Carrier-based dry powder inhalation: Impact of carrier modification on capsule filling processability and in vitro aerodynamic performance

Faulhammer, Eva; Wahl, Verena; Zellnitz, Sarah; Khinast, Johannes G.; Paudel, Amrit

doi:10.1016/j.ijpharm.2015.06.044

Cited by 40 publications

(14 citation statements)

References 30 publications

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“…Specific surface area (SSA) values for the raw materials were taken from gas adsorption measurements described in our previous works ( 13 , 19 ). The SSA of the blends was assumed to be the sum of the weighted SSA of the SBS and MAN particles divided by the total mass of the blends (Table I ).…”

Section: Methodsmentioning

confidence: 99%

Tribo-Charging Behaviour of Inhalable Mannitol Blends with Salbutamol Sulphate

et al. 2019

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Purpose The performance of carrier-based dry powder inhaler (DPI) formulations can be critically impacted by interfacial interactions driven by tribo-electrification. Therefore, the aim of the present work was to understand how distinct API particle characteristics affect the charging behaviour of blends intended for DPI delivery. Methods Salbutamol sulphate (SBS) particles engineered via spray-drying and jet milling were used as model APIs. D-mannitol was selected as a model carrier. The materials were characterized concerning their different particle properties and their charge was analysed alone and in blends before and after flow over a stainless-steel pipe. Results The spray-dried SBS (amorphous and spherical) charged positively and to a higher extent than jet milled SBS (crystalline and acicular) that charged negatively and to a lower extent. D-mannitol charged positively and to a higher extent than the APIs. All drug-excipient blends charged negatively and differences were found between the spray-dried and jet milled SBS blends at 2% and 5% drug loads. Conclusions It was demonstrated how distinct solid-states, particle shape, size and morphology as well as different water contents of the different materials can affect tribo-charging. For their binary blends, the amount and nature of fines seem to govern inter-particle contacts critically impacting charge evolution. Electronic supplementary material The online version of this article (10.1007/s11095-019-2612-9) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Tribo-Charging Behaviour of Inhalable Mannitol Blends with Salbutamol Sulphate

et al. 2019

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“…For the sandwich, the API was placed between two even layers of lactose, and the half-filled vessels blended in a Turbula blender TC2 (Willy A. Bachofen Maschinenfabrik, Muttenz, Switzerland) for 90 min at 62 rpm. The homogeneity of the blends was confirmed as previously described [1,5], and characterization of the mixtures was only carried out once a homogenous sample was obtained.…”

Section: Blendingmentioning

confidence: 99%

“…Depending on the intended application for the DPI, distinct carrier characteristics might be necessary. For instance, it is known that carriers with different sizes and surface roughness can result in distinct forces involved in API attachment-detachment, influencing fluidization efficiency [5][6][7]. Fluidization efficiency will also depend upon the type of device used and its internal airflow resistance [8].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…• asthma (e.g. salbutamol, terbutaline, or fluticasone) [31,35,51,[75][76][77][78][79]89,[93][94][95][96][97][98],…”

Section: Applications Of Nano Spray Dried Pharmaceuticals On the Labomentioning

confidence: 99%

Pharmaceutical Particle Engineering via Nano Spray Drying - Process Parameters and Application Examples on the Laboratory-Scale

Arpagaus¹

2018

Int J Med Nano Res

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Spray drying plays a crucial role in the processing of pharmaceutical products such as pills, capsules, and tablets as it is used to convert drug-containing liquids into dried powdered forms. Nano spray drying is in particular used to improve drug formulation by encapsulating active ingredients in polymeric wall materials for protection and delivering the drugs to the right place and time in the body. The nano spray dryer developed in the recent years extends the spectrum of produced powder particles to the submicron-and nanoscale with very narrow size distributions and sample quantities in the milligram scale at high product yields. This enables the economical use of expensive active pharmaceutical ingredients and pure drugs. The present paper explains the concept of nano spray drying in the laboratory-scale and discusses the influence of the main process parameters on the final powder properties like particle size, morphology, encapsulation efficiency, and drug loading. Application results of nano spray drying for the formulation and encapsulation of different drugs are reviewed.

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Carrier-based dry powder inhalation: Impact of carrier modification on capsule filling processability and in vitro aerodynamic performance

Cited by 40 publications

References 30 publications

Tribo-Charging Behaviour of Inhalable Mannitol Blends with Salbutamol Sulphate

Tribo-Charging Behaviour of Inhalable Mannitol Blends with Salbutamol Sulphate

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

Pharmaceutical Particle Engineering via Nano Spray Drying - Process Parameters and Application Examples on the Laboratory-Scale

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