The tissue response to long-acting injectables (LAIs) suspension injection may impact the product in vivo performance. One such response is the formation of an inflammatory cell layer (ICL) resulting in an envelope around the injected particles. This study aims to use a mechanistic model to describe the clinical in vivo exposure and performance of an intramuscular LAI suspension and evaluate impact of ICL physiological respons...

Generic ophthalmic drug product development is challenging, and innovative methodologies to complement traditional bioequivalence (BE) studies for BE assessment are desirable to promote their evaluation. Ocular physiologically based pharmacokinetic (PBPK) models can provide insight into drug partitioning in eye tissues that are too invasive to access in humans. An approach has been previously validated to translate ocular expo...

Quantitative in silico tools may be leveraged to mechanistically predict the dermato-pharmacokinetics of compounds delivered from topical and transdermal formulations by integrating systems of rate equations that describe permeation through the formulation and layers of skin and pilo-sebaceous unit, and exchange with systemic circulation via local blood flow. Delivery of clobetasol-17 propionate (CP) from Dermovate TM cream wa...

Background The development of generic ophthalmic drug products is challenging due to the complexity of the ocular system, and a lack of sensitive testing to evaluate the interplay of physiology with ophthalmic formulations. While measurements of drug concentration at the site of action in humans are typically sparse, these measurements are more easily obtained in rabbits. The purpose of this study is to demonstrate the utility...

A physiologically based model describing the dissolution, diffusion, and transfer of drug from the intra-articular (IA) space to the plasma, was developed for GastroPlus® v9.8. The model is subdivided into compartments representing the synovial fluid, synovium, and cartilage. The synovium is broken up into two sublayers. The intimal layer acts as a diffusion barrier between the synovial fluid and the subintimal layer. The subi...

The purpose of this study was to develop a physiologically based pharmacokinetic (PBPK) model predicting the pharmacokinetics (PK) of different compounds in pregnant subjects. This model considers the differences in tissue sizes, blood flow rates, enzyme expression levels, glomerular filtration rates, plasma protein binding, and other factors affected during pregnancy in both the maternal and fetal models. The PBPKPlus™ module...

Purpose The purpose of this study is to show how the Ocular Compartmental Absorption & Transit (OCAT™) model in GastroPlus ® can be used to characterize ocular drug pharmacokinetic performance in rabbits for ointment formulations. Methods A newly OCAT™ model developed for fluorometholone, as well as a previously verified model for dexamethasone, were used to characterize the aqueous humor (AH) concentration following the admin...