Mannitol-coated hydroxypropyl methylcellulose as an alternative directly compressible controlled release excipient.

One of the most common forms of controlled release technology for oral drug delivery comprises an active ingredient dispersed in a hydrophilic matrix forming polymer such as hydroxypropyl methylcellulose (HPMC), which is tableted via direct compression. However, HPMC may pose problems in direct compression due to its poor flowability. Hence, mannitol syrup was spray-coated over fluidized HPMC particles to produce co-processed HPMC-mannitol at ratios of 20:80, 50:50, and 70:30. Particles of pure HPMC, co-processed HPMC-mannitol, and their respective physical mixtures were evaluated for powder flowability, compression profiles, and controlled release performance. It was found that co-processed HPMC-mannitol consisted of particles with improved flow compared to pure HPMC particles. Sufficiently strong tablets of >2 MPa could be produced at moderate to high compression forces of 150-200 MPa. The dissolution profile could be tuned to obtain desired release profiles by altering HPMC-mannitol ratios. Co-processed HPMC-mannitol offers an interesting addition to the formulator's toolbox in the design of controlled release formulations for direct compression.

Polysorbates versus Hydroxypropyl Beta-Cyclodextrin (HPßCD): Comparative Study on Excipient Stability and Stabilization Benefits on Monoclonal Antibodies.

Polysorbates (PS 20 and PS 80) are the most widely used surfactants in biopharmaceutical formulations to protect proteins from denaturation, aggregation, and surface adsorption. To date, around 70% of marketed therapeutic antibodies contain either PS 20 or PS 80 in their formulations. However, polysorbates are chemically diverse mixtures, which are prone to degradation by oxidation and hydrolysis to produce peroxides and fatty acids, which, in turn, induce protein oxidation, aggregation, and insoluble particle formation. These will negatively impact protein quality and stability. Thus, polysorbate degradation has emerged as one of the major challenges in the development and commercialization of therapeutic protein products. KLEPTOSE® HPßCD (hydroxypropyl beta-cyclodextrin), a new multifunctional excipient, has been shown to provide protein stabilization functions in biopharmaceutical downstream processes and in their final formulations. This study aims to evaluate HPßCD, a new molecule of its class, against polysorbates as a stabilizer in biologics formulations. In this study, the chemical stability of KLEPTOSE® HPßCDs is compared with polysorbates (20 and 80) under various stress conditions. When subjected to heat stress, HPßCDs show little change in product recovery (90.7-100.7% recovery for different HPßCDs), while polysorbates 20 and 80 show significant degradation, with only 11.5% and 7.3% undegraded product remaining, respectively. When subjected to other chemical stressors, namely, autoclave, light, and oxidative stresses, HPßCD remains almost stable, while polysorbates show more severe degradation, with 95.5% to 98.8% remaining for polysorbate 20 and 85.5% to 97.4% remaining for polysorbate 80. Further, profiling characterization and degradation analysis reveal that chemical structures of HPßCDs remain intact, while polysorbates undergo significant hydrolytic degradation and oxidation. Lastly, the physicochemical stability of monoclonal antibodies in formulations is investigated. When subjected to light stress, adalimumab, as a model mAb, formulated in the presence of HPßCD, shows a significant decrease in protein aggregation, and superior monomer and total protein recovery compared to PS 80-containing formulations. HPßCD also reduces both agitation and thermal stress-induced protein aggregation and prevents subvisible particle formation compared to PS 80.

Phase-selective synthesis of Cu2ZnSnS4 nanocrystals using different sulfur precursors.

Cu2ZnSnS4 (CZTS) holds great promises as an absorber material for sustainable and low cost thin film solar cells. Kesterite and wurtzite are two common phases of CZTS. Until now, the synthesis and the growth of both phases are not clearly understood. In this work, kesterite CZTS nanoparticles, wurtzite CZTS nanoparticles as well as CZTS particles with a mixture of both structures were prepared by using elemental sulfur, 1-dodecanethiol, and thioacetamide, respectively. Time dependent studies were conducted and the reaction rate of sulfur source was found to be the key factor in determining the phase formation. Elemental sulfur reacts with oleylamine to produce highly reactive small molecule H2S, which leads to the formation of kesterite phase. The reaction pathways of the long alkane chain 1-dodecanethiol yield the formation of wurtzite phase via a binary phase. Thioacetamide yields a mixture of kesterite and wurtzite phase in the final product. The optical and electrical properties of kesterite and wurtzite CZTS were also evaluated.

Enhancing the performance of solution-processed bulk-heterojunction solar cells using hydrogen-bonding-induced self-organization of small molecules.

Small-molecule solar-cell performance is highly sensitive to the crystallinity and intermolecular connectivity of the molecules. In order to enhance the crystallinity for the solution-processed small molecule, it is possible to make use of carboxylic acid end-functional groups to drive hydrogen-bonding-induced π-π stacking of conjugated molecules. Herein, we report the synthesis and characterization of quarterthiophenes with carboxylic acid as end groups. The formation of hydrogen bonds between neighboring acid groups gives rise to a pseudo-polymeric structure in the molecules, which leads to substantial improvement in the organization and crystallinity of the active layers. This resulted in a four-fold increase in the hole mobility and a two-fold improvement in the performance of the solar cell device for the acid-functionalized molecule, compared to its ester analogue. More importantly, optimal device performance for the acid-functionalized molecule was achieved for the as-cast film, thereby reducing the reliance on thermal annealing and solvent additives.