Influence of fine lactose and magnesium stearate on low dose dry powder inhaler formulations

2008 ◽  
Vol 348 (1-2) ◽  
pp. 10-17 ◽  
Author(s):  
R GUCHARDI ◽  
M FREI ◽  
E JOHN ◽  
J KAERGER
Keyword(s):  
Low Dose ◽  
Dry Powder Inhaler ◽  
Magnesium Stearate ◽  
Dry Powder

scholarly journals Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249683
Author(s):  
Md Abdur Rashid ◽  
Saiqa Muneer ◽  
Tony Wang ◽  
Yahya Alhamhoom ◽  
Llew Rintoul ◽  
...  
Keyword(s):  
Low Dose ◽  
Structural Integrity ◽  
Dry Powder Inhaler ◽  
Pulmonary Delivery ◽  
Magnesium Stearate ◽  
Hplc Method ◽  
Dry Powder ◽  
Scanning Calorimetry ◽  
X Ray

This study aims at developing and characterizing the puerarin dry powder inhaler (DPI) formulations for pulmonary delivery. The inhalable particles size (<2 μm) was accomplished by micronization and its morphology was examined by scanning electron microscopy (SEM). The puerarin-excipient interaction in powder mixtures was analyzed by using Fourier transform infrared spectroscopy (FTIR), Raman confocal microscopy, X-Ray powder Diffraction (XRD), and differential scanning calorimetry (DSC) methods. Using a Twin stage impinger (TSI), the in-vitro aerosolization of the powder formulations was carried out at a flow rate of 60 L/min and the drug was quantified by employing a validated HPLC method. No significant interactions between the drug and the excipients were observed in the powder formulations. The fine particle fraction (FPF) of the drug alone was 4.2% which has increased five to six-fold for the formulations with aerosolization enhancers. Formulation containing lactose as large carriers produced 32.7% FPF, which further increased with the addition of dispersibility enhancers, leucine and magnesium stearate (40.8% and 41.2%, respectively). The Raman and FTIR techniques are very useful tool for understanding structural integrity and stability of the puerarin in the powder formulations. The puerarin was found to be compatible with the excipients used and the developed DPI formulation may be considered as an efficient formulation for pulmonary delivery for the management of various diseases at a very low dose.

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.

scholarly journals Excipient Interactions in Glucagon Dry Powder Inhaler Formulation for Pulmonary Delivery

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 207 ◽  
Author(s):  
Md Abdur Rashid ◽  
Amged Awad Elgied ◽  
Yahya Alhamhoom ◽  
Enoch Chan ◽  
Llew Rintoul ◽  
...  
Keyword(s):  
Dry Powder Inhaler ◽  
Pulmonary Delivery ◽  
Magnesium Stearate ◽  
Dry Powder ◽  
Scanning Calorimetry ◽  
Physical Interactions ◽  
A Minor ◽  
Excipient Interactions ◽  
Glucagon Concentration

Purpose: This study describes the development and characterization of glucagon dry powder inhaler (DPI) formulation for pulmonary delivery. Lactose monohydrate, as a carrier, and L-leucine and magnesium stearate (MgSt) were used as dispersibility enhancers for this formulation. Methods: Using Fourier-transform infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), and Raman confocal microscopy, the interactions between glucagon and all excipients were characterized. The fine particle fractions (FPFs) of glucagon in different formulations were determined by a twin stage impinger (TSI) using a 2.5% glucagon mixture, and the glucagon concentration was measured by a validated LC-MS/MS method. Results: The FPF of the glucagon was 6.4%, which increased six-fold from the formulations with excipients. The highest FPF (36%) was observed for the formulation containing MgSt and large carrier lactose. The FTIR, Raman, and DSC data showed remarkable physical interactions of glucagon with leucine and a minor interaction with lactose; however, there were no interactions with MgSt alone or mixed with lactose. Conclusion: Due to the interaction between L-leucine and glucagon, leucine was not a suitable excipient for glucagon formulation. In contrast, the use of lactose and MgSt could be considered to prepare an efficient DPI formulation for the pulmonary delivery of glucagon.

A generic fluticasone propionate and salmeterol dry powder inhaler: Evidence of usability, function, and robustness

2021 ◽  
Vol 42 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Donald P. Tashkin ◽  
Arkady Koltun ◽  
Róisín Wallace
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Fluticasone Propionate ◽  
Healthy Volunteers ◽  
Pulmonary Disease ◽  
Dry Powder Inhaler ◽  
Chemical Degradation ◽  
Chronic Obstructive ◽  
Dry Powder ◽  
Obstructive Pulmonary Disease ◽  
Flow Rates

Background: A generic combination of fluticasone propionate and salmeterol xinafoate inhalation powder in a premetered, multidose, nonreusable inhaler was recently approved. Objective: To assess the performance of the generic device. Methods: Findings from three studies with regard to device usability, function, and robustness were reviewed. Results: In a study to assess device function in patients and healthy volunteers, the generic device was successfully used by patients with asthma and chronic obstructive pulmonary disease who were either dry powder inhaler users or dry powder inhaler‐naive, even though they were not trained beyond being provided the instructions for use. In a study to measure inhaled flow rates generated by patients and healthy volunteers, the generic device consistently simulated the delivery of a full dose of drug, even to patients with severe respiratory disease and reduced inspiratory flow rates. Although the generic device had a slightly higher airflow resistance, this study demonstrated that this difference did not result in any clinically meaningful differences in terms of drug delivery. Pressure drop, a key parameter that drives the fluidization and aerosolization of the powder dose, was found to be comparable between the devices. In an open-label study, the generic device met all U.S. Food and Drug Administration specifications for device robustness after 21.5 days of twice-daily dosing via oral inhalation among 111 participants with asthma or chronic obstructive pulmonary disease. All inhalers tested demonstrated conformity with a pharmacopeia with respect to key quality parameters (assay, delivered dose uniformity, aerodynamic size distribution). There was no evidence of chemical degradation of the active ingredients, nor of microbial or water ingress into the powder, as a result of inhaler use.

scholarly journals Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Zhanying Zheng ◽  
Sharon Shui Yee Leung ◽  
Raghvendra Gupta
Keyword(s):  
Dry Powder Inhaler ◽  
Research Direction ◽  
Particle Methods ◽  
Future Research ◽  
High Dose ◽  
Dry Powder ◽  
Multi Scale ◽  
Wide Range ◽  
Computational Fluid Dynamics Cfd ◽  
Discrete Element Methods

Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients’ inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.

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