensions and hydrofluoroalkane (HFA) solutions or suspensions, were examined together with a number of drug products in late stage development and a variety of HFA 134a placebo pMDIs. Plume temperatures were observed to be lowest in the proximity of the product's actuator mouthpiece where rapid flashing and evaporation of the formulation's propellant and volatile excipients cause cooling. The ability to control plume temperature by judicious choice of formulation co-solvent content, metering volume and the actuator orifice diameter is identified. An ethanol based HFA 134a formulation delivered through a fine orifice is inherently warmer than one with 100% HFA 134a vehicle delivered through a coarse actuator orifice. Of the 10 commercial products evaluated, MMPTs ranged from −54 to +4 °C and followed the formulation class rank order, HFA suspensions < CFC suspensions < HFA solutions. For all systems examined it was possible to raise pMDI plume temperature to that of the ambient surroundings by use of an add-on or integrated spacer device.

Both bronchial and alveolar exhaled nitric oxide are reduced with extrafine beclomethasone dipropionate in asthma

Exhaled nitric oxide (NO) is a noninvasive marker of airway inflammation. Beclomethasone dipropionate (BDP) is the only inhaled corticosteroid (ICS) available as both extrafine and nonextrafine hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) formulation. The present study was designed to evaluate whether the different patterns of lung deposition of two HFA BDP formulations are associated with a different effect on bronchial and alveolar NO. This was a prospective double-blind, randomized, controlled, crossover study. After a 2-week placebo run-in period without ICSs, asthmatic patients were randomized to extrafine BDP, 100 μg, b.i.d. or nonextrafine BDP, 250 μg, b.i.d. for two 2-week periods separated by a 2-week washout period. Fourteen patients (5 men) with a mean age 37 years and mean baseline forced expiratory volume in 1 second (FEV₁) of 83% of predicted were analyzed. Exhaled bronchial NO was significantly (p < 0.001) reduced in both treatment groups when compared with the last week of run-in period, whereas alveolar NO was significantly (p < 0.001) reduced only with extrafine BDP. Moreover, extrafine BDP was superior to nonextrafine BDP in both parameters (p < 0.05). Extrafine but not nonextrafine BDP HFA formulation lowers both bronchial and alveolar exhaled NO in asthmatic patients. ICS distribution throughout the whole bronchial tree could be important in patients who do not gain optimal control of inflammation with conventional nonextrafine ICS.

Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: A real-world observational study

Long-term randomized trials comparing asthma outcomes between inhaled corticosteroids in real-world populations are lacking. As such, rigorously conducted observational studies to complement the findings of randomized trials are needed. We sought to compare asthma-related outcomes over 1 year as recorded in a large primary care database for patients aged 5 to 60 years receiving a first prescription (initiation population) or dose increase (step-up population) of hydrofluoroalkane (HFA)-beclomethasone or fluticasone. We used a retrospective matched cohort study in which patients were matched on baseline demographic and disease severity measures. Coprimary outcomes were asthma control (a composite measure comprising no unplanned visit or hospitalization for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and exacerbation rate. More than 80% of patients in each population achieved asthma control; 10% and 16% of patients in the initiation and step-up populations, respectively, received add-on or combination therapy during the year. Fluticasone was prescribed at significantly higher doses than HFA-beclomethasone for both populations (P <or= .001). In the initiation population (n = 1319 in each cohort) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.30 (95% CI, 1.02-1.65) relative to fluticasone. In the step-up population (cohorts: n = 250) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.22 (95% CI, 0.66-2.26). Exacerbation rates were similar between cohorts. In a real-world setting patients receiving HFA-beclomethasone had a similar or better chance of achieving asthma control at lower prescribed doses than with fluticasone.

The potential for the noninvasive delivery of polymeric nanocarriers using propellant-based inhalers in the treatment of Chlamydial respiratory infections

A novel strategy for pulmonary delivery of polymeric nanocarriers (NCs) pressurized-metered dose inhalers (pMDIs) is reported in this work. Core–shell particles consisting of a water soluble, hydrofluoroalkane(HFA)-philic biodegradable copolymer of chitosan and poly(lactic acid), and a core of poly( d, l-lactide-co-glycolide) (PLGA) NCs were prepared by a modified emulsification–diffusion methodology. Dispersions of the core–shell particles in HFA propellant revealed enhanced physical stability compared to polymeric NCs alone, and more importantly, excellent aerosol characteristics as determined by inertial impaction studies. Confocal microscopy revealed that the polymeric NCs from such core–shell particles are capable not only to be taken up by Calu-3 (airway epithelial) cells that have been infected with Chlamydia pneumoniae, an intracellular pathogen, but are also internalized within chlamydial inclusions. Our results suggest that the proposed methodology can be used as a general platform for the delivery of polymeric NCs to the respiratory tract using the inexpensive pMDIs, and that such an approach may be used to target and deliver drugs to treat chlamydial-related infections.

Templated Open Flocs of Anisotropic Particles for Pulmonary Delivery with Pressurized Metered Dose Inhalers

The challenges in forming stable drug suspensions in hydrofluoroalkane (HFA) propellants have limited drug dosages and efficiency of drug delivery with pressurized metered dose inhalers (pMDI). Herein, stable suspensions of weakly flocculated particles, in the shape of thin plates or needles, of a poorly water-soluble drug, itraconazole (Itz), are efficiently delivered by pMDI at high doses, up to 2.4 mg/actuation. These anisotropic particles pack inefficiently and form low-density flocs that stack upon each other to prevent settling. In contrast, spherical particles formed dense aggregates that settled within minutes. Upon actuation of the pMDI, atomized propellant droplets shear apart and thus template the highly friable flocs. Evaporation of the HFA compacts the flocs to yield porous particles with optimal aerodynamic properties. High fine particle fractions (49-64%) were achieved with the stable suspensions for drug loadings up to 50 mg/mL. Furthermore, the micron-sized particles, ideal for pulmonary delivery, are composed of nanoparticles that dissociate and facilitate rapid dissolution of poorly water-soluble drugs. Pulmonary delivery of stable suspensions of templated, open flocs is broadly applicable to a range of anisotropic particle morphologies for poorly water-soluble drugs and proteins for efficient delivery of high doses, up to several milligrams, using minimal amounts of excipients.

Systemic bioavailability of hydrofluoroalkane (HFA) formulations of fluticasone/salmeterol in healthy volunteers via pMDI alone and spacer

To compare a test version of HFA fluticasone/salmeterol (FP/SM) combination inhaler (Neolab, UK) with the reference product Seretide (GlaxoSmithKline, UK). An in vitro Anderson cascade impactor was used to compare the fine particle dose (<4.7 microm). Two separate randomized cross-over studies were performed to compare the systemic bioavailability of test vs. reference (T vs. R) formulations of FP/SM 250/25 microg pMDI in healthy volunteers. In study 1 blood pharmacokinetic analysis using oral charcoal block was performed over 24 h following a single dose of four puffs via pMDI alone. In study 2 systemic bioactivity was measured following single doses of four and eight puffs via a spacer device: serum potassium (K(+)) to reflect SM, and overnight urinary cortisol : creatinine (OUCC) for FP. An early pharmacokinetic profile was also assessed over 120 min. The in vitro fine particle dose was similar for test vs. reference pMDI alone and via spacer. The results of both studies were consistent: No significant differences between formulations were seen in terms of FP kinetics. Analysis of SM kinetics revealed superiority of the test product. No significant dose-response or difference in T : R ratio was noted for OUCC. Fall in K(+) revealed a significant dose-response with a non-significant T : R ratio. The in vitro fine particle dose may not predict pharmacokinetic and systemic pharmacodynamic outcomes. Single dosing studies with fluticasone/salmeterol 250/25 microg via pMDI or with spacer showed pharmacokinetic equivalence with FP, but not SM. No significant difference between formulations was seen with either adrenal suppression or hypokalaemia.

Repeat Dosing of Albuterol via Metered-Dose Inhaler in Infants With Acute Obstructive Airway Disease

Airway obstruction and bronchial hyperactivity often times lead to emergency department visits in infants. Inhaled short-acting beta2-agonist bronchodilators have traditionally been dispensed to young children via nebulizers in the emergency department. Delivery of bronchodilators via metered-dose inhalers (MDIs) in conjunction with holding chambers (spacers) has been shown to be effective. : Safety and efficacy evaluations of albuterol sulfate hydrofluoroalkane (HFA) inhalation aerosol in children younger than 2 years with acute wheezing caused by obstructive airway disease. A randomized, double-blind, parallel group, multicenter study of albuterol HFA 180 microg (n = 43) or 360 microg (n = 44) via an MDI with a valved holding chamber and face mask in an urgent-care setting. Assessments included adverse events, signs of adrenergic stimulation, electrocardiograms, and blood glucose and potassium levels. Efficacy parameters included additional albuterol use and Modified Tal Asthma Symptoms Score ([MTASS] reduction in MTASS representing improvement). Overall, adverse events occurred in 4 (9%) and 3 (7%) subjects in the 180-microg and 360-microg groups, respectively. Drug-related tachycardia (360 microg) and ventricular extrasystoles (180 microg) were reported in 1 patient each. Three additional instances of single ventricular ectopy were identified from Holter monitoring. No hypokalemia or drug-related QT or QTc prolongation was seen; glucose values and adrenergic stimulation did not significantly differ between treatment groups. In the 180-microg and 360-microg groups, mean change from baseline in MTASS during the treatment period was -2.8 (-49.8%) and -2.9 (-48.4%), and rescue albuterol use occurred in 4 (9%) and 3 (7%) subjects, respectively. Cumulative dosing with albuterol HFA 180 microg or 360 microg via MDI-spacer and face mask in children younger than 2 years did not result in any significant safety issues and improved MTASS by at least 48%.

Evaluation of metered dose inhaler (MDI) formulations of ciclosporin

Our purpose was to evaluate metered dose inhaler (MDI) formulations of cyclosporin (cyclosporine) for aerodynamic properties, chemical stability and bioactivity. Ciclosporin formulations (0.1, 0.5 and 1.0% w/w) were prepared in hydrofluoroalkane (HFA) propellants (134a and 227) containing 3 and 6% ethanol. Aerodynamic properties of the MDI formulations were analysed using an eight-stage Andersen cascade impactor and respirable mass and non-respirable mass, mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were determined from the impaction profiles. The chemical stability of 0.1% ciclosporin in HFA 227 containing 3% ethanol formulation stored at room temperature and 40 degrees C was evaluated by HPLC at 0, 14, 30 and 90 days. The bioactivity of ciclosporin MDI formulations was evaluated by determining the ciclosporin-mediated inhibition of interleukin-2 (IL-2) release from human Jurkat cells stimulated with phorbol 12-myristate 13-acetate (PMA). As ethanol concentration increased from 3 to 6%, respirable mass decreased from 2.3 mg per five actuations to 0.04 mg per five actuations for HFA 227 formulations, and from 1.5 mg to 0.09 mg per five actuations for HFA 134a formulations. The MMAD for both HFA 134a and 227 formulations increased with an increase in ciclosporin concentration. HPLC analysis showed ciclosporin to be extremely stable in HFA 227 at room temperature and 40 degrees C. Stimulation of Jurkat cells with PMA released significant amounts of IL-2, which was inhibited by ciclosporin in a dose-dependent manner. This study shows the feasibility of developing chemically stable and bioactive HFA-based MDI formulations of ciclosporin.

Patient perspectives in the management of asthma: improving patient outcomes through critical selection of treatment options

Asthma is a chronic inflammatory disorder of the airways that requires long-term treatment, the goal of which is to control clinical symptoms for extended periods with the least possible amount of drugs. International guidelines recommend the addition of an inhaled long-acting beta2-agonist (LABA) to a low- to medium-dose inhaled corticosteroid (ICS) when low doses of ICS fail to control asthma symptoms. The fixed combined administration of ICS/LABA improves patient compliance, reducing the risk of therapy discontinuation. The relative deposition pattern of the inhaled drug to the target site is the result of a complex interaction between the device used, the aerosol formulation and the patient's adherence to therapy. Different inhalation devices have been introduced in clinical practice over time. The new hydrofluoroalkane (HFA) solution aerosols allow for the particle size to be modified, thus leading to deeper penetration of the medication into the lung. The Modulite((R)) technology allows for the manipulation of inhaled HFA-based solution formulations, such as the fixed beclomethasone/formoterol combination, resulting in a uniform treatment of inflammation and bronchoconstriction. The success of any anti-asthmatic treatment depends on the choice of the correct device and the adherence to therapy.

Partitioning and phase equilibria of PEGylated excipients in fluorinated liquids

Mixtures of common polymeric excipients and hydrofluoroalkane (HFA) liquids show rich and complex phase behaviour. Phase diagrams and phase compositions are reported for poly(ethylene glycol)s with varying levels of end-group methylation in mixed solvent systems consisting of the model propellant 2H,3H-perfluoropentane (HPFP) and the fully fluorinated analogue perfluoropentane (PFP). Studies have been performed as a function of molecular weight as well as end group chemistry (monomethyl, MM; dimethyl, DM; and dihydroxyl, DH), and for binary polymer mixtures in HPFP/PFP solvent systems. The solvent composition required to induce phase separation by addition of the non-hydrogen bonding PFP is strongly dependent on end-group concentrations. It shows a linear increase with increasing methylation, whilst remaining insensitive to OH group concentration in dihydroxylated PEG systems. For single polymer systems it is observed that strong partitioning of the polymer is observed, and changes in polymer concentration occurring across the phase diagram are a result of changing solvent partitioning between upper and lower phases. These solvent effects are dependent on the composition (wt% PFP) in the solvent mixture. The linear dependence of solvent composition required to induce phase separation at fixed polymer concentration on end group concentrations can be used to predict the phase behaviour for mixtures of monomethylated PEG with either dimethyl or dihydroxyl PEGs, whereas mixtures of dihydroxyl with dimethyl end-capped PEGs show a deviation from linear behaviour with dominance of the dihydroxyl end groups, which is reflected in the obtained phase diagrams. This study hence progresses understanding of factors that influence solubility of PEG-type polymers in HFAs and will facilitate the identification of predictive methodologies for formulation.

Recent Development of Drug Delivery Systems for the Treatment of Asthma and Related Disorders

It is well established that airway inflammatory processes are pivotal as the pathological features of asthma. Prominent infiltration of eosinophils and Th2 lymphocytes is a hallmark of the allergic inflammation, and inhaled corticosteroids markedly suppress such inflammatory changes, resulting in clinical beneficial effects. Aerosol delivery of anti-asthma drugs such as corticosteroids is ideal from the standpoint of maximizing local effects in the lung as well as minimizing systemic side effects compared with oral therapy. The 1987 Montreal protocol banned chlorofluorocarbon (CFC) propellant in pressurized metered-dose inhalers (pMDIs), which has been replaced with hydrofluoroalkane (HFA) propellant. The aerodynamic diameters of HFA are much smaller than those of CFC, suggesting a greater distribution in peripheral airways. New types of dry powder inhalers (DPIs) and nebulizers, that do not use propellants, also have been introduced. Performance of each drug delivery device depends on a variety of factors including the device type, particle size and distribution, the product formulation and patient-related factors. Therefore, drug delivery can differ even when the same drug is delivered via an HFA pMDI, a CFC pMDI, a DPI or a nebulizer. New and advanced devices can be helpful to maximize the advantages of these modes of drug delivery, and patents of novel invention of inhalation devices are described.

Novel pMDI formulations for pulmonary delivery of proteins

In this paper, we demonstrate that co-spray-drying a model protein with sodium carboxymethylcellulose (NaCMC) protects protein integrity during spray-drying, and that the resultant spray-dried powders can be successfully dispersed in hydrofluoroalkane (HFA) propellant to prepare pressurised metered dose (pMDI) formulations that exhibit high respirable fractions. The spray-dried powders were formulated as HFA-134a pMDI suspensions in the absence of any other excipients (e.g. surfactants) or co-solvents (e.g. ethanol). The in vitro aerosolisation profile of these systems was assessed using the twin stage impinger; fine particle fractions (FPF) ≥50% of the recovered dose were obtained. Following storage for five months, the aerosolisation performance was reassessed; the NaCMC-free formulation demonstrated a significant decrease in FPF, whereas the performance of the NaCMC-modified formulations was statistically equivalent to their initial performance. Thus, formulation of pMDI suspensions using NaCMC-based spray-dried powders is a promising approach for the pulmonary delivery of proteins and peptides.

The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams

Nanocarriers may act as useful tools to deliver therapeutic agents to the skin. However, balancing the drug–particle interactions; to ensure adequate drug loading, with the drug–vehicle interactions; to allow efficient drug release, presents a significant challenge using traditional semi-solid vehicles. The aim of this study was to determine how the physicochemical properties of nanoparticles influenced minoxidil release pre and post dose application when formulated as a simple aqueous suspension compared to dynamic hydrofluoroalkane (HFA) foams. Minoxidil loaded lipid nanoparticles (LN, 1.4 mg/ml, 50 nm) and polymeric nanoparticles with a lipid core (PN, 0.6 mg/ml, 260 nm) were produced and suspended in water to produce the aqueous suspensions. These aqueous suspensions were emulsified with HFA using pluronic surfactant to generate the foams. Approximately 60% of the minoxidil loaded into the PN and 80% of the minoxidil loaded into the LN was released into the external aqueous phase 24 h after production. Drug permeation was superior from the PN, i.e. it was the particle that retained the most drugs, irrespective of the formulation method. Premature drug release, i.e. during storage, resulted in the performance of the topical formulation being dictated by the thermodynamic activity of the solubilised drug not the particle properties.

Systemic Exposure and Implications for Lung Deposition with an Extra-Fine Hydrofluoroalkane Beclometasone Dipropionate/Formoterol Fixed Combination

Foster is a fixed combination of beclometasone dipropionate/formoterol (BDP/F). It is formulated as an extra-fine solution and delivered via a pressurized metered-dose inhaler (pMDI) using a hydrofluoroalkane (HFA) propellant. The aims of this study were to compare the systemic exposure to BDP, to its active metabolite beclometasone-17-monopropionate (B17MP) and to formoterol after administration of BDP/F versus separate administration of a chlorofluorocarbon (CFC) formulation of BDP and formoterol HFA, and to explore a possible relationship between pharmacokinetic and pharmacodynamic findings. In this open-label, crossover, placebo-controlled study, 12 healthy male subjects received a single dose of BDP/F 400 microg/24 microg (four inhalations of Foster BDP/F 100 microg/6 microg), single doses of BDP CFC 1000 microg (four inhalations of Becotide Forte 250 microg) plus formoterol 24 microg (four inhalations of Atimos 6 microg) via separate MDIs, or placebo. Continuous pharmacokinetic variables for BDP, B17MP, formoterol, cortisol and potassium were evaluated. Cardiovascular effects, peak flow measurements and tolerability were also examined. Exposure to BDP was not significantly different between active treatment arms, but lower systemic exposure to B17MP was observed with the fixed combination than with the separate components (area under the plasma concentration-time curve [AUC] from time zero to infinity [AUC(infinity)] 5280 vs 8120 pg.h/mL; p = 0.001). Despite a lower total systemic exposure to B17MP with the fixed combination, B17MP plasma concentrations during the first 30 minutes after administration, indicative of pulmonary absorption, were 86% higher with BDP/F than with the separate components (AUC from 0 to 30 minutes [AUC(30 min)] 353 vs 190 pg x h/mL; p = 0.003). Twenty-four-hour serum cortisol concentrations were significantly higher with BDP/F than with BDP and formoterol administered separately (2.26 vs 1.90 microg x h/mL; p < 0.01). No significant differences in the pharmacokinetic parameters of formoterol and no clinically relevant differences in serum potassium and cardiovascular or spirometric parameters were observed between the treatments. Both active treatments were well tolerated. These pharmacokinetic data show that with a BDP dose from Foster that is 2.5 times less than a BDP dose from Becotide Forte, pulmonary absorption is 86% higher; however, systemic exposure is 35% lower, resulting in less cortisol suppression for a similar BDP dosage.

Insulin nanoparticles: Stability and aerosolization from pressurized metered dose inhalers

Nanoparticles containing insulin have been produced by emulsification processes followed by freeze-drying. Purified nanoparticles were suspended in hydrofluoroalkane (HFA) 134a, using essential oils (cineole and citral) as suspension stabilizers to form pressurized metered dose inhaler (pMDI) formulations. The retention of insulin integrity after formulation processing was determined using high performance liquid chromatography (HPLC), size exclusion chromatography (SEC), circular dichroism (CD) and fluorescence spectroscopy. The results indicated that the native structure of insulin was retained after formulation processing. Aerosolization properties of the manufactured pMDI formulations were determined using a multi-stage liquid impinger. The results showed that the nanoparticles were suitable for peripheral lung deposition, with a fine particle fraction (FPF <1.7 μm ) of approximately 45% (w/w). In conclusion, the pMDI formulations with nanoparticles containing insulin developed in this study have the potential to deliver protein therapeutics via inhalation for systemic action.

Engineering novel topical foams using hydrofluroalkane emulsions stabilised with pluronic surfactants

Aesthetics are very important for topical products and as a consequence elegant vehicles such as sprays and foams are often preferred by patients. Pressurised systems are ideal to dose foams, however, as so little is known about the influence of formulation characteristics on foam properties, the rational design of these systems difficult. This study aimed to assess the capability of pluronic surfactants to stabilise topical pressurised hydrofluoroalkane (HFA) emulsions and attempted to define the formulation characteristics that had an impact upon foam properties. In situ phase diagrams and conductivity measurements were used to characterise the HFA emulsions. Cryo-scanning electron microscopy images, collapse time ( C t) and wetting time ( W t) were used to assess the foams post dosing, i.e. after removal of the HFA. The results indicated that foam stability was a direct function of HFA emulsion type; HFA-in-water (HIW) emulsions generated stable foams, they had 30–100 μm bubble diameter with c.a. 40 bubbles in a 0.45 mm × 0.40 mm area; water-in-HFA (WIH) emulsions created quick-breaking foams they contained 20–200 μm sized bubbles and had 20 bubbles in an area of 0.45 mm × 0.40 mm. Therefore, the rational design of pressurised topical foams can be achieved if the formulation is analysed in situ.