Excipient Interactions in Glucagon Dry Powder Inhaler Formulation for Pulmonary Delivery

Abstract

Purpose: This study describes the development and characterization of glucagon dry powder inhaler (DPI) formulation for pulmonary delivery. Lactose monohydrate, as a carrier, and L-leucine and magnesium stearate (MgSt) were used as dispersibility enhancers for this formulation. Methods: Using Fourier-transform infrared (FTIR) spectroscopy, Differential Scanning Calorimetry (DSC), and Raman confocal microscopy, the interactions between glucagon and all excipients were characterized. The fine particle fractions (FPFs) of glucagon in different formulations were determined by a twin stage impinger (TSI) using a 2.5% glucagon mixture, and the glucagon concentration was measured by a validated LC-MS/MS method. Results: The FPF of the glucagon was 6.4%, which increased six-fold from the formulations with excipients. The highest FPF (36%) was observed for the formulation containing MgSt and large carrier lactose. The FTIR, Raman, and DSC data showed remarkable physical interactions of glucagon with leucine and a minor interaction with lactose; however, there were no interactions with MgSt alone or mixed with lactose. Conclusion: Due to the interaction between L-leucine and glucagon, leucine was not a suitable excipient for glucagon formulation. In contrast, the use of lactose and MgSt could be considered to prepare an efficient DPI formulation for the pulmonary delivery of glucagon.

Puerarin dry powder inhaler formulations for pulmonary delivery: Development and characterization

“…Using a mortar and pestle, the puerarin particles were reduced to inhalable size (0.5–2 μm) by hand milling (micronization) [ 21 ]. However, using a mortar and pestle is not the perfect method to produce inhalable drug particles for DPI formulation due to potential repeatability problems.…”

“…Lactose is the commonly used carrier by improving the flowability of powder, thus improving dose accuracy, minimizing dose variability as compared to the drug alone [ 19 ]. Leucine [ 20 ] and Magnesium stearate (Mg-St) [ 21 ] are used as dispersibility enhancers thereby enhancing the flow properties of the drug [ 22 ].…”

“…The compatibility of excipients (lactose, leucine, Mg-St, etc) with the drug used in the DPI formulation is important to ensure the stability and efficiency of the formulation. Recently, Rashid et al demonstrated the application of Raman spectroscopy, a non-destructive analytical method in observing the distribution of all components in powder mixtures to investigate the interactions and distribution of the active drug with other excipients in the inhaled powder formulations [ 21 ]. The FTIR, another non-destructive technique in investigating the stability of active drugs in the powder mixture [ 23 ] has also been used to understand the structural integrity of puerarin in the mixture.…”

Advances in Pulmonary Drug Delivery

“…Rashid and co-workers, on the other hand, followed the traditional approach and formulated a lactose carrier-based dry powder formulation of glucagon for pulmonary delivery [ 5 ]. They investigated L-leucine and magnesium stearate as dispersibility enhancers and found the highest fine particle fraction (FPF) for the formulation to contain Mg stearate (36%) and large carrier lactose, whereas leucine was not a suitable excipient for the pulmonary delivery of glucagon.…”

Development of an Innovative, Carrier-Based Dry Powder Inhalation Formulation Containing Spray-Dried Meloxicam Potassium to Improve the In Vitro and In Silico Aerodynamic Properties

“…This possibility can be explained by the fact that the lung has highly absorptive tissue with a large surface area, which has a thin adsorption membrane and excellent blood supply. Through this administration route, a lower dose is required compared to oral administration; thus, a more favorable side-effect profile can be achieved, and even the onset of the action could be faster [1][2][3][4].…”