scholarly journals Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 427
Author(s):  
Priya Muralidharan ◽  
Maria F. Acosta ◽  
Alexan I. Gomez ◽  
Carissa Grijalva ◽  
Haiyang Tang ◽  
...  
Keyword(s):  
Human Lung ◽  
Antioxidant Properties ◽  
Dry Powder Inhaler ◽  
Chinese Herbs ◽  
Dry Powder ◽  
Comprehensive Characterization ◽  
Spray Dried

This is the first study reporting on the design and development innovative inhaled formulations of the novel natural product antioxidant therapeutic, tetramethylpyrazine (TMP), also known as ligustrazine. TMP is obtained from Chinese herbs belonging to the class of Ligusticum. It is known to have antioxidant properties. It can act as a Nrf2/ARE activator and a Rho/ROCK inhibitor. The present study reports for the first time on the comprehensive characterization of raw TMP (non-spray dried) and spray dried TMP in a systematic manner using thermal analysis, electron microscopy, optical microscopy, and Raman spectroscopy. The in vitro aerosol dispersion performance of spray dried TMP was tested using three different FDA-approved unit-dose capsule-based human dry powder inhaler devices. In vitro human cellular studies were conducted on pulmonary cells from different regions of the human lung to examine the biocompatibility and non-cytotoxicity of TMP. Furthermore, the efficacy of inhaled TMP as both liquid and dry powder inhalation aerosols was tested in vivo using the monocrotaline (MCT)-induced PH rat model.

In Vitro and In Vivo Performance of Novel Spray Dried Andrographolide Loaded Scleroglucan Based Formulation for Dry Powder Inhaler

2017 ◽  
Vol 14 (7) ◽  
Author(s):  
Ashwin Jagannath Mali ◽  
Chellampillai Bothiraja ◽  
Ravindra Nandlal Purohit ◽  
Atmaram Pandurang Pawar
Keyword(s):  
Dry Powder Inhaler ◽  
Dry Powder ◽  
Spray Dried

Nano-Liposomal Dry Powder Inhaler of Amiloride Hydrochloride

2006 ◽  
Vol 6 (9) ◽  
pp. 3001-3009 ◽  
Author(s):  
Mahavir Bhupal Chougule ◽  
Bijay Kumar Padhi ◽  
Ambikanandan Misra
Keyword(s):  
Cystic Fibrosis ◽  
Drug Release ◽  
Phosphate Buffer ◽  
Dry Powder Inhaler ◽  
Dry Powder ◽  
Phosphate Buffer Saline ◽  
Amiloride Hydrochloride ◽  
Spray Dried

The purpose of this study was to encapsulate Amiloride Hydrochloride into nano-liposomes, incorporate it into dry powder inhaler, and to provide prolonged effective concentration in airways to enhance mucociliary clearance and prevent secondary infection in cystic fibrosis. Liposomes were prepared by thin film hydration technique and then dispersion was passed through high pressure homogenizer to achieve size of nanometer range. Nano-liposomes were separated by centrifugation and were characterized. They were dispersed in phosphate buffer saline pH 7.4 containing carriers (lactose/sucrose/mannitol), and glycine as anti-adherent. The resultant dispersion was spray dried. The spray dried powders were characterized and in vitro drug release studies were performed using phosphate buffer saline pH 7.4. in vitro and in vivo drug pulmonary deposition was carried out using Andersen Cascade Impactor and by estimating drug in bronchial alveolar lavage and lung homogenate after intratracheal instillation in rats respectively. Nano-liposomes were found to have mean volume diameter of 198 ± 15 nm, and 57% ± 1.9% of drug entrapment. Mannitol based formulation was found to have low density, good flowability, particle size of 6.7 ± 0.6 μm determined by Malvern MasterSizer, maximum fine particle fraction of 67.6 ± 0.6%, mean mass aerodynamic diameter 2.3 ± 0.1 μm, and geometric standard deviation 2.4 ± 0.1. Developed formulations were found to have prolonged drug release following Higuchi's Controlled Release model and in vivo studies showed maximal retention time of drug of 12 hrs within the lungs and slow clearance from the lungs. This study provides a practical approach for direct lung delivery of Amiloride Hydrochloride encapsulated in liposomes for controlled and prolonged retention at the site of action from dry powder inhaler. It can provide a promising alternative to the presently available nebulizers in terms of prolonged pharmacological effect, reducing systemic side effects such as potassium retention due to rapid clearance of the drug from lungs in patients suffering from cystic fibrosis.

Comprehensive characterization of the in vitro and in vivo metabolites of limonin in human samples using LC-Q-TOF/MS

2017 ◽  
Vol 1068-1069 ◽  
pp. 226-232 ◽  
Author(s):  
Shijia Liu ◽  
Peidong Chen ◽  
Nongshan Zhang ◽  
Luning Sun ◽  
Guoliang Dai ◽  
...  
Keyword(s):  
Human Samples ◽  
Comprehensive Characterization ◽  
Tof Ms

scholarly journals Citrus limon from Tunisia: Phytochemical and Physicochemical Properties and Biological Activities

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Mohamed Makni ◽  
Raoua Jemai ◽  
Walid Kriaa ◽  
Yassine Chtourou ◽  
Hamadi Fetoui
Keyword(s):  
Biological Activities ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Citrus Limon ◽  
Strand Breakage ◽  
Antibacterial And Antioxidant Activity

Natural plant extracts contain a variety of phenolic compounds which are assigned various biological activities. Our work aims to make a quantitative and qualitative characterization of the Zest (ZL) and the Flesh (FL) of lemon (Citrus limon), to valorize the pharmacological uses of lemon, by evaluating in vitro activities (DPPH, free radical scavenging and reducing power). The antibacterial, antifungal, and antiproliferative activities were sought in the ability of Citrus limon extracts to protect DNA and protein. We found that the ZL contains high amounts of phenolics responsible for the important antioxidant properties of the extract. However, the FL is richer in flavonoids than the ZL. The FL extract was also found to be more effective than the ZL in protecting plasmid DNA against the strand breakage induced by hydroxyl radicals. We also concluded that the FL extract exhibited potent antibacterial activity unlike ZL. Analysis by LC/MS-MS identified 6 compounds (Caffeoyl N-Tryptophan, Hydroxycinnamoyl-Oglucoside acid, Vicenin 2, Eriocitrin, Kaempferol-3-O- rutinoside, and Quercetin-3-rutinoside). These preliminary results showed that Citrus limon has antibacterial and antioxidant activity in vitro. It would be interesting to conduct further studies to evaluate the in vivo potential in an animal model.

scholarly journals Understanding Carrier Performance in Low-Dose Dry Powder Inhalation: An In Vitro–In Silico Approach

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 297
Author(s):  
Joana T. Pinto ◽  
Inês Cachola ◽  
João F. Pinto ◽  
Amrit Paudel
Keyword(s):  
Particle Size ◽  
In Silico ◽  
Low Dose ◽  
Drug Product ◽  
Dry Powder Inhaler ◽  
Dry Powder ◽  
Bulk Properties ◽  
Pbpk Models

The use of physiologically based pharmacokinetic (PBPK) models to support drug product development has become increasingly popular. The in vitro characterization of the materials of the formulation provides valuable descriptors for the in silico prediction of the drug’s pharmacokinetic profile. Thus, the application of an in vitro–in silico framework can be decisive towards the prediction of the in vivo performance of a new medicine. By applying such an approach, this work aimed to derive mechanistic based insights into the potential impact of carrier particles and powder bulk properties on the in vivo performance of a lactose-based dry powder inhaler (DPI). For this, a PBPK model was developed using salbutamol sulphate (SS) as a model drug and the in vitro performance of its low-dose blends (2% w/w) with different types of lactose particles was investigated using different DPI types (capsule versus reservoir) at distinct airflows. Likewise, the influence of various carrier’s particle and bulk properties, device type and airflow were investigated in silico. Results showed that for the capsule-based device, low-dose blends of SS had a better performance, when smaller carrier particles (Dv0.5 ≈ 50 μm) with about 10% of fines were used. This resulted in a better predicted bioavailability of the drug for all the tested airflows. For the reservoir type DPI, the mean particle size (Dv0.5) was identified as the critical parameter impacting performance. Shear cell and air permeability or compressibility measurements, particle size distribution by pressure titration and the tensile strength of the selected lactose carrier powders were found useful to generate descriptors that could anticipate the potential in vivo performance of the tested DPI blends.

Sign in / Sign up

Export Citation Format

Share Document