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Ali Nokhodchi - One of the best experts on this subject based on the ideXlab platform.
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Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate Dry Powder Inhaler
Drug Delivery and Translational Research, 2020Co-Authors: Mickey Socrates Ferdynand, Ali NokhodchiAbstract:Although in Dry Powder Inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a single solution. Spray-dried samples were blended with salbutamol sulfate to determine the efficiency of their aerosolization performance. Interestingly, note that lactose was in its amorphous state stabilized by the presence of mannitol in the samples. Spray-dried mannitol without lactose showed a combination of the α- and β-polymorphic forms which was the case in all other ratios of mannitol:lactose. It was shown that the highest fine particle fraction (FPF) was 62.42 ± 4.21% which was obtained for the distinct binary mixtures (1:3 mannitol:lactose) compared to a single carrier. This study opens a new window to investigate further the implementation of binary mixtures of sugar carriers containing leucine in DPI formulations to overcome poor aerosolization performance the mentioned DPI formulations.
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towards a more desirable Dry Powder Inhaler formulation large spray dried mannitol microspheres outperform small microspheres
Pharmaceutical Research, 2014Co-Authors: Waseem Kaialy, Ali Nokhodchi, Tariq Hussain, Amjad AlhalawehAbstract:Purpose To investigate, for the first time, the performance of a Dry Powder Inhaler (DPI, Aerolizer®) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid–state form but different sizes.
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freeze dried mannitol for superior pulmonary drug delivery via Dry Powder Inhaler
Pharmaceutical Research, 2013Co-Authors: Waseem Kaialy, Ali NokhodchiAbstract:Purpose To show for the first time the superior Dry Powder Inhaler (DPI) performance of freeze dried mannitol in comparison to spray dried mannitol and commercial mannitol.
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influence of lactose carrier particle size on the aerosol performance of budesonide from a Dry Powder Inhaler
Powder Technology, 2012Co-Authors: Waseem Kaialy, Ali Nokhodchi, Amjad Alhalaweh, Sitaram P VelagaAbstract:The purpose of this study was to evaluate the effect of carrier particle size on properties of Dry Powder and its effect on Dry Powder Inhaler (DPI) performance. Commercial α-lactose-monohydrate, a commonly used carrier in DPI formulations, was carefully sieved to obtain different lactose size fractions, namely Lac A (90-125μm), Lac B (63-90μm), Lac C (45-63μm), Lac D (20-45μm), and Lac E (<20μm). The lactose samples were analysed in terms of size, shape, solid state, density, and flowability. Lactose particles were blended with budesonide (<5μm) Powder to generate five different formulations. These formulations were then evaluated in terms of budesonide-lactose adhesion properties, drug content homogeneity, and in vitro aerosolisation performance. The results demonstrated that lactose samples with smaller particle volume mean diameter have higher amorphous lactose content, higher true density (linear, r 2=0.9932), higher surface smoothness (linear, r 2=0.8752), smaller angularity (linear, r 2=0.921), smaller bulk density, higher porosity (linear, r 2=0.914), poorer flowability, and higher specific surface area. In general, the smaller the lactose particles the smaller are the budesonide-lactose adhesion properties. Budesonide formulated with smaller lactose particles exhibited smaller aerodynamic diameter and higher amounts of budesonide were delivered to lower stages of the impactor indicating improved DPI aerosolisation performance. However, the use of lactose particles with smaller volume mean diameter had a detrimental effect on budesonide content homogeneity and caused an increase in the amounts of budesonide deposited on oropharyngeal region. Therefore, particle size of the lactose within Dry Powder Inhaler formulations should be selected carefully. Accordingly, higher drug aerosolisation efficiency of lactose particles with smaller size may have to be balanced due to considerations of other disadvantages including poorer flowability, reduced formulation stability, higher potential side effects, and higher dose variability. © 2012.
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effect of carrier particle shape on Dry Powder Inhaler performance
International Journal of Pharmaceutics, 2011Co-Authors: Waseem Kaialy, Amjad Alhalaweh, Sitaram P Velaga, Ali NokhodchiAbstract:The aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from Dry Powder Inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer® Inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER = 1.62 ± 0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER = 4.83 ± 0.18, ECM: ER = 5.89 ± 0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (Db), smaller tap density (Dt), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a "limit" as increasing carrier ER from 4.83 ± 0.18 (ACM) to 5.89 ± 0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in Inhaler device (drug loss) and deposited on throat. Linear relationship was established (r2 = 0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for carrier products with higher ER is disadvantageous in terms of DPI formulation dose metering and processing on handling scale. In conclusion, despite that using carrier particles with higher ER can considerably increase the amounts of drug delivered to lower airway regions; this enhancement is restricted to certain point. Also, other limitations should be taken into account including higher drug loss and poorer flowability. © 2011 Elsevier B.V. All rights reserved.
Waseem Kaialy - One of the best experts on this subject based on the ideXlab platform.
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towards a more desirable Dry Powder Inhaler formulation large spray dried mannitol microspheres outperform small microspheres
Pharmaceutical Research, 2014Co-Authors: Waseem Kaialy, Ali Nokhodchi, Tariq Hussain, Amjad AlhalawehAbstract:Purpose To investigate, for the first time, the performance of a Dry Powder Inhaler (DPI, Aerolizer®) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid–state form but different sizes.
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freeze dried mannitol for superior pulmonary drug delivery via Dry Powder Inhaler
Pharmaceutical Research, 2013Co-Authors: Waseem Kaialy, Ali NokhodchiAbstract:Purpose To show for the first time the superior Dry Powder Inhaler (DPI) performance of freeze dried mannitol in comparison to spray dried mannitol and commercial mannitol.
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influence of lactose carrier particle size on the aerosol performance of budesonide from a Dry Powder Inhaler
Powder Technology, 2012Co-Authors: Waseem Kaialy, Ali Nokhodchi, Amjad Alhalaweh, Sitaram P VelagaAbstract:The purpose of this study was to evaluate the effect of carrier particle size on properties of Dry Powder and its effect on Dry Powder Inhaler (DPI) performance. Commercial α-lactose-monohydrate, a commonly used carrier in DPI formulations, was carefully sieved to obtain different lactose size fractions, namely Lac A (90-125μm), Lac B (63-90μm), Lac C (45-63μm), Lac D (20-45μm), and Lac E (<20μm). The lactose samples were analysed in terms of size, shape, solid state, density, and flowability. Lactose particles were blended with budesonide (<5μm) Powder to generate five different formulations. These formulations were then evaluated in terms of budesonide-lactose adhesion properties, drug content homogeneity, and in vitro aerosolisation performance. The results demonstrated that lactose samples with smaller particle volume mean diameter have higher amorphous lactose content, higher true density (linear, r 2=0.9932), higher surface smoothness (linear, r 2=0.8752), smaller angularity (linear, r 2=0.921), smaller bulk density, higher porosity (linear, r 2=0.914), poorer flowability, and higher specific surface area. In general, the smaller the lactose particles the smaller are the budesonide-lactose adhesion properties. Budesonide formulated with smaller lactose particles exhibited smaller aerodynamic diameter and higher amounts of budesonide were delivered to lower stages of the impactor indicating improved DPI aerosolisation performance. However, the use of lactose particles with smaller volume mean diameter had a detrimental effect on budesonide content homogeneity and caused an increase in the amounts of budesonide deposited on oropharyngeal region. Therefore, particle size of the lactose within Dry Powder Inhaler formulations should be selected carefully. Accordingly, higher drug aerosolisation efficiency of lactose particles with smaller size may have to be balanced due to considerations of other disadvantages including poorer flowability, reduced formulation stability, higher potential side effects, and higher dose variability. © 2012.
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effect of carrier particle shape on Dry Powder Inhaler performance
International Journal of Pharmaceutics, 2011Co-Authors: Waseem Kaialy, Amjad Alhalaweh, Sitaram P Velaga, Ali NokhodchiAbstract:The aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from Dry Powder Inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer® Inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER = 1.62 ± 0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER = 4.83 ± 0.18, ECM: ER = 5.89 ± 0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (Db), smaller tap density (Dt), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a "limit" as increasing carrier ER from 4.83 ± 0.18 (ACM) to 5.89 ± 0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in Inhaler device (drug loss) and deposited on throat. Linear relationship was established (r2 = 0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for carrier products with higher ER is disadvantageous in terms of DPI formulation dose metering and processing on handling scale. In conclusion, despite that using carrier particles with higher ER can considerably increase the amounts of drug delivered to lower airway regions; this enhancement is restricted to certain point. Also, other limitations should be taken into account including higher drug loss and poorer flowability. © 2011 Elsevier B.V. All rights reserved.
Alex H. Gifford - One of the best experts on this subject based on the ideXlab platform.
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prevalence and copd phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the diskus Dry Powder Inhaler
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2013Co-Authors: Donald A. Mahler, Laurie A. Waterman, Alex H. GiffordAbstract:Abstract Background: Patients who exhibit a suboptimal peak inspiratory flow rate (PIFR) against the resistance (resist) of a Dry Powder Inhaler (DPI) may not be able to effectively inhale the medication into their lower respiratory tract. PIFRresist was measured using the In-Check DIAL® to simulate the resistance of the Diskus® DPI in patients with chronic obstructive pulmonary disease (COPD) who were ≥60 years of age and had forced expiratory volume in 1 sec (FEV1) of ≤50% predicted. Our objectives were to: establish the prevalence of a suboptimal PIFRresist (<60 L/min) in this population; identify a phenotype of patients with COPD who exhibit a suboptimal PIFRresist; and assess test–retest reliability of PIFRresist. Methods: PIFRresist and inspiratory capacity (IC) were measured after spirometry was performed in patients with advanced COPD. Repeat measurement of PIFRresist was performed in a subset of patients who returned for scheduled follow-up appointments. Results: The prevalence of a PIFRresist of...
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Prevalence and COPD phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the Diskus® Dry Powder Inhaler.
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2012Co-Authors: Donald A. Mahler, Laurie A. Waterman, Alex H. GiffordAbstract:Abstract Background: Patients who exhibit a suboptimal peak inspiratory flow rate (PIFR) against the resistance (resist) of a Dry Powder Inhaler (DPI) may not be able to effectively inhale the medication into their lower respiratory tract. PIFRresist was measured using the In-Check DIAL® to simulate the resistance of the Diskus® DPI in patients with chronic obstructive pulmonary disease (COPD) who were ≥60 years of age and had forced expiratory volume in 1 sec (FEV1) of ≤50% predicted. Our objectives were to: establish the prevalence of a suboptimal PIFRresist (
Omar S Usmani - One of the best experts on this subject based on the ideXlab platform.
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biophysical model to predict lung delivery from a dual bronchodilator Dry Powder Inhaler
International journal of pharmaceutics: X, 2019Co-Authors: Myrna B Dolovich, Andreas Kuttler, Thomas Dimke, Omar S UsmaniAbstract:Abstract A biophysical lung model was designed to predict inhaled drug deposition in patients with obstructive airway disease, and quantitatively investigate sources of deposition variability. Different mouth-throat anatomies at varying simulated inhalation flows were used to calculate the lung dose of indacaterol/glycopyrronium [IND/GLY] 110/50 µg (QVA149) from the Dry-Powder Inhaler Breezhaler®. Sources of variability in lung dose were studied using computational fluid dynamics, supported by aerosol particle sizing measurements, particle image velocimetry and computed tomography. Anatomical differences in mouth-throat geometries were identified as a major source of inter-subject variability in lung deposition. Lung dose was similar across inhalation flows of 30–120 L/min with a slight drop in calculated delivery at high inspiratory flows. Delivery was relatively unaffected by Inhaler inclination angle. The delivered lung dose of the fixed-dose combination IND/GLY matched well with corresponding monotherapy doses. This biophysical model indicates low extra-thoracic drug loss and consistent lung delivery of IND/GLY, independent of inhalation flows. This is an important finding for patients across various ages and lung disease severities. The model provides a quantitative, mechanistic simulation of inhaled therapies that could provide a test system for estimating drug delivery to the lung and complement traditional clinical studies.
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recent advances in capsule based Dry Powder Inhaler technology
Multidisciplinary Respiratory Medicine, 2017Co-Authors: Federico Lavorini, Massimo Pistolesi, Omar S UsmaniAbstract:Pulmonary drug delivery is currently the focus of accelerated research and development because of the potential to produce maximum therapeutic benefit to patients by directly targeting drug to the site of pathology in the lungs. Among the available delivery options, the Dry Powder Inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. However, because drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is proving to be a great challenge. Development of DPI systems that target the delivery of fine drug particles to the deeper airways in the lungs using a combination of improved drug formulations and enhanced delivery device technologies means that each of these factors contributes to overall performance of the aerosol system. There are a large range of devices that are currently available, or under development, for clinical use, however no individual device shows superior clinical efficacy. A major concern that is very relevant in day-to-day clinical practice is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs from the inhalation devices, where the extent of variability depends on the drug formulation, the device design, and the patient’s inhalation profile. This variability may result in under-dosing of drug to the patient and potential loss of pharmacological efficacy. This article reviews recent advances in capsule-based DPI technology and the introduction of the ‘disposable’ DPI device.
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nexthaler an innovative Dry Powder Inhaler delivering an extrafine fixed combination of beclometasone and formoterol to treat large and small airways in asthma
Expert Opinion on Drug Delivery, 2014Co-Authors: Massimo Corradi, Henry Chrystyn, Borja G Cosio, Michal Pirozynski, Stelios Loukides, Renaud Louis, Monica Spinola, Omar S UsmaniAbstract:Introduction: Airway inflammation and remodelling in asthma occur in the large airways and also in the small airways. The small airways are those < 2 mm in diameter and are significant sites of chronic asthmatic inflammation. It is important, therefore, to target the small as well as the large airways in any strategy for effective treatment of this disease.Areas covered: The present review deals with the recently developed fixed dose drug combination of beclometasone dipropionate/formoterol fumarate that emits extrafine particles when delivered from an innovative Dry Powder Inhaler (DPI), NEXThaler®. The aim is to present the technical and clinical aspects of aerosolized drug delivery to the lungs.Expert opinion: The data show that the NEXThaler DPI is an efficient device for the management of persistent asthma. The evaluation of the inhalation profiles through the NEXThaler DPI demonstrates that device activation and consistent dose delivery occurs at patient achievable inhalation flow rates, and support...
Mickey Socrates Ferdynand - One of the best experts on this subject based on the ideXlab platform.
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Co-spraying of carriers (mannitol-lactose) as a method to improve aerosolization performance of salbutamol sulfate Dry Powder Inhaler
Drug Delivery and Translational Research, 2020Co-Authors: Mickey Socrates Ferdynand, Ali NokhodchiAbstract:Although in Dry Powder Inhaler (DPI) formulations a single carrier is used, a single carrier is not able to provide an excellent aerosolization performance when it is used in DPI formulations. Thereby, the aim of this study was to engineer a suitable ternary mixture of mannitol-lactose-leucine to be used in a DPI formulation with enhanced aerosolization performance. To this end, binary mixtures of mannitol:lactose containing a constant amount of leucine (5% w/w of carriers) were spray-dried as a single solution. Spray-dried samples were blended with salbutamol sulfate to determine the efficiency of their aerosolization performance. Interestingly, note that lactose was in its amorphous state stabilized by the presence of mannitol in the samples. Spray-dried mannitol without lactose showed a combination of the α- and β-polymorphic forms which was the case in all other ratios of mannitol:lactose. It was shown that the highest fine particle fraction (FPF) was 62.42 ± 4.21% which was obtained for the distinct binary mixtures (1:3 mannitol:lactose) compared to a single carrier. This study opens a new window to investigate further the implementation of binary mixtures of sugar carriers containing leucine in DPI formulations to overcome poor aerosolization performance the mentioned DPI formulations.
