Surface energy considerations in ternary powder blends for inhalation

Bungert, Nicholas; Kobler, Mirjam; Scherließ, Regina

doi:10.1016/j.ijpharm.2021.121189

Cited by 8 publications

(2 citation statements)

References 29 publications

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“…For ternary blends in turn, we added the fine excipient (7.5% w / w ) in the first mixing step and the drug (1% w / w ) within the second, complemented with post-process sieving (mesh size: 250 µm). The drug content was matched to earlier studies, and the respective batch size was 30 g [ 14 , 18 ]. High-performance liquid chromatography (HPLC) analysis of 10 randomly picked samples provided data on blend homogeneity.…”

Section: Methodsmentioning

confidence: 99%

“…We found high SE fines to be superior and concluded that a higher SE will preferentially lead to more agglomeration with the drug and consequently higher drug detachment from the carrier. The different fine qualities originated from different manufacturing routes or storage conditions [ 18 ]. To evaluate and substantiate this theory, we engineered particles in the size level of fine lactose by co-milling.…”

Section: Introductionmentioning

confidence: 99%

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Proof-of-Concept for Adjusted Surface Energies and Modified Fines as a Novel Concept in Particle Engineering for DPI Formulations

Bungert

Kobler²,

Scherließ

2022

Pharmaceutics

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Currently marketed dry powder inhaler (DPI) medicine lacks drug delivery performance due to insufficient powder dispersion. In carrier-based blends, incomplete drug detachment is typically attributed to excessive adhesion forces between carrier and drug particles. Adding force control agents (FCA) is known to increase drug detachment. Several researchers accounted this effect to a decrease in carrier surface energy (SE). In turn, an increase in SE should impede drug detachment. In this proof-of-concept study, we investigated the influence of the SE of the carrier material in binary blends by intentionally inverting the FCA approach. We increased SEs by dry particle coating utilising high-shear mixing, which resulted in decreased respirable fractions of the respective blends. Thus, we confirmed the SE of the carrier influences drug delivery and should be considered in formulation approaches. Complementing engineering techniques on the carrier level, we evaluated a method to modify the SE of extrinsic fines in ternary powder blends for inhalation. By the co-milling of fine lactose and an additive, we tailored the SE and hence the adhesiveness of additional fine excipients. Thus, the extent and the strength of drug–fines agglomerates may be controllable. For ternary DPI formulations, this work highlights the potential benefits of matching the SE of both fines and drugs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%