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Modeling the Impact of Amorphous Drug-Polymer Colloids on the Absorption of Poorly Water Soluble Drugs

Formulation of amorphous solid dispersions, as means to improve absorption for poorly water soluble drugs, has proven to be a reliable and effective approach. In assessing how these formulations perform in vivo, it has been observed that they can dissolve into multiple species in biorelevant media. These species can be supersaturated free drug, drug partitioned into bile salt micelles and amorphous drug-polymer colloids, as well as precipitated amorphous or crystalline drug. Here, the impact of amorphous drug-polymer colloids on the absorption of several water insoluble drugs is modeled based on a modified permeability equation that takes these nano-sized colloids into account. The model simulations are compared to three literature in vivo studies, as well as the simulation for those using the standard permeability calculation. To learn more, download our poster.
Authors: Aaron Stewart
Publish Date: 05-Nov-2020

Case Study: Application of Colorista® Capsules for Rapid Product Development with Proof of Concept Data

The objective of this study was to design the most suitable solid oral delivery system with an acceptable shelf life at room temperature or at refrigerated conditions. This study was initiated with an extensive excipient compatibility study using pharmaceutical excipients and stabilizers, followed by a blend stability study, a manufacturing process and dosage form selection study, and an accelerated stability study using the final formulation in Colorista® capsules. To learn more, download our poster.
Authors: Namrata Vora
Publish Date: 05-Nov-2020

Methanol-assisted Secondary Drying to Accelerate Residual Solvent Removal in Spray-dried Polymers

Drug candidates with low aqueous solubility require bioavailability enhancement techniques to enable oral delivery. Spray drying has been used to manufacture amorphous solid dispersions with enhanced oral bioavailability, resulting in over a dozen commercial products and many more in clinical trials. After spray drying is used to convert a liquid feed to a solid powder, residual solvent remains in the product, which must be removed to meet ICH safety specifications. The process of residual solvent removal is called secondary drying. Typical secondary drying techniques, such as drying in the presence of water vapor or vacuum drying often suffice. Some spray-dried materials are more challenging, requiring 24 hours or longer to secondary dry at typical conditions. This work introduces methanol-assisted secondary drying, a technique which can be used to accelerate residual solvent removal from spray-dried products.
Publish Date: 05-Nov-2020

From Brick Dust to Blockbuster

David Lyon shares insights on the future of the small molecule industry. The pipeline of small molecule candidates has become larger as more approvals are fast-tracked. Smaller biotechs drive innovation in developing therapies for the high-demand areas such as oncology and immunology. However, these firms often lack the technology to manufacture large amounts of a drug needed for trials, especially for poorly soluble candidates.  Due to this, many companies turn to CDMOs in order to scale up or solve bioavailability issues.
Authors: David Lyon
Publish Date: 04-Nov-2020

Rapid Fire Presentation: Measuring Lipolytic Activity in Biologics Drug Substance and Drug Product

Polysorbate degradation is discussed being oxidatively and hydrolytically, via lipolytic activity of enzymes (Lipases) in HCP. We developed an analytical assay to detect and measure lipolytic activity in biopharmaceutical partly purified DS, drug substance (DS) and drug product (DP). The assay was optimized by variation of key parameters. The assay can support the optimization of the downstream purification process in order to remove HCPs with lipolytic activity. Furthermore it can be used to measure lipolytic activity in DS / DP samples and support root cause investigations related to polysorbate degradation. To learn more, download our rapid-fire presentation.
Authors: Andreas Zerr
Publish Date: 03-Nov-2020

Rapid Fire Presentation: Polysorbate in Biologics – Understanding Degradation by Applying Proper Analytics

Polysorbates are excipients in biopharmaceutical formulations that protect the therapeutic proteins from interfacial stress. The biopharmaceutical industry currently phases a problem due to observed degradation - oxidatively and hydrolytically - of polysorbate in drug product formulations, leading to increased formation of sub-visible and visible particles and to a potential loss of protecting propensity of the surfactant. Interestingly, mitigation of the effects observed in drug product often can be provided already during drug substance manufacturing and compounding. However, a proper analytical toolbox is necessary to spot polysorbate degradation at an early stage and to differentiate the degradation mechanisms. In this work, we present an optimized analytical toolbox to control polysorbate quantity and quality. Additionally we present analytical strategies to be applied for root cause investigations once polysorbate degradation is observed. To learn more, download our presentation.
Authors: Michael Jahn
Publish Date: 02-Nov-2020

Rapid Fire Presentation: in vivo Protein Stability - What Happens After Administration?

Knowledge of the stability of therapeutic proteins in vivo, or after administration to patients, is limited. This talk explains the relevance of in vitro studies to assess the stability of therapeutic proteins under simulating physiologic conditions. in vivo degradation of a therapeutic protein may alter treatment efficacy and/or patient safety. Moreover, in vitro studies can support the selection of better molecules in early stages of pharmaceutical development. In our study, we compared the physical stability of 8 different monoclonal antibodies (mAbs) in phosphate-buffered saline (PBS) and human serum. mAbs were characterized with respect to fragmentation, aggregation, and proteinaceous particle formation. To learn more, download our rapid fire presentation. 
Publish Date: 02-Nov-2020

Rapid Fire Presentation: Modeling Phase Separation Risk During Spray Drying from Mixed Solvents

Low organic solubility compounds in need of bioavailability enhancement by spray drying are increasingly prevalent in many development pipelines. Using mixed aqueous/organic solvents is one way to improve organic solubility, thereby increasing process throughput, though this approach may impart phase separation risks by solvent enrichment during drying. Practical tools for predicting the impacts of mixed solvents on the properties and performance of spray-dried dispersions is an important gap in process and formulation development. This work presents a model for droplet drying and phase behavior in a four-component system, incorporating two different solvents. To learn more, download our rapid fire presentation.
Authors: Jonathan Cape
Publish Date: 29-Oct-2020

Rapid Fire Presentation: Processing Low Viscosity Products Using Liquid Filling and Banding Technology

Alongside the ability to formulate and deliver challenging poorly aqueous soluble APIs, liquid-filled capsule-based systems have a number of advantages. Lipid-based formulations can be formulated and manufactured in soft gel capsules or hard capsule shells. When developing a liquid-filled hard capsule, capsule selection is fundamental and needs to be assessed early on in the process, with a view to scale up to be performed. When enhancing bioavailability with lipid-based systems, a number of oils and surfactants are employed and often these materials are of low viscosity. This rapid fire presentation focuses on the processing of such oils and scale up considerations.
Authors: Jenifer Mains
Publish Date: 29-Oct-2020

A Novel Architecture for High Drug-loaded Amorphous Solid Dispersion Tablets; Assessment of in vitro and in vivo Performance, Stability and Manufacturability

Amorphous solid dispersions (ASDs) can increase solubility and dissolution rate of poorly water soluble drugs. However, ASD dosage forms are often large or require multiple units to meet dose requirements due to incorporation of concentration-sustaining polymers (CSPs) in the formulation. To address this challenge, a high-loaded dosage form (HLDF) architecture for ASDs was developed, in which a drug is first spray-dried with a high glass transition temperature (Tg) dispersion polymer to facilitate high drug loading while maintaining physical stability. The ASD is then granulated with a CSP to extend supersaturation in solution. The HLDF approach differs from traditional ASD architectures in which the dispersion polymer inside the ASD has the dual purpose of maintaining physical stability and extending supersaturation in solution, thereby constraining the formulation and often resulting in low dosage form drug loading. The HLDF platform has the potential to reduce tablet mass by at least 40% while maintaining performance, stability and manufacturability. This presentation describes case studies highlighting the HLDF architecture, including physical stability, in vitro and in vivo performance and manufacturability.
Authors: Deanna Mudie
Publish Date: 28-Oct-2020