Development of High Dose Oseltamivir Phosphate Dry Powder for Inhalation Therapy in Viral Pneumonia

Oseltamivir phosphate (OP) is an antiviral drug available only as oral therapy for the treatment of influenza and as a potential treatment option when in combination with other medication in the fight against the corona virus disease (COVID-19) pneumonia. In this study, OP was formulated as a dry powder for inhalation, which allows drug targeting to the site of action and potentially reduces the dose, aiming a more efficient therapy. Binary formulations were based on micronized excipient particles acting like diluents, which were blended with the drug OP. Different excipient types, excipient ratios, and excipient size distributions were prepared and examined. To investigate the feasibility of delivering high doses of OP in a single dose, 1:1, 1:3, and 3:1 drug/diluent blending ratios have been prepared. Subsequently, the aerosolization performance was evaluated for all prepared formulations by cascade impaction using a novel medium-resistance capsule-based inhaler (UNI-Haler). Formulations with micronized trehalose showed relatively excellent aerosolization performance with highest fine-particle doses in comparison to examined lactose, mannitol, and glucose under similar conditions. Focusing on the trehalose-based dry-powder inhalers’ (DPIs) formulations, a physicochemical characterization of extra micronized grade trehalose in relation to the achieved performance in dispersing OP was performed. Additionally, an early indication of inhaled OP safety on lung cells was noted by the viability MTT assay utilizing Calu-3 cells.

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The Development of a Novel High-Dose Pressurized Aerosol Dry-Powder Device (PADD) for the Delivery of Pumactant for Inhalation Therapy

Journal of Aerosol Medicine ◽

10.1089/0894268041457219 ◽

2004 ◽

Vol 17 (2) ◽

pp. 123-128 ◽

Cited By ~ 18

Author(s):

Paul M. Young ◽

Jim Thompson ◽

Derek Woodcock ◽

Mo Aydin ◽

Robert Price

Keyword(s):

Inhalation Therapy ◽

High Dose ◽

Dry Powder

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Preparation and physicochemical characterization of spray-dried and jet-milled microparticles containing bosentan hydrate for dry powder inhalation aerosols

Drug Design Development and Therapy ◽

10.2147/dddt.s120356 ◽

2016 ◽

Vol Volume 10 ◽

pp. 4017-4030 ◽

Cited By ~ 11

Author(s):

Hyo-Jung Lee ◽

Ji-Hyun Kang ◽

Hong-Goo Lee ◽

Dong-Wook Kim ◽

Yun-Seok Rhee ◽

...

Keyword(s):

Physicochemical Characterization ◽

Dry Powder Inhalation ◽

Dry Powder ◽

Spray Dried

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Favipiravir at high doses has potent antiviral activity in SARS-CoV-2−infected hamsters, whereas hydroxychloroquine lacks activity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2014441117 ◽

2020 ◽

Vol 117 (43) ◽

pp. 26955-26965 ◽

Cited By ~ 11

Author(s):

Suzanne J. F. Kaptein ◽

Sofie Jacobs ◽

Lana Langendries ◽

Laura Seldeslachts ◽

Sebastiaan ter Horst ◽

...

Keyword(s):

Antiviral Drug ◽

Virus Transmission ◽

Small Animal ◽

Antiviral Effect ◽

Viral Disease ◽

Scientific Basis ◽

Infection Model ◽

High Dose ◽

High Doses

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2−infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects.

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Scanning Probe Microscopy for Surface Roughness Characterization of Lactose Carriers Used in Dry Powder Inhalation Therapy

Journal of Scanning Probe Microscopy ◽

10.1166/jspm.2007.004 ◽

2007 ◽

Vol 2 (1) ◽

pp. 5-9 ◽

Cited By ~ 2

Author(s):

A. D. Karande ◽

Q. Zhou ◽

L. W. Chan ◽

P. W. S. Heng ◽

C. V. Liew

Keyword(s):

Surface Roughness ◽

Scanning Probe Microscopy ◽

Scanning Probe ◽

Inhalation Therapy ◽

Dry Powder Inhalation ◽

Dry Powder ◽

Probe Microscopy

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Study of the Potential Employment of Malvaceae Species in Composites Materials

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.668.75 ◽

2015 ◽

Vol 668 ◽

pp. 75-85

Author(s):

Bárbara Maria Gama Guimarães ◽

Diana Cayuela Marín ◽

Welton Fernando Zonatti ◽

Waldir Mantovani ◽

Cátia Relvas ◽

...

Keyword(s):

Textile Industry ◽

Rupture Strength ◽

Physicochemical Characterization ◽

Scanning Calorimetry ◽

Vegetal Fibers ◽

Composites Materials ◽

Medium Resistance ◽

Sida Cordifolia ◽

Malvastrum Coromandelianum

The employ of vegetal fibers for textiles and composites represents a great potential in economic and social sustainable development. Some Malvaceae species are considered tropical cosmopolitans, such as from Sida genus. Several species of this genus provide excellent textile bast fibers, which are very similar in qualities to the jute textile fiber. The objective of the present study is present the physicochemical characterization of six Brazilian vegetal fibers: Sida rhombifolia L.; Sida carpinifolia L. f.; Sidastrum paniculatum (L.) Fryxell; Sida cordifolia L.; Malvastrum coromandelianum (L.) Gurck; Wissadula subpeltata (Kuntze) R.E.Fries. Respectively the two first species are from Brazilian Atlantic Forest biome and the four remaining from Brazilian Cerrado biome, despite of present in other regions of the planet. The stems of these species were retted in water at 37oC for 20 days. The fibers were tested in order to determine tensile rupture strength, tenacity, elongation, Young’s modulus, cross microscopic structure, Scanning Electronic Microscopy (SEM), regain, combustion, acid, alkali, organic solvent and cellulase effects, pH of the aqueous extract, Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). The obtained values were compared with those from fibers of recognized applicability in the textile industry including hemp. The results are promising in terms of their employment in thermoset and thermoplastic medium resistance composites.

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The Effect of High Dose Vitamin C (ascorbic acid) on Proinflammatory Cytokines in COVID-19

Medical and Health Science Journal ◽

10.33086/mhsj.v5i1.1884 ◽

2021 ◽

Vol 5 (1) ◽

pp. 46-50

Author(s):

MD Ayu Mira Cyntia Dewi

Keyword(s):

Free Radicals ◽

Vitamin C ◽

Proinflammatory Cytokines ◽

Viral Infections ◽

Antiviral Drug ◽

The Body ◽

High Dose ◽

Literature Study ◽

Inflammatory Reactions ◽

High Doses

Background: COVID-19 is a new pandemic that has claimed many lives in many countries. This pandemic was caused by the SARSCoV2. Until now, there is no specific antiviral drug or vaccine against Covid-19 for potential therapy in humans. This virus can cause cytokine storms which can worsen symptoms in sufferers due to an imbalance between increased oxidant production and available antioxidants. Vitamin C is an important antioxidant that protects the body from various bad effects of free radicals. At high concentrations vitamin C plays an important role in immunomodulation. This study was conducted to determine the effect of high doses of vitamin C on levels of pro-inflammatory cytokines in Covid-19. Method: This research type is literature study. The population in this study were journals about Covid-19, vitamin C, antioxidants and free radicals, inflammatory reactions due to viral infections with samples taken from indexed journals published from 2015 to 2020. There are also clinical trials of high doses of vitamin C against inflammation in Covid-19 from these journals. Results: The results of the study in a clinical trial conducted on 54 patients enrolled in 3 hospitals given a 1: 1 ratio for high-dose intravenous vitamin C (HDIVC) or placebo administration. The HDIVC group received 12 g of vitamin C / 50 ml every 12 hours for 7 days at a rate of 12 ml / hour, and the placebo group received bacteriostatic water for injection in the same way. HDIVC administration showed a reduction in inflammatory markers compared to placebo. Conclusion: The conclusion of this study shows that high doses of vitamin C play a role in reducing levels of proinflammatory cytokines.

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Opioid Disposition in Human Sweat after Controlled Oral Codeine Administration

Clinical Chemistry ◽

10.1373/clinchem.2006.067983 ◽

2006 ◽

Vol 52 (8) ◽

pp. 1539-1545 ◽

Cited By ~ 26

Author(s):

Eugene W Schwilke ◽

Allan J Barnes ◽

Sherri L Kacinko ◽

Edward J Cone ◽

Eric T Moolchan ◽

...

Keyword(s):

Drug Testing ◽

Solid Phase ◽

Gas Chromatography Mass Spectrometry ◽

High Dose ◽

Opioid Use ◽

Complex Processes ◽

Sweat Testing ◽

High Doses ◽

Sweat Tests

Abstract Background: Characterization of opioid excretion in sweat is important for accurate interpretation of sweat tests in drug treatment, criminal justice, and workplace drug testing programs. Methods: Participants (n = 20) received placebo, 3 low (60 mg/70 kg) or 3 high (120 mg/70 kg) codeine sulfate doses (used as a model for opioid excretion) within 1 week. Codeine and metabolites in sweat were collected with PharmChek® Sweat Patches; hourly patches were applied for 1 to 15 h (n = 775) and weekly patches for 7 days (n = 118). Patches were analyzed by solid-phase extraction and gas chromatography–mass spectrometry for codeine, norcodeine, morphine, normorphine, and 6-acetylmorphine. Limits of quantification were 2.5 ng/patch (codeine and morphine) and 5 ng/patch (other analytes). Results: Codeine was the only analyte identified in 12.6% of hourly patches and 83.3% of weekly sweat patches worn during dosing. Weekly patch concentrations (SD) were 38.6 (59.9) ng/patch [median (range), 15.9 (0–225.1) ng/patch] for low and 34.1 (32.7) ng/patch [24.0 (0–96.2) ng/patch] for high codeine doses. Codeine detected 1 week after dosing was 4.6 (5.3) ng/patch [median (range), 4.0 (0–17.1) ng/patch; n = 11] after low and 7.7 (7.1) ng/patch [6.9 (0–20.5) ng/patch; n = 10] after high doses. In total, 2.6% of hourly, 38.5% of low-dose, and 45.5% of high-dose weekly patches contained codeine at the proposed Substance Abuse and Mental Health Services Administration cutoff. Conclusions: Codeine was the only analyte detected, at highly variable concentrations, up to 2 weeks after dosing. These results are consistent, considering the complex processes of codeine deposition in sweat. Sweat testing is a useful alternative technique for qualitative monitoring of opioid use.

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