Dry Powder Inhaler Research Articles

Inhalable Microparticles Embedding Biocompatible Magnetic Iron-Doped Hydroxyapatite Nanoparticles.

Recently, there has been increasing interest in developing biocompatible inhalable nanoparticle formulations, as they have enormous potential for treating and diagnosing lung disease. In this respect, here, we have studied superparamagnetic iron-doped calcium phosphate (in the form of hydroxyapatite) nanoparticles (FeCaP NPs) which were previously proved to be excellent materials for magnetic resonance imaging, drug delivery and hyperthermia-related applications. We have established that FeCaP NPs are not cytotoxic towards human lung alveolar epithelial type 1 (AT1) cells even at high doses, thus proving their safety for inhalation administration. Then, D-mannitol spray-dried microparticles embedding FeCaP NPs have been formulated, obtaining respirable dry powders. These microparticles were designed to achieve the best aerodynamic particle size distribution which is a critical condition for successful inhalation and deposition. The nanoparticle-in-microparticle approach resulted in the protection of FeCaP NPs, allowing their release upon microparticle dissolution, with dimensions and surface charge close to the original values. This work demonstrates the use of spray drying to provide an inhalable dry powder platform for the lung delivery of safe FeCaP NPs for magnetically driven applications.

Performance and biocompatibility of a novel inhalable dry powder formulation based on hyaluronic acid intended to protect the respiratory tract mucosa

Hyaluronic acid (HA) is a key component of the respiratory mucosa. By acting as a natural moisturizer, it provides hydration to the airways. In normal conditions, high molecular weight HA molecules form viscous gels providing a protective shield against external insults. This is particularly important in the upper airways where the HA protective barrier helps to prevent environmental agents to reach the lungs. Most respiratory diseases are characterized by inflammatory processes causing degradation of HA into small fragments which reduces the HA barrier effect and increases the risk of exposure to external insults. Dry powder inhalers (DPIs) are efficient devices used to deliver therapeutic molecules in the form of dry powder to the respiratory tract. PolmonYDEFENCE/DYFESA™ is a novel formulation based on HA delivered to the airways using the PillHaler® DPI device. In this study we report the results of in vitro inhalation performances of PolmonYDEFENCE/DYFESA™ as well as its mechanism of action in human cells. We found that the product targets the upper airways and that HA molecules form a protective barrier on cell surface. Furthermore, exposure to the device is safe in animal models. The promising pre-clinical results of this study provide the bases for future clinical investigation.

The Extra Cost Due to Non-Adherence to Inhaled Treatments in Adolescents with Mild-to-Moderate Persistent Asthma

A 12-month estimation of the economic impact of non-adherence to inhalation treatments in adolescents with mild-to-moderate atopic asthma. Non-smoking adolescents aged 12-19 years, without any significant comorbidity, prescribed with inhaled cortico-steroids (ICS) or ICS/long-acting beta(2)-adrenergics (LABA) via dry powder inhalers (DPIs) on a regular basis were automatically selected from the institutional database. Spirometric lung function, clinical outcomes, and pharmacological information were collected. The adolescents' adherence to their prescribed regimen was calculated monthly. Adolescents were divided in two sub-groups based on their adherence to prescriptions: ≤70% (not adherent) or >70% (adherent), and statistically compared (Wilcoxon test, assuming p < 0.05). Overall, 155 adolescents fulfilled the inclusion criteria (males, 49.0%; mean age, 15.6 years ± 2.9 SD; mean BMI, 19.1 ± 1.3 SD). Mean values of lung function were: FEV1 = 84.9% pred. ± 14.8 SD, FEV1/FVC = 87.9 ± 12.5 SD; MMEF = 74.8% pred. ± 15.1 SD and V25 = 68.4% pred. ± 14.9 SD. ICS had been prescribed in 57.4% of subjects and ICS/LABA in 42.6%. Mean adherence to original prescriptions was 46.6% ± 9.2 SD in non-adherent and 80.3% ± 6.6 SD in adherent adolescents, respectively (p < 0.001). The mean rates of hospitalizations, exacerbations, and GP visits; the average duration of absenteeism; the frequency of systemic steroids and antibiotics courses needed over the study period were significantly and substantially lower in adolescents adherent to prescriptions (all p < 0.001). The mean total annual extra cost calculated in the two sub-groups was EUR 705.8 ± 420.9 SD in non-adherent adolescents and EUR 192.1 ± 68.1 SD in adherent adolescents, respectively (p < 0.001), which was 3.7 times higher than in non-adherent adolescents. In adolescents, the clinical control of mild-to-moderate atopic asthma is directly and strictly related to the degree of adherence to prescribed inhalation therapies. All clinical and economic outcomes prove dramatically poor when adherence is low, and treatable asthma can be frequently mistaken for refractory asthma in these cases. Adolescents' non-adherence impacts the burden of the disease quite substantially. Much more effective strategies centered specifically on adolescents' asthma are needed.

Effects of the mouthpiece and chamber of Turbuhaler® on the aerosolization of API-only powder formulations

Powder dispersion in dry powder inhalers (DPIs) is affected by powder formulations as well as the design of a device. This paper conducted a numerical investigation based on the coupled computational fluid dynamics (CFD) and discrete element method (DEM) to evaluate the changes of the design of a commercial DPI device Turbuhaler® on the aerosolization of an API-only formulation. Six different designs were proposed by modifying the mouthpiece and chamber of the original geometry which was reconstructed from a CT-scan of the Turbuhaler, and their performances in terms of powder deposition in the device and fine powder fraction (FPF) were evaluated. The resistance of the device was observed to vary with different designs. For the change of the mouthpiece, the device with a cylindrical mouthpiece had the least resistance and the lowest FPF emitted among all the devices, confirming the important role of the spiral mouthpiece on powder dispersion. Reducing the mouthpiece size caused more powder deposition in the inhaler due to higher airflow velocity, but FPF emitted increased compared to the original design as more powder dispersion occurred inside the mouthpiece. The half-length mouthpiece design reduced device resistance to increase airflow velocity and average collision energy, resulting in an increase in FPF loaded but a decrease in the number of collisions. For the change of the chamber, the domed chamber design increased the powder dispersion time and thus enhanced the frequency and energy of particle collisions, which eventually led to an increase in FPF loaded. At fixed flow rates, the powder dispersion efficiency was a function of the device resistance with higher device resistance causing an increase in the FPF loaded. However, it is important for the patient’s attainable pressure drop to be considered in this context. Correlations between the aerosolization efficiency and the ratio of the average collision energy and cohesion energy were established based on model-predicted quantities.

Reducing carbon footprint by switching to reusable soft-mist inhalers.

Inhalation therapy is the cornerstone of COPD, together with non-pharmacological treatments. Long-acting muscarinic antagonists (LAMAs), alone or in combination with long-acting β-agonists (LABAs), are commonly used. Pressurised metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) and soft-mist inhalers (SMIs) are used, each with different carbon footprints. This study aimed to assess the carbon footprint of hypothetically replacing LAMA or LAMA/LABA inhalers with an SMI, Respimat Reusable, within the same therapeutic class. An environmental impact model was established to assess the change in carbon footprint of replacing pMDIs/DPIs with Respimat Reusable within the same therapeutic class (LAMA or LAMA/LABA) across 12 European countries and the USA over 5 years. Inhaler use for country and disease-specific populations was derived from international prescribing data and the associated carbon footprint (CO2 equivalents (CO2e)) was identified from published sources. Over 5 years and across all countries, replacing LAMA inhalers with Spiriva Respimat Reusable reduced CO2e emissions by 13.3-50.9%, saving 93-6228 tonnes of CO2e in the different countries studied. Replacing LAMA/LABA inhalers with Spiolto Respimat Reusable reduced CO2e emissions by 9.5-92.6%, saving 31-50 843 tonnes of CO2e. In scenario analyses, which included total replacement of DPIs/pMDIs, consistent CO2e savings were estimated. Sensitivity analyses showed that results were sensitive to changes in several parameters including varying assumptions around reusability of inhalers and potential CO2e impact. Replacement of pMDIs and DPIs with Respimat Reusable within the same therapeutic class would result in substantial reductions in CO2e emissions.

Effect of Inhalation Profile on Delivery of Treprostinil Palmitil Inhalation Powder.

Treprostinil palmitil (TP), a prodrug of treprostinil, is being developed as an inhalation powder (TPIP) for the treatment of patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension due to interstitial lung disease (PH-ILD). In ongoing human clinical trials, TPIP is administered via a commercially available high resistance (HR) RS01 capsule-based dry powder inhaler (DPI) device manufactured by Berry Global (formerly Plastiape), which utilizes the patient's inspiratory flow to provide the required energy to deagglomerate and disperse the powder for delivery to their lungs. In this study, we characterized the aerosol performance of TPIP in response to changes in inhalation profiles to model more realistic use scenarios, i.e., for reduced inspiratory volumes and with inhalation acceleration rates that differ from those described in the compendia. The emitted dose of TP for all combinations of inhalation profiles and volumes ranged narrowly between 79 and 89% for the 16 and 32 mg TPIP capsules at the 60 LPM inspiratory flow rate but was reduced to 72-76% for the 16 mg TPIP capsule under the scenarios at the 30 LPM peak inspiratory flow rate. There were no meaningful differences in the fine particle dose (FPD) at all conditions at 60 LPM with the 4 L inhalation volume. The FPD values for the 16 mg TPIP capsule ranged narrowly between 60 and 65% of the loaded dose for all inhalation ramp rates with a 4 L volume and at both extremes of ramp rates for inhalation volumes down to 1 L, while the FPD values for the 32 mg TPIP capsule ranged between 53 and 65% of the loaded dose for all inhalation ramp rates with a 4 L volume and at both extremes of ramp rates for inhalation volumes down to 1 L for the 60 LPM flow rate. At the 30 LPM peak flow rate, the FPD values for the 16 mg TPIP capsule ranged narrowly between 54 and 58% of the loaded dose at both extremes of the ramp rates for inhalation volumes down to 1 L. Based on these in vitro findings, the TPIP delivery system appears not to be affected by the changes in inspiratory flow profiles or inspiratory volumes that might be expected to occur in patients with PAH or PH associated with underlying lung conditions such as ILD.

A varying-swirl design concept for dry powder inhalers

The de-agglomeration potential of a dry powder inhaler (DPI) strongly affects its aerosol performance. Typically, a swirling flow is employed for the entrainment and de-agglomeration of drug powder into the inhalation air flow. Here, we propose a novel design concept that passively modifies the DPI swirling-flow, and thereby the de-agglomeration process, in order to achieve higher lung deposition. The essence of this design is a varying inner cross-section of the pipe-shaped device, realised in the form of converging and diverging circular sections placed after the tangential inlets in the device. An improved aerosol performance was shown for this device, with the fine particle fraction reaching 68.4% of the emitted dose, compared with 66.8% from that of the baseline device. This was found to be a direct effect of the modified flow characteristics generated within the device and thereafter emerging from its mouthpiece. These flow characteristics were determined from computational fluid dynamics simulations and particle image velocimetry measurements.Adaptations of this DPI design concept were achieved through the use of a honeycomb grid placed either after the device tangential inlets, or at the device mouthpiece exit. When placed after the inlets, a 10.4% reduction in the fine particle fraction was observed, as the air flow was straightened due to the influence of the grid which significantly reduced the flow-swirl before the flow entered the converging–diverging sections. Whereas, when placed at the mouthpiece exit, the flow-straightening effect of the grid resulted in reduced lateral spreading of the emitted aerosol but did not significantly affect throat deposition.

Impact of dispersion media and carrier type on spray-dried proliposome powder formulations loaded with beclomethasone dipropionate for their pulmonary drug delivery via a next generation impactor.

Drug delivery via aerosolization for localized and systemic effect is a non-invasive approach to achieving pulmonary targeting. The aim of this study was to prepare spray-dried proliposome (SDP) powder formulations to produce carrier particles for superior aerosolization performance, assessed via a next generation impactor (NGI) in combination with a dry powder inhaler. SDP powder formulations (F1-F10) were prepared using a spray dryer, employing five different types of lactose carriers (Lactose monohydrate (LMH), lactose microfine (LMF), lactose 003, lactose 220 and lactose 300) and two different dispersion media. The first dispersion medium was comprised of water and ethanol (50:50% v/v ratio), and the second dispersion medium comprised wholly of ethanol (100%). In the first dispersion medium, the lipid phase (consisting of Soya phosphatidylcholine (SPC as phospholipid) and Beclomethasone dipropionate (BDP; model drug) were dissolved in ethanol and the lactose carrier in water, followed by spray drying. Whereas in second dispersion medium, the lipid phase and lactose carrier were dispersed in ethanol only, post spray drying. SDP powder formulations (F1-F5) possessed significantly smaller particles (2.89 ± 1.24-4.48 ± 1.20 μm), when compared to SDP F6-F10 formulations (10.63 ± 3.71-19.27 ± 4.98 μm), irrespective of lactose carrier type via SEM (scanning electron microscopy). Crystallinity of the F6-F10 and amorphicity of F1-F15 formulations were confirmed by XRD (X-ray diffraction). Differences in size and crystallinity were further reflected in production yield, where significantly higher production yield was obtained for F1-F5 (74.87 ± 4.28-87.32 ± 2.42%) then F6-F10 formulations (40.08 ± 5.714-54.98 ± 5.82%), irrespective of carrier type. Negligible differences were noted in terms of entrapment efficiency, when comparing F1-F5 SDP formulations (94.67 ± 8.41-96.35 ± 7.93) to F6-F10 formulations (78.16 ± 9.35-82.95 ± 9.62). Moreover, formulations F1-F5 demonstrated significantly higher fine particle fraction (FPF), fine particle dose (FPD) and respirable fraction (RF) (on average of 30.35%, 890.12 μg and 85.90%) when compared to counterpart SDP powder formulations (F6-F10). This study has demonstrated that when a combination of water and ethanol was employed as dispersion medium (formulations F1-F5), superior formulation properties for pulmonary drug delivery were observed, irrespective of carrier type employed.

Pressure Drop Characteristics of the Reduced NGI Configuration with Several Common Glass Fiber Filters.

Background: Measurement of aerodynamic particle size distribution, a clinically relevant in vitro attribute of inhalable drug products, involves multistage cascade impactors and is tedious and expensive. A leading candidate for a quicker method is the reduced NGI™ (rNGI). This method involves placing glass fiber filters on top of the nozzles of a chosen NGI stage, selected often to collect all particles with an aerodynamic diameter smaller than approximately five microns. These filters contribute additional flow resistance that can alter the flow rate start-up curve, potentially affecting the size distribution and mass of the drug product dispensed by passive dry powder inhalers (DPIs). The magnitude of these additional flow resistance measurements is currently unreported in the literature. Materials and Methods: We placed glass fiber filters on top of the stage 3 nozzles of an NGI, along with the necessary support screen and hold-down ring. We measured the pressure drop across NGI stage 3 with the assistance of a delta P lid and a high-precision pressure transducer. With each filter material type and multiple individual filters, we gathered eight replicates at flow rates of 30, 45, and 60 L/min. Results: The filters typically doubled the total pressure drop through the NGI. For example, at a flow rate of 60 L/min, the Whatman 934-AH filters introduced a pressure drop of about 9800 Pa at stage 3, reducing the absolute pressure exiting the NGI to about 23 kPa below ambient, compared with a typical value of 10 kPa for the NGI alone at this flow rate. Conclusions: The pressure drop across typical filters is approximately equal to that through the NGI alone and therefore will affect the flow start-up rate intrinsic to compendial testing of passive DPIs. This change in start-up rate could cause differences between results of the rNGI configuration and those of the full NGI and will increase the required vacuum pump capacity.

RELIABLE SPECTROSCOPIC ANALYTICAL PROCEDURE FOR QUANTITATIVE ESTIMATION OF OSIMERTINIB MESYLATE IN LIPOSOMAL DRY POWDER INHALER FORMULATION

Objective: The objective of the present study was to develop an economical UV spectrophotometric method with a simple, rapid, accurate, precise, sensitive, and reproducible for the quantitative estimation of Osimertinib Mesylate (OM) in bulk and newly prepared Liposomal Dry Powder Inhaler (LDPI) formulation which has not been reported earlier. Methods: Different dilutions were prepared in methanol in the range of 4-16 µg/ml, scanned between 400-200 nm, and determined the maximum absorbance was to confirm the drug’s λmax. Linearity, accuracy, precision, the limit of detection (LOD), and the limit of quantitation (LOQ) were used as parameters to validate the method. The concentration of the OM was calculated based on a linear regression equation of the calibration curve. Results: The UV spectrum of OM showed λmax at 267 nm and a linear calibration curve with a regression coefficient (R2) of more than 0.997. The RSD for recovery studies was found ˂ 2 % and confirmed the accuracy of the proposed method. The LOD and LOQ were observed at 0.021 µg/ml and 0.063 µg/ml, respectively for bulk and 0.056 µg/ml and 0.170 µg/ml for OM LDPI formulation. The method was found to be precise with an RSD ˂ 2 %. Conclusion: The present UV spectrophotometric method can be used to successfully estimate OM in LDPI, and there is no interference of excipients during the study. The method is validated in compliance with International Conference on Harmonization (ICH) guidelines and it should be used as a routine quality control analysis i.e., assay for such dosage forms.

Co-Delivery of D-LAK Antimicrobial Peptide and Capreomycin as Inhaled Powder Formulation to Combat Drug-Resistant Tuberculosis

IntroductionThe emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) posed a severe challenge to tuberculosis (TB) management. The treatment of MDR-TB involves second-line anti-TB agents, most of which are injectable and highly toxic. Previous metabolomics study of the Mtb membrane revealed that two antimicrobial peptides, D-LAK120-A and D-LAK120-HP13, can potentiate the efficacy of capreomycin against mycobacteria.AimsAs both capreomycin and peptides are not orally available, this study aimed to formulate combined formulations of capreomycin and D-LAK peptides as inhalable dry powder by spray drying.Methods and ResultsA total of 16 formulations were prepared with different levels of drug content and capreomycin to peptide ratios. A good production yield of over 60% (w/w) was achieved in most formulations. The co-spray dried particles exhibited spherical shape with a smooth surface and contained low residual moisture of below 2%. Both capreomycin and D-LAK peptides were enriched at the surface of the particles. The aerosol performance of the formulations was evaluated with Next Generation Impactor (NGI) coupled with Breezhaler®. While no significant difference was observed in terms of emitted fraction (EF) and fine particle fraction (FPF) among the different formulations, lowering the flow rate from 90 L/min to 60 L/min could reduce the impaction at the throat and improve the FPF to over 50%.ConclusionsOverall, this study showed the feasibility of producing co-spray dried formulation of capreomycin and antimicrobial peptides for pulmonary delivery. Future study on their antibacterial effect is warranted.

Dry Powder Inhaler with the technical and practical obstacles, and forthcoming platform strategies.

A Dry Powder Inhaler (DPI) is a technique as well as a device used to inhale formulation which is in the form of dry powder, and is inhaled through the nose or mouth. It was developed for the purpose of treating conditions like chronic obstructive pulmonary disease (COPD), Asthma, and even cystic fibrosis etc. The aim of the review is to discuss the different methods of preparation of dry powders along with the characterization of DPI. Here we present the outline of different methods like supercritical fluid extraction (SCF), spray drying, and milling. The review focussed on various devices including single and multi-dose devices used in the DPI. It also highlights on recent advances in the DPI including nano particulate system, siRNA-based medication, liposomes, and pro-liposomes based delivery. In COVID-19 silver nanoparticles-based DPIs provide very prominent results in the infected lungs. Moreover, this review states that the AI-based DPI development provides and improvement in the bioavailability and effectiveness of the drug along with the role of artificial neural networks (ANN). The study also showed that nasally administered drugs (nose to brain) can easily cross the blood-brain barrier (BBB) and enter the central nervous system (CNS) through the olfactory and trigeminal pathway which provides effective CNS concentrations at lower dosage. It is suggested that DPIs not only target respiratory complications but also treat CNS complications too. This review provides support and guides the researcher in the recent development and evaluation of DPI.

Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers

The incidence of fungal pulmonary infections is known to be on the increase, and yet there is an alarming gap in terms of marketed antifungal therapies that are available for pulmonary administration. Amphotericin B (AmB) is a highly efficient broad-spectrum antifungal only marketed as an intravenous formulation. Based on the lack of effective antifungal and antiparasitic pulmonary treatments, the aim of this study was to develop a carbohydrate-based AmB dry powder inhaler (DPI) formulation, prepared by spray drying. Amorphous AmB microparticles were developed by combining 39.7 % AmB with 39.7 % γ-cyclodextrin, 8.1 % mannose and 12.5 % leucine. An increase in the mannose concentration from 8.1 to 29.8 %, led to partial drug crystallisation. Both formulations showed good in vitro lung deposition characteristics (80 % FPF < 5 µm and MMAD < 3 µm) at different air flow rates (60 and 30 L/min) when used with a DPI, but also during nebulisation upon reconstitution in water.

Smart Specification Setting for Dry Powder Inhalation Carriers

The specifications of excipients are important to pharmaceutical manufacturers to ensure that the final product can be manufactured robustly over the entire lifecycle of a drug product. Particle size specifications are key for dry powder inhalation excipients and they should be agreed between users and suppliers. The current paper evaluates two development strategies to set particle size specifications. It is shown that the application of quality-by-design principles to specification setting could result in broader specifications, while it guarantees that efficacy, safety and manufacturing of the medication is not affected. A multitude of reasons exist to keep specifications broader than the production capability range, including improved risk-mitigation and potentially reduced regulatory challenges during and after registration.

Drug Combination of Ciprofloxacin and Polymyxin B for the Treatment of Multidrug-Resistant Acinetobacter baumannii Infections: A Drug Pair Limiting the Development of Resistance.

Polymyxins are considered as last-resort antibiotics to treat infections caused by Acinetobacter baumannii. However, there are increasing reports of resistance in A. baumannii to polymyxins. In this study, inhalable combinational dry powders consisting of ciprofloxacin (CIP) and polymyxin B (PMB) were prepared by spray-drying. The obtained powders were characterized with respect to the particle properties, solid state, in vitro dissolution and in vitro aerosol performance. The antibacterial effect of the combination dry powders against multidrug-resistant A. baumannii was assessed in a time-kill study. Mutants from the time-kill study were further investigated by population analysis profiling, minimum inhibitory concentration testing, and genomic comparisons. Inhalable dry powders consisting of CIP, PMB and their combination showed a fine particle fraction above 30%, an index of robust aerosol performance of inhaled dry powder formulations in the literature. The combination of CIP and PMB exhibited a synergistic antibacterial effect against A. baumannii and suppressed the development of CIP and PMB resistance. Genome analyses revealed only a few genetic differences of 3-6 SNPs between mutants and the progenitor isolate. This study suggests that inhalable spray-dried powders composed of the combination of CIP and PMB is promising for the treatment of respiratory infections caused by A. baumannii, and this combination can enhance the killing efficiency and suppress the development of drug resistance.

Intranasal Delivery: A Review of Nasal Delivery Devices and Influence in the Therapeutic Management

Nasal drug delivery and various remedies for drug delivery via the nasal route draws more scientific interest in recent years. In recent years, more attention has been paid to achieving systemic drug action through the nose as an entry point into the body. It is considered a very popular and attractive route for needleless vaccination. It is the choice route for the treatment of local diseases like allergic, non-allergic rhinitis, and sinusitis in nasal-paranasal sinuses. The nasal airway helps to protect the lungs from hazardous exposure. Nasal delivery helps to overcome poor bioavailability, slow absorption, and enzymatic degradation and helps to avoid first-pass metabolism. It also achieves systemic delivery through rapid absorption to give the desired effect. The various devices commonly include nebulizers, dry powder inhalers, nasal spray, nasal implants, etc. This review is mainly focused on the mechanism of nasal absorption, administration of drugs via the nasal route, various devices used in nasal administration, and recent advances to minimize clinical hazards. Keywords: Nasal Drug Delivery; Mechanism; Nasal Cycle; Nasal Delivery Devices

Thinking "Green" When Treating "Pink Puffers" and "Blue Bloaters"-Reducing Carbon Footprint When Prescribing Inhalers.

The impact of man-made climate change is already affecting millions of people worldwide. The health care sector in the US is a relevant contributor, accounting for about 8 to 10% of national greenhouse gas emissions. This special communicationdescribes the harmful impact of propellant gases in metered dose inhalers (MDI) on the climate and summarizes and discusses current knowledge and recommendations from European countries. Dry powder inhalers (DPI) are a good alternative to MDIs and are available for all inhaler drug classes recommended in current asthma and COPD guidelines. Changing an MDI to PDI can significantly reduce carbon footprints. The majority of the US population is willing to do more to protect the climate. Primary care providers can engage in this by addressing the impacts of drug therapy on climate change in medical decision making.

Impact of Leucine and Magnesium Stearate on the Physicochemical Properties and Aerosolization Behavior of Wet Milled Inhalable Ibuprofen Microparticles for Developing Dry Powder Inhaler Formulation.

This study investigated the development and characterization of leucine and magnesium stearate (MgSt) embedded wet milled inhalable ibuprofen (IBF) dry powder inhaler (DPI) formulations. IBF microparticles were prepared by a wet milling homogenization process and were characterized by SEM, FTIR, DSC, XRD and TGA. Using a Twin-Stage Impinger (TSI), the in vitro aerosolization of the formulations with and without carrier lactose was studied at a flow rate of 60± 5 L/min and the IBF was determined using a validated HPLC method. The flow properties were determined by the Carr's Index (CI), Hausner Ratio (HR) and Angle of Repose (AR) of the milled IBF with 4-6.25% leucine and leucine containing formulations showed higher flow property than those of formulations without leucine. The fine particle fraction (FPF) of IBF from the prepared formulations was significantly (p = 0.000278) higher (37.1 ± 3.8%) compared to the original drug (FPF 3.7 ± 0.9%) owing to the presence of leucine, which enhanced the aerosolization of the milled IBF particles. Using quantitative phase analysis, the XPRD data revealed the crystallinity and accurate weight percentages of the milled IBF in the formulations. FTIR revealed no changes of the structural integrity of the milled IBF in presence of leucine or MgSt. The presence of 2.5% MgSt in the selected formulations produced the highest solubility (252.8 ± 0.6 µg/mL) of IBF compared to that of unmilled IBF (147.4 ± 1.6 µg/mL). The drug dissolution from all formulations containing 4-6.25% leucine showed 12.2-18.6% drug release in 2.5 min; however, 100% IBF dissolution occurred in 2 h whereas around 50% original and dry milled IBF dissolved in 2 h. The results indicated the successful preparation of inhalable IBF microparticles by the wet milling method and the developed DPI formulations with enhanced aerosolization and solubility due to the presence of leucine may be considered as future IBF formulations for inhalation.

Recent Studies on the Drug Delivery of Nebulizers - A Review

This article provides a summary of some of the most current research on the delivery of drugs to the lungs, as well as a discussion of some of the limitations of these studies. Nebulizers have been in use for more than a century to deliver aerosolized drugs to patients suffering from respiratory disorders. Aerosol devices such as these are the best option for people who have trouble managing their inhalation. Because of the actuation required, pressurised Metered-Dose Inhalers (pMDI) and Dry Powder Inhalers (DPI) are unable to generate the necessary inspiratory flow required for successful aerosol drug delivery. Currently, we are looking into how the working mechanism of different nebulizers interacts with the physicochemical features of the formulations. We are looking into a wide range of devices, such as jet, ultrasonic, and vibrating-mesh nebulizers. In this study, the researchers hope to describe the many different types of nebulizers that are currently available on the market, evaluate their performance in aerosol drug delivery, and recommend treatment approaches for patients with chronic obstructive pulmonary disease.

Role of dispersion enhancer selection in the development of novel tratinterol hydrochloride dry powder inhalation formulations

Tratinterol hydrochloride (TH) is a new long-acting bronchodilator with strong β2 adrenoceptor stimulation activity. The aim of this study was to design a new carrier-based dry powder inhalation (DPI) formulation for TH and to investigate the effect of dispersion enhancers on the aerosol performance of TH in vitro. To this end, coarse lactose was used as a carrier. TH was micronized by using a jet mill and blended with the carrier to obtain a reference DPI formulation. Commercial magnesium stearate (MgSt) as received, micronized MgSt (MgSt-M), and fine lactose (FL) were used as the dispersion enhancers and formulated with the micronized TH (TH-M) and the carrier as DPI formulations. The obtained DPI formulations were characterized using dynamic light scattering (DLS), X-ray powder diffraction (XRPD), thermal analysis, powder rheometer, and Raman microscopy. A next generation pharmaceutical impactor (NGI) was used to evaluate the aerodynamic performance of the dry powders. The results showed that TH-M was in an inhalable particle size range, and based on the XRPD and thermal analysis, the solid form of TH-M did not change compared to the starting materials. The NGI results showed that the fine particle fraction (FPF) of TH could be increased with the addition of MgSt and FL as dispersion enhancers in the reference formulation. In addition, the FPF of TH could be increased with a decrease in the particle size of MgSt or an increase in the amount of FL. A combination of MgSt-M and FL could further improve the aerosol performance of TH. Raman spectroscopic imaging confirmed the spatial location of MgSt and TH at the surface of the carrier. This study demonstrates that TH could be formulated into carrier-based dry powder formulation for inhalation using coarse lactose as the carrier. The dual strategy based on using both MgSt and FL as dispersion enhancers improved the aerosol performance of a novel TH dry powder formulation.