Formulation design and evaluation of amorphous ABT-102 nanoparticles.

Amorphous nanoparticles are able to enhance the kinetic solubility and concomitant dissolution rates of BCS class II and BCS class II/IV molecules due to their characteristic increased supersaturation levels, smaller particle size and greater surface area. A DoE approach was applied to investigate formulation and spray drying process parameters for the preparation of spray dried amorphous ABT-102 nanoparticles. Stability studies were performed on the optimized formulations to monitor physical and chemical changes under different temperature and humidity conditions. SLS/soluplus and SLS/PVP K25 were the best stabilizer combinations. Trehalose was used to prevent nanoparticle aggregation during spray drying. Particle size distribution, moisture content, PXRD, PLM, FTIR and in vitro dissolution were utilized to characterize the spray dried nanoparticle formulations. The formulations prepared using soluplus showed enhanced dissolution rate compared to those prepared using PVP K25. Following three months storage, it was observed that the formulations stored at 4°C were stable in terms of particle size distribution, moisture content, and crystallinity, whereas those stored at 25°C/60%RH and 40°C/75%RH were unstable. A predictive model to prepare stable solid spray dried amorphous ABT-102 nanoparticles, incorporating both formulation and process parameters, was successfully developed using multiple linear regression analysis.

Fabrication of inhalable spore like pharmaceutical particles for deep lung deposition.

An innovative strategy of fabricating uniform spore like drug particles to improve pulmonary drug delivery efficiency was disclosed in the present study. Spore like particles were prepared through combination of high gravity controlled precipitation and spray drying process with insulin as model drug first, showing rough surface and hollow core. The shell of such spore-like particle was composed of nanoparticles in loose agglomerate and could form nanosuspension upon contacting antisolvent. Further characterization confirmed secondary structure and bio-activity was well preserved in spore like particles of insulin. Stable aerosol performance at different dosages with fine powder fraction (FPF) of 80% and comparable FPF (69-76%) for formulated powder were achieved, significantly higher than marketed product Exubera. On the other hand spore like particles of bovine serum albumin, lysozyme and salbutamol sulfate showed similar high FPF of 80%, regardless of different shape of primary nanoparticles, indicating various application of this new process in significant improvement of pulmonary drug delivery.