The effect of carrier surface treatment on drug particle detachment from crystalline carriers in adhesive mixtures for inhalation

Dickhoff, Bastiaan H.J.; Boer, de Anne; Lambregts, Dorette; Frijlink, Henderik W.

doi:10.1016/j.ijpharm.2006.07.017

Cited by 53 publications

(21 citation statements)

References 23 publications

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“…Therefore, it would be desirable to use more effective methods for the removal of intrinsic lactose fines. Other workers have used techniques that included submersion of the carrier material in ethanol based solutions [10], [11]. Although such techniques may result in lower intrinsic fines contents, they also change carrier surface properties like surface roughness and the degree of contamination with protein residues.…”

Section: Discussionmentioning

confidence: 99%

New Mechanisms to Explain the Effects of Added Lactose Fines on the Dispersion Performance of Adhesive Mixtures for Inhalation

et al. 2014

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Fine excipient particles or ‘fines’ have been shown to improve the dispersion performance of carrier-based formulations for dry powder inhalation. Mechanistic formulation studies have focussed mainly on explaining this positive effect. Previous studies have shown that higher drug contents may cause a decrease in dispersion performance, and there is no reason why this should not be true for fines with a similar shape, size and cohesiveness as drug particles. Therefore, the effects on drug detachment of ‘fine lactose fines’ (FLF, X50 = 1.95 µm) with a similar size and shape as micronised budesonide were studied and compared to those of ‘coarse lactose fines’ (CLF, X50 = 3.94 µm). Furthermore, interactions with the inhalation flow rate, the drug content and the mixing order were taken into account. The observed effects of FLF are comparable to drug content effects in that the detached drug fraction was decreased at low drug content and low flow rates but increased at higher flow rates. At high drug content the effects of added FLF were negligible. In contrast, CLF resulted in higher detached drug fractions at all flow rates and drug contents. The results from this study suggest that the effects of fines may be explained by two new mechanisms in addition to those previously proposed. Firstly, fines below a certain size may increase the effectiveness of press-on forces or cause the formation of strongly coherent fine particle networks on the carrier surface containing the drug particles. Secondly, when coarse enough, fines may prevent the formation of, or disrupt such fine particle networks, possibly through a lowering of their tensile strength. It is recommended that future mechanistic studies are based on the recognition that added fines may have any effect on dispersion performance, which is determined by the formulation and dispersion conditions.

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Section: Discussionmentioning

confidence: 99%

New Mechanisms to Explain the Effects of Added Lactose Fines on the Dispersion Performance of Adhesive Mixtures for Inhalation

et al. 2014

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“…Blending time could promote significant changes in the agglomeration state and deposition profiles of drugs aerosolised from DPIs [78]. In general, it could be expected that increasing blending time (up to a specific limit) will improve the drug content homogeneity and the stability (determined by the tendency to segregation) of a DPI formulation blend due to an increased drugdrug deagglomeration and drug-carrier adhesion.…”

Section: Blending Time and Speedmentioning

confidence: 99%

“…The mechanisms by which carrier surface roughness affects ordered blending are also complicated by the interactions between the surface properties, the type of inhaler device, as well as the concentration and size of drug. For example, a low carrier surface roughness has been shown to promote the FPF during aerosolisation when turbulent shear inhalers are used [184,239]; but it may be disadvantageous when inhalers that generate inertial separation forces are used, although this has additionally been shown later to be dependent on blending intensity too [78]. Kulvanich and Stewart [250] argued that, during blending, drug particulates assemble in the discontinuities on the surface of coarse carrier particles that have macroroughness properties, although evidence to support this was restricted to SEM.…”

Section: Surface Propertiesmentioning

confidence: 99%

On the effects of blending, physicochemical properties, and their interactions on the performance of carrier-based dry powders for inhalation — A review

Kaialy

2016

Advances in Colloid and Interface Science

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Blending drug and carrier powders to produce homogeneous drug-carrier adhesive mixtures is a key step in the production of dry powder inhaler (DPI) formulations. Although the blending conditions can result in different conclusions or probably change the outcome of a study entirely if being selected differently, there is a scarcity of data on the influence of blending processes on the physicochemical properties of bulk powder formulations and the follow-on effects on DPI performance. This paper provides an overview of the interactions between variables related to blending conditions (e.g. blending equipment, time, speed and sequence as well as environmental humidity) and powder physicochemical properties (e.g. size distribution, shape distribution, density, anomeric composition, electrostatic charge, surface, and bulk properties), and their effects on the performance of adhesive mixtures for inhalation in terms of drug content homogeneity, drug-carrier adhesion, and drug aerosolisation behaviour. The relevance of carrier payload, batch size and segregation was also discussed. Challenges and future directions were identified. This review therefore contributes towards a better understanding of the blending process, powder physicochemical properties, and their interlinked effects on the fundamental understanding of adhesive mixtures for inhalation. The knowledge gained is essential to ensure optimum blending and thereby controlled functionality of DPIs.

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“…Thereby, modifying surface morphological properties may be an effective way to alter cohesion/adhesion, thus, influencing aerosol performance. (17)(18)(19) The current methods for overcoming such issues include the production of new lactose carriers with controlled shape and roughness and ''filling'' the potential active sites by increasing the fine-particle content of the drug or excipient on the carrier surface or pacifying the effects of active sites by surface treatment and/or the addition of force-control agents. (20)(21)(22) To reduce surface passivation of high surface free energy sites, some studies using force control agents such as leucine, (23) magnesium stearate, (5,24) and polaxamer (25) have been explored.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Evaluation of Surface Modified Lactose Particles for Improved Performance of Fluticasone Propionate Dry Powder Inhaler

Singh

Jain

Soni³

et al. 2015

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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The effect of carrier surface treatment on drug particle detachment from crystalline carriers in adhesive mixtures for inhalation

Cited by 53 publications

References 23 publications

New Mechanisms to Explain the Effects of Added Lactose Fines on the Dispersion Performance of Adhesive Mixtures for Inhalation

New Mechanisms to Explain the Effects of Added Lactose Fines on the Dispersion Performance of Adhesive Mixtures for Inhalation

On the effects of blending, physicochemical properties, and their interactions on the performance of carrier-based dry powders for inhalation — A review

Preparation and Evaluation of Surface Modified Lactose Particles for Improved Performance of Fluticasone Propionate Dry Powder Inhaler

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