Dry Powder Inhaler Formulations Research Articles

Fine excipient materials in carrier-based dry powder inhalation formulations: The interplay of particle size and concentration effects

The contributions of fine excipient materials to drug dispersibility from carrier-based dry powder inhalation (DPI) formulations are well recognized, although they are not completely understood. To improve the understanding of these contributions, we investigated the influences of the particle size of the fine excipient materials on characteristics of carrier-based DPI formulations. We studied two particle size grades of silica microspheres, with volume median diameters of 3.31 μm and 8.14 μm, as fine excipient materials. Inhalation formulations, each composed of a lactose carrier material, one of the fine excipient materials (2.5% or 15.0% w/w), and a drug (fluticasone propionate) material (1.5% w/w) were prepared. The physical microstructure, the rheological properties, the aerosolization pattern, and the aerodynamic performance of the formulations were studied. At low concentration, the large silica microspheres had a more beneficial influence on the drug dispersibility than the small silica microspheres. At high concentration, only the small silica microspheres had a beneficial influence on the drug dispersibility. The results reveal influences of fine excipient materials on mixing mechanics. At low concentration, the fine particles improved deaggregation and distribution of the drug particles over the surfaces of the carrier particles. The large silica microspheres were associated with a greater mixing energy and a greater improvement in the drug dispersibility than the small silica microspheres. At high concentration, the large silica microspheres kneaded the drug particles onto the surfaces of the carrier particles and thus impaired the drug dispersibility. As a critical attribute of fine excipient materials in carrier-based dry powder inhalation formulations, the particle size demands robust specification setting.

Developing Dry Powder Inhaler Formulations.

This section aims to provide a concise and contemporary technical perspective and reference resource covering dry powder inhaler (DPI) formulations. While DPI products are currently the leading inhaled products in terms of sales value, a number of confounding perspectives are presented to illustrate why they are considered surprisingly, and often frustratingly, poorly understood on a fundamental scientific level, and most challenging to design from first principles. At the core of this issue is the immense complexity of fine cohesive powder systems. This review emphasizes that the difficulty of successful DPI product development should not be underestimated and is best achieved with a well-coordinated team who respect the challenges and who work in parallel on device and formulation and with an appreciation of the handling environment faced by the patient. The general different DPI formulation types, which have evolved to address the challenges of aerosolizing fine cohesive drug-containing particles to create consistent and effective DPI products, are described. This section reviews the range of particle engineering processes that may produce micron-sized drug-containing particles and their subsequent assembly as either carrier-based or carrier-free compositions. The creation of such formulations is then discussed in the context of the material, bulk, interfacial and ultimately drug-delivery properties that are considered to affect formulation performance. A brief conclusion then considers the future DPI product choices, notably the issue of technology versus affordability in the evolving inhaler market.

Compatibility study of formoterol fumarate-lactose dry powder inhalation formulations: Spray drying, physical mixture and commercial DPIs

Formoterol fumarate (FF) is a long-acting beta-adrenergic receptor agonist that is administered as a dry powder inhaler (DPI) for chronic respiratory conditions. In most DPI formulations, the drug substance and the carrier are the two major components. Lactose is the most common carrier, which can undergo a Maillard reaction in the presence of primary and secondary amines. FF contains a secondary amine. Since the potential for Maillard reaction in DPI formulations has not been investigated yet, this study aims to investigate any potential reaction between lactose and FF. The formulations were prepared using a tubular mixer and spray drying techniques. FF and lactose were blended using a tubular mixer (TM FF-Lac). In the spray drying method, FF and lactose were dissolved in distilled water: MeOH and then spray dried (SD FF-Lac). The samples were stored at both ambient conditions and elevated temperature and humidity (40 °C ± 2, 75% ± 5 RH), and subsequently analyzed to identify any signs of incompatibilities. Differential scanning calorimetry (DSC), field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS-MS) were employed for sample analysis. The in vitro aerosolization performance was evaluated using a next-generation impactor (NGI). The results showed that the colour of the DPI formulations changed from white to brown after storage at elevated temperature and humidity. Although the SD FF-Lac had better aerosolization properties, it was more vulnerable to degradation due to its amorphous nature. The FF-lactose adduct was formed in all samples. Interestingly, adduct compounds were also detectable before the storage for stability and stress tests. Incompatibility was confirmed by HPLC-PDA analysis. The mass spectra revealed the m/z of the adduct compound and confirmed the Millard reaction. Browning occurred in the prepared DPI formulations following storage at elevated temperature and humidity. Moreover, adduct compounds were also found in DPI formulations kept at ambient conditions and commercial DPI. Overall, mass spectroscopy was capable of detecting the incompatibility.

Triple combination dry powder formulation of pretomanid, moxifloxacin, and pyrazinamide for treatment of multidrug-resistant tuberculosis

Both latent and multidrug-resistant tuberculosis (TB) have been causing significant concern worldwide. A novel drug, pretomanid (PA-824), has shown a potent bactericidal effect against both active and latent forms of Mycobacterium tuberculosis (MTb) and a synergistic effect when combined with pyrazinamide and moxifloxacin. This study aimed to develop triple combination spray dried inhalable formulations composed of antitubercular drugs, pretomanid, moxifloxacin, and pyrazinamide (1:2:8 w/w/w), alone (PaMP) and in combination with an aerosolization enhancer, L-leucine (20 % w/w, PaMPL). The formulation PaMPL consisted of hollow, spherical, dimpled particles (<5 μm) and showed good aerosolization behaviour with a fine particle fraction of 70 %. Solid-state characterization of formulations with and without L-leucine confirmed the amorphous nature of moxifloxacin and pretomanid and the crystalline nature of pyrazinamide with polymorphic transformation after the spray drying process. Further, the X-ray photoelectron spectroscopic analysis revealed the predominant surface composition of L-leucine on PaMPL dry powder particles. The dose–response cytotoxicity results showed pyrazinamide and moxifloxacin were non-toxic in both A549 and Calu-3 cell lines up to 150 µg/mL. However, the cell viability gradually decreased to 50 % when the pretomanid concentration increased to 150 µg/mL. The in vitro efficacy studies demonstrated that the triple combination formulation had more prominent antibacterial activity with a minimum inhibitory concentration (MIC) of 1 µg/mL against the MTb H37Rv strain as compared to individual drugs. In conclusion, the triple combination of pretomanid, moxifloxacin, and pyrazinamide as an inhalable dry powder formulation will potentially improve treatment efficacy with fewer systemic side effects in patients suffering from latent and multidrug-resistant TB.

Critical attributes of fine excipient materials in carrier-based dry powder inhalation formulations: The particle shape and surface properties

The potential of fine excipient materials to improve the aerodynamic performance of carrier-based dry powder inhalation (DPI) formulations is well acknowledged but not fully elucidated. To improve the understanding of this potential, we studied two fine excipient materials: micronized lactose particles and silica microspheres. Inhalation formulations, each composed of a coarse lactose carrier, one of the two fine excipient materials (0.0–15.0 % w/w), and a spray-dried drug (fluticasone propionate) material (1.5 % w/w) were prepared. The physical structure, the flow behavior, the aerosolization behavior, and the aerodynamic performance of the formulations were studied. The two fine excipient materials similarly occupied carrier surface macropores. However, only the micronized lactose particles formed agglomerates and appeared to increase the tensile strength of the formulations. At 2.5 % w/w, the two fine excipient materials similarly improved drug dispersibility, whereas at higher concentrations, the micronized lactose material was more beneficial than the silica microspheres. The findings suggest that fine excipient materials improve drug dispersibility from carrier-based DPI formulations at low concentrations by filling carrier surface macropores and at high concentrations by forming agglomerates and/or enforcing fluidization. The study emphasizes critical attributes of fine excipient materials in carrier-based DPI formulations.

Synergistic combination of antimicrobial peptide and isoniazid as inhalable dry powder formulation against multi-drug resistant tuberculosis

Multidrug-resistant tuberculosis (MDR-TB) has posed a serious threat to global public health, and antimicrobial peptides (AMPs) have emerged to be promising candidates to tackle this deadly infectious disease. Previous study has suggested that two AMPs, namely D-LAK120-A and D-LAK120-HP13, can potentiate the effect of isoniazid (INH) against mycobacteria. In this study, the strategy of combining INH and D-LAK peptide as a dry powder formulation for inhalation was explored. The antibacterial effect of INH and D-LAK combination was first evaluated on three MDR clinical isolates of Mycobacteria tuberculosis (Mtb). The minimum inhibitory concentrations (MICs) and fractional inhibitory concentration indexes (FICIs) were determined. The combination was synergistic against Mtb with FICIs ranged from 0.25 to 0.38. The INH and D-LAK peptide at 2:1 mole ratio (equivalent to 1: 10 mass ratio) was identified to be optimal. This ratio was adopted for the preparation of dry powder formulation for pulmonary delivery, with mannitol used as bulking excipient. Spherical particles with mass median aerodynamic diameter (MMAD) of around 5 µm were produced by spray drying. The aerosol performance of the spray dried powder was moderate, as evaluated by the Next Generation Impactor (NGI), with emitted fraction and fine particle fraction of above 70 % and 45 %, respectively. The circular dichroism spectra revealed that both D-LAK peptides retained their secondary structure after spray drying, and the antibacterial effect of the combination against the MDR Mtb clinical isolates was successfully preserved. The combination was found to be effective against MDR Mtb isolates with KatG or InhA mutations. Overall, the synergistic combination of INH with D-LAK peptide formulated as inhaled dry powder offers a new therapeutic approach against MDR-TB.

Detection of Excipient–Excipient Interaction in Dry Powder Inhaler Formulation Prepared by Spray Drying

Background: Dry powder inhalers (DPIs) are dosage forms that are used via the pulmonary route. Their formulations include two major parts; drug substance and carrier. For many years, DPIs have been made with lactose, a particularly popular carrier. Leucine has drawn more attention in recent years when it comes to DPI formulations made using the spray drying technique. Leucine was utilized in conjunction with carriers like lactose to enhance physicochemical and aerosolization properties. Method: In this investigation, when lactose and leucine were co-spray dried, the color of powders around the cyclone separators of the spray dryer turned brown while the produced powder in the collector was white. Both the white powder inside the collector and the brown powder around the cyclone separators were investigated by differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), x-ray diffraction (XRD), and liquid chromatography with tandem mass spectrometry (LC-MS-MS) to determine the identity of the degraded chemicals and to look for any potential interactions. Results: A new peak at 177 ºC in DSC analysis is a sign of interaction. Also, FT-IR analysis shows the new peak at 1627 cm-1 which is related to the carbonyl group. According to SEM and XRD analysis co spray dried leucine-lactose is amorphous. Obtained data from LC-MS analysis indicates the adduct compound of leucine-lactose that resulted from the Maillard reaction was detected in both white and brown powder. Also, the reaction proceeded to form n-formyl compound. Conclusion: There is a possibility of lactose and leucine incompatibility during DPIs manufacturing, especially in elevated temperature and humidity.

Quality by design approach for development and optimization of rifampicin loaded nanoparticles and characterization

Background: Rifampicin is an effective in the treatment of sensitive, non-resistant strains of mycobacterium tuberculosis. Thus there is need to develop a rifampicin loaded nanoparticles. Aim: This study is focused on development of RFM loaded nanoparticles, characterization to achieve lung targeting using quality by design approach. Objectives: The main objective of this study is optimizing particle size and entrapment efficiency of rifampicin-loaded nanoparticles and making them suitable for nebulizer application using QbD approach. Methods: Quality target product profile was defined along with critical quality attributes for the formulation. Preparation of nanoparticle dry powder inhaler formulation were numerous methods such as microemulsion solvent evaporation, ionic gelation and modified ionic gelation followed by probe sonication were employed for the preparation of nanoparticles and the final method of preparation was selected based on particle size, zeta potential, entrapment efficiency and drug loading. Results: The optimized RFM-loaded nanoparticles were characterized by UV spectroscopy, FTIR, DSC techniques. The observed nanoparticles were spherical in shape. The TPP concentration, stirring speed and concentration of acetic acid were playing a crucial role in the successful formation of nanoparticles and were selected for optimization. In vitro release study showed 100% release of pure RFM within 12 hrs and the optimized chitosan nanoparticle formulation loaded with RFM showed nearly 90% release of RFM within 24 hr. Conclusion: Rifampicin loaded nanoparticle DPI formulations achieve lung targeting and the delivery of drug into the lungs will also prevent the first pass metabolism, thus, leading to reduction in the dose of the drug as well as related side effects. These drug targeting approaches may serve as a boon in the effective treatment of tuberculosis.

An experimental study of the effect of individual upper airway anatomical features on the deposition of dry powder inhaler formulations

This study aims to investigate the effects of different pharynx anatomical features on the delivery of inhaled aerosols. Six in-vitro upper airway models reconstructed using anatomical images acquired by Magnetic Resonance Imaging (MRI) were used for the experiments. A geometrically accurate airway model was produced, and five other different airway models, each missing one or more specific anatomical features: the uvula, epiglottis, and/or soft palate, were derived from the original model. Hence, the geometrical boundaries of the six models were the same except at regions where specific anatomical structures were removed, and this was done to allow meaningful comparisons between the different geometries to be made using specific measurements. Spray-dried mannitol powder (volume median particle size and span were 3.22 μm and 1.90 μm, respectively) was loaded into a capsule-based dry powder inhaler with different resistance, an Osmohaler™ (low resistance), or Handihaler® (high resistance), attached to the inlet of the airway model, which its outlet was connected to a Next-Generation Impactor (NGI). The studies were performed using flow rates of 30 and 60 LPM. High-performance liquid chromatography (HPLC) was used to quantify the mass deposition of particles in different stages of the NGI and airway replicas. Results from this study show that widening the space between the oral cavity and oropharynx, exemplified by one of the six replicas developed, significantly decreases upper airway deposition as well as increases the fine particle fraction. The case with the highest deposition (63.5%) occurred in the pharynx replica with the soft palate present (at 60 LPM with the Hanihaler), while the lowest deposition (26.0%) occurred in the replica without the soft palate and epiglottis (at 30 LPM with the Osmohaler). This study highlights that in addition to the resistance of the inhalers, their interactions with the human airway anatomical features are likely to play important roles in the subsequent lung dose. Results from this study are novel because while the effects of different inhaler resistance in a given airway replica is known, the effects contributed by specific pharynx anatomical features on particle transport behaviour have not been studied experimentally or reported on in the literature. This study shows that space adjacent to the soft palate affects particle deposition dramatically but the effect appears to be more significant when using the Handihaler and for the high flow rate cases.

The effect of mixing on the dispersibility of adhesive mixtures for inhalation. Comparison of high shear and Turbula mixers

This study investigates the effect of different mixers and the applicability of the mixing energy (ME) concept to dry powder formulations for inhalation. With the aim to step-wise build and expand this concept, adhesive mixtures of 2 % budesonide and lactose carrier were investigated, both with 1 % magnesium stearate (MgSt) added in a ‘coating’ step, and without, the latter referred to as ‘naked’ formulations. For high shear mixed formulations, the fine particle fraction (FPF) was found to increase with increasing ME up to 60 % and thereafter decreased, using the Novolizer device. The data could be well fitted to the modeling equation, thus confirming the validity of the ME concept. The naked formulations displayed a linear decrease in FPF with increasing ME, again showing the validity of the ME concept.For Turbula mixed formulations, FPF increased with increased mixing time (and mixing energy) for all batches. The naked (binary) composition reached to higher FPF values than for high shear mixing and the formulation with MgSt reached to FPF values around 60 %, demonstrating that it is possible to achieve the same high drug dispersibility with the Turbula mixer as for high shear mixer.An equation for calculation of mixing energy in Turbula mixing was set up in an analogous way to the equation for high shear mixing, which enabled direct comparison between the two mixers.

Stability of Naked Nucleic Acids under Physical Treatment and Powder Formation: Suitability for Development as Dry Powder Formulations for Inhalation.

A number of functional nucleic acids, including plasmid DNA (pDNA) and small interfering RNA (siRNA), have been attracting increasing attention as new therapeutic modalities worldwide. Dry pDNA and siRNA powder formulations for inhalation are considered practical in clinical applications for respiratory diseases. However, physical stresses in the powder-forming process may destabilize nucleic acids, particularly when vectors with stabilizing effects are not used. We herein compare the stability of naked pDNA and siRNA through various physical treatments and two powder-forming processes. The structural and functional integrities of pDNA were markedly reduced via sonication, heating, and atomization, whereas those of siRNA were preserved throughout all of the physical treatments investigated. Spray-dried and spray-freeze-dried powders of siRNA maintained their structural and functional integrities, whereas those of pDNA did not. These results demonstrate that siRNA is more suitable for powder formation in the naked state than pDNA due to its higher stability under physical treatments. Furthermore, a spray-freeze-dried powder with a high content of naked siRNA (12% of the powder) was successfully produced that preserved its structural and functional integrities, achieving high aerosol performance with a fine particle fraction of approximately 40%.

Creationa and Assessment of Dry Powder Inhalation Formulations of Gamma Oryzanol Based on Chitosan Nanoparticles

Gamma oryzanol is an antioxidant and anticancer medication that is taken orally by a traditional method. It comes from plants. Its utility is nonetheless restricted by its erratic absorption and frequent administration. An alternative method that can maintain the release of Gamma Oryzanol in the lungs for several hours was considered: giving the drug via the pulmonary route as nanoparticles. Gamma Oryzanol was coated with chitosan, a biodegradable polymer, and then freeze-dried to create a dry powder inhaler (DPI) with an aerodynamic particle size of 1.54μm. Initial burst release was seen in an in vitro release investigation, which was followed by continuous release up to 97.51% in 24 hours. In vivo research and in vitro release showed further correlation. After a single dosage was administered, the prepared DPI enhanced the Gamma Oryzanol via pulmonary route residence in the lung tissue for more than 24 hours and sustained the Gamma Oryzanol through pulmonary pathway concentration above MIC for more than 12 hours. A decrease in the amount administered in the lungs was also seen in an animal investigation; this will help with tumour treatment.

Inhalation Dosage Forms: A Focus on Dry Powder Inhalers and Their Advancements.

In this review, an extensive analysis of dry powder inhalers (DPIs) is offered, focusing on their characteristics, formulation, stability, and manufacturing. The advantages of pulmonary delivery were investigated, as well as the significance of the particle size in drug deposition. The preparation of DPI formulations was also comprehensively explored, including physico-chemical characterization of powders, powder processing techniques, and formulation considerations. In addition to manufacturing procedures, testing methods were also discussed, providing insights into the development and evaluation of DPI formulations. This review also explores the design basics and critical attributes specific to DPIs, highlighting the significance of their optimization to achieve an effective inhalation therapy. Additionally, the morphology and stability of 3 DPI capsules (Spiriva, Braltus, and Onbrez) were investigated, offering valuable insights into the properties of these formulations. Altogether, these findings contribute to a deeper understanding of DPIs and their development, performance, and optimization of inhalation dosage forms.

Co-Delivery of a High Dose of Amphotericin B and Itraconazole by Means of a Dry Powder Inhaler Formulation for the Treatment of Severe Fungal Pulmonary Infections.

Over the past few decades, there has been a considerable rise in the incidence and prevalence of pulmonary fungal infections, creating a global health problem due to a lack of antifungal therapies specifically designed for pulmonary administration. Amphotericin B (AmB) and itraconazole (ITR) are two antifungal drugs with different mechanisms of action that have been widely employed in antimycotic therapy. In this work, microparticles containing a high dose of AmB and ITR (20, 30, and 40% total antifungal drug loading) were engineered for use in dry powder inhalers (DPIs) with an aim to improve the pharmacological effect, thereby enhancing the existing off-label choices for pulmonary administration. A Design of Experiment (DoE) approach was employed to prepare DPI formulations consisting of AmB-ITR encapsulated within γ-cyclodextrin (γ-CD) alongside functional excipients, such as mannitol and leucine. In vitro deposition indicated a favourable lung deposition pattern characterised by an upper ITR distribution (mass median aerodynamic diameter (MMAD) ~ 6 µm) along with a lower AmB deposition (MMAD ~ 3 µm). This offers significant advantages for treating fungal infections, not only in the lung parenchyma but also in the upper respiratory tract, considering that Aspergillus spp. can cause upper and lower airway disorders. The in vitro deposition profile of ITR and larger MMAD was related to the higher unencapsulated crystalline fraction of the drug, which may be altered using a higher concentration of γ-CD.

Supercritical antisolvent-fluidized bed for the preparation of dry powder inhaler for pulmonary delivery of nanomedicine

The supercritical antisolvent-fluidized bed coating process (SAS-FB) shows great potential as a technique to manufacture dry powder inhaler (DPI) that incorporate nanodrugs onto micronized matrix particles, capitalizing on the merits of both nanoparticle and pulmonary delivery. In this study, naringin (NAR), a pharmacologically active flavonoid with low solubility and in vivo degradation issues, was utilized as a model active pharmaceutical ingredient to construct nanomedicine-based DPI through SAS-FB. It is showed that processed NAR exhibited a near-spherical shape and an amorphous structure with an average size of around 130 nm. Notably, SAS-FB products prepared with different fluidized matrices resulted in varying deposition patterns, particularly when mixed with a coarse lactose to enhance the fine particle fraction (FPF) of the formulations. The FPF was positively associated with specific surface area of the SAS-FB products, while the specific surface area was directly related to surface roughness and particle size. In vitro dissolution studies using simulated lung fluid revealed that the NAR nanoparticles coated on the products were released immediately upon contact with solution, with a cumulative dissolution exceeding 90% within the first minute. Importantly, compared to oral raw NAR, the optimized DPI formulation demonstrated superior in vivo plasmatic and pulmonary AUC0→∞ by 51.33-fold and 104.07-fold respectively in a Sprague-Dawley rat model. Overall, SAS- FB technology provides a practical approach to produce nanomedicine DPI product that combine the benefits of nanoparticles with the aerodynamics properties of inhaled microparticles.

Recent developments in dry powder inhalation (DPI) formulations for lung-targeted drug delivery

Recent developments in dry powder inhalation (DPI) formulations for lung-targeted drug delivery

Preparing dry powder inhalation formulation of salbutamol sulfate using an ultrasonic atomizer device

Inhaled particles must possess certain morphological characteristics to ensure effective drug delivery to the targeted site in the lungs. A modified version of ultrasonic spray pyrolysis was employed to prepare salbutamol sulfate in the form of dry powder. A solution of salbutamol sulfate was atomized using ultrasonic nebulization, and the droplets were transformed into solid drug particles through exposure to high temperature airflow. The engineered salbutamol sulfate samples underwent physical characterization, including particle size, morphology, thermal behavior, and crystallinity analysis. The aerodynamic particle size distribution (APSD) and in vitro deposition of the dry powder inhalation formulation were assessed using the Next Generation Impactor (NGI). The salbutamol sulfate dry powder prepared by the ultrasonic atomizer exhibited an aerodynamic diameter ranging from 1 to 5 μm, as supported by the SEM images. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results showed a significant drop in the crystallinity of the engineered particles. Aerosolization performance studies demonstrated a fine particle fraction (FPF) value (below 5 μm) of 25% for the engineered salbutamol sulfate produced using the ultrasonic atomizer technique, which is acceptable for inhalation purposes. Based on the observed results, this newly introduced method appears to be suitable for producing dry powder formulations of different drugs, with a minimized need for the use of surfactants or stabilizers in the formulation.

Impact of high shear blending on distribution of magnesium stearate on lactose for dry powder inhaled formulations

The use of magnesium stearate along with lactose in Dry Powder Inhaler (DPI) formulations is increasing.The impact of different conditions of high shear blending on the distribution of magnesium stearate on lactose particles was investigated in this study. The formulated blends were manufactured using high shear blending of pre-blended coarse and fine lactose particles with 1.0% (w/w) magnesium stearate under different blending conditions, specifically blending speed and time. The effects of blending conditions on the distribution of magnesium stearate on lactose particles were clearly identifiable by characterizing the formulated blends by means of rheological evaluations, scanning electron microscopy, and chemical surface analysis using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Rheological properties were significantly affected in blends with magnesium stearate compared to blends without magnesium stearate. Blending speed exhibited a strong influence on the distribution of magnesium stearate on lactose surface, while blending time had relatively minor effect.

Inhalation of vaccines and antiviral drugs to fight respiratory virus infections: reasons to prioritize the pulmonary route of administration.

Many of the current pandemic threats are caused by viruses that infect the respiratory tract. Remarkably though, the majority of vaccines and antiviral drugs are administered via alternative routes. In this perspective, we argue that the pulmonary route of administration deserves more attention in the search for novel therapeutic strategies against respiratory virus infections. Firstly, vaccines administered at the viral portal of entry can induce a broader immune response, employing the mucosal arm of the immune system; secondly, direct administration of antiviral drugs at the target site leads to superior bioavailability, enabling lower dosing and reducing the chance of side effects. We further elaborate on why the pulmonary route may induce a superior effect compared to the intranasal route of administration and provide reasons why dry powder formulations for inhalation have significant advantages over standard liquid formulations.

Formulation and Evaluation of Moxifloxacin Dry Powder Inhaler Combined with Mucolytic Agent for Pulmonary Diseases

The DPI is the device that administers the drug through the dry powder to the lungs. People with Multi-drug resistant tuberculosis or other lung diseases frequently use such devices to take their prescribed medicines. Numerous approaches have been used to formulate dry powder inhalation formulation and enhance the delivery performance of dry powder inhaler preparation. In the case of multi-drug resistance tuberculosis, a high dose of combination therapy was delivered, resulting in resistance to the anti-TB medications in the majority of patients. Moxifloxacin and levofloxacin are being used to minimize the need for a high-dose treatment regimen. This study aimed to achieve local lung administration of tumor-targeting Moxifloxacin, by administering microspheres that can be inhaled as a dry powder inhaler for targeting Phagocytes of alveoli via pulmonary passage. Spray drying had been used to formulate MXN-DPI formulations, afterward optimized with the 23-factorial design model. Two different amounts of lactose, leucine, and medication were used to make the eight batches. The developed formulation was studied for physicochemical properties like morphology and particle size. The particle dimensions of the MXN-DPI compositions have been confirmed to be in the range of 1.4 to 4.1 μm. The prepared formulations effectively showed drug release up to 93% in 5 hours, which was observed through in-vitro diffusion studies.