Thorough understanding and control of the different crystal forms of a drug product is key for fine chemistry and materials science; it ultimately determines the product's physicochemical properties and performance.
Structural and conformational determinants of macrocycle cell permeability
Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood.
Forecasting oral absorption across biopharmaceutics classification system classes with physiologically based pharmacokinetic models
The aim of this study was (1) to determine how closely physiologically based pharmacokinetic (PBPK) models can predict oral bioavailability using a priori knowledge of drug-specific properties and (2) to...
In vitro and in silico investigation of electrospun terbinafine hydrochloride-loaded buccal nanofibrous sheets
Terbinafine hydrochloride-loaded nanofibrous buccal films were formulated with the aim to improve the solubility and dissolution behavior; thus, the local effectiveness of the antifungal agent.
Vitamin K epoxide reductase expression and prostate cancer risk
Purpose: Increasing evidence has demonstrated that men taking the anticoagulant warfarin have a lower risk of developing prostate cancer. This phenomenon is not observed...
An in vitro and in silico study of the impact of engineered surface modifications on drug detachment from model carriers
In silico modeling was used to predict the impact of carrier surface modifications on the in vivo plasma concentration of an active pharmaceutical ingredient (API) and as a tool to support formulation development.
Synthesis and structure-activity relationship study of tacrine-based pyrano[2,3-c]pyrazoles targeting AChE/BuChE and 15-LOX
A series of tacrine-based pyrazolo[4′,3′:5,6]pyrano[2,3-b]quinolines and related compounds were designed and synthesized for targeting AChE, BuChE and 15-LOX enzymes in the field of Alzheimer's disease therapy.
Physiologically Based Pharmacokinetic (PBPK) Modeling of Pharmaceutical Nanoparticles
With the great interests in the discovery and development of drug products containing nanoparticles, there is a great demand of quantitative tools for assessing quality, safety, and efficacy of these products.
The Prediction of the Relative Importance of CYP3A/P-gp to the Non-linear Intestinal Absorption of Drugs by Advanced Compartmental Absorption and Transit (ACAT) Model
Intestinal CYP3A and P-glycoprotein (P-gp) decrease the intestinal absorption of substrate drugs. Since substrate specificity of CYP3A often overlaps that of P-gp, and estimation of their saturability in the...
Using Physiologically Based Pharmacokinetic (PBPK) Modeling to Evaluate the Impact of Pharmaceutical Excipients on Oral Drug Absorption: Sensitivity Analyses
Drug solubility, effective permeability, and intestinal metabolism and transport are parameters that govern intestinal bioavailability and oral absorption.
Utilizing In Vitro Dissolution-Permeation Chamber for the Quantitative Prediction of pH-Dependent Drug-Drug Interactions with Acid-Reducing Agents: a Comparison with Physiologically Based Pharmacokinetic Modeling
For many orally administered basic drugs with pH-dependent solubility, concurrent administration with acid-reducing agents (ARAs) can significantly impair their absorption and exposure.
Folate-targeted amphiphilic cyclodextrin.siRNA nanoparticles for prostate cancer therapy exhibit PSMA mediated uptake, therapeutic gene silencing in vitro and prolonged circulation in vivo
In this study, a folate targeted cyclodextrin (CD) nanoparticle was prepared by co-formulating CD.siRNA complexes with DSPE-PEG5000-folate to target the prostate specific membrane antigen (PSMA).
Physiologically Based Absorption Modeling to Design Extended-Release Clinical Products for an Ester Prodrug
Absorption modeling has demonstrated its great value in modern drug product development due to its utility in understanding and predicting in vivo performance.
Intracellular unbound drug concentrations: methodology and application for understanding cellular drug exposure
Most known drug targets and metabolizing enzymes are located inside cells.
High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents
Human semen is principal vehicle for transmission of HIV-1 and other enveloped viruses.
Predicting Exposure After Oral Inhalation of the Selective Glucocorticoid Receptor Modulator, AZD5423, Based on Dose, Deposition Pattern, and Mechanistic Modeling of Pulmonary Disposition
Exposure following oral inhalation depends on the deposition pattern of the inhaled aerosol, the extent and rate of oral and pulmonary absorption, as well as systemic distribution and clearance.
Comprehensive QSRR modeling as a starting point in characterization and further development of anticancer drugs based on 17α-picolyl and 17(E)-picolinylidene androstane structures.
The selection of the most promising anticancer compounds from the pool of the huge number of synthesized molecules is a quite complex task.
Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults
A previously presented physiologically-based pharmacokinetic model for immediate release (IR) methylphenidate (MPH) was extended to characterize the pharmacokinetic behaviors of oral extended release (ER) MPH formulations in adults for the first time.
Homology modeling and virtual screening for inhibitors of lipid kinase PI (4) K from Plasmodium
Malaria parasite strains have emerged to tolerate the therapeutic effects of the prophylactics and drugs presently available.