A Systematic Approach to the Development of Cilostazol Nanosuspension by Liquid Antisolvent Precipitation (LASP) and Its Combination with Ultrasound

Nanosizing is an approach to improve the dissolution rate of poorly soluble drugs. The first aim of this work was to develop nanosuspension of cilostazol with liquid antisolvent precipitation (LASP) and its combination with ultrasound. Second, to systematically study the effect of bottom-up processing factors on precipitated particles’ size and identify the optimal settings for the best reduction. After solvent and stabilizer screening, in-depth process characterization and optimization was performed using Design of Experiments. The work discusses the influence of critical factors found with statistical analysis: feed concentration, stabilizer amount, stirring speed and ultrasound energy governed by time and amplitude. LASP alone only generated particle size of a few microns, but combination with ultrasound was successful in nanosizing (d10 = 0.06, d50 = 0.33, d90 = 1.45 µm). Micro- and nanosuspension’s stability, particle morphology and solid state were studied. Nanosuspension displayed higher apparent solubility than equilibrium and superior dissolution rate over coarse cilostazol and microsuspension. A bottom-up method of precipitation-sonication was demonstrated to be a successful approach to improve the dissolution characteristics of poorly soluble, BCS class II drug cilostazol by reducing its particle size below micron scale, while retaining nanosuspension stability and unchanged crystalline form.

Single-Cell Transcriptomics Analysis of Human Small Antral Follicles

Human ovarian folliculogenesis is a highly regulated and complex process. Characterization of follicular cell signatures during this dynamic process is important to understand follicle fate (to grow, become dominant, or undergo atresia). The transcriptional signature of human oocytes and granulosa cells (GCs) in early-growing and ovulatory follicles have been previously described; however, that of oocytes with surrounding GCs in small antral follicles have not been studied yet. Here, we have generated a unique dataset of single-cell transcriptomics (SmartSeq2) consisting of the oocyte with surrounding GCs from several individual (non-dominant) small antral follicles isolated from adult human ovaries. We have identified two main types of (healthy) follicles, with a distinct oocyte and GC signature. Using the CellphoneDB algorithm, we then investigated the bi-directional ligand–receptor interactions regarding the transforming growth factor-β (TGFβ)/bone morphogenetic protein (BMP), wingless-type (MMTV)-integration site (WNT), NOTCH, and receptor tyrosine kinases (RTK) signaling pathways between oocyte and GCs within each antral follicle type. Our work not only revealed the diversity of small antral follicles, but also contributes to fill the gap in mapping the molecular landscape of human folliculogenesis and oogenesis.

Evaluation of Starch-Biopolymer Synthesized from Chaffs of Common Beans (Phaseolus Vulgaris)

The resilience and resistance of plastics to decomposition have led to the imperative need to develop biodegradable plastics as a viable solution. Starch biodegradable films have been synthesized recently as a sustainable replacement for synthetic plastics. Acid hydrolysis was used to synthesize starch nanoparticles from the chaffs of Common Beans (Phaseolus vulgaris) which was mixed with varying percentages of Low-Density Polyethene (LDPE: C-S; 95:5, 90:10, 85:15, 80:20) by the heating process. Characterization of the starch nanoparticles was done using the FTIR, TEM, and EDX while the physicochemical properties (Compression, Hardness, and Biodegradation) of the produced biopolymers (LDPE-Starch) were also studied. Starch spectrum was observed at 3436cm-1 and other functional groups such as Carbonyl group, Sulphones, and Acetylenic groups were also revealed by Fourier Transmission Infra-Red Spectroscopy. The starch nanoparticles were observed to be flake-like shapes with a size of 50nm as shown by the TEM analysis. Of all the varying compositions of starch biopolymer synthesized, 90:10LDPE/B-S had the best hardness properties with 40.78HD and constant degradation was observed within weeks 3 and 4 in 95:5 (LDPE-B.S) with a peak value of 0.7705%. The study revealed the economical and sustainable production of starch nanoparticles from the chaffs of Common beans (Phaseolus vulgaris) and its use for the improvement of biodegradable plastic films.

Integrated Process Model Applications Linking Bioprocess Development to Quality by Design Milestones

Maximizing the value of each available data point in bioprocess development is essential in order to reduce the time-to-market, lower the number of expensive wet-lab experiments, and maximize process understanding. Advanced in silico methods are increasingly being investigated to accomplish these goals. Within this contribution, we propose a novel integrated process model procedure to maximize the use of development data to optimize the Stage 1 process validation work flow. We generate an integrated process model based on available data and apply two innovative Monte Carlo simulation-based parameter sensitivity analysis linearization techniques to automate two quality by design activities: determining risk assessment severity rankings and establishing preliminary control strategies for critical process parameters. These procedures are assessed in a case study for proof of concept on a candidate monoclonal antibody bioprocess after process development, but prior to process characterization. The evaluation was successful in returning results that were used to support Stage I process validation milestones and demonstrated the potential to reduce the investigated parameters by up to 24% in process characterization, while simultaneously setting up a strategy for iterative updates of risk assessments and process controls throughout the process life-cycle to ensure a robust and efficient drug supply.