The Effects of Formulation Components on the Stability and Aerosol Performance of Spray Freeze-Dried Desmopressin Publisher



N Khanderu NEGAR ; H Faghihi HOMA ; M Asadi MEHDI ; M Rostamnezhad MOSTAFA ; Ar Vatanara Alireza REZA
Source: Journal of Drug Delivery Science and Technology Published:2025

Abstract

The type and ratio of excipients are determining factors in preventing peptide conformational changes and destabilization during the spray freeze drying (SFD) process and storage. The present study aimed to develop a stable desmopressin formulation for lung delivery. The combination of three categories of protective agents (sugars, amino acids, and cyclodextrins (CDs)) was assumed to produce a stable formulation of spray freeze-dried desmopressin. The formulations were characterized regarding chemical stability after 1 and 3 months of storage at 40 °C using reversed-phase high-performance liquid chromatography (RP-HPLC). Fourier transform infrared spectroscopy (FTIR) analyzed the desmopressin conformation, and the crystalline structure of samples was assessed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The particle properties were evaluated using a particle size analyzer, scanning electron microscope (SEM), and twin-stage impinger (TSI). The particle sizes were in the range of 2.49 ± 0.08 to 10.09 ± 0.10 μm. The highest fine particle fractions (FPF), 57.7 ± 0.6 and 53.8 ± 0.5 %, were obtained by F8 and F13, containing highly branched cyclodextrin (HBCD) 2.5 and 5 % as well as leucine (Leu) 10 %. Excluding F3, (containing Leu 10 %), with shattered morphology, samples demonstrated a spherical-porous shape. Thermograms confirmed the existence of amorphous microparticles after SFD. F3 showed the least stability profile (76.75 ± 0.5 %), while F9, containing HBCD 2.5 % and phenylalanine (Phe) 5 % was the most stable sample (92.78 ± 0.8 %). The secondary structure of F8 was well-preserved compared to desmopressin. The results revealed that using HBCD enhanced both stability and aerosolization performance. Phe showed more stabilizing effects than Leu during the storage period. © 2025 Elsevier B.V., All rights reserved.