Chemical Engineering Commons^™

Understanding Absorption, Supersaturation, And Drug Activity In Solution: Working Towards Developing A More Biorelevant Media, Freddy Arce

Theses and Dissertations--Pharmacy

With the looming dominance of poorly water-soluble chemical entities within the pharmaceutical pipeline, the pharmaceutical industry has leaned on the use of supersaturating drug delivery systems (SDDSs) to achieve efficacious concentrations within the gastrointestinal fluids. SDDSs aim to achieve concentrations in solutions greater than the solubility of the lowest energy crystalline form. However, the generation of supersaturated solutions of active pharmaceutical ingredients (APIs) creates a strong crystallization potential, which is undesirable.

In product development, supersaturating products often fail in Phase I and Phase II clinical trials due to poor oral bioavailability and a lack of in vivo efficacy. Pre-clinical testing …

Understanding The Thermodynamics And Oral Absorption Potential Of Pharmaceutical Amorphous Solid Dispersions, Nico Setiawan

Theses and Dissertations--Pharmacy

Supersaturating drug delivery systems, such as amorphous solid dispersions (ASDs), have been used extensively to elevate the apparent solubility and oral bioavailability of poorly water-soluble drugs. However, despite the numerous examples of success in increasing solubility and oral bioavailability using ASDs, physical stability challenges remain as formulators seek to employ high drug loading for cost reduction and improved patient compliance. Therefore, stability in both the solid and solution state must be considered for ASDs to be successful. In the solid state, the drug must remain amorphous in the solid matrix throughout the shelf life of the product. Although excipients, such …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

The Critical Role Of Mechanism-Based Models For Understanding And Predicting Liposomal Drug Loading, Binding And Release Kinetics, Sweta Modi

Theses and Dissertations--Pharmacy

Liposomal delivery systems hold considerable promise for improvement of cancer therapy provided that critical formulation design criteria can be met. The main objective of the current project was to enable quality by design in the formulation of liposomal delivery systems by developing comprehensive, mechanism-based mathematical models of drug loading, binding and release kinetics that take into account not only the therapeutic requirement but the physicochemical properties of the drug, the bilayer membrane, and the intraliposomal microenvironment.

Membrane binding of the drug affects both drug loading and release from liposomes. The influence of bilayer composition and phase structure on the partitioning …