Influence of surface interaction between drug and excipient in binary mixture for dry powder inhaler applications
The present study documents the drug-excipient incompatibility in the physical mixtures and its influence on bulk homogeneity and flowability for dry powder inhalers (DPI) applications. Binary mixtures with the model drugs (aceclofenac; salbutamol sulphate) and lactose monohydrate were prepared separately at varied drug loading (1–33 wt.%), and their physicochemical properties were assessed using various characterization techniques.
Highlights
Drug with protic groups (-OH, -NH, -COOH) is incompatible with lactose in DPI blend.
Incompatibility influence the bulk properties of binary mixture by adduct formation.
Adduct arise due to solid state chemical reaction in physical mixtures.
Blends with the surface coated excipient can eliminate unwanted adduct formation.
Coated blends resulted in the significant improvement in mixing and flow properties.
The DSC, P-XRD and FT-IR studies show a significant shift in the signature peak of drug and excipient while ss-NMR, LC-MS show the absence of peaks. In contrast, new peaks are observed in LC-MS and GC studies. The insights are comprehended through a series of XPS studies. The findings indicated the formation of condensed or addition compound. This is attributed to an interaction between polar protic groups (-NH-, -COOH, -OH) and hemiacetal carbon (HO-C-OR) of drug and excipient in the solid-state. It induces crystal strain and alters bulk properties related to mixing (relative standard deviation, %RSD), cohesion and flow function coefficient (FFC).
However, surface modification of excipient using MgSt and aerosil R972 (model nano-particle) eliminates such inter-particle interactions, crystal level changes. It improves the bulk properties of binary mixtures pivotal for DPI performance.
Article information: Neetu Varun, Arnab Dutta, Chinmay Ghoroi, Influence of surface interaction between drug and excipient in binary mixture for dry powder inhaler applications, Advanced Powder Technology, Volume 33, Issue 3, 2022. https://doi.org/10.1016/j.apt.2022.103443.