Dry Powder Research Articles

Multilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment

Background: Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules’ size, degradation, and pharmacokinetics. We are working on new drug delivery systems that provide adequate therapeutic concentrations for these cytokines and prolong their half-life in the circulation, such as nanoformulations. Methods: Through nanoencapsulation using electrospray technology and biocompatible and biodegradable polymers, we are developing a controlled release system based on nanoparticles for viral infections of the respiratory tract. Results: We developed a controlled release system for viral respiratory tract infections. A prototype nanoparticle with a core was created, which hydrolyzed the polyvinylpyrrolidone (PVP) shell , releasing the active ingredients interferon-alpha (IFN-α) and interferon-gamma (IFN-γ). The chitosan (QS) core degraded slowly, with a controlled release of IFN-α. The primary and rapid effect of the interferon combination ensured an antiviral and immunoregulatory response from day one, induced by IFN-α and enhanced by IFN-γ. The multilayer design demonstrated an optimal toxicity profile. Conclusions: This formulation is an inhaled dry powder intended for the non-invasive intranasal route. The product does not require a cold chain and has the potential for self-administration in the face of emerging viral infections. This novel drug has applications in multiple infectious, oncological, and autoimmune conditions, and further development is proposed for its therapeutic potential. This prototype would ensure greater bioavailability, controlled release, fewer adverse effects, and robust biological action through the simultaneous action of both molecules.

Powder Compaction Characteristics and Modeling of Calendering Process for Powder-based Solvent-free Manufacturing of Electrodes for Lithium-ion Batteries

Abstract Powder-based solvent-free manufacturing of electrodes for Li-ion batteries represents an emerging and promising technology in electrode fabrication. This method involves a two-roll powder calendering process, where electrode powder materials are compressed onto a current collector to form electrodes with desired properties. The calendering or compaction of dry powders onto a current collector is a crucial step in solvent-free electrode manufacturing, significantly impacting the microstructures, mechanical properties, and electrochemical performance of the produced electrodes. In this paper, we investigate the compaction characteristics of electrode powders to gain insights into their behavior. A powder-on-current collector calendering model is developed based on Johanson's rolling theory of granular solids. This model enables us to infer the underlying calendering parameters essential for the solvent-free manufacturing of Li-ion batteries. To validate the model, we compare it with experimental calendering results, utilizing measured powder properties and roll design parameters as inputs. This approach offers a comprehensive understanding of the effects of roll geometries, particularly roll diameter, and various equipment design parameters on final electrode properties. Such insights have not been thoroughly explored in the emerging field of solvent-free battery electrode manufacturing, thereby contributing to advancements in this area.

Prioritising Patients and Planet: Advocating for Change in Respiratory Care

The global burden of respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD), continues unabated. Suboptimal management places a significant strain on both patients and urgent or emergency care services. With an ageing population in many countries, the demand for these services is set to increase further. At the same time, healthcare systems are striving to reduce their carbon footprint and achieve net zero emissions, as the healthcare sector is a significant contributor to carbon emissions worldwide. Although these two goals may appear contradictory, they need not be in conflict. This article reviews an industry-sponsored symposium held at the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, in September 2024. The session addressed the urgent need to change the delivery model for respiratory healthcare in response to the increasing prevalence of respiratory diseases and the challenges posed by climate change. Co-chair John Hurst, Professor of Respiratory Medicine at University College London (UCL), UK, underscored the importance of innovative solutions for managing respiratory diseases and highlighted the challenges faced by healthcare decision-makers. This was further elaborated on by Omar Usmani, Professor of Respiratory Medicine at Imperial College London, UK, who emphasised the importance of clinical choice. He stated that inhaled medicines, which form the cornerstone of treatment, should not be considered interchangeable. He also discussed ongoing efforts to maintain access to essential medicines by developing novel next-generation propellants (NGP) for pressurised metered-dose inhaler (pMDI) devices, which will reduce their carbon footprint to levels comparable with dry powder inhalers (DPI). Additionally, he described the European Chemicals Agency (ECHA) proposal to restrict a broad range of chemicals classed as per- and polyfluoroalkyl substances (PFAS). This precautionary measure would affect both current propellants in pMDIs and the transition to NGPs, with global implications for inhaled medicines. Erika Penz, Associate Professor of Respirology, Critical Care, and Sleep Medicine at the University of Saskatchewan, Canada, noted that suboptimal management of respiratory disease is associated with a disproportionately high burden on both patients and the environment. The forthcoming availability of pMDI medicines with NGPs alone will not resolve this larger issue. As every healthcare interaction carries a carbon footprint, which increases with the intensity of treatment, the implementation of guidelines into clinical practice would improve patient outcomes and reduce the demand on healthcare services and the associated carbon emissions. Co-chair Helen Reddel, Clinical Professor and Research Leader at the Woolcock Institute of Medical Research, Australia, concluded by re-emphasising the urgent need to implement guidelines immediately for the benefit of both patients and the environment.

Evaluation of asthma control after reinforcement of proper inhaler techniques in a tertiary care center in northern India.

Asthma is an obstructive lung disease with high prevalence. Symptom control in asthma remains poor despite significant advancements in treatment guidelines and inhalational devices. This is often attributed to inadequate patient adherence to the inhaler technique and insufficient education on its long-term use. Through this study, we aimed to assess the impact of reinforcement of proper inhaler technique on asthma symptom control and quality of life. A prospective cohort of 400 asthma patients using dry powder inhalers and metered dose inhalers was recruited in the outpatient clinic of our hospital. At the time of recruitment, the correctness of inhaler technique usage was assessed, and the pre-test Inhaler Technique Score (ITS) was recorded for each patient. Then, a ten-step inhalation technique was taught through demonstration, and the post-test ITS score was recorded again. This was done for each patient at monthly intervals for 3 months. Along with it, two tailored questionnaires, the Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ), were administered at each visit to assess disease control and quality of life. Significant enhancements in inhalation technique were noted from the first to the third visit using the ten-step inhalation usage scores, which improved from 6.91 to 9.87 (out of 10) (p<0.001), paralleled by ACT score increases from 17.06 to 19.37 (out of 25) (p<0.001) from visits one to two, and from 19.37 to 20.52 (out of 25) (p<0.001) from visits two to three, signifying improvement in symptom control. Quality of life similarly improved from 4.45 to 5.12 to 5.45 (out of 7) (p<0.001) across the three visits as assessed by AQLQ. In conclusion, promoting proper inhaler technique through structured education programs is crucial for optimizing long-term asthma management and enhancing patients' quality of life.

Revolutionizing Influenza Treatment: A Deep Dive into Targeted Drug Delivery Systems.

Influenza, a highly transmissible respiratory infection caused by influenza viruses A and B, poses a persistent threat to global public health due to its high mutation rate, ability to develop resistance to existing antiviral drugs, and capacity for rapid spread. Current treatment options, including four main classes of antiviral agents-adamantanes, neuraminidase inhibitors, RNA-dependent RNA polymerase inhibitors, and polymerase acidic endonuclease inhibitors- are limited by the emergence of drug-resistant viral strains, non-specific drug distribution, and adverse side effects. Moreover, the effectiveness of traditional vaccines is often compromised by antigenic drift and shift, necessitating the development of alternative therapeutic strategies. This review comprehensively explores the potential of novel targeted drug delivery systems to address these limitations and improve influenza management. Nanotechnology-based platforms, including lipid-based, polymer-based, inorganic, and hybrid nanoparticles, offer enhanced drug delivery through improved bioavailability, targeted action, and controlled release, thus minimizing systemic toxicity and optimizing therapeutic outcomes. Inhalation delivery systems such as dry powder inhalers (DPIs), nebulizers, and nanotechnology-based inhalation formulations provide direct delivery of antiviral agents to the respiratory tract, ensuring rapid onset of action with reduced systemic side effects. Transdermal delivery methods, including microneedle patches and hydrogel-based systems, offer non-invasive alternatives that enhance patient compliance and allow for sustained drug release. Furthermore, this review discusses recent innovations, such as responsive drug delivery systems and multifunctional nanoparticles capable of simultaneous delivery of multiple therapeutic agents, representing a significant advancement in the fight against influenza. These novel approaches promise improved targeting and efficacy and enable personalized treatment strategies, enhancing patient outcomes in both seasonal flu and pandemic scenarios. Integrating these advanced drug delivery systems into clinical practice could revolutionize the management of influenza, offering a promising pathway toward more effective and safer therapies.

Inhalable cyclodextrin metal-organic framework dry powder enhanced direct pulmonary delivery of paclitaxel for the treatment of lung cancer

Inhalation dry powders are in great demand for the treatment of lung diseases due to their unique advantages such as excellent direct delivery, rapid onset of action, and reduced systemic side effects. Herein, this work highlights the successful development of an inhalable paclitaxel dry powder, which is facilely constructed through the optimization of the formulation between chemotherapy components (paclitaxel) and a metal-organic framework (MOF) carrier (γ-cyclodextrin and KOH). Moderate pore and particle size distribution, as well as low hygroscopicity endow the dry powder with excellent loading efficiency and resistance to degradation. All ingredients and their interactions confer favorable emptying rates, flowability, and pulmonary deposition, as well as direct lung drug delivery and release. These attractive characteristics enable the dry powder to effectively enhance cytotoxicity, improve pharmacokinetics, promote lung accumulation, and reduce the side effects of paclitaxel. Thus, this paclitaxel dry powder may open a new avenue for the inhalation treatment of diseases, greatly advancing its clinical application.

Formulation and evaluation of carrier-based dry powders containing budesonide and arformoterol for inhalation therapy

ABSTRACT Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health issues, with inhalation therapy being a primary treatment method. However, dry powder inhalers (DPIs) often face the issue of drug particle aggregation, which can reduce drug delivery efficiency. This study aims to investigate particle aggregation and optimize the cohesion–adhesion balance to improve inhalation efficiency. Advanced techniques such as atomic force microscopy and Raman imaging were employed to analyze particle interactions and aggregation behavior, focusing on lactose ratios, particle shapes, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing Budesonide (BUD) and Arformoterol (AFT) was evaluated in an asthma model. Specifically, sRAW, neutrophil count, and tidal volume values were significantly improved compared to the positive control group, with p-values below 0.01. AFT demonstrated equivalent efficacy to Formoterol at half the dose. Additionally, pharmacokinetic (PK) studies showed that both drugs exhibited similar in vivo behavior, confirming the therapeutic superiority of AFT. (p-value for AUC0-t and Cmax: 0.646 and 0.153, respectively) The key findings highlight that formulation optimization significantly reduces particle aggregation and improves drug delivery efficiency in DPI (FPF for AFT and BUD: 39.4% and 50.6%, respectively), suggesting the potential for enhanced clinical outcomes in asthma and COPD patients. This study provides valuable insights for the formulation development of inhalable therapies.

In Vitro Analysis of Aerodynamic Properties and Co-Deposition of a Fixed-Dose Combination of Fluticasone Furoate, Umeclidinium Bromide, and Vilanterol Trifenatate.

Effective airway delivery of a fixed-dose combination of triple-aerosolized inhaled corticosteroid (ICS)/long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) is likely to positively affect therapeutic responses predicted in patients with asthma and chronic obstructive pulmonary disease. This study aimed to conduct in vitro fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide depositions in a Next Generation Impactor. The aerodynamic properties of these inhaled medications influence the spatial distribution and drug abundance, particularly in the smaller airways, to reverse or alleviate disease pathology. The Next Generation Impactor was used to demonstrate the aerodynamic particle size distributions of fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide delivered from a dry powder inhaler at different flow rates across all stages of the impactors. This in vitro study analyzed the distribution pattern of individual drug components to simulate mono-component deposition and co-deposition in the official model in the United States Pharmacopeia. An Andersen cascade impactor together with scanning electron microscope-energy-dispersive X-ray was employed to observe the drug deposition on each stage of the impactor. We found that the distribution pattern of each component at the same cascade level was comparable, and the aerosol particles of the three drugs reached the in vitro representation of the lower airway compartment. The specified flow rates generated the desired fine particle fraction, fine particle dose, and mass median aerodynamic diameter. Our results also demonstrated visualized deposition patterns of the delivered drugs from different stages of the cascade impactor that may predict deposition as it occurs in vivo. Spatial distribution and abundance of ICS/LABA/LAMA in the same cascade levels were closely comparable, and the aerosol particles were able to reach the small aerosol-sized cascades at the lower levels to some extent.

Inhaler personalisation based on peak inspiratory flow (PIF) among dry powder inhaler users: a pilot randomised control trial (RCT) in COPD.

Dry powder inhalers (DPIs) are commonly used among patients with Chronic Obstructive Pulmonary Disease (COPD). These inhalers are breath-actuated, and require patients to generate sufficient peak inspiratory flow (PIF) to disaggregate the drug powder into respirable fine particles and deliver it to the lower airway tracts. Inhaler personalisation based on PIF among DPI users has not been studied in Malaysia, thus we conducted the present pilot study to determine the feasibility of conducting such research among COPD patients. This was an open-label pilot randomised control trial, conducted from June 2021-January 2022 at the respiratory clinic of Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia. Measurement of PIF was performed with In-Check DIAL G16 among adult COPD patients treated with DPI and had suboptimal PIF. Eligible subjects were randomised using block randomisation into two groups, either the interventional group or the control group. Twenty-two COPD patients fulfilled the study criteria and were randomised to intervention (n = 11) and control (n = 11) groups. For the interventional group, there were statistically significant improvements between baseline and at 12 weeks for both FEV1 and CAT scores. The mean (% predicted) FEV1 were 54.6 ± 20.4% and 56.6 ± 19.8% (p = 0.026), pre-and post-intervention. The mean CAT score at baseline was 24.4 ± 5.8 and reduced to 19.6 ± 4.4 at 12 weeks (p = 0.012). For the control group, the mean (% predicted) FEV1 at baseline was 58.0 ± 21.9% and 56.5 ± 20.7% at 12 weeks, with no statistical significance difference (p = 0.143). However, there was a statistically significant difference in CAT scores at baseline and 12 weeks, with a mean of 26.5 ± 6.1 and 23.3 ± 5.6, respectively (p = 0.010). The findings from the present pilot RCT highlighted that inhaler personalisation based on PIF among COPD patients was feasible and practical.

Comparative Preclinical Pharmacokinetics and Disposition of Favipiravir Following Pulmonary and Oral Administration as Potential Adjunct Therapy Against Airborne RNA Viruses.

Favipiravir is administered orally, even against airborne RNA viruses, in a loading-dose/maintenance dose regimen. We investigated whether-(a) pulmonary delivery of favipiravir would generate high concentrations in the luminal side of the respiratory tract; and (b) avoiding first-pass metabolism by the liver by inhaled drug would generate comparable pharmacokinetics (PK) with doses significantly smaller than the oral maintenance dose. A dry powder inhalation (DPI) of favipiravir formulated by mixing with Inhalac 400® was prepared and characterized. Inhalations of ~ 120µg dose strength, with or without a prior oral loading dose were administered to mice. Comparator mice received human-equivalent oral doses (3mg). Three mice per sampling time point were sacrificed and favipiravir concentrations in the blood plasma, bronchio-alveolar lavage fluid (BALF) and lung tissue homogenate determined by HPLC. One-compartment PK modeling of concentration-time data indicated that the area under the curve (AUC0-24h) generated in the BALF recovered from mice receiving inhalations of ~ 1/25th of the oral dose subsequent to an oral loading dose was 86.72 ± 4.48µg⋅mL-1⋅h. This was consistently higher than the AUC observed in the BALF of orally-dosed mice (56.71 ± 53.89µgmL-1⋅h). In blood serum, the respective values of AUC were 321.55 ± 124.91 and 354.71 ± 99.60µg⋅mL-1⋅h. Pulmonary delivery of significantly smaller doses of favipiravir generates meaningful drug disposition and pharmacokinetics at the site of respiratory viral infections. We provide the rationale for designing a self-administered, non-invasive, low-cost, targeted drug delivery system against airborne RNA virus infection.

Advanced Spray-Dried Inhalable Microparticles/Nanoparticles of an Innovative Mitophagy Activator for Targeted Lung Delivery: Design, Comprehensive Characterization, Human Lung Cell Culture, and In Vitro Aerosol Dispersion Performance.

Urolithin A (UA) has demonstrated the ability to stimulate mitophagy and enhance mitochondrial and cellular health in skeletal muscles in humans after oral administration. It is hypothesized that targeted delivery of UA as inhaled dry powders to the lungs will enhance mitochondrial health through mitochondrial biogenesis. This study aimed to engineer inhalable excipient-free powders of UA as dry powder inhalers (DPIs) for targeted pulmonary delivery. The particles were designed by particle engineering from dilute organic solutions of UA using the state-of-the-art spray drying technology in a closed mode. Comprehensive physicochemical characterization and advanced microscopy techniques were conducted to examine phase behavior, molecular properties, and particle properties, which are necessary for the rational design of advanced pulmonary inhalation aerosols. Molecular fingerprinting was conducted by using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and Raman spectroscopy. Chemical imaging and mapping were conducted using confocal Raman microscopy (CRM) and IR microscopy. The advanced spray-dried (SD) excipient-free powders were successfully produced at different spraying pump feed rates and exhibited favorable molecular and particle properties. The excipient-free SD powders exhibited outstanding in vitro aerosol dispersion performance with an FDI-approved human DPI device (Neohaler) and correlated with the spray drying pump rate. In vitro, cell viability of various human pulmonary cells from different lung regions demonstrated biocompatibility and safety at different doses of UA. The transepithelial electrical resistance (TEER) assay shows that UA maintains cell membrane integrity and barrier tightness, indicating its potential for safe and effective localized drug delivery without long-term adverse effects. These results demonstrated that UA has favorable physicochemical and in vitro properties for inhalation and can be successfully engineered into excipient-free inhalable microparticles/nanoparticles as DPIs.

Environmental impact of pressurised metered dose inhalers versus dry powder and soft mist inhalers at a tertiary Melbourne hospital.

The carbon footprint of devices to deliver inhaled respiratory medications has come into focus as climate change has been identified as a worldwide emergency. Metered dose inhalers (MDIs) contain hydrofluorocarbons that have significant global warming potential compared to dry powder inhalers (DPIs) and soft mist inhalers (SMIs), which do not use a propellant gas. A 12-month pharmacy inpatient dispensing audit demonstrated that inpatient MDI use significantly outweighed that of DPIs and SMIs and accounted for approximately 99% of inhaler-related greenhouse gas emissions at our hospital.

Development of a dry powder formulation for pulmonary delivery of azithromycin-loaded nanoparticles.

The COVID-19 pandemic has raised concern regarding respiratory system diseases and oral inhalation stands out as an attractive non-invasive route of administration for pulmonary diseases such as chronic bronchitis, cystic fibrosis, COVID-19 and community-acquired pneumonia. In this context, we encapsulated azithromycin in polycaprolactone nanoparticles functionalized with phospholipids rich in dipalmitoylphosphatidylcholine and further produced a fine powder formulation by spray drying with monohydrated lactose. Nanoparticles obtained by the emulsion/solvent diffusion-evaporation technique exhibited a mean hydrodynamic diameter around 195-228nm with a narrow monomodal size distribution (PdI < 0.2). Nanoparticle dispersions were spray-dried at different inlet temperatures, atomizing air-flow, aspirator air flow, and feed rate, using lactose as a drying aid, resulting in a maximal process yield of 63% and an encapsulation efficiency of 83%. Excipients and the dry powder formulations were characterized in terms of morphology, chemical structure, thermal analyses and particle size by SEM, FTIR, DSC/TGA and laser light diffraction. The results indicated spherical particles with 90% at 4.06µm or below, an adequate size for pulmonary delivery. Aerosolization performance in a NGI confirmed good aerodynamic properties. Microbiological assays showed that the formulation preserves AZM antimicrobial effect against Staphylococcus aureus and Streptococcus pneumoniae strains, with halos above 18mm. In addition, no formulation-related cytotoxicity was observed against the human cell lines BEAS-2B (lung epithelial), HUVEC (endothelial) and HFF1 (fibroblasts). Overall, the approach described here allows the production of AZM-PCL nanoparticles incorporated into inhalable microparticles, enabling more efficient pulmonary therapy of lung infections.

Oral Manifestations in Asthmatic Patients Using Metered Dose Inhaler and Dry Powder Inhaler

Background: The prevalence of asthma indicates the importance of studying oral manifestations of inhalers as one of the indications of asthma. This study compares two methods of using inhalers, Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) in asthmatic patients. Methods: 100 asthmatic patients (50 MDI-treated, 50 DPI-treated) and 50 healthy individuals were selected by convincing sampling. The three sampled groups were gender- and age-matched. We performed a clinical examination, recorded the information, and analyzed the data by SPSS21 software using a t-test and one-way ANOVA for quantitative and Pearson’s chi-square test for qualitative indicators. Results: DMFT index (p-value 0.001), fissured tongue (p-value 0.005), xerostomia (p-value 0.001), and dental erosion (p-value: 0.011) in MDI-treated patients were significantly higher than the other two groups, while the geographic tongue (p-value 0.008) was significantly higher in DPI-treated patients than in the other two groups. It showed that periodontal disease and median rhomboid glossitis had no significant difference between the three groups. Conclusion: Due to the higher incidence of manifestations in MDI, it is expected that physicians give more attention to prescribing inhalers and give them the necessary training to maintain oral and dental hygiene.

Challenges and Opportunities in COPD Management in Latin America: A Review of Inhalation Therapies and Advanced Drug Delivery Systems.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries, where it poses a significant burden. In Latin America, the estimated prevalence of COPD is notably high, but the management and treatment of the disease have progressed slowly. This review examines the current status of inhalation therapy for COPD in Latin America, focusing on pharmacological therapies, inhalation devices, and the potential of advanced drug delivery systems. Pharmacological management predominantly relies on inhaled bronchodilators and corticosteroids, though access to these therapies varies considerably across the region. Inhalation devices, such as metered-dose inhalers (MDIs) and dry powder inhalers (DPIs), play a critical role in effective treatment delivery. However, their usage is often compromised by incorrect technique, low adherence, and limited availability, especially for DPIs. Emerging technologies, including nanoformulations, represent a promising frontier for the treatment of COPD by improving drug delivery and reducing side effects. However, significant barriers, such as high development costs and inadequate infrastructure, hinder their widespread adoption in the region. This review highlights the need for a multifaceted approach to enhance COPD management in Latin America, including optimizing access to existing inhalation therapies, strengthening healthcare infrastructure, improving provider training, and engaging patients in treatment decisions. Overcoming these challenges is crucial to improving COPD outcomes across the region.

Thin-film freeze-drying of an influenza virus hemagglutinin mRNA vaccine in unilamellar lipid nanoparticles with blebs

Messenger RNA (mRNA) vaccines have revolutionized the fight against infectious diseases and are poised to transform other therapeutic areas. Lipid nanoparticles (LNP) represent the most successful delivery system for mRNA. While the mRNA-LNP products currently in clinics are stored as frozen suspensions, there is evidence that freeze-drying mRNA-LNP into dry powders can potentially enable their storage and handling at non-freezing temperatures. Previously, we successfully applied thin-film freeze-drying (TFFD) to transform a polyadenylic acid [poly(A)]-LNP formulation from a liquid suspension to dry powders. The poly(A)-LNP were structurally multilamellar spheres without blebs, but the mRNA vaccines in clinics are comprised of mRNA-LNP that are structurally spheres surrounded by a unilamellar lipid bilayer, with some containing blebs, and it was reported that the presence of blebs increases the sensitivity of mRNA-LNP to freeze-drying-induced stress. In the present study, using an influenza A virus hemagglutinin (HA) mRNA in LNP that were structurally similar to that in the COVID-19 mRNA vaccines currently in clinic, we studied the effect of TFFD on the physical properties, internal structure, as well as immunogenicity of the HA mRNA-LNP vaccine. We concluded that TFFD can be utilized to prepare dry powders of the HA mRNA-LNP, but a sufficient amount of excipients were needed to minimize changes in the physical properties, structure, and immunogenicity of the HA mRNA-LNP vaccine.

Application of 28.1 kDa Alginate Oligosaccharide Improves the Yield and Quality of Grain in Rice

AbstractWe conducted a phase‐wise study to evaluate the efficacy of the gamma ray‐produced oligosaccharides of alginate and chitosan in enhancing the yield in rice. Initially, we irradiated the dry powder of alginate and chitosan with 200–500 kGy dose of gamma ray to produce their oligosaccharides. Subsequently, we assessed efficiency of the aqueous solution (50–400 ppm) of these oligosaccharides to stimulate the growth in rice seedling. The elicitors which stimulated the seedling growth were later tested in the field for their ability to enhance the growth and yield in rice under six different treatment regimens. In the next two seasons we evaluated the elicitor and treatment regimen, which enhanced the yield and yield contributing factors, at a larger scale. The observations suggest that 200 ppm of alginate oligosaccharide (28.1 kDa) produced by 500 kGy of gamma ray enhances the yield in rice by 13% and improves the seed quality when sprayed during seedling, pre‐flowering and grain‐filling stages. Such treatment improves the overall growth and development of the plant, which probably enhances the yield and grain quality of the produce.

Detailed Pharmacognostical Standardisation and Phytochemical Analysis of Whole Plant of &lt;i&gt;Tephrosia barber&lt;/i&gt; — An Endemic Novel Medicinal Plant

Background: Tephrosia barberi J. R. Drumm. is a perennial herb belonging to the Fabaceae family. Aim: The present research work is focused on carrying out the pharmacognostic standardisation and primary phytochemical analysis of the whole plant of T. barberi. Methods: The morphology, microscopy, powder microscopy, quantitative analysis of leaf constants, fluorescence analysis and physio-chemical parameters were included in the pharmacognostical work for the whole plant followed WHO prescribed quality control methods. The primary phytochemical analysis is carried out for powder with different solvent extracts using standard procedure. Results: The study reveals that the microscopical character of the whole plant of T. barberi includes the presence of cork, phloem fibres, xylem vessels, starch grains, tracheids, unicellular warty trichomes, anamocytic type of stomata and prismatic type calcium oxalate crystal sheath. The total ash, acid insoluble ash, water soluble ash value, sulphated ash, and loss on drying were quantified as physiochemical parameters, which were observed by 3%, 1%, 2%, 5% and 8%, respectively, using T. barberi dry powder. Under daylight, long and short UV, extracts of the whole plant and with various reagents were seen as various fluorescent reflection shades, which showed satisfactory results. Additionally, the primary phytochemical analysis of different extracts of T. barberi showed the presence of alkaloids, flavonoids, steroidal glycosides, polyphenols and terpenoids. Conclusion: All these findings ensured that the whole plant profile for T. barberi could be accomplished, which may provide proper identification and probable to minimise the adulteration of other plant species. Furthermore, the primary phytochemical screening study would be useful to carry out the isolation of phytoconstituents and their therapeutic potency in future.

Liquisolid Technique for Solubility Enhancement of Poorly Soluble Drug - A Brief Review.

Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.

Inhalable Advanced Co-Spray Dried Microparticles/Nanoparticles of a Novel RhoA/Rho Kinase Inhibitor with Lung Surfactant Biomimetic Phospholipids for Targeted Lung Delivery.

Co-spray dried inhalable powder formulations of fasudil monohydrochloride salt (FMCS) and inhalable lung surfactant-based nanocarriers composed of synthetic phospholipids, zwitterionic DPPC (1,2-palmitoyl-sn-glycero-3-phosphocholine) and anionic DPPG (1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]) sodium salt, were designed and optimized using organic solution advanced spray drying. FMCS can potentially be used for the treatment of various complex pulmonary diseases with this current work focusing on pulmonary arterial hypertension. Comprehensive physicochemical characterization, electron and optical microscopy imaging, thermal analysis, molecular fingerprinting spectroscopy, in vitro aerosol dispersion performance with human dry powder inhaler (DPI) devices, in vitro membrane permeation and drug release, and in vitro human cellular studies were conducted. Well-defined, small, and smooth nanoparticles/microparticles in the solid state were engineered at different molar ratios of FMCS/DPPC/DPPG (25:75, 50:50, and 75:25) and successfully produced as inhalable powders having the properties necessary for targeted pulmonary delivery as dry powder inhalers. In vitro aerosol performance demonstrated excellent aerosol dispersion with different DPI devices. The phospholipid bilayer biophysical properties were confirmed and retained following cospray drying. Sustained release of fasudil drug and in vitro biocompatibility were demonstrated on human lung cells from different airway regions.