Formulation, stability and pharmacokinetics of sugar-based salmon calcitonin-loaded nanoporous/nanoparticulate microparticles (NPMPs) for inhalation

Abstract

A challenge exists to produce dry powder inhaler (DPI) formulations with appropriate formulation stability, biological activity and suitable physicochemical and aerosolisation characteristics that provide a viable alternative to parenteral formulations. The present study aimed to produce sugar-based nanoporous/nanoparticulate microparticles (NPMPs) loaded with a therapeutic peptide - salmon calcitonin (sCT). The physicochemical properties of the powders and their suitability for pulmonary delivery of sCT were determined. Production of powders composed of sCT loaded into raffinose or trehalose with or without hydroxypropyl-β-cyclodextrin was carried out using a laboratory scale spray dryer. Spray dried microparticles were spherical, porous and of small geometric size (≤2 μm). Aerodynamic assessment showed that the fine particle fraction (FPF) less than 5 μm ranged from 45 to 86%, depending on the formulation. The mass median aerodynamic diameter (MMAD) varied between 1.9 and 4.7 μm. Compared to unprocessed sCT, sCT:raffinose composite systems presented a bioactivity of approximately 100% and sCT:trehalose composite systems between 70-90% after spray drying. Storage stability studies demonstrated composite systems with raffinose to be more stable than those containing trehalose. These sugar-based salmon calcitonin-loaded NPMPs retain reasonable sCT bioactivity and have micromeritic and physicochemical properties which indicate their suitability for pulmonary delivery. Formulations presented a similar pharmacokinetic profile to sCT solution. Hence the advantage of a dry powder formulation is its non-invasive delivery route and ease of administration of the sCT.

Optimization of levofloxacin-loaded crosslinked chitosan microspheres for inhaled aerosol therapy

“…the fraction of LVX in particles with aerodynamic diameters below 5.0 µm, was calculated by interpolation, from the inverse of the standard normal cumulative mass percentage distribution, and considering stages 1 to 3. The mass median aerodynamic diameter (MMAD) of the particles was calculated from a similar plot (considering stages 1 to 6) as the particle aerodynamic diameter at which the line crosses the 50% mark [37][38][39]. The fine particle fraction (FPF) was calculated by converting the FPD mass as the percentage of the ED.…”

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers

“…Spray‐drying is a process where the formulation is presented as a feed solution, suspension or emulsion and converted into fine droplets, followed by exposure to rapid hot air‐stream resulting in dry respirable‐sized powders. In addition to the composition of the feed formulation, several operational parameters greatly affect the quality and quantity of the final formulation such as inlet temperature, air flow, aspiration capacity and feed rate . Biocompatible excipients (carbohydrates, amino acids and lipids) are typically added to the formulation feed to afford dry powders with bulk and to promote the production of a desirable aerodynamic particle size which upon inhalation allows rapid release of NPs in the lung fluid .…”

Development of dry powder inhaler containing tadalafil-loaded PLGA nanoparticles

“…The addition of leucine changed the smooth surface of PLGA-NPs to a rough surface that may be attributed to earlier precipitation of leucine with lower solubility in the drying process (17). …”

“…In order to reach the deep lung and optimize systemic drug absorption, MMAD should be between 1 and 3 μm (17). The MMAD for spray dried TAD-PLGA-NPs ranged between 1.45 and 2.8 μm indicating the potential of the prepared particles for DPI application.…”