scholarly journals Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 87
Author(s):  
Khaled Almansour ◽  
Iman M. Alfagih ◽  
Alhassan H. Aodah ◽  
Fawaz Alheibshy ◽  
Raisuddin Ali ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Fine Particle ◽  
Fungal Infections ◽  
Particle Mass ◽  
Fine Particle Fraction ◽  
Particle Fraction ◽  
Absolute Increase ◽  
Inhalation Device ◽  
Mass Median ◽  
Spray Dried

Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler® and the high resistance Handihaler® as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler® and the Handihaler®. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 ± 0.67% w/w and particle mass median aerodynamic diameters of down to 1.90 ± 0.20 μm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 ± 3.46% w/w and particle mass median aerodynamic diameters of down to 6.79 ± 0.82 μm. When leucine was used as an excipient, using 50% w/w rather than 25% w/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w/w (95% confidence interval = 6.40–12.73% w/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler® outperformed the Handihaler® as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w/w (95% confidence interval = 8.17–10.16% w/w).

scholarly journals Aerosolization Performance of Jet Nebulizers and Biopharmaceutical Aspects

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 406 ◽  
Author(s):  
Greta Adorni ◽  
Gerrit Seifert ◽  
Francesca Buttini ◽  
Gaia Colombo ◽  
Luciano A. Stecanella ◽  
...  
Keyword(s):  
Fine Particle ◽  
Drug Product ◽  
Patient Characteristics ◽  
Relevant Information ◽  
Fine Particle Fraction ◽  
Particle Fraction ◽  
Dose Delivery ◽  
Aerosol Emission ◽  
Jet Nebulizers

In this work, 13 jet nebulizers, some of which in different configurations, were investigated in order to identify the biopharmaceutical constraints related to the quality attributes of the medicinal products, which affect their safety, efficiency, compliance, and effectiveness. The aerosolization parameters, including the aerosol output, aerosol output rate, mass median aerodynamic diameter, and fine particle fraction, were determined according to the European Standard EN 13544-1, using sodium fluoride as a reference formulation. A comparison between the aerosol output nebulization time and the fine particle fraction displayed a correlation between the aerosol quality and the nebulization rate. Indeed, the quality of the nebulization significantly increased when the rate of aerosol emission was reduced. Moreover, the performance of the nebulizers was analyzed in terms of respirable delivered dose and respirable dose delivery rate, which characterize nebulization as the rate and amount of respirable product that could be deposited into the lungs. Depending on which of these two latter parameters was used, the nebulizers showed different performances. The differences, in terms of the rate and amount of delivered aerosol, could provide relevant information for the appropriate choice of nebulizer as a function of drug product, therapy, and patient characteristics.

Optimization of the Fine Particle Fraction of a Lyophilized Lysozyme Formulation for Dry Powder Inhalation

2013 ◽  
Vol 30 (6) ◽  
pp. 1698-1713 ◽  
Author(s):  
Sarah Claus ◽  
Claudius Weiler ◽  
Joerg Schiewe ◽  
Wolfgang Friess
Keyword(s):  
Fine Particle ◽  
Fine Particle Fraction ◽  
Particle Fraction ◽  
Dry Powder Inhalation ◽  
Dry Powder

scholarly journals Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

2013 ◽  
Vol 49 (2) ◽  
pp. 221-231 ◽  
Author(s):  
Gopala Krishna Murthy Talasila ◽  
Bala Vishnu Priya Mukkala ◽  
Satyanarayana Vattikuri
Keyword(s):  
Quality Control ◽  
Fine Particle ◽  
Beclomethasone Dipropionate ◽  
Dry Powder Inhalers ◽  
Fine Particle Fraction ◽  
Particle Fraction ◽  
Metered Dose Inhalers ◽  
Spray Pattern ◽  
Metered Dose ◽  
Emitted Dose

Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI) for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI) with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

scholarly journals Providing calves different feed source early in life would not affect feed sorting and rumen fermentation for a long term

2020 ◽  
Author(s):  
Jianxin Xiao ◽  
Muhammad Zahoor Khan ◽  
Gibson Maswayi Alugongo ◽  
Wei Wang ◽  
Yajing Wang ◽  
...  
Keyword(s):  
Fine Particle ◽  
Volatile Fatty Acids ◽  
Rumen Fluid ◽  
Rumen Fermentation ◽  
Fine Particle Fraction ◽  
Particle Fraction ◽  
Calf Health ◽  
Rumen Ph ◽  
Short Period

Abstract This study aimed to investigate the short and long-term effect of early in life exposure to different feed sources on feed sorting and rumen fermentation of calves. Forty newborn female Holstein calves were randomly divided based on supplementation of concentrate (CON) or hay (HAY) only during the milk-feeding stage (d 1 to 56). After that, all calves were offered a total mixed ration (TMR) containing 43% of forage and 57% of concentrate until the end of the experiment (d 57 to 196). Calves were weighed immediately after birth and raised in individual hutches until d 70. The calves were then transferred to a heifer barn, housed within treatment in pairs (2 calves/pen). Rectal temperature, feed intake, body weight, body structural measurement, fecal and cough score were recorded ranges from day 1 to 196. Fresh and orts feed were sampled daily at the first two weeks (d 57-70) once TMR was offered and at the last week of the experiment (d 190 to 196) for analysis of feed sorting. Rumen fluid samples were collected at ranges from d 14-190 for detecting rumen pH and volatile fatty acids (VFA) concentrations. Our findings showed that early feed exposure did not influence calf health and growth performance but affected feed sorting in a short period. Upon transition to the same mixed diet, differences were found between treatments in the sorting of the different particle fractions. At week 9 and 10, calves early exposed to concentrates began to sort for fine particle fraction (primarily concentrate in this fraction), and against the long particle fraction (solely forage in this fraction), whereas calves early fed hay sorted for the long particle fraction, and against the fine particle fraction. However, no carryover effect was found, the differences between treatments fade away when detecting feed sorting at the last week, all calves sorted for short and fine particle fractions, and sort against long and medium particle fractions. Although the pattern of feed sorting initially differed between treatments, the rumen pH and VFA concentration were not altered once all calves transitioned to a TMR. These results suggested that the feed familiarity established early in life would not affect diet selection and rumen fermentation in heifer later in life, the dietary experience after transition to same TMR would eventually override the effect of early feed experience.

scholarly journals Providing calves different feed source early in life would not affect feed sorting and rumen fermentation for a long term

2020 ◽  
Author(s):  
Jianxin Xiao ◽  
Muhammad Zahoor Khan ◽  
Gibson Maswayi Alugongo ◽  
Wei Wang ◽  
Yajing Wang ◽  
...  
Keyword(s):  
Fine Particle ◽  
Volatile Fatty Acids ◽  
Rumen Fluid ◽  
Rumen Fermentation ◽  
Fine Particle Fraction ◽  
Particle Fraction ◽  
Calf Health ◽  
Rumen Ph ◽  
Short Period

Abstract This study aimed to investigate the short and long-term effect of early in life exposure to different feed sources on feed sorting and rumen fermentation of calves. Forty newborn female Holstein calves were randomly divided based on supplementation of concentrate (CON) or hay (HAY) only during the milk-feeding stage (d 1 to 56). After that, all calves were offered a total mixed ration (TMR) containing 43 % of forage and 57 % of concentrate until the end of the experiment (d 57 to 196). Rectal temperature, feed intake, body weight, body structural measurement, fecal and cough score were recorded ranges from day 1 to 196. Fresh and orts feed were sampled daily at the first two weeks (d 57-70) once TMR was offered and at the last week of the experiment (d 190 to 196) for analysis of feed sorting. Rumen fluid samples were collected at ranges from d 14-190 for detecting rumen pH and volatile fatty acids (VFA) concentrations. Our findings showed that early feed exposure did not influence calf health and growth performance but affected feed sorting in a short period. Upon transition to the same mixed diet, differences were found between treatments in the sorting of the different particle fractions. At week 9 and 10, calves early exposed to concentrates began to sort for fine particle fraction, and against the long particle fraction, whereas calves early fed hay sorted for the long particle fraction, and against the fine particle fraction. However, no carryover effect was found, the differences between treatments fade away when detecting feed sorting at the last week, all calves sorted for short and fine particle fractions, and sort against long and medium particle fractions. Although the pattern of feed sorting initially differed between treatments, the rumen pH and VFA concentration were not altered once all calves transitioned to a TMR. These results suggested that the feed familiarity established early in life would not affect diet selection and rumen fermentation in heifer later in life, the dietary experience after transition to same TMR would eventually override the effect of early feed experience.

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