Andersen Cascade Impactor Research Articles

In vitro biological activity of resveratrol using a novel inhalable resveratrol spray-dried formulation

The aim of the study was to prepare inhalable resveratrol by spray drying for the treatment of chronic obstructive pulmonary disease (COPD). Resveratrol, with a spherical morphology and particle diameter less than 5μm, was successfully manufactured. Fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of spray-dried resveratrol was 39.9±1.1% and 3.7±0.1μm, respectively, when assessed with an Andersen cascade impactor (ACI) at 60l/min. The cytotoxicity results of resveratrol on Calu-3 revealed that the cells could tolerate high concentration of resveratrol (up to 160μM). In addition, in transport experiments using Snapwells, it was observed that more than 80% of the deposited dry powder was transported across the Calu-3 cells to the basal chamber within four hours. The expression of interleukin-8 (IL-8) from Calu-3 induced with tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β1) and lipopolysaccharide (LPS) were significantly reduced after treatment with spray-dried resveratrol. The antioxidant assay (radical scavenging activity and nitric oxide production) showed spray-dried resveratrol to possess an equivalent antioxidant property as compared to vitamin C. Results presented in this investigation suggested that resveratrol could potentially be developed as a dry powder for inhalation for the treatment of inflammatory lung diseases like COPD.

Site-related and seasonal variation of bioaerosol emission in an indoor wastewater treatment station: level, characteristics of particle size, and microbial structure

The emission of the airborne bacteria and fungi from an indoor wastewater treatment station adopting an integrated oxidation ditch with a vertical circle was investigated. Microbial samples were collected by the six-stage viable Andersen cascade impactor, and the samples were collected in triplicate in each sampling site per season. Culture-based method was applied to determine the concentrations of the airborne bacteria and fungi, while the cloning/sequencing method was used to characterize the genetic structure and community diversity of airborne bacteria. The highest concentrations of airborne bacteria (4155 ± 550 CFU/m3) and fungi (883 ± 150 CFU/m3) were obtained in June (summer). The lowest concentration of bacteria (1458 ± 434 CFU/m3) was determined in January (winter), and the lowest concentration of fungi (169 ± 40 CFU/m3) was found in March (spring), respectively. The particle size distribution analysis showed that most culturable bacteria obtained in all the sampling sites were in the particle size range of 1.1–4.7 µm. Most culturable fungi had particle sizes in the range 1.1–3.3 µm. Microbial population analysis showed that Bacillus sp., Acinetobacter sp., and Lysinibacillus were the main groups obtained in S1. Enterobacter was the dominant group in sampling site S2. Both the concentrations and particle size distribution of the bioaerosols in the enclosed space presented a seasonal and site-related variation. Concentration and richness of microorganisms in bioaerosols in June were higher than in September and January. The particle size distribution varied between the sampling sites, and proportion of large particles was higher in S2 than in S1 because of the settlement of large particles. Pathogenic species, such as Acinetobacter lwoffii, Staphylococcus saprophyticus, and Enterobacter sp., were isolated from the bioaerosols, which could pose serious latent danger to sewage workers’ health.

Fast monitoring of indoor bioaerosol concentrations with ATP bioluminescence assay using an electrostatic rod-type sampler.

A culture-based colony counting method is the most widely used analytical technique for monitoring bioaerosols in both indoor and outdoor environments. However, this method requires several days for colony formation. In this study, our goal was fast monitoring (Sampling: 3 min, Detection: < 1 min) of indoor bioaerosol concentrations with ATP bioluminescence assay using a bioaerosol sampler. For this purpose, a novel hand-held electrostatic rod-type sampler (110 mm wide, 115 mm long, and 200 mm tall) was developed and used with a commercial luminometer, which employs the Adenosine triphosphate (ATP) bioluminescence method. The sampler consisted of a wire-rod type charger and a cylindrical collector, and was operated with an applied voltage of 4.5 kV and a sampling flow rate of 150.7 lpm. Its performance was tested using Staphylococcus epidermidis which was aerosolized with an atomizer. Bioaerosol concentrations were measured using ATP bioluminescence method with our sampler and compared with the culture-based method using Andersen cascade impactor under controlled laboratory conditions. Indoor bioaerosol concentrations were also measured using both methods in various indoor environments. A linear correlation was obtained between both methods in lab-tests and field-tests. Our proposed sampler with ATP bioluminescence method may be effective for fast monitoring of indoor bioaerosol concentrations.

The formulation of a pressurized metered dose inhaler containing theophylline for inhalation

BackgroundTheophylline (TP) is a bronchodilator used orally to treat chronic obstructive pulmonary disease (COPD) that has been associated with multiple side effects, tempering its present use. This study aims to improve COPD treatment by creating a low-dose pressurized metered dose inhaler (pMDI) inhalable formulation of TP. MethodsAerosol performance was assessed using Andersen Cascade Impaction (ACI). Solubility of TP in HFA 134/ethanol mixture was measured and morphology of the particles analyzed with a scanning electron microscope (SEM). Calu-3 cell viability, epithelial cell transport and inflammatory-response assays were conducted to study the impact of the formulation on lung epithelial cells. ResultsThe mass deposition profile of the formulation showed an emitted dose of 250.04±14.48μg per 5 actuations, achieving the designed nominal dose (50μg/dose). SEM showed that the emitted particles were hollow with spherical morphology. Approximately 98% of TP was transported across Calu-3 epithelial cells and the concentration of interleukin-8 secreted from Calu-3 cells following stimulation with tissue necrosis factor-α (TNF-α) resulted in significantly lower level of interleukin-8 released from the cells pre-treated with TP (1.92±0.77ng·ml−1 TP treated vs. 8.83±2.05ng·ml−1 TNF-α stimulated, respectively). ConclusionsThe solution pMDI formulation of TP developed in present study was shown to be suitable for inhalation and demonstrated anti-inflammatory effects at low doses in Calu-3 cell model.

Is the cellular uptake of respiratory aerosols delivered from different devices equivalent?

The study focuses on the application of a cell integrated modified Andersen Cascade Impactor (ACI) as an in vitro lung model for the evaluation of aerosols’ behaviour of different formulation devices, containing the same active drug, specifically nebuliser, pressurised metered dose inhaler (pMDI) and dry powder inhaler (DPI). Deposition and transport profiles of the three different inhaled salbutamol sulphate (SS) formulations with clinically relevant doses were evaluated using a modified ACI coupled with the air interface Calu-3 bronchial cell model. Reproducible amounts of SS were deposited on Snapwells for the different formulations, with no significant difference in SS deposition found between the standard ACI plate and modified plate. The transport of SS aerosols produced from pMDI formulation had similar transport kinetics to nebulised SS but significantly higher compared to the DPI, which could have led to the differences in clinical outcomes. Furthermore, drug absorption of different inhaled formulation devices of the same aerodynamic fraction was found not to be equivalent due to their physical chemical properties upon aerosolisation. This study has established an in vitro platform for the evaluation of the different inhaled formulations in physiologically relevant pulmonary conditions.

Computational fluid dynamics (CFD) investigation of the gas–solid flow and performance of Andersen cascade impactor

The Andersen cascade impactor (ACI) is a device designed to fractionate aerosols by their aerodynamic diameters. This work developed a computational fluid dynamics (CFD) model to investigate flow characteristics and particle deposition behaviour in an ACI. A novel Iterative Simulation (IS) modelling technique was adopted to map the flow information between the source and target zones of individual models, hence enabling the establishment of flow fields across the whole device as a single domain. Particle trajectories and deposition were evaluated using the Lagrangian tracking approach in conjunction with the application of a kinetic energy criterion (KEc). The model was validated by comparing the simulation results with literature and manufacturer's data. The effect of flow rate was evaluated by using the standard and high flow rates of 28.3 and 60Lmin−1. The results showed that operating the ACI at high flow rates reduced the impactor performance by magnifying the cross-flow interactions and recirculation vortices. The heavy wall losses observed at Stages 2 and 3 of the impactor were attributed to more pronounced recirculation vortices at these stages. Increasing particle deposits underneath Stages 0 and 1 around the central ring of jet outlets can be attributed to counter-current flows arising from the central holes in the plates. These conclusions have significant implications for the design and operation of the ACI.

Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation.

In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by oral inhalation were prepared. The OT dry powders were prepared by spray drying using excipients chosen to promote OT stability including trehalose, isoleucine, polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts (zinc chloride and zinc citrate). Characterization by laser diffraction indicated that the OT dry powders had a median particle size of 2 μm, making them suitable for delivery by inhalation. Aerodynamic performance upon discharge from proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI) and in an anatomically correct airway (ACA) model, and confirmed that the powders had excellent aerodynamic performance, with respirable fractions up to 77% (ACI, 30 L/min). Physicochemical characterization demonstrated that the powders were amorphous (X-ray diffraction) with high glass transition temperature (modulated differential scanning calorimetry, MDSC), suggesting the potential for stabilization of the OT in a glassy amorphous matrix. OT assay and impurity profile were conducted by reverse phase HPLC and liquid chromatography-mass spectrometry (LC-MS) after storage up to 32 weeks at 40°C/75%RH. Analysis demonstrated that OT dry powders containing a mixture of citrate and zinc salts retained more than 90% of initial assay after 32 weeks storage and showed significant reduction in dimers and trisulfide formation (up to threefold reduction compared to control).

NanoCluster Itraconazole Formulations Provide a Potential Engineered Drug Particle Approach to Generate Effective Dry Powder Aerosols.

Itraconazole (ITZ), a triazole antifungal agent, is a poorly water-soluble drug that is orally administered for treatment of fungal infections such as allergic bronchopulmonary aspergillosis (ABPA) and invasive aspergillosis (IA). ABPA is relatively well controlled but IA can be fatal, especially in immunosuppressed patients. Aerosolized ITZ delivered to the lung may provide a local treatment and prophylaxis against IA at the primary site of infection in the lungs. Variations of the percent fine particle fraction (FPF), the percent emitted dose, and the physical properties of the aerosol (e.g., crystallinity) can confound consistent delivery. ITZ NanoClusters were formulated via milling (top-down process) or precipitation (bottom-up process) without using any excipients. Itraconazole formulations (ITZ) were prepared by milling 1 gram of micronized itraconazole in 300 mL of fluid. The suspension was collected at 0.5, 1, and 2 hours milling time. Milled ITZ was compared to ITZ prepared by anti-solvent precipitation and to the stock micronized itraconazole. The aerosolization performance of ITZ formulations was determined using an Andersen Cascade Impactor (ACI). The physicochemical properties and aerosol performance of different ITZ NanoClusters suggested an optimized wet milling was the preferred process compared to precipitation. ITZ NanoClusters prepared by wet milling showed better aerosol performance compared to micronized ITZ as received and ITZ NanoClusters prepared by precipitation. ITZ NanoClusters prepared by precipitation methods also showed an amorphous state, while ITZ milled in 10% EtOH maintained the crystalline character of ITZ throughout a 2 hour milling time. The aerosol performance of milled ITZ NanoClusters was dramatically improved compared to micronized ITZ as received due to the difference of drug particle structures. ITZ NanoCluster formulations represent a potential engineered drug particle approach for inhalation therapy, providing effective aerosol properties and stability due to the crystalline state of the drug powders.

Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation.

Pneumocystis carinii pneumonia (PCP) is a major opportunistic infection that affects patients with human immunodeficiency virus. Although orally administered dapsone leads to high hepatic metabolism, decreasing the therapeutic index and causing severe side effects, this drug is an effective alternative for the treatment of PCP. In this context, microencapsulation for pulmonary administration can offer an alternative to increase the bioavailability of dapsone, reducing its adverse effects. The aim of this work was to develop novel dapsone-loaded chitosan microcapsules intended for deep-lung aerosolized drug delivery. The geometric particle size (D 4,3) was approximately 7 μm, the calculated aerodynamic diameter (d aero) was approximately 4.5 μm, and the mass median aerodynamic diameter from an Andersen cascade impactor was 4.7 μm. The in vitro dissolution profile showed an efficient dapsone encapsulation, demonstrating the sustained release of the drug. The in vitro deposition (measured by the Andersen cascade impactor) showed an adequate distribution and a high fine particles fraction (FPF = 50%). Scanning electron microscopy of the pulmonary tissues demonstrated an adequate deposition of these particles in the deepest part of the lung. An in vivo toxicity experiment showed the low toxicity of the drug-loaded microcapsules, indicating a protective effect of the microencapsulation process when the particles are microencapsulated. In conclusion, the pulmonary administration of the novel dapsone-loaded microcapsules could be a promising alternative for PCP treatment.

Immunomodulatory effects of a low-dose clarithromycin-based macrolide solution pressurised metered dose inhaler.

The aim of this study was to assess the effects of low-dose clarithromycin, formulated as solution pressurized metered dose inhaler, following deposition on the Calu-3 respiratory epithelial cells. Clarithromycin was deposited on the air-interface culture of Calu-3 cells using a modified Andersen cascade impactor. Transport of fluorescein-Na, production of mucus and interleukin-8 release from Calu-3 cells following stimulation with transforming growth factor-β and treatment with clarithromycin was investigated. The deposition of clarithromycin had significant effect on the permeability of fluorescein-Na, suggesting that the barrier integrity was improved following a short-term treatment with clarithromycin (apparent permeability values were reduced to 3.57 × 10(-9) ± 2.32 × 10(-9)cm.s(-1), compared to 1.14 × 10(-8) ± 4.30 × 10(-8)cm.s(-1) for control). Furthermore, the amount of mucus produced was significantly reduced during the course of clarithromycin treatment. The concentration of interleukin-8 secreted from Calu-3 cells following stimulation with transforming growth factor-β resulted in significantly lower level of interleukin-8 released from the cells pre-treated with clarithromycin (5.2 ± 0.5ng.ml(-1) clarithromycin treated vs. 7.7 ± 0.8ng.ml(-1) control, respectively). Our data demonstrate that treatment with clarithromycin decreases the paracellular permeability of epithelial cells, mucus secretion and interleukin-8 release and therefore, inhaled clarithromycin holds potential as an anti-inflammatory therapy.

Roughness-controlled self-assembly of mannitol/LB agar microparticles by polymorphic transformation for pulmonary drug delivery.

Novel roughness-controlled mannitol/LB Agar microparticles were synthesized by polymorphic transformation and self-assembly method using hexane as the polymorphic transformation reagent and spray-dried mannitol/LB Agar microparticles as the starting material. As-prepared microparticles were characterized by Fourier transform infrared spectra (FTIR), X-ray diffraction spectra (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and Andersen Cascade Impactor (ACI). The XRD and DSC results indicate that after immersing spray-dried mannitol/LB Agar microparticles in hexane, β-mannitol was completely transformed to α-mannitol in 1 h, and all the δ-mannitol was transformed to α form after 14 days. SEM shows that during the transformation the nanobelts on the spray-dried mannitol/LB Agar microparticles become more dispersed and the contour of the individual nanobelts becomes more noticeable. Afterward, the nanobelts self-assemble to nanorods and result in rod-covered mannitol/LB Agar microparticles. FTIR indicates new hydrogen bonds were formed among mannitol, LB Agar, and hexane. SEM images coupled with image analysis software reveal that different surface morphology of the microparticles have different drug adhesion mechanisms. Comparison of ACI results and image analysis of SEM images shows that an increase in the particle surface roughness can increase the fine particle fractions (FPFs) using the rod-covered mannitol microparticles as drug carriers. Transformed microparticles show higher FPFs than commercially available lactose carriers. An FPF of 28.6 ± 2.4% was achieved by microparticles transformed from spray-dried microparticles using 2% mannitol(w/v)/LB Agar as feed solution. It is comparable to the highest FPF reported in the literature using lactose and spray-dried mannitol as carriers.

Airborne Virus Survivability During Long-Term Sampling Using a Non-Viable Andersen Cascade Impactor in an Environmental Chamber

In order to evaluate the survivability of airborne viruses and the sampling performance of an eight-stage non-viable Andersen impactor in typical indoor environments featuring low viral aerosol concentrations, aerosols of a male-specific bacteriophage (MS2), human adenovirus type 1 (HAdV-1), and avian influenza virus (AIV) were sampled size-selectively using the impactor in an environmental chamber. Live virus titer, total virus RNA or DNA concentration, and intensity of a fluorescein tracer were measured to calculate relative virus recovery and virus survival. Viral aerosols were first sampled for 1 and 6 h at 25°C and 50% relative humidity (RH). Virus inactivation and plate overloading were found to be significant in the impactor. Viral aerosols were then sampled at different temperature and humidity levels. MS2 and AIV showed higher survival at lower temperature. Absolute humidity (AH) was found to be a better predictor of virus survival than RH, and the interaction between AH and temperature was not s...

Collection and measurement of aerosols of viable influenza virus in liquid media in an Andersen cascade impactor

Collection and measurement of aerosols of viable influenza virus in liquid media in an Andersen cascade impactor

Nano spray-dried pyrazinamide-l-leucine dry powders, physical properties and feasibility used as dry powder aerosols

Objective: The aim of this study was to investigate the effect of adding l-leucine and using an ethanolic solvent on the physicochemical properties and aerodynamic behavior of nano spray-dried pyrazinamide (PZA)-l-leucine powders.Materials and methods: A nano spray dryer was employed to prepare PZA-l-leucine powders. The physicochemical properties were evaluated using a scanning electron microscope (SEM), differential scanning calorimetry and X-ray diffraction. The Andersen cascade impactor was used to evaluate the in vitro aerosolization performance of the sprayed powders.Results and discussion: The incorporation of l-leucine at 10% improved the percentage fine particle fraction (%FPF) in all ethanolic solvent formulations by up to nearly twofold (20.0–23.4%) compared to the normal spray-dried PZA of (8.8–13.0%). Changes in the particle density and morphology were also observed. The dense solid particles of PZA were completely converted to bulk hollow particles with a thin shell by increasing the l-leucine content up to 50%. Higher ethanol concentration resulted in larger dimensions of the hollow particle but did not directly affect the aerosolization performance. The co-spray dried PZA with 20% l-leucine in a 10% ethanol feed solvent gave the best aerosolization performance (FPF = 33.0%).Conclusions: The co-spray dried PZA with a suitable l-leucine content using a nano spray drying technique could be applied to formulate the PZA DPI.

Evaluation of the Filtration Efficiency of the N95 Filtering Facepiece Respirator for Airborne Methicillin-Resistant Staphylococcus aureus

<abstract> <bold><sc>Abstract.</sc></bold> Airborne methicillin-resistant Staphylococcus aureus (MRSA) was detected inside a swine facility that presented a risk of respiratory colonization and infection to swine and swine workers. Viable airborne MRSA was sampled using an Andersen cascade impactor, and total airborne particulates were sampled using an optical particle counter. The filter efficiency of the N95 filtering facepiece respirator (FFR) was evaluated to determine its effectiveness for airborne MRSA. Our study showed that the filter for the N95 FFR had efficiency greater than 95% for airborne MRSA.

Factors influencing aerodynamic particle size distribution of suspension pressurized metered dose inhalers.

Pressurized metered dose inhalers (pMDIs) are frequently used for the treatment of asthma and chronic obstructive pulmonary disease. The aerodynamic particle size distribution (APSD) of the residual particles delivered from a pMDI plays a key role in determining the amount and region of drug deposition in the lung and thereby the efficacy of the inhaler. In this study, a simulation model that predicts the APSD of residual particles from suspension pMDIs was utilized to identify the primary determinants for APSD. These findings were then applied to better understand the effect of changing drug concentration and micronized drug size on experimentally observed APSDs determined through Andersen Cascade Impactor testing. The experimental formulations evaluated had micronized drug mass median aerodynamic diameters (MMAD) between 1.2 and 2.6 μm and drug concentrations ranging from 0.01 to 1% (w/w) with 8.5% (w/w) ethanol in 1,1,1,2-tetrafluoroethane (HFA-134a). It was determined that the drug concentration, micronized drug size, and initially atomized droplet distribution have a significant impact in modulating the proportion of atomized droplets that contain multiple suspended drug particles, which in turn increases the residual APSD. These factors were found to be predictive of the residual particle MMAD for experimental suspension HFA-134a formulations containing ethanol. The empirical algebraic model allows predicting the residual particle size for a variety of suspension formulations with an average error of 0.096 μm (standard deviation of 0.1 μm).

Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: Development, in vitro characterization and antioxidant activity

Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.

Effect of turbulent kinetic energy on dry powder inhaler performance

Dry powder inhalers (DPIs) have been extensively used for delivering medication to the lungs. Different designs of DPI devices affect the aerosolization processes of the drug particles. The processes cannot be easily visualized in experiments, thus computational fluid dynamics were used to investigate the turbulence kinetic energy and particle impaction. In this research, 3 size ranges of lactose carrier and the Cyclohaler® and Inhalator® devices were used as models for the computational simulations. The velocity vector, the turbulence kinetic energy (TKE) and particle trajectory were obtained. An aerosol dispersion experiment was performed using the Andersen Cascade Impactor. The TKE was directly related to the flow-rate. The TKE in the Cyclohaler® was lower than that in the Inhalator® due to its narrow geometry and this resulted in a high velocity air-flow. In the Cyclohaler® the probability of deagglomeration by impaction was high because of the cyclone-like design while the cross grid of the Inhalator® was an important factor for deagglomeration of the particles. The FPF varied from 7 to 30% and the FPF increased as the flow-rate increased. The MMAD was in the range of 4–6μm. The carrier size also affected the probability of deagglomeration at 60 and 90L/min, but not at 30L/min. In summary, maximizing the TKE and the particle impaction rate by adding a grid and providing a cyclone-like design was key factor to achieve a high deagglomeration of the particles.

Improved lung delivery of budesonide from biopolymer based dry powder inhaler through natural inhalation of rat

Budesonide, an inhaled glucocorticoid, is used for the treatment of large and small calibre airway inflammation associated with asthma. Conventional dry powder inhalers (DPIs) show least deposition efficiency in the lung due to agglomeration, increased particle size and minimum fluidisation. There is a need for controlled release budesonide DPI in order to improve maximum lung deposition with least toxicity and improve patient compliance. Budesonide loaded biopolymer based microparticles were prepared by controlled gelation of sodium alginate using calcium chloride and chitosan. Microparticles were evaluated for physical characteristics, in vitro lung deposition by Andersen cascade impactor and in vivo regional lung deposition by fabricated apparatus with measured respiratory minute volume of rats from plethysmography. The effect of DPI on the histology of lung tissues was also studied. The particle size, encapsulation efficiency, ζ potential, mass median aerodynamic diameter and fine particle fraction of the DPI were 3·059±0·03 μm, 87·16±1·11%, −17·5 mV, 1·16±0·01 μm and 56·18±0·01% respectively, which revealed the potential for pulmonary delivery. Formulation demonstrated a 14-fold increased drug deposition in the lung as compared to commercial DPI indicating pulmonary targeting potential. The formulation showed the controlled drug release up to 24 h. The histopathology revealed safety of the formulation. Developed DPI markedly improved regional lung deposition and safety of budesonide. This technology would facilitate the administration of glucocorticoid in the clinical testing.

Novel simvastatin inhalation formulation and characterisation.

Simvastatin (SV), a drug of the statin class currently used orally as an anti-cholesterolemic via the inhibition of the 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase, has been found not only to reduce cholesterol but also to have several other pharmacological actions that might be beneficial in airway inflammatory diseases. Currently, there is no inhalable formulation that could deliver SV to the lungs. In this study, a pressurised metered-dose inhaler (pMDI) solution formulation of SV was manufactured, with ethanol as a co-solvent, and its aerosol performance and physico-chemical properties investigated. A pMDI solution formulation containing SV and 6% w/w ethanol was prepared. This formulation was assessed visually and quantitatively for SV solubility. Furthermore, the aerosol performance (using Andersen Cascade impactor at 28.3L/min) and active ingredient chemical stability up to 6months at different storage temperatures, 4 and 25°C, were also evaluated. The physico-chemical properties of the SV solution pMDI were also characterised by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and laser diffraction. The aerosol particles, determined using scanning electron microscopy (SEM), presented a smooth surface morphology and were spherical in shape. The aerosol produced had a fine particle fraction of 30.77 ± 2.44% and a particle size distribution suitable for inhalation drug delivery. Furthermore, the short-term chemical stability showed the formulation to be stable at 4°C for up to 6months, whilst at 25°C, the formulation was stable up to 3months. In this study, a respirable and stable SV solution pMDI formulation for inhalation has been presented that could potentially be used clinically as an anti-inflammatory therapy for the treatment of several lung diseases.