Modulation of growth, innate immunity, and disease resistance of Nile tilapia (Oreochromis niloticus) culture under biofloc system by supplementing pineapple peel powder and Lactobacillus plantarum.

Eight weeks feeding experiment was managed to evaluate the impacts of dietary addition of pineapple peel powder (PAPP) and Lactobacillus plantarum CR1T5 (LP) individual or mixed on growth performance, skin mucus and serum immunities, as well as disease resistance of Nile tilapia. Fish (average weight 20.91 ± 0.11 g) were fed four diets: Diet 1 (0 g kg-1 PAPP and 0 CFU g-1 L. plantarum, Diet 2 (10 g kg-1 PAPP), Diet 3 (108 CFU g-1L. plantarum), and Diet 4 (10 g kg-1 PAPP + 108 CFU g-1L. plantarum). Serum and mucus immune responses, as well as growth rate, were assessed every 4 weeks. Ten fish were chosen for the challenge test with Streptococcus agalactiae after 8 weeks post-feeding. The findings showed that PAPP and/or LP diets increased (P ≤ 0.05) growth performance, skin mucus, and serum immune responses. The best data were obtained in fish fed a mixture of PAPP and LP. Nevertheless, no variation (P > 0.05) was recorded between groups fed PAPP or LP. The relative survival percentage (RSP, %) in Diet 2, Diet 3, and Diet 4 was 46.15%, 50.0%, and 73.08%. Fish fed mixture of PAPP + LP recorded the best (P < 0.05) survival rate versus other treatments. The current findings recommended using a mixture of PAPP and LP as promising functional additives for aquaculture practice.

Impaired exercise capacity in electrostatic polyester powder paint workers.

PURPOSE: Limited number of studies investigated the effects of Electrostatic powder paints (EPP) on human health. We investigated the effects of EPP exposure on lung function, exercise capacity, and quality of life, and the factors determining exercise capacity in EPP workers. METHODS: Fifty-four male EPP workers and 54 age-matched healthy male individuals (control group) were included. Lung function and respiratory muscle strength were measured. The lower limit of normal (LLN) cut-points for FEV1 and FEV1/FVC were calculated. An EPT was used to evaluate bronchial hyperactivity. The handgrip and quadriceps muscle strength were evaluated using a hand-held dynamometer. An ISWT was used to determine exercise capacity. The physical activity level was questioned using the IPAQ. The SGRQ and NHP were used to assessing respiratory specific and general quality of life, respectively. RESULTS: Duration of work, FEV1, MIP, handgrip strength, and ISWT distance were significantly lower, and the change in FEV1 after EPT and %HRmax were significantly higher in the EPP group compared to the control group (p < 0.05). There were no subjects with a < LLN for FEV1 and FEV1/FVC in both groups. In the EPP group, ISWT distance was significantly related to age, height, duration of work, FEV1, change in FEV1 after EPT, MIP, MEP, handgrip strength, IPAQ, SGRQ, and NHP total scores (p < 0.05). The change in FEV1 after EPT, MIP, and duration of work explained % 62 of the variance in the ISWT distance (p < 0.001). CONCLUSIONS: Changes in lung function based on LLN for the FEV1 and FEV1/FVC were not clinically relevant in EPP workers. Exercise capacity is impaired in EPP workers. Degree of exercise-induced bronchospasm, inspiratory muscle strength, and duration of work are the determinants of exercise capacity in EPP workers.

New Fast Acting Glucagon for Recovery from Hypoglycemia, a Life-Threatening Situation: Nasal Powder and Injected Stable Solutions.

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989-1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.

Effects of bamboo charcoal powder, bamboo vinegar, and their combination in laying hens on performance, egg quality, relative organ weights, and intestinal bacterial populations.

This experiment examines the effects of bamboo charcoal (BC) powder, bamboo vinegar (BV), and their combination (BCV) in the diet of laying hens on performance, egg quality, relative organ weights, and intestinal bacterial populations. A total of 320 laying hens (36 weeks of age) were divided into 4 treatment groups, with 10 replicates per treatment and 8 hens per replicate. They were fed on a control diet, the control diet supplemented with 0.8% BC, the control diet supplemented with 0.4% BV, or the control diet supplemented with a combination of BC (0.8%) and BV (0.4%) from 36 to 51 weeks of age. Egg production increased in the hens fed the BV and BCV diets during 48 to 51 weeks of age (P < 0.05). Damaged egg rate decreased in the hens fed the BV and BCV diets for the whole experiment (P < 0.05). Shell thickness was highest in the BCV-fed group at week 43, and shell strength was higher in the BV-fed group at week 51 (P < 0.05). Supplementation of BC or BCV in the diet resulted in a decreased abdominal fat pad (P < 0.05). In the ileal content, the population of Salmonella spp. decreased in the BV and BCV groups and the population of Lactobacillus spp. increased in the BV group (P < 0.05). The present results indicate that feeding BV or BCV alleviates damaged egg rate and decreases intestinal pathogenic bacteria, while feeding BC benefits by reducing abdominal fat. These results suggest that the effect of BCV seems to be induced by the synergistic effect of BC and BV, and that the BCV contributes to the effective use of bamboo on the laying hen's production.

Development of an Excipient-Free Peptide Dry Powder Inhalation for the Treatment of Pulmonary Fibrosis.

The caveolin scaffolding domain peptide (CSP) is being developed for the therapeutic intervention of a lethal lung disease, idiopathic pulmonary fibrosis. While direct respiratory delivery of CSP7 (a 7-mer fragment of CSP) is considered an effective route, proper formulation and processing of the peptide are required. First, air-jet milling technology was performed in order to micronize the neat peptide powder. Next, the fine particles were subjected to a stability study with physical and chemical characterizations. In addition, the in vivo efficacy of processed CSP7 powder was evaluated in an animal model of lung fibrosis. The results revealed that, with jet milling, the particle size of CSP7 was reduced to a mass median aerodynamic diameter of 1.58 ± 0.1 µm and 93.3 ± 3.3% fine particle fraction, optimal for deep lung delivery. A statistically significant reduction of collagen was observed in diseased lung tissues of mice that received CSP7 powder for inhalation. The particles remained chemically and physically stable after micronization and during storage. This work demonstrated that jet milling is effective in the manufacturing of a stable, excipient-free CSP7 inhalation powder for the treatment of pulmonary fibrosis.

Randomized controlled trial of hemostatic powder versus endoscopic clipping for non-variceal upper gastrointestinal bleeding.

BACKGROUND AND AIMS: Despite advances in pharmacological and endoscopic management of non-variceal upper gastrointestinal bleeding (NVUGIB), mortality is still relevant. TC-325 (Hemospray-Cook Medical) is a mineral powder with adsorptive properties, designed for endoscopic hemostasis. There are still no comparative trials studying this new hemostatic modality. The objective of this research was to compare the use of TC-325 (associated with epinephrine injection) with the combined technique of endoscopic clipping and epinephrine injection for the treatment of patients with NVUGIB. METHODS: We conducted a pilot randomized controlled trial with patients that presented NVUGIB with an actively bleeding lesion at the endoscopic evaluation. Patients were randomized either to the Hemospray or Hemoclip group. The randomization list was generated by a computer program and remained unknown throughout the entire trial. All patients underwent second-look endoscopy. RESULTS: Thirty-nine patients were enrolled. Peptic ulcer was the most frequent etiology. Primary hemostasis was achieved in all Hemospray cases and in 90% of Hemoclip group (p = 0.487). Five patients in Hemospray group underwent an additional hemostatic procedure during second-look endoscopy, while no patient in the Hemoclip group needed it (p = 0.04). Rebleeding, emergency surgery and mortality rates were similar in both groups. No toxicity, allergy events, or gastrointestinal obstruction signs were observed in Hemospray group. CONCLUSIONS: TC-325 presents similar hemostatic results when compared with conventional dual therapy for patients with NVUGIB. Hemospray's excellent primary hemostasis rate certifies it as a valuable tool in arduous situations of severe bleeding or difficult location site.

Combining Powder Formulations of Drugs with Food and Beverages to Improve Palatability.

The taste of medicines can significantly affect patient adherence. Pediatric patients often cannot take powder medicines because of their unpleasant taste. Therefore, patients' parents and health care professionals, including pharmacists, often combine medicines with food or beverages to make them easier for pediatric patients to consume because this can reduce their unpleasant taste. The purpose of this study was to evaluate the palatability of powder formulations of azithromycin and carbocysteine and explore their combination with food or beverages to improve palatability for pediatric patients. We quantitatively evaluated the palatability of powder formulations by performing the gustatory sensation test using the visual analog scale score. The gustatory sensation tests were performed on 16 healthy adult volunteers (age 23.0 ± 2.6 years) and indicated that some food and beverages improved the palatability of the powder formulations of azithromycin and carbocysteine. The results of this study indicate that ice cream improves the palatability of azithromycin, while yogurt improves the palatability of carbocysteine. Moreover, the subjects recommended these same combinations for pediatric patients. This study suggests that some foods and beverages improve the palatability of powder formulations, thereby decreasing the possibility that pediatric patients will refuse medications because of their unpleasant taste.

Individual differences in the perception of orthonasal irritation induced by food.

Oral responsiveness to the burning/spicy sensation affects food behaviors and diet; therefore, it is reasonable to hypothesize that the variation in nasal responsiveness to irritant foods may play a role in modulating food behaviors. This study explored the variation among individuals in orthonasal irritation induced by smelling food ingredients containing irritant compounds: mustard oil (2.0, 10.0, and 100.0% v/v mustard oil in corn oil; irritant compound: allyl isothiocyanate); vinegar (3.5, 42.3, and 98.6% v/v vinegar in water; irritant compound: acetic acid); and wasabi (0.1, 0.2, and 0.4% w/w wasabi powder in water; irritant compound: allyl isothiocyanate). Sixty-eight subjects (40% males; 19-87 years) smelled the nine samples and rated their perceived intensity of odor, irritation and liking. Wide individual variation in the perception of irritation and odor intensity was found, especially at the highest concentrations. Young individuals were the most sensitive to all stimuli. No significant differences were found between males and females. Fifty-seven percent of subjects were "HYPO" and 43 percent "HYPER" responsive to irritation, respectively. Perceived irritation was positively correlated with odor intensity and tended to be negatively correlated with liking, especially in familiar stimuli. The results suggest that the variation in nasal responsiveness to irritant foods may contribute to influencing food acceptance and therefore, to modulating food behaviors.

Incorporation of Bifidobacterium sp. into powder products through a fluidized bed process for enteric targeted release.

Considering the increase in evidence regarding the benefits of probiotics on human health, there is interest in developing solid products with proper functional characteristics, such as temperature and pH stability, that can be added to oral solid dosage forms or to dairy products to release microorganisms directly at their site of action. The aim of this work was to develop a product with an enteric coat containing probiotics that is stable at room temperature and resists low pH to ensure that the probiotics are passed through the stomach and reach the colon. We obtained 2 enteric-release products based on the incorporation of Bifidobacterium sp. using commercial microcrystalline cellulose (BIP-Av) and prebiotic inulin (BIP-In) as cores. Both products had an initial concentration of approximately 1 × 108 bifidobacteria per gram (cfu/g) and showed a suitable resistance to acid; complete release from the products at a pH of 7.5 was observed at 120 min for BIP-In and 180 min for BIP-Av. The viability of bacteria in both products decreased by approximately 3 orders of magnitude. The death rate constant corresponded to 0.1143 for BIP-Av and 0.1466 for BIP-In, which means that in these storage conditions, the viability decreased slightly. Both products protected bifidobacteria for more than 2 yr, delivering a concentration of more than 1 × 105 cfu/g. Due to these characteristics, the products could be incorporated into solid pharmaceutical forms for oral administration. These products could have significant advantages over existing products on the market and provide protection for bacteria, allowing their passage through the stomach to reach the colon, and the viability of bacteria was maintained after storage at room temperature for more than 1 yr.

Formulation and evaluation of letrozole-loaded spray dried liposomes with PEs for topical application.

Letrozole (LET), an aromatase inhibitor widely used as a first-line drug for the estrogen-dependent breast cancer treatment in postmenopausal women. In this study, an attempt has been made to develop LET topical drug delivery which would be a more efficient system to treat elevated blood levels of estrogen found in breast cancer patients. The technique involves, encapsulation of the LET in phospholipids using spray dryer. The LET spray-dried powder (LT-SDP) powder was tested by Fourier transform infrared, X-RD, and differential scanning calorimetry. These studies confirm the entrapment efficiency (EE) of the system. The LT-SDP in the form dispersion was further evaluated. The confocal laser scanning microscopy (CLSM) showed spherical vesicles, the particle size, polydispersity index, and the EE was found to be 284.0 nm, 0.247, and 59.08%, respectively. LT-SDP dispersion was added into a cream base with peppermint and olive oil as natural penetration enhancers. Optimized formulation showed superior skin targeting in in vitro and in vivo studies. Cell proliferation assay and flow cytometry was carried out using human cancer cell line of breast MDA-MB-231 which showed superior anti-proliferative action and enhanced apoptosis activity of LT-SDP cream (43.9%) in comparison. The CLSM micrograph, skin irritation, and histopathology studies showed the penetration ability and inertness of the LT-SDP cream, respectively. In vivo bioavailability studies showed an almost four-fold increase in the plasma concentration (11.3 versus 4.2) while the mean residence time (81.11 versus 64.42 h) and half-life (51.01 versus 39.36 h) were reasonably higher than plain LET cream.

Investigation of the Absorption of Nanosized lamotrigine Containing Nasal Powder via the Nasal Cavity.

Nasal drug delivery has become a popular research field in the last years. This is not surprising since the nose possesses unique anatomical and physical properties. Via the nasal mucosa local, systemic, and directly central nerve systemic (CNS) effect is achievable. Powders have favorable physicochemical properties over liquid formulations. Lamotrigine (LAM) is an antiepileptic agent with a relatively mild side effect spectrum, but only available in tablet form on market. Reducing the particle size to the nano range can affect the bioavailability of pharmaceutical products. The aim of this article was to continue the work started, compare the in vitro properties of a nanonized lamotrigine containing nasal powder (nanoLAMpowder) and its physical mixture (PM) that were prepared by dry milling. Moreover, to study their trans-epithelial absorption to reach the blood and target the brain by axonal transport. Due to the dry milling technique, the particle size of LAM, their surface and also their structure changed that led to higher in vitro dissolution and permeability rate. The results of the in vivo tests showed that the axonal transport of the drug was assumable by both intranasal formulations because the drug was present in the brain within a really short time, but the LAM from the nanoLAMpowder liberated even faster.

Intake of Alpha-Linolenic Acid-Rich Perilla frutescens Leaf Powder Decreases Home Blood Pressure and Serum Oxidized Low-Density Lipoprotein in Japanese Adults.

Oxidized low-density lipoprotein (Ox-LDL) is known to be highly atherogenic. Thus, decreasing the blood levels of Ox-LDL through dietary means is an important approach to reduce cardiovascular events in high-risk individuals. In this randomized placebo-controlled human interventional trial, we aimed to evaluate whether Perilla frutescens leaf powder (PLP) ameliorates Ox-LDL and home blood pressure, along with its biological antioxidant potential. Healthy Japanese volunteers aged 30-60 years (n = 60) were randomized to PLP and placebo groups. The PLP group consumed PLP dried using a microwave under reduced pressure, and the placebo group consumed pectin fiber daily for 6 months. Home blood pressure, serum biochemical parameters, and fatty acid profiles of erythrocyte plasma membranes were analyzed. Plasma Ox-LDL levels significantly decreased in the PLP group but not in the placebo group. Mean changes in the biological antioxidant potential and alpha-linolenic acid levels in the erythrocyte plasma membrane were significantly increased in the PLP group than in the placebo group. In subjects with prehypertension (systolic blood pressure [SBP] ³ 120 mmHg), the mean reduction in morning or nocturnal SBP was significantly greater in the PLP group than in the placebo group. Thus, PLP intake may be an effective intervention to prevent cardiovascular diseases.

Development of Dry Powder Inhaler Patient Interfaces for Improved Aerosol Delivery to Children.

The objective of this study was to explore different internal flow passages in the patient interface region of a new air-jet-based dry powder inhaler (DPI) in order to minimize device and extrathoracic aerosol depositional losses using computational fluid dynamics (CFD) simulations. The best-performing flow passages were used for oral and nose-to-lung (N2L) aerosol delivery in pediatric extrathoracic airway geometries consistent with a 5-year-old child. Aerosol delivery conditions were based on a previously developed and tested air-jet DPI device and included a base flow rate of 13.3 LPM (delivered from a small ventilation bag) and an inhaled air volume of 750 mL. Initial CFD models of the system clearly established that deposition on either the back of the throat or nasal cannula bifurcation was strongly correlated with the maximum velocity exiting the flow passage. Of all designs tested, the combination of a 3D rod array and rapid expansion of the flow passage side walls was found to dramatically reduce interface and device deposition and improve lung delivery of the aerosol. For oral aerosol administration, the optimal flow passage compared with a base case reduced device, mouthpiece, and mouth-throat deposition efficiencies by factors of 8-, 3-, and 2-fold, respectively. For N2L aerosol administration, the optimal flow pathway compared with a base case reduced device, nasal cannula, and nose-throat deposition by 16-, 6-, and 1.3-fold, respectively. In conclusion, a new patient interface design including a 3D rod array and rapid expansion dramatically improved transmission efficiency of a dry powder aerosol.

Effect of different doses of lyophilized beetroot on fertility and reproductive hormones.

Infertility has recently been a common issue for which multiple medicinal as well as surgical treatments are available. Beta vulgaris commonly referred to as garden beet is one of the most utilized vegetable especially in salad dressings. The Present study was conducted to evaluate the effect of lyophilized beet root on fertility and reproductive hormones. The study was carried out in January 2017 on two different animal models. For fertility purpose albino mice of both genders weighing 20-25gm were divided into 5 pairs for each group, First group was control given distilled water, next was treated I being given beetroot 500mg/kg and last one was given 1000mg/kg beetroot. Similarly 5 pairs were made of buck and doe's weighing 1.75gm-2.5gm and labelled as Control, Treated I and Treated II and were administered distilled water, 500mg/kg and 1000mg/kg beetroot respectively. The pups were again mated after they grew up and in this way F1 generation was also observed. The kits were observed for presence of anomaly. The estrogen, progesterone and testosterone levels were evaluated at baseline, during pregnancy and post pregnancy in rabbit model. Improved fertility with no anomalies in the pups and kits were observed. The reproductive hormones were also highly significantly increased (p<0.001) as compared to baseline values. The study suggests that beetroot would be very beneficial in improving fertility and maintaining hormonal level during fertility hence it would prove to be very beneficial in maintaining pregnancy as well as treating infertility.

[The effectiveness of local application of vancomycin powder in the prevention of surgical site infections in spine surgery: a meta-analysis]. / Effektivnost' lokal'nogo primeneniya poroshka vankomitsina v profilaktike infektsii oblasti khirurgicheskogo vmeshatel'stva v spinal'noi khirurgii: metaanaliz.

OBJECTIVE: To perform a meta-analysis of studies examining the effectiveness of the local application of vancomycin powder for the prophylaxis of surgical site infections (SSIs) in spine surgery. MATERIAL AND METHODS: Retrospective cohort studies and prospective randomized clinical trials were searched for in the Pubmed, EMBASE, Cochrane Library and eLibrary databases published from 2008 to December 2018. For the resulting variables, the odds ratio and 95% confidence interval were calculated using random and fixed effects models. Estimation of the degree of heterogeneity is estimated using the coefficient I2. Statistically significant differences were considered differences p<0.05. RESULTS: The meta-analysis included 28 clinical studies that included the results of the local application of vancomycin powder in 17,469 patients after performing various spinal surgical interventions. Two publications had a prospective, randomized, controlled study design. Topical application of vancomycin powder reduces the incidence of SSIs after spine surgery (p<0.0001). The use of vancomycin powder reduces the incidence of SSIs in patients operated on with stabilizing implants (p=0.004). On the other hand, the topical application of vancomycin powder did not affect the prevalence of SSIs in respondents who were operated on without the use of stabilizing implants (p=0.12) or due to deformities of the spine (p=0.06). CONCLUSION: Topical application of vancomycin powder is highly effective in preventing the development of SSIs in patients after spinal surgical interventions.

Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children. STUDY DESIGN: In total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression. RESULTS: At baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P < .001), with no impact on stunting (37.1%-41.3% across the groups, P = .37). The micronutrient powder reduced iron deficiency by 44%-55% compared with other groups (P < .001), with no overall impact on anemia (P = .14). Micronutrient powder tended to reduce anemia by 11%-16% among children who were anemic at baseline (P = .06). CONCLUSIONS: Despite improving zinc status, preventive zinc and micronutrient powder had no impact on growth. The micronutrient powder improved iron status and tended to reduce anemia among the subset of previously anemic children. TRIAL REGISTRATION: ClinicalTrials.govNCT02428647.

Naked pDNA Inhalation Powder Composed of Hyaluronic Acid Exhibits High Gene Expression in the Lungs.

Gene therapy is a breakthrough treatment strategy against several intractable and lethal diseases that previously lacked established treatments. Viral and nonviral vectors have been studied to realize higher gene transfection efficiencies and to suppress the degradation of gene by nucleolytic enzymes in vivo. However, it is often the case that the addition of a vector results in adverse effects. In this study, we identified formulations of dry naked plasmid DNA (pDNA) powders with no vector showing significantly higher gene expression than pDNA solutions including vectors such as polyethylenimine (PEI) in the lungs of mice. We prepared the naked pDNA powders by spray-freeze-drying with various excipients. The gene expression of naked pDNA powders exceeded those of pDNA solutions containing PEI, naked pDNA solution, and reconstituted pDNA powder. Gene expression of each naked pDNA powder was dependent on the composition of excipients. Among them, the mice that were administered the pDNA powder composed of low-molecular-weight hyaluronic acid (LHA) as an excipient showed the highest gene expression. The lactate dehydrogenase activity and concentration of inflammatory cytokines in bronchoalveolar lavage fluid were comparable to those caused by ultrapure water. The results suggest that useful dry naked nucleic acid powders for inhalation could be created by optimizing the excipients, offering new insights into the development of pulmonary gene therapy.

Use of Computational Fluid Dynamics (CFD) Dispersion Parameters in the Development of a New DPI Actuated with Low Air Volumes.

PURPOSE: To determine the predictive power of computational fluid dynamics (CFD)-based dispersion parameters in the development of a new inline DPI that is actuated with low volumes of air. METHODS: Four new versions of a dose aerosolization and containment (DAC)-unit DPI were created with varying inlet and outlet orifice sizes and analyzed with results from five previous designs. A concurrent in vitro and CFD analysis was conducted to predict the emitted dose (ED; as a % of loaded dose) and aerosol mass median aerodynamic diameter (MMAD) produced by each device when actuated with 10 ml air bursts. CFD simulations of device operation were used to predict flow field and particle-based dispersion parameters. RESULTS: Comparisons of experimental and CFD results indicated that multiple flow field and particle-based dispersion parameters could be used to predict ED (minimum RMS Error = 4.9%) and MMAD (minimum RMS Error = 0.04 µm) to a high degree of accuracy. Based on experiments, the best overall device produced mean (standard deviation; SD) ED = 82.9(4.3)% and mean MMAD (SD) = 1.73(0.07)µm, which were in close agreement with the CFD predictions. CONCLUSIONS: A unique relationship was identified in the DAC-unit DPI in which reducing turbulence also reduced the MMAD.

On-Demand Manufacturing of Direct Compressible Tablets: Can Formulation Be Simplified?

PURPOSE: Oral direct compressible tablets are the most frequently used drug products. Manufacturing of tablets requires design and development of formulations, which need a number of excipients. The choice of excipients depends on the concentration, manufacturability, stability, and bioavailability of the active pharmaceutical ingredients (APIs). At MIT, we developed a miniature platform for on-demand manufacturing of direct compressible tablets. This study investigated how formulations could be simplified to use a small number of excipients for a number of different API's in which long term stability is not required. METHOD: Direct compressible tablets of five pharmaceutical drugs, Diazepam, Diphenhydramine HCl, Doxycycline Monohydrate, Ibuprofen, and Ciprofloxacin HCl, with different drug loadings, were made using direct compression in an automated small scale system.. The critical quality attributes (CQA) of the tablets were assessed for the quality standards set by the United States Pharmacopeia (USP). RESULTS: This miniature system can manufacture tablets - on-demand from crystalline API using the minimum number of excipients required for drug product performance. All drug tablets met USP quality standards after manufacturing and after 2 weeks of accelerated stability test, except for slightly lower drug release for Ibuprofen. CONCLUSIONS: On-demand tablets manufacturing where there is no need for long term stability using a flexible, miniature, automated (integrated) system will simplify pharmaceutical formulation design compared to traditional formulations. This advancement will offer substantial economic benefits by decreasing product time-to-market and enhancing quality.

Aerosol drug delivery to the lungs during nasal high flow therapy: an in vitro study.

BACKGROUND: Aerosol delivery through a nasal high flow (NHF) system is attractive for clinicians as it allows for simultaneous administration of oxygen and inhalable drugs. However, delivering a fine particle fraction (FPF, particle wt. fraction < 5.0 µm) of drugs into the lungs has been very challenging, with highest value of only 8%. Here, we aim to develop an efficient nose-to-lung delivery system capable of delivering improved quantities (FPF > 16%) of dry powder aerosols to the lungs via an NHF system. METHODS: We evaluated the FPF of spray-dried mannitol with leucine with a next generation impactor connected to a nasopharyngeal outlet of an adult nasal airway replica. In addition, we investigated the influence of different dispersion (20-30 L/min) and inspiratory (20-40 L/min) flow rates, on FPF. RESULTS: We found an FPF of 32% with dispersion flow rate at 25 L/min and inspiratory flow rate at 40 L/min. The lowest FPF (21%) obtained was at the dispersion flow rate at 30 L/min and inspiratory flow rate at 30 L/min. A higher inspiratory flow rate was generally associated with a higher FPF. The nasal cannula accounted for most loss of aerosols. CONCLUSIONS: In conclusion, delivering a third of inhalable powder to the lungs is possible in vitro through an NHF system using a low dispersion airflow and a highly dispersible powder. Our results may lay the foundation for clinical evaluation of powder aerosol delivery to the lungs during NHF therapy in humans.