The Influence of Crystal Habit on the Prediction of Dry Powder Inhalation Formulation Performance Using the Cohesive–Adhesive Force Balance Approach

Hooton, Jennifer C.; Jones, Matthew; Harris, Haggis; Shur, Jagdeep; Price, Robert

doi:10.1080/03639040802149087

Cited by 31 publications

(27 citation statements)

References 15 publications

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“…The gradient of each the plot was equated to determine the CAB ratio of the micronised budesonide. The CAB value of the micronised budesonide 0.62±0.02 was similar to previously reported CAB measurements of commercially supplied micronised budesonide with lactose monohydrate (35,36). These data suggest that for an equivalent force of cohesion the adhesion of the micronised budesonide to lactose is approximately 1.61 times greater than its drug-drug interaction and is therefore a highly suitable candidate molecule for investigating the role of fines for an adhesive drug.…”

Section: Physicochemical Characterisation Of the Raw Materialssupporting

confidence: 74%

Defining the Critical Material Attributes of Lactose Monohydrate in Carrier Based Dry Powder Inhaler Formulations Using Artificial Neural Networks

Kinnunen

Hebbink²,

Peters³

et al. 2014

AAPS PharmSciTech

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Abstract. The study aimed to establish a function-based relationship between the physical and bulk properties of pre-blended mixtures of fine and coarse lactose grades with the in vitro performance of an adhesive active pharmaceutical ingredient (API). Different grades of micronised and milled lactose (Lactohale (LH) LH300, LH230, LH210 and Sorbolac 400) were pre-blended with coarse grades of lactose (LH100, LH206 and Respitose SV010) at concentrations of 2.5, 5, 10 and 20 wt.%. The bulk and rheological properties and particle size distributions were characterised. The pre-blends were formulated with micronised budesonide and in vitro performance in a Cyclohaler device tested using a nextgeneration impactor (NGI) at 90 l/min. Correlations between the lactose properties and in vitro performance were established using linear regression and artificial neural network (ANN) analyses. The addition of milled and micronised lactose fines with the coarse lactose had a significant influence on physical and rheological properties of the bulk lactose. Formulations of the different pre-blends with budesonide directly influenced in vitro performance attributes including fine particle fraction, mass median aerodynamic diameter and pre-separator deposition. While linear regression suggested a number of physical and bulk properties may influence in vitro performance, ANN analysis suggested the critical parameters in describing in vitro deposition patterns were the relative concentrations of lactose fines %< 4.5 μm and %<15 μm. These data suggest that, for an adhesive API, the proportion of fine particles below %<4.5 μm and %<15 μm could be used in rational dry powder inhaler formulation design.

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Section: Physicochemical Characterisation Of the Raw Materialssupporting

confidence: 74%

Defining the Critical Material Attributes of Lactose Monohydrate in Carrier Based Dry Powder Inhaler Formulations Using Artificial Neural Networks

Kinnunen

Hebbink²,

Peters³

et al. 2014

AAPS PharmSciTech

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“…Other strategies have modulated the adhesion forces between the drug and carrier by modifying the crystal habit of the drug to change the molecular orientation of the crystal faces on the surface. However, no direct effect was observed on the rank order of the cohesion-adhesion force balance values obtained with the different carriers that have shown a correlation with the aerosol performance [37]. In the case of the lactose carrier, the reduction of the roughness was initially the most frequently investigated strategy because it leads to a reduction of the surface area and consequently a decrease in the van der Waals adhesion forces (see Section 3.1.3).…”

Section: Surface Propertiesmentioning

confidence: 99%

“…Islam et al underlined the importance of the probing tip particle size and geometry in the contact area with the roughness of the lactose used as a substrate and their impact on the magnitude of adhesion force measurements [171]. Surface forces have also been examined using the colloid probe technique with cohesive-adhesive balance [37,172]. Overall, AFM is a very useful tool for studying the underlying mechanisms of the interparticulate interaction between drug and carrier and understanding the physico-chemical and environmental factors that govern their magnitude and may have an impact on in vitro aerosol performance.…”

Section: Direct Interparticulate Adhesion Force Determinationmentioning

confidence: 99%

Lactose characteristics and the generation of the aerosol

Pilcer¹,

Wauthoz²,

Amighi³

2012

Advanced Drug Delivery Reviews

178

113

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“…However, it is challenging to exploit the use of particle shape unless constructive particle engineering can be employed, as destructive particle engineering such as micronisation tend to create particles with reduced morphological features. In cases where constructive particle engineering is used to prepare API particles, Hooton et al [31]. demonstrated that this gives the potential for influencing the cohesive–adhesive balance through control of crystal faces.…”

Section: The Role Of Api Properties Solid Form and Particle Engineermentioning

confidence: 99%

Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design

Ticehurst

Marziano

2015

Journal of Pharmacy and Pharmacology

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This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised.A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery.

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The Influence of Crystal Habit on the Prediction of Dry Powder Inhalation Formulation Performance Using the Cohesive–Adhesive Force Balance Approach

Cited by 31 publications

References 15 publications

Defining the Critical Material Attributes of Lactose Monohydrate in Carrier Based Dry Powder Inhaler Formulations Using Artificial Neural Networks

Defining the Critical Material Attributes of Lactose Monohydrate in Carrier Based Dry Powder Inhaler Formulations Using Artificial Neural Networks

Lactose characteristics and the generation of the aerosol

Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design

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