Quality by design based synthesis and characterization of novel maleyl functionalized albumin solid dry powder for pulmonary targeting

Abstract

Dry powder inhalers (DPIs) are propellant-free portable devices used to provide medicines to the lung. Lactose monohydrate is the most common drug carrier for DPIs. However, the lactose monohydrate exhibits several limitations such as Maillard reaction, hypersensitivity, and lactose intolerance. Hence, there is a need to develop a better alternative carrier excipient that offers all the benefits with no or minimal limitations. In this investigation, we synthesized and evaluated a novel albumin-based carrier excipient for dry powder application via albumin modification by the QbD approach. We conjugated the maleic group on the lysine residue of albumin. Maleic conjugated BSA (^ɱ+BSA) was investigated using instrumental techniques FTIR, NMR, FESEM, and XRD. Characterization of ^ɱ+BSA displays a zeta potential of −28 ± 0.4 mV, an emitted fraction (EF) of 91.29 ± 0.6%, fine particle fraction (FPF) of 74.31 ± 0.8%, mean mass aerodynamic diameter (MMAD) of 1.20 ± 1.6 µm, and geometric standard deviation (GSD) of 2.44 ± 0.34. Additionally, the ^ɱ+BSA was found to exhibit favorable powder characteristics, as revealed by Carr’s index, Hausner’s ratio, and BET analysis. Histological examination revealed that inhaled ^ɱ+BSA is safe for lung tissues in rats. These findings illustrate the exceptional features of ^ɱ+BSA for aerodynamic performance and appear to be a promising DPI carrier.

Graphical Abstract

Keywords:

• Albumin
• pulmonary drug delivery
• quality by design
• inhalation
• powder technology(s)
• particle size

Acknowledgments

The opinions presented in this publication belong to the author(s) and may not necessarily reflect the perspectives of any industries, organizations, or institutions. Gratitude is extended to SVKM's Institute of Pharmacy, Dhule for in-house research assistance. Meggle incorporation for supplying Inhalac® 500 and related information is thankfully acknowledged.

Author contributions

Conceptualization, Methodology, Formal analysis, and investigation, Writing - original draft preparation: Vinit Agnihotri; Writing - review and editing, Resources, Supervision: Dr. Ashish Gorle.

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.