Dry Powder Formulation Research Articles

Dissolution and Absorption of Inhaled Drug Particles in the Lungs.

Dry powder inhalation therapy has been effective in treating localized lung diseases such asthma, chronic obstructive pulmonary diseases (COPD), cystic fibrosis and lung infections. In vitro characterization of dry powder formulations includes the determination of physicochemical nature and aerosol performance of powder particles. The relationship between particle properties (size, shape, surface morphology, porosity, solid state nature, and surface hydrophobicity) and aerosol performance of an inhalable dry powder formulation has been well established. However, unlike oral formulations, there is no standard dissolution method for evaluating the dissolution behavior of the inhalable dry powder particles in the lungs. This review focuses on various dissolution systems and absorption models, which have been developed to evaluate dry powder formulations. It covers a summary of airway epithelium, hurdles to developing an in vitro dissolution method for the inhaled dry powder particles, fine particle dose collection methods, various in vitro dissolution testing methods developed for dry powder particles, and models commonly used to study absorption of inhaled drug.

AV-101, a novel inhaled dry-powder formulation of imatinib, in healthy adult participants: a phase 1 single and multiple ascending dose study.

Oral imatinib has been shown to be effective, but poorly tolerated, in patients with advanced pulmonary arterial hypertension (PAH). To maintain efficacy while improving tolerability, AV-101, a dry powder inhaled formulation of imatinib, was developed to deliver imatinib directly to the lungs. This phase 1, placebo-controlled, randomised single ascending dose (SAD) and multiple ascending dose (MAD) study evaluated the safety/tolerability and pharmacokinetics of AV-101 in healthy adults. The SAD study included five AV-101 cohorts (1 mg, 3 mg, 10 mg, 30 mg, 90 mg) and placebo, and a single-dose oral imatinib 400-mg cohort. The MAD study included three AV-101 cohorts (10 mg, 30 mg, 90 mg) and placebo; dosing occurred twice daily for 7 days. 82 participants (SAD n=48, MAD n=34) were enrolled. For the SAD study, peak plasma concentrations of imatinib occurred within 3 h of dosing with lower systemic exposure compared to oral imatinib (p<0.001). For the MAD study, systemic exposure of imatinib was higher after multiple doses of AV-101 compared to a single dose, but steady-state plasma concentrations were lower for the highest AV-101 cohort (90 mg) compared to simulated steady-state oral imatinib at day 7 (p=0.0002). Across AV-101 MAD dose cohorts, the most common treatment-emergent adverse events were cough (n=7, 27%) and headache (n=4, 15%). AV-101 was well tolerated in healthy adults, and targeted doses of AV-101 significantly reduced the systemic exposure of imatinib compared with oral imatinib. An ongoing phase 2b/phase 3 study (IMPAHCT; clinicaltrials.gov identifier NCT05036135) will evaluate the safety/tolerability and clinical benefit of AV-101 for PAH.

Lyophilization of Curcumin-Albumin Nanoplex with Sucrose as Cryoprotectant: Aqueous Reconstitution, Dissolution, Kinetic Solubility, and Physicochemical Stability.

An amorphous curcumin (CUR) and bovine serum albumin (BSA) nanoparticle complex (nanoplex) was previously developed as a promising anticancer nanotherapy. The CUR-BSA nanoplex had been characterized in its aqueous suspension form. The present work developed a dry-powder form of the CUR-BSA nanoplex by lyophilization using sucrose as a cryoprotectant. The cryoprotective activity of sucrose was examined at sucrose mass fractions of 33.33, 50.00, and 66.66% by evaluating the lyophilized nanoplex’s (1) aqueous reconstitution and (2) CUR dissolution and kinetic solubility. The physicochemical stabilizing effects of sucrose upon the nanoplex’s 30-day exposures to 40 °C and 75% relative humidity were examined from (i) aqueous reconstitution, (ii) CUR dissolution, (iii) CUR and BSA payloads, (iv) amorphous form stability, and (v) BSA’s structural integrity. The good cryoprotective activity of sucrose was evidenced by the preserved BSA’s integrity and good aqueous reconstitution, resulting in a fast CUR dissolution rate and a high kinetic solubility (≈5–9× thermodynamic solubility), similar to the nanoplex suspension. While the aqueous reconstitution, CUR dissolution, and amorphous form were minimally affected by the elevated heat and humidity exposures, the treated nanoplex exhibited a lower BSA payload (≈7–26% loss) and increased protein aggregation postexposure. The adverse effects on the BSA payload and aggregation were minimized at higher sucrose mass fractions.

Sustainable colorimetric/luminescent sensors enabled by armored lipid nanoparticles

In this study, we developed a highly stable polymeric vesicle using a nanosilica-armor membrane to achieve a sustainable colorimetric/luminescent response. The silica armor can be grown directly as ~ 5 nm spherical nanoparticles on the surface of the diacetylene (DA) vesicle with liposomal structure. This can be accomplished via the modified Stöber reaction in pure water on a layer of amine linkers deposited on the vesicles. Once formed, the structural stability of the DA vesicles dramatically increased and remained so even in a dried powder form that could be stored for a period of approximately 6 months. Then, redispersed in water, the armored vesicles did not agglomerate because of the electric charge of the silica armor. After polymerization, the polydiacetylene (PDA) vesicles maintained an average of 87.4% their sensing capabilities compared to unstored vesicles. Furthermore, the silica membrane thickness can be controlled by reiteration of the electrostatic layer-by-layer approach and the direct hydrolysis of silica. As the number of silica armor membranes increases, the passage of the stimuli passing through the membranes becomes longer. Consequently, three layers of silica armor gave the PDA vesicles size-selective recognition to filter out external stimuli. These discoveries are expected to have large-scale effects in the chemo- and biosensor fields by applying protective layers to organic nanomaterials.Graphical

The applications of Machine learning (ML) in designing dry powder for inhalation by using thin-film-freezing technology

Dry powder inhalers (DPIs) are one of the most widely used devices for treating respiratory diseases. Thin--film--freezing (TFF) is a particle engineering technology that has been demonstrated to prepare dry powder for inhalation with enhanced physicochemical properties. Aerosol performance, which is indicated by fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD), is an important consideration during the product development process. However, the conventional approach for formulation development requires many trial-and-error experiments, which is both laborious and time consuming. As a state-of-the art technique, machine learning has gained more attention in pharmaceutical science and has been widely applied in different settings. In this study, we have successfully built a prediction model for aerosol performance by using both tabular data and scanning electron microscopy (SEM) images. TFF technology was used to prepare 134 dry powder formulations which were collected as a tabular dataset. After testing many machine learning models, we determined that the Random Forest (RF) model was best for FPF prediction with a mean absolute error of ± 7.251%, and artificial neural networks (ANNs) performed the best in estimating MMAD with a mean absolute error of ± 0.393 μm. In addition, a convolutional neural network was employed for SEM image classification and has demonstrated high accuracy (>83.86%) and adaptability in predicting 316 SEM images of three different drug formulations. In conclusion, the machine learning models using both tabular data and image classification were successfully established to evaluate the aerosol performance of dry powder for inhalation. These machine learning models facilitate the product development process of dry powder for inhalation manufactured by TFF technology and have the potential to significantly reduce the product development workload. The machine learning methodology can also be applied to other formulation design and development processes in the future.

Towards more efficient inhalable chemotherapy: Fabrication of nanodiamonds-releasing microspheres

Nanodiamonds (NDs) are among the most promising chemotherapy vectors, however, they tend to aggregate upon storage, or when exposed to mild changes in pH or ionic strength. Therefore, fabrication of dried NDs with minimal change in particle size is highly desirable. In this study, we have developed a dried powder form of NDs with controlled particle size to be eligible for pulmonary delivery, after screening different drying protectants for their effect on NDs particle size and surface charge. Results showed that the nanospray-drying process in the presence of mannitol prevented the aggregation of NDs. Nanospray-dried NDs microparticles exhibited an optimal aerodynamic size for pulmonary delivery, and the in vitro aerosol deposition testing showed that NDs-embedded mannitol microspheres could deliver more than half of the emitted fraction to the lower stage of the Twin impinger device; indicating high pulmonary delivery potential. Upon loading NDs with doxorubicin (NDX) prior to spray dryng, they were able to deliver 2.6 times more drug to A549 lung cancer cell line compared to the free drug. Pharmacokinetics study in rats showed that inhaled NDX microparticles could efficiently limit the biodistribution of the drug to the lungs, and minimize the drug fraction reaching the systemic circulation. To conclude, nanospray-dried NDs microparticles present a promising vehicle for the pulmonary delivery of chemotherapeutic agents for treatment of lung cancer.

Assessment of Inhaled Treprostinil Palmitil, Inhaled and Intravenous Treprostinil, and Oral Selexipag in a Sugen/Hypoxia Rat Model of Pulmonary Arterial Hypertension.

Treprostinil palmitil (TP), a long-acting inhaled pulmonary vasodilator prodrug of treprostinil (TRE), has beneficial effects in a Sugen5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension (PAH) that compare favorably to the oral phosphodiesterase 5 inhibitor (PDE5) sildenafil. In this study in male Sprague-Dawley rats, a dry powder formulation of TP (TPIP) was compared with inhaled and intravenous TRE and oral selexipag to evaluate inhibition of hemodynamic and pathologic changes in the lungs and heart induced by Su/Hx challenge. Su (20 mg/kg) was injected subcutaneously followed by 3 weeks of Hx (10% O2/balance N2) and then initiation of test article administration over 5 weeks with room air breathing. Hemodynamics and histopathology were measured at the end of the study. Su/Hx challenge approximately doubled the mean pulmonary arterial blood pressure (mPAP) and the Fulton index, decreased cardiac output (CO), doubled the wall thickness and muscularization of the small (10-50 μm) and medium (51-100 μm) sized pulmonary arteries, and increased the percentage of obliterated pulmonary blood vessels. Even though inhaled TRE (65 μg/kg, 4× daily), intravenous TRE (810 ng/kg/min), and oral selexipag (30 mg/kg, twice daily) provided some beneficial effects against the Su/Hx challenge, the overall benefit was generally greater with TPIP at high dose (117 μg/kg, once daily). These results demonstrate that TPIP compares favorably to inhaled and intravenous TRE and oral selexipag with respect to inhibition of the pathophysiological changes induced by Su/Hx challenge in rats. SIGNIFICANCE STATEMENT: Treprostinil palmitil (TP) is a long-acting pulmonary vasodilator prodrug of treprostinil (TRE) formulated for inhaled administration by dry powder [treprostinil palmitil inhalation powder (TPIP)]. Comparison of the activity of TPIP, inhaled and intravenous TRE, and oral selexipag in a Sugen5416/hypoxia (Su/Hx) rat model of pulmonary arterial hypertension demonstrated that each of these drugs exert protection against the hemodynamic and histopathological changes induced by the Su/Hx challenge, with the greatest effect on these changes produced by TPIP.

Phytochemical Analysis, Antioxidant and Anticancer Effects of Clitoria ternatae Extract on Breast T47D Cancer Cells

Background: Breast cancer is one of the most common and deadly forms of cancer in the world. Cancer is a multi-factorial disease. Genetic factors, environment and lifestyle have a role in the development of cancer. One of the mechanisms of cancer development is when an imbalance between free radicals and antioxidants in the human body occurs. Uncontrolled and excessive amount of free radicals and cause cell damage and uncontrolled cell growth. Clitoria ternate is a plant that is often found in Asia and many of the benefits of this flower have been studied. This study aims to determine the phytochemical constituents, antioxidant activity, and cytotoxic activity of Clitoria ternatea against T47D breast cancer cells. Method: Clitoria ternatea in the form of dry powder is macerated in a multi-level manner with n-hexane, ethyl acetate, and ethanol as solvents, producing a Clitoria ternatea extract of the respective solvents. Each extract is then evaluated for its phytochemical constituents, antioxidant activity, and cytotoxic activity using phytochemical test, thin layer chromatography (TLC), DPPH assay, and MTT assay respectively. Results: Phytochemical analysis of Clitoria ternatea shows the presence of glycosides, flavonoids, tannins and triterpenoids with TLC revealing the presence of ten phytochemical constituents. DPPH assay reveals that Clitoria ternatea exhibits a very active antioxidant activity. MTT assay revels Clitoria ternatea has a high cytotoxic activity towards T47D breast cancer cell line with IC50 value ranging from 1.27 μg/mL to 32.38 μg/mL. Conclusion: Chemical constituents of Clitoria ternatea is responsible for the antioxidant and cytotoxic activity towards T47D breast cancer cell line.

Improved Aerosolization Stability of Inhalable Tobramycin Powder Formulation by Co-Spray Drying with Colistin.

Tobramycin shows synergistic antibacterial activity with colistin and can reduce the toxic effects of colistin. The purpose of this study is to prepare pulmonary powder formulations containing both colistin and tobramycin and to assess their in vitro aerosol performance and storage stability. The dry powder formulations were manufactured using a lab-scale spray dryer. In vitro aerosol performance was measured using a Next Generation Impactor. The storage stability of the dry powder formulations was measured at 22°C and two relative humidity levels - 20 and 55%. Colistin composition on the particle surface was measured using X-ray photoelectron spectroscopy. Two combination formulations, with 1:1 and 1:5 molar ratios of colistin and tobramycin, showed fine particle fractions (FPF) of 85%, which was significantly higher than that of the spray dried tobramycin (45%). FPF of the tobramycin formulation increased significantly when stored for four weeks at both 20% and 55% RH. In contrast, FPF values of both combination formulations and spray dried colistin remained stable at both humidity levels. Particle surface of each combination was significantly enriched in colistin molecules; 1:5 combination showed 77% by wt. colistin. The superior aerosol performance and aerosolization stability of 1:1 and 1:5 combination formulations of colistin and tobramycin could be attributed to enrichment of colistin on the co-spray dried particle surface. The observed powder properties may be theresult of a surfactant-like assembly of these colistin molecules during spray drying, thus forming a hydrophobic particle surface.

Inhalable microparticle platform based on a novel shell-forming lipid excipient and its feasibility for respirable delivery of biologics

Administration of biologics such as proteins, vaccines, and phages via the respiratory route is becoming increasingly popular. Inhalable powder formulations for the successful delivery of biologics must first ensure both powder dispersibility and physicochemical stability. A lipid-based inhalable microparticle platform combining the stability advantages offered by dry powder formulations and high dispersibility afforded by a rugose morphology was spray dried and tested. A new simplified spray drying method requiring no organic solvents or complicated feedstock preparation processes was introduced for the manufacture of the microparticles. Trehalose was selected to form the amorphous particle core, because of its well-known ability to stabilize biologics, and also because of its ability to serve as a surrogate for small molecule actives. Phospholipid distearoyl phosphatidylcholine (DSPC), the lipid component in this formulation, was used as a shell former to improve powder dispersibility. Effectiveness of the lipid excipient in modifying trehalose particle morphology and enhancing powder dispersibility was evaluated at different lipid mass fractions (5%, 10%, 25%, 50%) and compared with that of several previously published shell-forming excipients at their effective mass fractions, i.e., 5% trileucine, 20% leucine, and 40% pullulan. A strong dependence of particle morphology on the lipid mass fraction was observed. Particles transitioned from typical smooth spherical trehalose particles without lipid to highly rugose microparticles at higher lipid mass fractions (>5%). In vitro aerosol performance testing demonstrated a significant improvement of powder dispersibility even at lipid mass fractions as low as 5%. Powder formulations with excellent aerosol performance comparable to those modified with leucine and trileucine were achieved at higher lipid mass fractions (>25%). A model biologic-containing formulation with 35% myoglobin, 35% glass stabilizer (trehalose), and 30% lipid shell former was shown to produce highly rugose particle structure as designed and excellent aerosol performance for efficient pulmonary delivery. A short-term stability at 40 °C proved that this protein-containing formulation had good thermal stability as designed. The results demonstrated great potential for the new lipid microparticle as a platform for the delivery of both small-molecule APIs and large-molecule biologics to the lung.

Spray-Dried and Spray-Freeze-Dried Powder Formulations of an Anti-Interleukin-4Rα Antibody for Pulmonary Delivery.

The therapeutic options for severe asthma are limited, and the biological therapies are all parenterally administered. The purpose of this study was to formulate a monoclonal antibody that targets the receptor for IL-4, an interleukin implicated in the pathogenesis of severe asthma, into a dry powder intended for delivery via inhalation. Dehydration was achieved using either spray drying or spray freeze drying, which exposes the thermolabile biomacromolecules to stresses such as shear and adverse temperatures. 2-hydroxypropyl-beta-cyclodextrin was incorporated into the formulation as protein stabiliser and aerosol performance enhancer. The powder formulations were characterised in terms of physical and aerodynamic properties, while the antibody was assessed with regard to its structural stability, antigen-binding ability, and in vitro biological activity after drying. The spray-freeze-dried formulations exhibited satisfactory aerosol performance, with emitted fraction exceeding 80% and fine particle fraction of around 50%. The aerosolisation of the spray-dried powders was hindered possibly by high residual moisture. Nevertheless, the antigen-binding ability and inhibitory potency were unaffected for the antibody in the selected spray-dried and spray-freeze-dried formulations, and the antibody was physically stable even after one-year storage at ambient conditions. The findings of this study establish the feasibility of developing an inhaled dry powder formulation of an anti-IL-4R antibody using spray drying and spray freeze drying techniques with potential for the treatment of severe asthma.

Validation of a cell integrated next-generation impactor to assess in vitro drug transport of physiologically relevant aerosolised particles

The development of novel inhaled formulations in the pre-clinical stage has been impeded by a lack of meaningful information related to drug dissolution and transport at the lung epithelia due to the absence of physiologically relevant in vitro respiratory models. The objective of the present study was to develop an in vitro experimental model, which combined the next generation impactor (NGI) and two respiratory epithelial cell lines, for examining the aerodynamic performance of dry powder inhalers and the fate of aerosolised drugs following lung deposition. The NGI impaction plates of stage 3 (i.e., a cut-off diameter of 2.82–4.46 µm) and stage 7 (i.e., a cut-off diameter of 0.34–0.55 µm) were modified to accommodate 3 cell cultures inserts. Specifically, Calu-3 cells and H441 cells, which are representative of the bronchial and alveolar epithelia in the lung, respectively, were cultivated at the air–liquid interface on SnapwellsTM with polycarbonate membranes. The aerodynamic particle size distribution of the modified NGI was investigated using resveratrol dry powder formulation (as a model drug). The suitability of such an in vitro model was confirmed by examining the in vitro aerodynamic performance of the model drug as compared to the conventional NGI setup (i.e., without the integrated Snapwell inserts), as well as the effect of experimental conditions (e.g., 60 L/min airflows) on the cells in the integrated Snapwell inserts. After deposition of the aerodynamically fractioned resveratrol, the permeation of the drug across the cell layer to the basolateral chamber of the Snapwell inserts was evaluated over 24 h. Results obtained from the drug transport study showed that the cell-integrated NGI provided realistic drug delivery conditions to the cells that can be used to assess the fate of fractionated aerosol particles. This system enables a better understanding of the in vitro drug deposition in the lungs and allows studies on both aerodynamic characterisation and drug transport (drug biological interactions with the cells) to be performed simultaneously.

Inhalable Composite Microparticles Containing siRNA-Loaded Lipid-Polymer Hybrid Nanoparticles: Saccharides and Leucine Preserve Aerosol Performance and Long-Term Physical Stability

Thermostable dry powder formulations with high aerosol performance are attractive inhalable solid dosage forms for local treatment of lung diseases. However, preserved long-term physical stability of dry powder inhaler (DPI) formulations is critical to ensure efficient and reproducible delivery to the airways during the shelf life of the drug product. Here, we show that ternary excipient mixtures of the disaccharide trehalose (Tre), the polysaccharide dextran (Dex), and the shell-forming dispersion enhancer leucine (Leu) stabilize siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) during spray drying into nanocomposite microparticles, and result in inhalable solid dosage forms with high aerosol performance and long-term stability. The stabilizing roles of Tre and Dex were also studied separately by investigating DPI formulations containing binary mixtures of Leu/Tre and Leu/Dex, respectively. DPI formulations containing binary Leu/Dex mixtures were amorphous and displayed preserved long-term physical stability of LPNs and chemical stability of siRNA in accelerated stability studies under exaggerated storage conditions (ambient temperature and relative humidity). In contrast, powders containing binary Leu/Tre mixtures were amorphous, and hence metastable, and were recrystallized after six months of storage. Ternary mixtures of Tre, Leu, and Dex provided the most efficient protection of the LPNs during the spray drying process and prevented recrystallization of amorphous Tre. Hence, in ternary mixtures, Leu, Tre, and Dex have the following functions: the shell-forming Leu functions as a dispersion enhancer and is essential for high aerosol performance, the disaccharide Tre provides LPN protection during manufacturing and storage due to efficient coverage of the LPN surface, and the polysaccharide Dex promotes the formation of porous particles and prevents recrystallization of Tre during long-term storage. Therefore, the use of ternary excipient mixtures composed of Leu, Tre, and Dex, may prevent instability problems of DPI formulations and preserve the aerosol performance during long-term storage, which is essential for effective pulmonary drug delivery.

Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin Dry Powder.

SARS-CoV-2, the causative agent of COVID-19, predominantly affects the respiratory tract. As a consequence, it seems intuitive to develop antiviral agents capable of targeting the virus right on its main anatomical site of replication. Ivermectin, a U.S. FDA-approved anti-parasitic drug, was originally shown to inhibit SARS-CoV-2 replication in vitro, albeit at relatively high concentrations, which is difficult to achieve in the lung. In this study, we tested the spray-drying conditions to develop an inhalable dry powder formulation that could ensure sufficient antiviral drug concentrations, which are difficult to achieve in the lungs based on the oral dosage used in clinical trials. Here, by using ivermectin as a proof-of-concept, we evaluated spray-drying conditions that could lead to the development of antivirals in an inhalable dry powder formulation, which could then be used to ensure sufficient drug concentrations in the lung. Thus, we used ivermectin in proof-of-principle experiments to evaluate our system, including physical characterization and in vitro aerosolization of prepared dry powder. The ivermectin dry powder was prepared with a mini spray-dryer (Buchi B-290), using a 23 factorial design and manipulating spray-drying conditions such as feed concentration (0.2% w/v and 0.8% w/v), inlet temperature (80 °C and 100 °C) and presence/absence of L-leucine (0% and 10%). The prepared dry powder was in the size range of 1–5 μm and amorphous in nature with wrinkle morphology. We observed a higher fine particle fraction (82.5 ± 1.4%) in high feed concentration (0.8% w/v), high inlet temperature (100 °C) and the presence of L-leucine (10% w/w). The stability study conducted for 28 days confirmed that the spray-dried powder was stable at 25 ± 2 °C/<15% RH and 25 ± 2 °C/ 53% RH. Interestingly, the ivermectin dry powder formulation inhibited SARS-CoV-2 replication in vitro with a potency similar to ivermectin solution (EC50 values of 15.8 µM and 14.1 µM, respectively), with a comparable cell toxicity profile in Calu-3 cells. In summary, we were able to manipulate the spray-drying conditions to develop an effective ivermectin inhalable dry powder. Ongoing studies based on this system will allow the development of novel formulations based on single or combinations of drugs that could be used to inhibit SARS-CoV-2 replication in the respiratory tract.

INSPIRE: Safety and tolerability of inhaled Yutrepia (treprostinil) in pulmonary arterial hypertension (PAH).

The INSPIRE trial was a Phase 3, open‐label, multicenter trial (LTI‐301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry‐powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial. Transition patients initiated Yutrepia at a dose comparable to their nebulized treprostinil dose while prostacyclin naïve patients received 26.5‐mcg QID; up‐titration in 26.5‐mcg increments was permitted for both groups. A total of 121 patients were enrolled, of which 29 patients discontinued from the trial, with the most common reason being AEs. Eighty percent of the Transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg QID at Day 360, respectively, with one patient achieving a dose of 212‐mcg QID. The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment‐related though mild to moderate in severity and expected for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1 year of treatment. Yutrepia was found to be a convenient, safe, and well‐tolerated inhaled prostacyclin treatment option for PAH patients.

Anti-Hypertensive Effect of Gooseberry

Phyllanthus emblica, also known as emblic, Indian gooseberry, or amla, is a deciduous tree of the family Phyllanthaceae. The berries are tiny and round, with a bright or yellow-green in color. The Indian gooseberry (Phyllanthus emblica) is an Indian and Middle Eastern tree. For thousands of years, it has been prescribed in Ayurvedic treatment. Objective: The aim of this review was to identify scientific evidence regarding the effects of gooseberry on hypertension. Methods: Electronic search of Google scholar, Medline and PubMed databases were conducted. When the force of blood pushing against the walls of blood vessels, is consistently too high. It is known as hypertension. Scientific evidence indicates that polyphenols are central components in fruits and other sections of the amla tree, as well as vitamin Results: Previous studies suggested that Gooseberry is highly effective to manage hypertension. Indian gooseberries are able to keep both diastolic and systolic blood pressure levels in their normal ranges as well significantly decrease the high levels of both of them. It has other health benefits as well which includes normalizing blood sugar levels, protests against kidney disorders, several types of cancers, also prevents cancer from spreading to other parts of the body and many more health benefits. Most of the studies that were done on Phyllanthus emblica to determine their effects on high blood pressure of patients done by giving them in the form of capsules either in their aqueous state or in their dried powder form two or three times a day after meal for weeks. And the results were visible from second or fourth weeks onwards. Conclusion: These studies indicated that Indian gooseberries are highly efficient and a great remedy to treat hypertension.

Triclosan and ⍺-bisabolol–loaded nanocapsule functionalized with ascorbic acid as a dry powder formulation against A549 lung cancer cells

Lung cancer is between the primary causes of cancer death showing a high mortality rate. Traditional therapies lead to serious side-effects pushing the development of new and more specific treatments. This study proposes an innovative inhalable powder intended for lung cancer on-site action, by developing new nanocapsules functionalized powder formulation carrying triclosan, dispersed in α-bisabolol and functionalized with ascorbic acid. Nanocapsules were obtained by interfacial deposition of the preformed polymer method. Functionalization was performed via a three-step interfacial reaction process forming a chitosan-iron-ligand complex. After spray-drying, powders were obtained using two strategies. All formulations were characterized and had their antiproliferative activities tested, along with their irritability potential. Functionalized nanocapsules were subsequently spray-dried to produce dispersible powders. Using combined data from infrared spectroscopy was observed an interaction between the components after each step of the surface functionalization. The same components interactions were verified before and after obtaining the powder, which were adequate for lung administration, suffering deposition mainly in the respirable fraction within 15 min. The powder showed an effective concentration against lung cancer cells (A549), with nontoxic effects in irritability assay. By the results, the formulation can be administered at safe triclosan concentrations. Thus, the proposed formulations are appropriate and promising candidates for further research in lung cancer treatment.

SIRT 1 Activator Loaded Inhaled Antiangiogenic Liposomal Formulation Development for Pulmonary Hypertension.

Pulmonary hypertension (PH) is characterized by the rise in mean pulmonary arterial pressure (≥ 20mmHg at rest) due to the narrowing of the pulmonary arterial networks. Current treatments provide symptomatic treatment and the underlying progress of PH continues leading to higher mortality rates due to non-reversal of the disease. This warrants the need for drug therapies targeting angiogenesis and vascular remodeling mechanisms. Resveratrol, SIRT 1 activator, alters various signaling pathways, inhibits apoptosis, and negatively regulates angiogenesis either by increasing the production of anti-angiogenic factors or inhibiting pro-angiogenic factors. Our work describes the liposomal formulation development, physicochemical characterization, and in vitro aerosolization performance of resveratrol liposomal dry powder formulation. The resveratrol liposomal dry powder formulation reduces the right ventricular systolic pressure measured during right jugular vein catheterization and significantly reverses the PH disease pathological changes as demonstrated by histological observations of pulmonary arterial lumen and ventricular hypertrophy. The developed resveratrol liposomal dry powder formulation alleviates the pulmonary arterial remodeling through its antiangiogenic mechanism and indicates a promising therapeutic strategy for PH treatment.

Agaricus brasiliensis (Sun mushroom): antioxidant capacity and HMG-CoA reductase inhibition potential of dried powder formulations in vitro and hepatic alterations in hypercholesterolemic rats

This study investigues the chemical composition of the mushroom Agaricus brasiliens is prepared in different commercially available forms: dehydrated whole mushrooms, mushroom powder, and capsules. The most active form was subsequently examined in vivo to investigate its possible

Effect of Particulate Properties of Inhaled Dry Powder Formulation on Bioavailability, Dissolution Rate of Drug Particles and Rate of Drug Removal from the Body

Introduction: The use of pulmonary drug delivery as a non-invasive drug delivery system for the systemic treatment of diseases as well as the topical treatment of respiratory diseases is increasing. Among the various inhaled formulations, inhaled dry powders show advantages over the other forms of inhaled medicines due to high stability, bioavailability and ease of use. The effect of particle properties on the rate of drug delivery to the lungs in inhaled dry powders has been investigated in previous papers.&#x0D; Conclusion: Since the physicochemical properties of particles of dry powder inhalation formulations such as particle size, surface and particle shape, as well as the electrical charge of the particles play a decisive role in drug pharmacokinetics, in the present review article we intended to discuss the effect of these parameters of inhaled dry powder formulations on bioavailability, dissolution rate of drug particles and the rate of drug clearance from the body.