Assessing Drug Product Shelf Life Using the Accelerated Stability Assessment Program: A Case Study of a GLPG4399 Capsule Formulation.

To evaluate and project the shelf life of GLPG4399, an early-phase clinical drug formulation by applying the Accelerated Stability Assessment Program (ASAP) approach. Forced degradation conditions were implemented to identify the stability-limiting degradation product. The drug and its degradation products were separated using a validated liquid chromatography method.

Influence of Crystal Disorder on the Forced Oxidative Degradation of Vortioxetine HBr.

The present study investigates the impact of the solid-state disorder of vortioxetine hydrobromide (HBr) on oxidative degradation under accelerated conditions. A range of solid-state disorders was generated via cryogenic ball milling. The solid-state properties were evaluated by calorimetry, infrared-, and Raman spectroscopies.

Role of Crystal Disorder and Mechanoactivation in Solid-State Stability of Pharmaceuticals.

Common energy-intensive processes applied in oral solid dosage development, such as milling, sieving, blending, compaction, etc. generate particles with surface and bulk crystal disorder. An intriguing aspect of the generated crystal disorder is its evolution and repercussion on the physical- and chemical stabilities of drugs.

Influence of PLGA End Groups on the Release Profile of Dexamethasone from Ocular Implants.

The present study deals with the development of dexamethasone (DM)-loaded implants using ester end-capped Resomer RG 502 poly(lactic acid-co-glycolic acid) (PLGA) (502), acid end-capped Resomer RG 502H PLGA (502H), and a 502H:502 mixture (3:1) via hot melt extrusion (HME). The prepared intravitreal implants (20 and 40% DM loaded in each PLGA) were thoroughly investigated to determine the effect of different end-capped PLGA and drug loading on the long-term release profile of DM. The implants were characterized for solid-state active pharmaceutical ingredient (APIs) using DSC and SWAXS, water uptake during stability study, the crystal size of API in the implant matrix using hot-stage polarized light microscopy, and in vitro release profile.

A Tribute to Professor Saranjit Singh - A Critical Thinker, Innovator, Mentor, and Educator.

This commentary presents contributions and accomplishments of Professor Saranjit Singh, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, India, to pharmaceutical research and education. Prof. Singh completed his successful tenure in October 2021.

On Absorption Modeling and Food Effect Prediction of Rivaroxaban, a BCS II Drug Orally Administered as an Immediate-Release Tablet.

The present work evaluates the food effect on the absorption of rivaroxaban (Riva), a BCS II drug, from the orally administered commercial immediate-release tablet (Xarelto IR) using physiologically based pharmacokinetic (PBPK) and conventional in vitro-in vivo correlation (IVIVC) models. The bioavailability of Riva upon oral administration of Xarelto IR tablet is reported to exhibit a positive food effect. The PBPK model for Riva was developed and verified using the previously reported in vivo data for oral solution (5 and 10 mg) and Xarelto IR tablet (5 and 10 mg dose strength).

Interplay of Aging and Lot-to-Lot Variability on the Physical and Chemical Properties of Excipients: A Case Study of Mono- and Diglycerides.

The present study investigates the chemical composition governing the physical properties of mono- and diglycerides (MDGs) at the microstructural level, as a function of aging and lot-to-lot variability. The physical structure of the MDG plays a vital role in ameliorating the emulsion stability and is widely explored in diverse research horizons related to the pharmaceutical, cosmetic, and food industries. In an effort to understand the mechanism of emulsion stabilization, physical properties were extensively evaluated in selective commercial lots to determine if there is a correlation between the chemical composition of MDG and physical properties.

Quantitative Chemical Profiling of Commercial Glyceride Excipients via H NMR Spectroscopy.

Glycerides are the main components of oils, and fats, used in formulated products in the food and cosmetic industry as well as in the pharmaceutical product industry. However, there is limited literature available on the analysis of the chemical composition of glycerides. The lack of a suitable analytical method for complete chemical profiling of glycerides is one of the bottlenecks in understanding and controlling the change in chemical composition during processing, formulation, and storage.

Understanding Concomitant Physical and Chemical Transformations of Simvastatin During Dry Ball Milling.

The present study investigates concomitant processes of solid-state disordering and oxidation of simvastatin during milling. The separate dry ball milling of crystalline and amorphous powders of simvastatin were conducted at ambient temperature for 10 and 60 min each. The relative crystallinity was determined using X-ray scattering and oxidative degradation was analyzed using liquid chromatography.

Feasibility of rapidly assessing reactive impurities mediated excipient incompatibility using a new method: A case study of famotidine-PEG system.

The present work demonstrates the utility of temperature controlled set up with pressurized headspace oxygen as an approach to effectively reduce the time required for solid-state drug-excipient compatibility study. To illustrate the utility, the incompatibility of polyethylene glycol (PEG) and polyethylene oxide (PEO) with Famotidine (Fam) was shown. Owing to thermal and oxidative stress, polyethylene ether moieties of PEG generated reactive impurities, resulting in the degradation of Fam.

PVP-HO Complex as a New Stressor for the Accelerated Oxidation Study of Pharmaceutical Solids.

Reactive impurities, such as hydrogen peroxide in excipients, raise a great concern over the chemical stability of pharmaceutical products. Traditional screening methods of spiking impurities into solid drug-excipient mixtures oversimplify the micro-environment and the physical state of such impurities in real dosage form. This can lead to an inaccurate prediction of the long-term product stability.

Solid-State Reactivity of Mechano-Activated Simvastatin: Atypical Relation to Powder Crystallinity.

The present study investigated the impact of solid-state disorders generated during milling on the chemical reactivity of simvastatin. An amorphous and a partially crystalline simvastatin powders were generated via cryomilling simvastatin crystals for either 90 or 10 min, respectively. The thoroughly characterized milled powders were stored at 40°C/75% RH, in open and closed containers.

Stress degradation studies on lornoxicam using LC, LC-MS/TOF and LC-MSn.

Lornoxicam was subjected to forced degradation studies under hydrolytic (acidic, basic and neutral), oxidative, photolytic and thermal stress conditions, as defined under ICH guideline Q1A (R2). The drug degraded significantly in hydrolytic, oxidative and photoneutral conditions, leading to the formation of eight degradation products in total. It was stable on exposure to light and dry heat in the solid state.