Among the many methods available for solubility enhancement, mesoporous carriers are generating significant industrial interest. Owing to the spatial confinement of drug molecules within the mesopore network, low solubility crystalline drugs can be converted into their amorphous counterparts, which exhibit higher solubility. This work aims to understand the impact of drug overloading, i.e., above theoretical monolayer surface coverage, within mesoporous silica on the release behaviour and the thermal properties of loaded drugs. The study also looks at the inclusion of hypromellose acetate succinate (HPMCAS) to improve amorphisation. Various techniques including DSC, TGA, SEM, assay and dissolution were employed to investigate critical formulation factors of drug-loaded mesoporous silica prepared at drug loads of 100–300% of monolayer surface coverage, i.e., monolayer, double layer and triple layer coverage. A significant improvement in the dissolution of both Felodipine and Furosemide was obtained (96.4% and 96.2%, respectively). However, incomplete drug release was also observed at low drug load in both drugs, possibly due to a reversible adsorption to mesoporous silica. The addition of a polymeric precipitation inhibitor HPMCAS to mesoporous silica did not promote amorphisation. In fact, a partial coating of HPMCAS was observed on the exterior surface of mesoporous silica particles, which resulted in slower release for both drugs.

NucleationCrystal growth dispersion Thermodynamic a b s t r a c t In recent years, engineering the total morphology of pharmaceutical materials particles to desirable shape, size and surface area has long been actively increased because it has many advantages especially for improving physicochemical properties of Active Pharmaceutical Ingredients (APIs). This article therefore considers the potential utility of crystal engineering as a tool for controlling and designing properties of pharmaceutical solid particles in purpose to developing efficacious performance of solid dosage form, fundamentals of crystallization process, applications. In addition, understanding the relationship between molecular recognition, thermodynamic, and kinetics which controls the crystallization process so that it benefits in designing successful experiments to have desirable crystal habit for materials.

Inhalation of nanoparticles for pulmonary drug delivery offers the potential to harness nanomedicine formulations of emerging therapeutics, such as curcumin, for treatment of lung cancer. Biocompatible nanoparticles composed of poly(2-methacryloyloxyethyl phosphorylcholine)-b-poly(2-(diisopropylamino)ethyl methacrylate) (MPC-DPA) have been shown to be suitable nanocarriers for drugs, whilst N-trimethyl chitosan chloride (TMC) coating of nanoparticles has been reported to further enhance their cellular delivery efficacy; the combination of the two has not been previously investigated. Development of effective systems requires the predictable, controllable, and reproducible ability to prepare nanosystems possessing particle sizes, and drug loading capacities, appropriate for successful airway travel, lung tissue penetration, and tumor suppression. Although a number of MPC-DPA based nanosystems have been described, a complete understanding of parameters controlling nanoparticle formation, size, and morphology has not been reported; in particular the effects of differing solvents phases remains unclear. In this current study a matrix of 31 solvent combinations were examined to provide novel data pertaining to the formation of MPC-DPA nanoparticles, and in doing so afforded the selection of systems with particle sizes appropriate for pulmonary delivery applications to be loaded with curcumin, and coated with TMC. This paper presents the first report of novel data detailing the successful preparation, characterisation, and optimisation of MPC-DPA nanoparticles of circa 150-180nm diameter, with low polydispersity, and a curcumin loading range of circa 2.5-115μM, tunable by preparation parameters, with and without TMC coating, and thus considered suitable candidates for inhalation drug delivery applications.