Investigating the drug-excipient compatibility and physicochemical stability of powders produced by spray dry, freeze dry and tubular mixer

Abstract

Introduction: In most DPI (dry powder inhaler) formulations, drug substance and carrier are two major components. Lactose is the most common carrier, which can undergo Maillard reaction in the presence of primary and secondary amines. Salbutamol sulphate (SS) and formoterol fumarate (FF) contain secondary amine and formulate as DPIs. Aim: Since Maillard reaction in DPI formulations has not been investigated yet, this study aims to investigate any potential of Maillard reaction.Also the inhalation forms of celecoxib were recently investigated for lung cancer treatment, in this study different formulations of celecoxib have been prepared to improve the physicochemical characteristics. Material and methods: First the compatibility was checked by preparing binary mixtures of drug: excipient. Then different formulations were prepared using a tubular mixer, spray drying and freeze drying. Samples were stored at both ambient and stress conditions (40°C ± 2, 75% ± 5 RH). Differential scanning calorimetry (DSC), field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS-MS) were employed for sample analysis. The in vitro aerosolization performance was evaluated using a next-generation impactor (NGI). Results: The results showed that the colour of some formulations changed to brown after storage in the case of FF formulations and spray dried salbutamol (SDSS). Incompatibility was confirmed by HPLC-PDA analysis. The mass spectra revealed the m/z of the adduct compound and confirmed the Millard reaction. In the case of celecoxib results show leucine was compatible excipient. Conclusion: Due to the presence of micronized particles in DPIs formulations Maillard reaction is more possible, which is proved in SS and FF DPIs. Environmental factors such as temperature and humidity are of great importance in the manufacturing process of these products. Powder produced by spray drying is more vulnerable to degradation.