2019 Research Conference – Research Project Presentations

Thank you to these researchers for their work

Jayshil Bhatt

Title: Challenging Assay Development for two different Lidocaine Topical Systems by Using UPLC-PDA in support of Clinical Studies 2. Clinical Results and application

Summary: Lidocaine, a local anesthetic widely used drug for pain relief is among the highest selling transdermal patches in the United States. Read the abstract

Mustafa Bookwala

Title: Amorphous Solid Dispersion Formation is Not Completely Predicted by Drug-Polymer Miscibility

Summary: Poorly water-soluble drugs can potentially be formulated as amorphous solid dispersions (ASD), allowing improvement in API apparent solubility. Intimate interaction with the carrier polymer further improves the physical stability of the amorphous API, preventing spontaneous recrystallization. Molecular mixing between drug and polymer is desirable so that a single-phase amorphous system can be formed. In an in-house, 15-member API library, the dispersion tendencies of the API in polyvinylpyrrolidone-vinyl acetate (PVPva) was successfully predicted for all API. In the present research, dispersability (defined as intimate mixing of drug with polymer to undergo cosolidification without recrystallization) in PVPva will be related to API miscibility in the polymer via the interaction parameter from the Flory-Huggins lattice-based model. Read the abstract

Kandarp Dave

Title: Screening and in vitro transfection parameter optimization of BDNF siRNA loaded lipidoid-nanoparticles for the treatment of chronic neuropathic pain

Summary: Model biodegradable LNPs have characteristic size 100-200 nm with nearly 50% siRNA encapsulation efficiency. U-87 MG cells express GAPDH and BDNF proteins hence, studied for gene silencing efficacy of siRNA loaded LNP. Model LNP showed considerable gene knockdown in U-87 MG cells. Lead lipidoid containing LNPs showed greater entrapment of siRNA than a model LNPs with particle size nearly 200 nm and a narrow polydispersity index. All eight siGFP 50 nM LNPs and five out of eight siGAPDH 50 nM LNPs were well tolerated by U-87 MG cells for 24 h transfection time. One of the lead LNP showed nearly 40% target protein knockdown without intracellular toxicity. Read the abstract

Title: Characterization of the SIM-A9 cell line as a novel microglia activation model to screen potential therapeutics for neuropathic pain

Summary: SIM-A9 expressed microglial phenotypes such as P2X4R, Iba1, and BDNF—involved in the pathogenesis of PNI-induced neuropathic pain. ATP at a safe dose showed a time-dependent increase in Iba1 and BDNF expression without causing intracellular toxicity. LPS stimulation was found to be toxic to SIM-A9 cells. Hence, an ATP activated SIM-A9 cell line model system can be utilized for screening of neuropathic pain therapeutics targeting P2X4R and/or BDNF knockdown, including small molecule as well as macromolecular therapies such as proteins and nucleic acids. Read the abstract

Daniel Davis

Title: Transdermal Patch Design for Fixed-Dose Combination Delivery

Summary: A transdermal drug delivery system (TDDS) is designed to deliver an active pharmaceutical ingredient (API) through skin. Permeation of an API through skin is controlled for systemic effects by adjusting drug concentration, excipient composition and patch design. A bilayer, drug-in-adhesive TDDS design affords improved regulation of the drug release profile by varying thicknesses and spatial distribution of an API across each layer. In this study, we evaluate the co-release of two fixed-dose APIs from a bilayer TDDS by modifying spatial distribution and layer thickness while maintaining the same overall formulation composition. Read the abstract

Ashwini Gumireddy

Title: Molecular Structure Predicts the Tendency of Six API to Form Amorphous Solid Dispersions Using Melt-Quenching, Rotary-Evaporation, and Spray-Drying

Summary: Read the abstract

Seok-Hoon Hong

Title: Antimicrobial toxin engineering, biofilms, drug discovery

Summary: My research focuses on developing novel biological platforms with various applications through interdisciplinary approaches, specifically a combination of synthetic biology, cell-free biology, and biofilm engineering. Specific research areas include i) Engineering beneficial microbes for controlling deleterious biofilms, ii) Developing a platform for novel drug discovery, iii) Identifying natural products for use as anti-biofilm and anti-persister agents, and iv) Expanding the genetic code using cell-free protein synthesis platforms. Read the abstract

Shreya Kulkarni, PhD

Title: Reconstitution Time for High Concentrated Lyophilized Proteins: Role of Formulation and Protein

Summary: The factors influencing reconstitution time of highly concentrated proteins in lyophilized formulations are yet to be fully elucidated and are the focus of the present work. Read the abstract

Jun Li, PhD

Title: Novel Lyophilized Dosage Form of Taxane Formation (ZY-010) With Unique Drug Release Profiles

Summary: A vitamin modified polymeric carbohydrate (VMPC) was developed in ZY Therapeutics. The first drug candidate, ZY-010-PNP, is a VMPC encapsulated paclitaxel (PTX) nanoparticle (average < 150 nm), which is supplied as a lyophilized powder with in use stability up to 24 hrs. The time- and concentration-dependent release profile of ZY-010-PNP is quite different from the burst release profile of all other marketed PTX nano-formulations.

Read the abstract

Yue Li

Title: Integrating Lattice Boltzmann and Bonded Particle Models to Simulate Tablet Disintegration and Dissolution

Summary: As the mostly used oral dosage form, tablets are widely manufactured, tested, and regulated. Disintegration of a tablet and, subsequently, release kinetics of the active pharmaceutical ingredient (API), is facilitated by utilizing swelling polymers and/or polysaccharides as disintegrants. The disintegration process governs the drug release kinetics, playing a key role in determining drug dissolution and eventual absorption and bioavailability. It is thus of great importance to fully understand and predict the disintegration and dissolution processes, enabling the rational design of tablet formulation. Current computational methods [1,2], nonetheless, neglect the fluid dynamics around the tablet (for example, in a testing device or even in the gastrointestinal tract) and, more importantly, fail to realistically model the mutual influence between the fluid and drug/excipient particles. Herein, we aim to develop a high-fidelity, physics-based simulation method of tablet disintegration and dissolution. We have developed a computational platform which can simulate three basic processes of tablet dissolution, including fluid-solid interaction, particle disintegration and particle dissolution. For this purpose, we have utilized the Lattice Boltzmann Method (LBM) as the general framework and integrated Bonded Particle Model (BPM, which is a variation of Discrete Element Model) with immersed moving boundary method. Read the abstract

Xiuling Lu, PhD

Title: Perfluorocarbon-loaded Nanocapsules Increase X-ray Computed Tomography Contrast of Subcutaneous and Intraperitoneal Tumors in Mice

Summary: An amphiphilic triblock copolymer (PEG-b-PCL(Ch)) was designed in-house to form and stabilize nanocapsules loaded with perfluorooctyl bromide (PFOB), a perfluorocarbon that exhibits high X-ray attenuation. PFOB-loaded nanocapsules were superior to Iohexol in enhancing CT contrast in subcutaneous and intraperitoneal tumors. This platform showed potential for clinical applications in image-guided cancer therapy through better understanding and detection of tumor leakiness and heterogeneity due to its ability to enhance image contrast and assess intratumoral distribution. Read the abstract

Pradeep Velekar

Title: A Design of Experiments (DOE) Approach to Determine the Criticality of Process Parameters and Press Type on Tablet CQAs of a Complex formulation

Summary: The main objective of the study was a) to understand the criticality of the compaction process parameters, and b) to determine whether the press type (rotary press vs compaction simulator) had any effect on the critical quality attributes (CQAs) of a complex formulation. A Design of Experiment (DOE) approach, in support of Quality by Design (QbD) was used to guide the study. Read the abstract

Hui Wei

Title: Challenging Assay Development for two different Lidocaine Topical Systems in support of Clinical Studies 1: Extraction Method Development

Summary: To develop extraction methods for commercial lidocaine 5% topical systems. Complete extraction of topical polymeric systems can be challenging but is a necessary part of assuring the quality of the products. Read the abstract

Feng Zhang, PhD

Title: Twin-Screw Wet Granulation of Gabapentin: A Design of Experiment Study on the Effects of Processing Variables on Drug Stability and Granule Physical Properties

Summary: The results demonstrate the role of processing parameters (e.g. screw speed, feed rate and L/S ratio) and their interrelationships on the quality attributes of GABA granules produced using TSWG process. Higher screw speed, low feed rate and higher L/S ratio resulted in granules with more GABA crystal defects and higher amorphous GABA content. As a result, granules prepared under these parameters degraded faster during the storage. The tabletability of GABA granules was mainly dependent on L/S ratio with more tabletable granules at higher L/S ratio. Read the abstract