The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Hiroyuki Yoshino - One of the best experts on this subject based on the ideXlab platform.
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improved nasal absorption of salmon calcitonin by powdery formulation with n acetyl l cysteine as a Mucolytic Agent
Journal of Controlled Release, 2006Co-Authors: Takahiro Matsuyama, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hiroyuki YoshinoAbstract:To establish a new formulation technology for the nasal delivery of peptide and protein drugs, we examined whether a Mucolytic Agent, N-acetyl-L-cysteine (NAC), could enhance the nasal absorption of a powder form of salmon calcitonin, a model peptide drug. We used ethylcellulose as an inert water-insoluble excipient. Various test formulations were prepared, and the effects on nasal absorbability were evaluated in rats and dogs. The powder formulation with NAC gave significant nasal absorption of SCT in both animal models, with absolute bioavailabilities of 30.0% in rats and 24.9% in dogs. Also, nasal administration of this formulation gave a quicker absorption rate than subcutaneous administration of SCT. NAC may reduce nasal fluid viscocity and improve accessibility of the drug to the epithelial membrane. The powder SCT/NAC/ethylcellulose formulation did not induce irritation or histological damage to the nasal membrane in rabbits. These results suggest that this formulation technology may be widely applicable for the nasal delivery of peptide or protein drugs.
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synergistic absorption enhancement of salmon calcitonin and reversible mucosal injury by applying a Mucolytic Agent and a non ionic surfactant
International Journal of Pharmaceutics, 2006Co-Authors: Shinya Takatsuka, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Atsushi Koguchi, Hiroyuki YoshinoAbstract:The present study investigated the intestinal absorption enhancement of salmon calcitonin (SCT) and the intestinal mucosal damage when a Mucolytic Agent and a non-ionic surfactant were administered simultaneously to rats. N-acetylcysteine (NAC) and p-t-octyl phenol polyoxyethylene-9.5 (Triton X -100, TX-100) were chosen as the model Mucolytic Agent and the non-ionic surfactant, respectively. Dosing solutions containing these Agents were administered directly into the rat jejunum, and the bioavailability of SCT up to 2 h was determined. NAC and TX-100, when they were used alone at a dose of 1 mg/head, did not show the apparent enhancement compared to the control. However, simultaneous use of NAC and TX-100 enhanced the intestinal absorption of SCT in a synergistic manner, and absolute bioavailability increased 12.5-fold compared to the control. The effect of NAC and TX-100 on SCT absorption was not dependent on their doses over the range of 0.2-2 mg/head, and the maximum effect was obtained at a dose of 1mg/head. Absorption enhancement of SCT by a combination of NAC and TX-100 was compared to those from the classical absorption enhancers. Absorption-enhancing ability of the combination of NAC and TX-100 was significantly higher than those of sodium deoxycholate, citrate, and the combination of citrate and taurocholate, and was comparable with that of the combination of citrate and taurodeoxycholate. Finally, the intestinal mucosal damage caused by the combination of NAC and TX-100 was assessed using a capsule device. Acute damage on intestinal mucosa was observed when they were exposed into rat intestine, but this morphological damage was found to be reversible. All these results suggest that simultaneous use of a Mucolytic Agent and a non-ionic surfactant would offer a potentiality for peroral delivery of peptide drugs like SCT.
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enhancement of nasal absorption of large molecular weight compounds by combination of Mucolytic Agent and nonionic surfactant
Journal of Controlled Release, 2006Co-Authors: Takahiro Matsuyama, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hiroyuki YoshinoAbstract:Abstract For improving the nasal absorption of poorly absorbable hydrophilic compounds, the suitability of a combination of a Mucolytic Agent, N-acetyl- l -cysteine (NAC), and a nonionic surfactant, polyoxyethylene (C25) lauryl ether (laureth-25), was examined. Rat studies with fluorescent isothiocyanate-labeled dextran (molecular weight ca. 4.4 kDa, FD-4) as a model hydrophilic compound revealed dramatic enhancement of nasal absorption when NAC and laureth-25 were simultaneously applied. The nasal bioavailability of FD-4 in saline solution was 8.2 ± 0.6% but increased to 40.0 ± 5.5% when 5% NAC and 5% laureth-25 were added. This synergistic enhancement could result from the Mucolytic activity of NAC in reducing mucous viscosity by which the accessibilities of FD-4 and laureth-25 to the epithelial membrane were increased. Further rat studies proved that this formulation increased nasal absorption of salmon calcitonin. Absolute bioavailability from saline solution containing 5% NAC and 1% laureth-25 was 26.8 ± 2.2%, 3.5 times that of the commercial calcitonin nasal spray Miacalcin (7.7 ± 2.1%). The potential of the new formulation to cause tissue damage in terms of hemolytic activity and liberation of phospholipid from the nasal membranes was nil or slight. The combination of NAC and laureth-25 appears suitable for use in development of nasal products for poorly absorbable drugs, especially peptide and protein drugs.
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Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of Mucolytic Agent and non-ionic surfactant
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2005Co-Authors: Shinya Takatsuka, Takahiro Morita, Yuji Horikiri, Takeo Kitazawa, Hiroyuki YoshinoAbstract:Abstract The effect of co-administration of a Mucolytic Agent with a penetration enhancer was assessed on the intestinal absorption of poorly absorbed hydrophilic compounds. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound, and N -acetylcysteine (NAC) was used as a Mucolytic Agent. Sodium caprate (C10), tartaric acid (TA), sodium taurodeoxycholate (TDC), sodium dodecyl sulfate (SDS), p - t -octyl phenol polyoxyethylene-9.5 (Triton X ® −100, TX-100) were selected as penetration enhancers with different mechanisms of action. Various dosing solutions containing a penetration enhancer in the absence or in the presence of NAC were directly administered into the exposed rat jejunum, and the bioavailability of FD-4 up to 2 h was determined. The extent of improvement by co-administration was highly dependent on the penetration enhancer species applied. The observed enhancement was thought to result from the Mucolytic activity of NAC, which can reduce the mucus viscosity and facilitate the penetration of FD-4 to mucosal membrane. Among the combinations tested, the simultaneous administration of NAC and TX-100 provided the highest enhancement (22.5-fold) of intestinal FD-4 absorption compared to the control. Although the detailed mechanism for the observed drastic improvement is unclear, one possible reason was thought to be due to the improved diffusivity of TX-100 micellar system in the mucus layer. All these results suggest that the combination of a Mucolytic Agent and a non-ionic surfactant may have potential as an enhancing system for peroral delivery of poorly absorbed hydrophilic compounds like protein and peptide drugs.
Maurizio Moretti - One of the best experts on this subject based on the ideXlab platform.
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erdosteine reduces inflammation and time to first exacerbation postdischarge in hospitalized patients with aecopd
International Journal of Chronic Obstructive Pulmonary Disease, 2015Co-Authors: Maurizio Moretti, Stefano FagnaniAbstract:Purpose Mucolytics can improve disease outcome in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The objectives of this study were to investigate the effects of erdosteine (ER), a Mucolytic Agent with antioxidant activity, on systemic inflammation, symptoms, recurrence of exacerbation, and time to first exacerbation postdischarge in hospitalized patients with AECOPD.
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erdosteine its relevance in copd treatment
Expert Opinion on Drug Metabolism & Toxicology, 2009Co-Authors: Maurizio MorettiAbstract:Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by airflow limitation, which is largely irreversible; the oxidant/antioxidant imbalance is important in the pathogenesis of this condition. Obiective: To show that administration of erdosteine, a Mucolytic Agent with a prevalent antioxidant activity, could play a beneficial role in COPD. Methods: To review the experimental and clinical trials on erdosteine in COPD and chronic bronchitis. Results: Erdosteine is a thiol Agent with a multifactorial mechanism of action, namely: Mucolytic, antibacterial, antioxidant and anti-inflammatory activity. In the acute exacerbation of chronic bronchitis/COPD, addition of erdosteine 300 mg twice a day for 7 – 10 days to standard treatment improves the symptoms and reduces the time of disease. In clinically stable COPD, long-term treatment is associated with a reduction in acute exacerbation and hospitalization rate and a significant improvement of quality of life. Erdostein...
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pharmacology and clinical efficacy of erdosteine in chronic obstructive pulmonary disease
Expert Review of Respiratory Medicine, 2007Co-Authors: Maurizio MorettiAbstract:Erdosteine is a multimechanism, Mucolytic Agent that decreases the sputum viscoelastic properties and bacterial adhesion to the cell membrane, endowed with bronchial anti-inflammatory activity and a scavenging effect on free oxidant radicals. Erdosteine is a prodrug and metabolite I is the active metabolite of erdosteine owing to its free thiol group. In acute infective exacerbation of chronic bronchitis or chronic obstructive pulmonary disease (COPD), adding erdosteine to standard treatment significantly modified the outcome by improving the symptoms and reducing the length of disease. Furthermore, erdosteine has shown a synergism with antibiotic therapy. In stable COPD patients, long-term treatment with erdosteine had a protective effect against exacerbations by reducing the rate of exacerbations and hospitalizations in the study period. A total of 8 months of treatment with erdosteine significantly improved the patients’ health status and preserved lung function. Erdosteine has a scavenging effect on f...
I A Murdoch - One of the best experts on this subject based on the ideXlab platform.
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intratracheal recombinant human deoxyribonuclease in acute life threatening asthma refractory to conventional treatment
BJA: British Journal of Anaesthesia, 2000Co-Authors: Alpesh Patel, E Harrison, A Durward, I A MurdochAbstract:Recombinant human deoxyribonuclease (rhDNase) is a Mucolytic Agent used to relieve peripheral airway obstruction in patients with cystic fibrosis. We report dramatic sustained improvement following the intratracheal administration of rhDNase to a 3-yr-old boy with acute life-threatening asthma in whom 48 h of aggressive therapy had failed.
Takahiro Matsuyama - One of the best experts on this subject based on the ideXlab platform.
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improved nasal absorption of salmon calcitonin by powdery formulation with n acetyl l cysteine as a Mucolytic Agent
Journal of Controlled Release, 2006Co-Authors: Takahiro Matsuyama, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hiroyuki YoshinoAbstract:To establish a new formulation technology for the nasal delivery of peptide and protein drugs, we examined whether a Mucolytic Agent, N-acetyl-L-cysteine (NAC), could enhance the nasal absorption of a powder form of salmon calcitonin, a model peptide drug. We used ethylcellulose as an inert water-insoluble excipient. Various test formulations were prepared, and the effects on nasal absorbability were evaluated in rats and dogs. The powder formulation with NAC gave significant nasal absorption of SCT in both animal models, with absolute bioavailabilities of 30.0% in rats and 24.9% in dogs. Also, nasal administration of this formulation gave a quicker absorption rate than subcutaneous administration of SCT. NAC may reduce nasal fluid viscocity and improve accessibility of the drug to the epithelial membrane. The powder SCT/NAC/ethylcellulose formulation did not induce irritation or histological damage to the nasal membrane in rabbits. These results suggest that this formulation technology may be widely applicable for the nasal delivery of peptide or protein drugs.
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enhancement of nasal absorption of large molecular weight compounds by combination of Mucolytic Agent and nonionic surfactant
Journal of Controlled Release, 2006Co-Authors: Takahiro Matsuyama, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hiroyuki YoshinoAbstract:Abstract For improving the nasal absorption of poorly absorbable hydrophilic compounds, the suitability of a combination of a Mucolytic Agent, N-acetyl- l -cysteine (NAC), and a nonionic surfactant, polyoxyethylene (C25) lauryl ether (laureth-25), was examined. Rat studies with fluorescent isothiocyanate-labeled dextran (molecular weight ca. 4.4 kDa, FD-4) as a model hydrophilic compound revealed dramatic enhancement of nasal absorption when NAC and laureth-25 were simultaneously applied. The nasal bioavailability of FD-4 in saline solution was 8.2 ± 0.6% but increased to 40.0 ± 5.5% when 5% NAC and 5% laureth-25 were added. This synergistic enhancement could result from the Mucolytic activity of NAC in reducing mucous viscosity by which the accessibilities of FD-4 and laureth-25 to the epithelial membrane were increased. Further rat studies proved that this formulation increased nasal absorption of salmon calcitonin. Absolute bioavailability from saline solution containing 5% NAC and 1% laureth-25 was 26.8 ± 2.2%, 3.5 times that of the commercial calcitonin nasal spray Miacalcin (7.7 ± 2.1%). The potential of the new formulation to cause tissue damage in terms of hemolytic activity and liberation of phospholipid from the nasal membranes was nil or slight. The combination of NAC and laureth-25 appears suitable for use in development of nasal products for poorly absorbable drugs, especially peptide and protein drugs.
Takahiro Morita - One of the best experts on this subject based on the ideXlab platform.
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influence of various combinations of Mucolytic Agent and non ionic surfactant on intestinal absorption of poorly absorbed hydrophilic compounds
International Journal of Pharmaceutics, 2008Co-Authors: Shinya Takatsuka, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hideo SajiAbstract:Abstract The absorption enhancing effects of various combinations of a Mucolytic Agent and a non-ionic surfactant on the intestinal absorption of poorly absorbed hydrophilic compounds were examined. Fluorescein isothiocyanate-labeled dextran with an average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound. Cysteine derivatives such as N -acetylcysteine (NAC), S -carboxymethylcysteine (SCMC), S -ethylcysteine (SEC), and S -methylcysteine (SMC) were selected as Mucolytic Agents. A homogeneous series of single chain polyoxyethylene alkyl ethers were employed as non-ionic surfactants. Various dosing solutions were administered into rat jejunum, and the bioavailability of FD-4 was determined. Unlike NAC, the Agents such as SCMC, SEC, and SMC, which do not possess a free thiol group, did not show any apparent enhancement of intestinal FD-4 absorption, when they were co-administered with p - t -octyl phenol polyoxyethylene-9.5 (Triton ® X-100, TX-100). In addition, the absorption enhancement was dependent on the kinds of polyoxyethylene alkyl ethers used, when used in combination with NAC. For a constant alkyl chain of 12 with a varying polyoxyethylene (POE) chain length, the surfactant with a short to medium POE chain length such as lauryl poly (4.2) oxyethylene ether (BL-4.2) and lauryl poly (9) oxyethylene ether (BL-9) were effective. In addition, for a constant alkyl chain of 18 with a varying POE chain length, the surfactants with a longer POE chain length such as oleyl poly (15) oxyethylene ether (BO-15) and stearyl poly (20) oxyethylene ether (BS-20) showed the effective enhancement. All these results suggest that a Mucolytic Agent not possessing a free thiol group is not effective for enhancing the intestinal absorption of poorly absorbed hydrophilic compounds. Also, they indicate that the combination of a Mucolytic Agent possessing a free thiol group and a non-ionic surfactant either with a short to medium POE chain length and a medium alkyl chain length, or with a longer POE chain length and a longer alkyl chain length shows the effective enhancement. This fundamental information might be useful for finding the optimal combination.
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Influence of various combinations of Mucolytic Agent and non-ionic surfactant on intestinal absorption of poorly absorbed hydrophilic compounds.
International journal of pharmaceutics, 2007Co-Authors: Shinya Takatsuka, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hideo SajiAbstract:The absorption enhancing effects of various combinations of a Mucolytic Agent and a non-ionic surfactant on the intestinal absorption of poorly absorbed hydrophilic compounds were examined. Fluorescein isothiocyanate-labeled dextran with an average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound. Cysteine derivatives such as N-acetylcysteine (NAC), S-carboxymethylcysteine (SCMC), S-ethylcysteine (SEC), and S-methylcysteine (SMC) were selected as Mucolytic Agents. A homogeneous series of single chain polyoxyethylene alkyl ethers were employed as non-ionic surfactants. Various dosing solutions were administered into rat jejunum, and the bioavailability of FD-4 was determined. Unlike NAC, the Agents such as SCMC, SEC, and SMC, which do not possess a free thiol group, did not show any apparent enhancement of intestinal FD-4 absorption, when they were co-administered with p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100). In addition, the absorption enhancement was dependent on the kinds of polyoxyethylene alkyl ethers used, when used in combination with NAC. For a constant alkyl chain of 12 with a varying polyoxyethylene (POE) chain length, the surfactant with a short to medium POE chain length such as lauryl poly (4.2) oxyethylene ether (BL-4.2) and lauryl poly (9) oxyethylene ether (BL-9) were effective. In addition, for a constant alkyl chain of 18 with a varying POE chain length, the surfactants with a longer POE chain length such as oleyl poly (15) oxyethylene ether (BO-15) and stearyl poly (20) oxyethylene ether (BS-20) showed the effective enhancement. All these results suggest that a Mucolytic Agent not possessing a free thiol group is not effective for enhancing the intestinal absorption of poorly absorbed hydrophilic compounds. Also, they indicate that the combination of a Mucolytic Agent possessing a free thiol group and a non-ionic surfactant either with a short to medium POE chain length and a medium alkyl chain length, or with a longer POE chain length and a longer alkyl chain length shows the effective enhancement. This fundamental information might be useful for finding the optimal combination.
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absorption enhancement of poorly absorbed hydrophilic compounds from various mucosal sites by combination of Mucolytic Agent and non ionic surfactant
International Journal of Pharmaceutics, 2007Co-Authors: Shinya Takatsuka, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hideo SajiAbstract:Absorption enhancement of poorly absorbed hydrophilic compounds from various mucosal sites by co-administration of a Mucolytic Agent and a non-ionic surfactant was examined in rats. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4 kDa (FD-4), and salmon calcitonin (SCT) were used as model compounds. N-acetylcysteine (NAC) and p-t-octyl phenol polyoxyethylene-9.5 (Triton X®-100, TX-100) were selected as a Mucolytic Agent and a non-ionic surfactant, respectively. Dosing solutions containing these Agents were administered into various mucosal sites including the nose, the lung and the large intestine, and the bioavailabilities were determined. The combination of 5% NAC and 5% TX-100 significantly enhanced the nasal, the pulmonary and the large intestinal absorption of FD-4 compared to the control, and the enhancement ratios relative to the control were 7.2-, 2.8- and 4.5-fold, respectively. The different enhancement ratio among the administration sites explored indicates that the absorption enhancing effect of the combination of NAC and TX-100 is site-dependent. This combination also improved the nasal and the pulmonary absorption of SCT, and the enhancement ratios relative to the control were 6.1- and 8.1-fold, respectively. All these results suggest that the combination strategy of a Mucolytic Agent and a non-ionic surfactant may be widely applicable to various mucosal deliveries of poorly absorbed hydrophilic compounds.
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improved nasal absorption of salmon calcitonin by powdery formulation with n acetyl l cysteine as a Mucolytic Agent
Journal of Controlled Release, 2006Co-Authors: Takahiro Matsuyama, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Hiroyuki YoshinoAbstract:To establish a new formulation technology for the nasal delivery of peptide and protein drugs, we examined whether a Mucolytic Agent, N-acetyl-L-cysteine (NAC), could enhance the nasal absorption of a powder form of salmon calcitonin, a model peptide drug. We used ethylcellulose as an inert water-insoluble excipient. Various test formulations were prepared, and the effects on nasal absorbability were evaluated in rats and dogs. The powder formulation with NAC gave significant nasal absorption of SCT in both animal models, with absolute bioavailabilities of 30.0% in rats and 24.9% in dogs. Also, nasal administration of this formulation gave a quicker absorption rate than subcutaneous administration of SCT. NAC may reduce nasal fluid viscocity and improve accessibility of the drug to the epithelial membrane. The powder SCT/NAC/ethylcellulose formulation did not induce irritation or histological damage to the nasal membrane in rabbits. These results suggest that this formulation technology may be widely applicable for the nasal delivery of peptide or protein drugs.
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synergistic absorption enhancement of salmon calcitonin and reversible mucosal injury by applying a Mucolytic Agent and a non ionic surfactant
International Journal of Pharmaceutics, 2006Co-Authors: Shinya Takatsuka, Takahiro Morita, Yuji Horikiri, Hiroshi Yamahara, Atsushi Koguchi, Hiroyuki YoshinoAbstract:The present study investigated the intestinal absorption enhancement of salmon calcitonin (SCT) and the intestinal mucosal damage when a Mucolytic Agent and a non-ionic surfactant were administered simultaneously to rats. N-acetylcysteine (NAC) and p-t-octyl phenol polyoxyethylene-9.5 (Triton X -100, TX-100) were chosen as the model Mucolytic Agent and the non-ionic surfactant, respectively. Dosing solutions containing these Agents were administered directly into the rat jejunum, and the bioavailability of SCT up to 2 h was determined. NAC and TX-100, when they were used alone at a dose of 1 mg/head, did not show the apparent enhancement compared to the control. However, simultaneous use of NAC and TX-100 enhanced the intestinal absorption of SCT in a synergistic manner, and absolute bioavailability increased 12.5-fold compared to the control. The effect of NAC and TX-100 on SCT absorption was not dependent on their doses over the range of 0.2-2 mg/head, and the maximum effect was obtained at a dose of 1mg/head. Absorption enhancement of SCT by a combination of NAC and TX-100 was compared to those from the classical absorption enhancers. Absorption-enhancing ability of the combination of NAC and TX-100 was significantly higher than those of sodium deoxycholate, citrate, and the combination of citrate and taurocholate, and was comparable with that of the combination of citrate and taurodeoxycholate. Finally, the intestinal mucosal damage caused by the combination of NAC and TX-100 was assessed using a capsule device. Acute damage on intestinal mucosa was observed when they were exposed into rat intestine, but this morphological damage was found to be reversible. All these results suggest that simultaneous use of a Mucolytic Agent and a non-ionic surfactant would offer a potentiality for peroral delivery of peptide drugs like SCT.