Stability test of novel combined formulated dry powder inhalation system containing antibiotic: physical characterization andin vitro–in silicolung deposition results

Abstract

Objective: The aim was to study the stability of dry powder inhaler (DPI) formulations containing antibiotic with different preparation wayscarrier-based, carrier-free, and novel combined formulationand thereby to compare their physicochemical and in vitro-in silico aerodynamical properties before and after storage. Presenting a novel combined technology in the field of DPI formulation including the carrierbased and carrier-free methods, it is the most important reason to introduce this stable formulation for the further development of DPIs. Methods: The structure, the residual solvent content, the interparticle interactions, the particle size distribution and the morphology of the samples were studied. The aerodynamic values were determined based on the cascade impactor in vitro lung model. We tested the in silico behavior of the novel combined formulated samples before and during storage. Results: The physical measurements showed that the novel combined formulated sample was the most favorable. It was found that thanks to the formulation technique and the use of magnesium stearate (MgSt) has a beneficial effect on the stability compared with the carrier-based formulation without MgSt and carrier-free formulations. The results of in vitro and in silico lung models were consistent with the physical results, so the highest deposition was found for the novel combined formulated sample during the storage. Conclusions: It can be established that after the storage a novel combined formulated DPI contained amorphous drug to have around 2.5 lm mass median aerodynamic diameter and nearly 50% fine particle fraction predicted high lung deposition in silico also.

Stability and In Vitro Aerodynamic Studies of Inhalation Powders Containing Ciprofloxacin Hydrochloride Applying Different DPI Capsule Types

“…As regards morphology, it can be stated that there is a remarkable difference between the samples stored in different capsule types. After 1 month, recrystallization can be detected in the GEL capsule, which correlates well with our previous stability study (performed under different conditions) [ 31 ]. The formulation in this type of capsule appears to be increasingly prone to agglomeration as the stability test progresses.…”

“…Two of our previously published communications provide the background for this study. In the prior article, results/findings related to the development of the above-mentioned formulations are found [ 30 ], while in the second article, stability test results of the same samples were reported at the conditions of 25 ± 2 °C with 50 ± 5% RH (room conditions), stored in open containers for one month [ 31 ]. GEL capsules were used in both cases.…”

Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment

“…MMAD is the mass median aerodynamic diameter and determined using online software (MMAD calculator.com). 32 All experiments were carried out in triplicate (n = 3).…”

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

“…The traditional, carrier-based dry powder inhalers (DPIs) are the most widely used formulations in this therapy, which means an interactive physical mixture of large carrier particles and particle size-optimized drugs [5,6]. The formulations produced by milling and sieving, etc., could be advantageous for those drugs that have high cohesion properties or low doses [7]. However, it should also be noted that the carrier-based DPI formulations still have only 20-30% of the fine particle fraction (FPF) values [8].…”

“…In the case of carrier-free systems, various technological processes (e.g., spray drying, spray freeze drying, and supercritical-fluid technology) and different excipients could be applied, which resulted in beneficial aerodynamic properties [ 9 , 10 ]. However, their disadvantages could be the swelling of the API particles during storage, as well as aggregation because of the high cohesive forces between the small particles [ 7 , 11 ].…”