Leadership and mentorship of Professor Lynne S. Taylor: A personal account from former mentees.

This article highlights the profound impact of Professor Lynne S. Taylor, Retter Distinguished Professor of Pharmacy at Purdue University, on her mentees in terms of scientific and professional experience. The former students summarize some of her important contributions, including her emphasis on critical thinking, collaboration, and work-life balance, which have shaped her students into dedicated scientists advancing the pharmaceutical sciences.

Chronic pulmonary aspergillosis in a tertiary tuberculosis institute: A common entity missed commonly.

The disease chronic pulmonary aspergillosis (CPA), which has 3 million cases globally, has a substantial impact on global health. The morbidity and mortality it cause are also rather severe. Patients with modest immune suppression or those with underlying structural and chronic lung illnesses are more likely to develop this condition.

Crystallization from Supersaturated Solutions: Role of Lecithin and Composite Simulated Intestinal Fluid.

Purpose: The overall purpose of this study was to understand the impact of different biorelevant media types on solubility and crystallization from supersaturated solutions of model compounds (atazanavir, ritonavir, tacrolimus and cilnidipine). The first aim was to understand the influence of the lecithin content in FaSSIF. As the human intestinal fluids (HIFs) contain a variety of bile salts in addition to sodium taurocholate (STC), the second aim was to understand the role of these bile salts (in the presence of lecithin) on solubility and crystallization from supersaturated solutions, METHODS: To study the impact of lecithin, media with 3 mM STC concentration but varying lecithin concentration were prepared.

Origin of Nanodroplet Formation Upon Dissolution of an Amorphous Solid Dispersion: A Mechanistic Isotope Scrambling Study.

It has been observed that certain amorphous solid dispersions (ASDs), upon dissolution, generate drug-rich amorphous nanodroplets. These nanodroplets, present as a dispersed phase, can potentially enhance oral bioavailability of poorly soluble drugs by serving as a drug reservoir that efficiently feeds the continuous aqueous solution phase following absorption of drug. The purpose of this study is to probe the formation mechanism of the nanodroplets.

Impact of Micellar Surfactant on Supersaturation and Insight into Solubilization Mechanisms in Supersaturated Solutions of Atazanavir.

Purpose: The goals of this study were to determine: 1) the impact of surfactants on the "amorphous solubility"; 2) the thermodynamic supersaturation in the presence of surfactant micelles; 3) the mechanism of solute solubilization by surfactant micelles in supersaturated solutions.

Methods: The crystalline and amorphous solubility of atazanavir was determined in the presence of varying concentrations of micellar sodium dodecyl sulfate (SDS). Flux measurements, using a side-by-side diffusion cell, were employed to determine the free and micellar-bound drug concentrations.

Exploiting the Phenomenon of Liquid-Liquid Phase Separation for Enhanced and Sustained Membrane Transport of a Poorly Water-Soluble Drug.

Recent studies on aqueous supersaturated lipophilic drug solutions prepared by methods including antisolvent addition, pH swing, or dissolution of amorphous solid dispersions (ASDs) have demonstrated that when crystallization is slow, these systems undergo liquid-liquid phase separation (LLPS) when the concentration of the drug in the medium exceeds its amorphous solubility. Following LLPS, a metastable equilibrium is formed where the concentration of drug in the continuous phase corresponds to the amorphous solubility while the dispersed phase is composed of a nanosized drug-rich phase. It has been reasoned that the drug-rich phase may act as a reservoir, enabling the rate of passive transport of the drug across a membrane to be maintained at the maximum value for an extended period of time.

Using Environment-Sensitive Fluorescent Probes to Characterize Liquid-Liquid Phase Separation in Supersaturated Solutions of Poorly Water Soluble Compounds.

Purpose: Highly supersaturated aqueous solutions of poorly soluble compounds can undergo liquid-liquid phase separation (LLPS) when the concentration exceeds the "amorphous solubility". This phenomenon has been widely observed during high throughput screening of new molecular entities as well as during the dissolution of amorphous solid dispersions. In this study, we have evaluated the use of environment-sensitive fluorescence probes to investigate the formation and properties of the non-crystalline drug-rich aggregates formed in aqueous solutions as a result of LLPS.

Impact of Solubilizing Additives on Supersaturation and Membrane Transport of Drugs.

Purpose: Many enabling formulations give rise to supersaturated solutions wherein the solute possesses higher thermodynamic activity gradients than the solute in a saturated solution. Since flux across a membrane is driven by solute activity rather than concentration, understanding how solute thermodynamic activity varies with solution composition, particularly in the presence of solubilizing additives, is important in the context of passive absorption.

Methods: In this study, a side-by-side diffusion cell was used to evaluate solute flux for solutions of nifedipine and felodipine in the absence and presence of different solubilizing additives at various solute concentrations.

Trends in the precipitation and crystallization behavior of supersaturated aqueous solutions of poorly water-soluble drugs assessed using synchrotron radiation.

Amorphous materials are high-energy solids that can potentially enhance the bioavailability of poorly soluble compounds. A major impediment to their widespread use as a formulation platform is the tendency of amorphous materials to crystallize. The aim of this study was to evaluate the relative crystallization tendency of six structural analogues belonging to the dihydropyridine class, in an aqueous environment in the absence and presence of polymers, using wide-angle X-ray scattering synchrotron radiation and polarized light microscopy.

Impact of polymers on the crystallization and phase transition kinetics of amorphous nifedipine during dissolution in aqueous media.

The commercial and clinical success of amorphous solid dispersions (ASD) in overcoming the low bioavailability of poorly soluble molecules has generated momentum among pharmaceutical scientists to advance the fundamental understanding of these complex systems. A major limitation of these formulations stems from the propensity of amorphous solids to crystallize upon exposure to aqueous media. This study was specifically focused on developing analytical techniques to evaluate the impact of polymers on the crystallization behavior during dissolution, which is critical in designing effective amorphous formulations.

Enhancements and limits in drug membrane transport using supersaturated solutions of poorly water soluble drugs.

Amorphous solid dispersions (ASDs) give rise to supersaturated solutions (solution concentration greater than equilibrium crystalline solubility). We have recently found that supersaturating dosage forms can exhibit the phenomenon of liquid-liquid phase separation (LLPS). Thus, the high supersaturation generated by dissolving ASDs can lead to a two-phase system wherein one phase is an initially nanodimensioned and drug-rich phase and the other is a drug-lean continuous aqueous phase.

Classification of the crystallization behavior of amorphous active pharmaceutical ingredients in aqueous environments.

Purpose: To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments.

Methods: A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was selected for this study. Two experimental setups were employed to characterize the crystallization behavior of the amorphous API in an aqueous environment.

FRET-based localization of fluorescent protein insertions within the ryanodine receptor type 1.

Fluorescent protein (FP) insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM) maps of large protein complexes. However, little is known as to the precise spatial relationship between the location of the fused FP and its insertion site within a larger protein. To gain insights into these structural considerations, Förster resonance energy transfer (FRET) measurements were used to localize green fluorescent protein (GFP) insertions within the ryanodine receptor type 1 (RyR1), a large intracellular Ca(2+) release channel that plays a key role in skeletal muscle excitation contraction coupling.