An Investigation into the Dispersion Mechanisms of Ternary Dry Powder Inhaler Formulations by the Quantification of Interparticulate Forces

Jones, Matthew; Hooton, Jennifer C.; Dawson, Michelle L.; Ferrie, Alan; Price, Robert

doi:10.1007/s11095-007-9467-1

Cited by 65 publications

(42 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on "active sites," "agglomerates," or alternative hypotheses (22)(23)(24), Aerolizer/ Formulation B would be expected to have a lower FPM than Aerolizer/Formulation A and provide a closer FPM match to the reference product. However, during the formulation screening, a greater FPM of Aerolizer/Formulation B was observed at 60 LPM relative to Aerolizer/Formulation A.…”

Section: Aerolizer With Test Formulationsmentioning

confidence: 99%

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

Adams¹,

Lee

Plourde

et al. 2012

AAPS J

View full text Add to dashboard Cite

Abstract. The study examined the sensitivity of DPI in vitro performance to formulation and device changes. Rotahaler/Rotacaps was selected as the reference DPI drug product, and Aerolizer was selected as the test device. Since the test device was recognized to have much greater efficiency of dispersion, simple modifications to both formulation and device were made in an effort to provide a closer match to the in vitro performance of the reference product. The modifications included varying the drug and lactose particle sizes and/or lactose fine particle content in the test formulations, as well as lowering the specific resistance of the test device. These modifications were intended to address variables important for drug product performance for a defined experimental design and were not intended to mimic the extensive formulation and device design strategies that are employed in an industrial setting. Formulation and device modifications resulted in a modified test product that approached the reference product in the in vitro performance.

show abstract

Section: Aerolizer With Test Formulationsmentioning

confidence: 99%

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

Adams¹,

Lee

Plourde

et al. 2012

AAPS J

View full text Add to dashboard Cite

show abstract

“…The traditional theories proposed for this mechanism of action are the active site theory (8,9) and fine particle multiplet theory (6,7). The active site theory supports the hypothesis of the presence of high-energy "hot spots" on the surface of the coarse lactose.…”

Section: Introductionmentioning

confidence: 83%

“…It is also well known that the extrinsic addition of lactose fines (a Geldart group C powder) to the coarse lactose carrier (Geldart group A powder) significantly enhances the aerosolization performance and delivery of the API (6,7). The traditional theories proposed for this mechanism of action are the active site theory (8,9) and fine particle multiplet theory (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…These "hot spots" are preferentially occupied by the fine lactose particles allowing the API particles adhere to lowenergy sites from where they are readily dispersed upon inspiration (9)(10)(11). In contrast, the fine particle multiplet theory suggests that the improvement in DPI performance is due to the formation of mixed API/fines agglomerates that are better elutriated from the carrier particle surface than free API particles due to greater aerodynamic drag forces acting on the agglomerates (2,6,7). More recently, Shur et al, reported a third possible mechanism, which suggested that the addition of lactose fines increases the cohesive strength of the formulation that in turn leads to greater deagglomeration efficiencies and an increase in fine particle delivery (12).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Investigation into the Effect of Fine Lactose Particles on the Fluidization Behaviour and Aerosolization Performance of Carrier-Based Dry Powder Inhaler Formulations

Kinnunen

Hebbink²,

Peters³

et al. 2014

AAPS PharmSciTech

Self Cite

View full text Add to dashboard Cite

Abstract. The effect of milled and micronized lactose fines on the fluidization and in vitro aerosolization properties of dry powder inhaler (DPI) formulations was investigated, and the suitability of static and dynamic methods for characterizing general powder flow properties of these blends was assessed. Lactose carrier pre-blends were prepared by adding different lactose fines (Lactohale® (LH) 300, 230 and 210) with coarse carrier lactose (Lactohale100) at 2.5, 5, 10 and 20 wt% concentrations. Powder flow properties of lactose pre-blends were characterized using the Freeman Technology FT4 and Schulze RST-XS ring shear tester. A strong correlation was found between the basic flow energy (BFE Norm ) measured using the Freeman FT4 Rheometer and the flowability number (ff c ) measured on Schulze RST-XS. These data indicate that both static and dynamic methods are suitable for characterizing general powder flow properties of lactose carriers. Increasing concentration of fines corresponded with an increase in the normalized fluidization energy (FE Norm ). The inclusion of fine particles of lactose resulted in a significant (p<0.05) increase in fine particle delivery of budesonide and correlated with FE Norm . This trend was strongest for lactose containing up to 10 wt% LH300. A similar trend was found for the milled lactose grades LH230 and LH210. However, the increase in FE Norm upon addition of milled fines only corresponded to a very slight improvement in the performance. These data suggest that whilst the fluidization energy correlated with fine particle delivery, this relationship is specific to lactose grades of similar particle size.

show abstract

“…6) appeared to be sensitive to shift in the balance of forces between FP and SX upon FP lagering. As has been indicated in a number of studies, the greater the adhesive tendency between FP and SX, the more significant is the improvement in aerosolization performance of SX (1,16,19). These studies proposed that higher deaggregation efficiency of the SX occurred as a result of the greater propensity of FP and SX to form fine particle agglomerates during blending.…”

Section: In Vitro Aerosolization Performance Of Binary Dpi Formulationsmentioning

confidence: 89%

The Influence of Secondary Processing on the Structural Relaxation Dynamics of Fluticasone Propionate

et al. 2014

Self Cite

View full text Add to dashboard Cite

ABSTRACT. This study investigated the structural relaxation of micronized fluticasone propionate (FP) under different lagering conditions and its influence on aerodynamic particle size distribution (APSD) of binary and tertiary carrier-based dry powder inhaler (DPI) formulations. Micronized FP was lagered under low humidity (LH 25 C, 33% RH [relative humidity]), high humidity (HH 25°C, 75% RH) for 30, 60, and 90 days, respectively, and high temperature (HT 60°C, 44% RH) for 14 days. Physicochemical, surface interfacial properties via cohesive-adhesive balance (CAB) measurements and amorphous disorder levels of the FP samples were characterized. Particle size, surface area, and rugosity suggested minimal morphological changes of the lagered FP samples, with the exception of the 90-day HH (HH90) sample. HH90 FP samples appeared to undergo surface reconstruction with a reduction in surface rugosity. LH and HH lagering reduced the levels of amorphous content over 90-day exposure, which influenced the CAB measurements with lactose monohydrate and salmeterol xinafoate (SX). CAB analysis suggested that LH and HH lagering led to different interfacial interactions with lactose monohydrate but an increasing adhesive affinity with SX. HT lagering led to no detectable levels of the amorphous disorder, resulting in an increase in the adhesive interaction with lactose monohydrate. APSD analysis suggested that the fine particle mass of FP and SX was affected by the lagering of the FP. In conclusion, environmental conditions during the lagering of FP may have a profound effect on physicochemical and interfacial properties as well as product performance of binary and tertiary carrier-based DPI formulations.

show abstract

An Investigation into the Dispersion Mechanisms of Ternary Dry Powder Inhaler Formulations by the Quantification of Interparticulate Forces

Cited by 65 publications

References 47 publications

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

Effects of Device and Formulation on In Vitro Performance of Dry Powder Inhalers

An Investigation into the Effect of Fine Lactose Particles on the Fluidization Behaviour and Aerosolization Performance of Carrier-Based Dry Powder Inhaler Formulations

The Influence of Secondary Processing on the Structural Relaxation Dynamics of Fluticasone Propionate

Contact Info

Product

Resources

About