European Journal of Pharmaceutical Sciences最新文献

The glass stability of lyophilized amorphous peptide formulations, intended for incorporation into solid oral dosage forms, require stabilisation against the challenges of manufacturing, storage and handling temperature and humidity. High glass transition temperature (Tg) polymers, polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone-vinyl acetate (PVPVA), were added to insulin-sucrose formulations to enhance glass stability when exposed to temperature and humidity. Tg and onset glass transition humidity (RHg) parameters were experimentally determined as indicators of formulation glass stability with respect to temperature and humidity, respectively. A mixture design of experiment approach was employed to determine the influence of insulin, sucrose and polymer composition on formulation Tg and RHg. Statistical regression models were established to evaluate the relationship between formulation composition and the corresponding glass transition parameters, Tg and RHg. Phase separation noted for PVPVA-containing formulations, undermined regression model goodness of fit. Insulin content was shown to have a negative effect on both formulation Tg and RHg. Formulation Tg appeared to be influenced by insulin's dynamical temperature rather than a previously reported insulin Tg value. Insulin-sucrose and insulin-polymer interactive effects resulted in increased Tg and RHg values, indicating enhanced formulation glass stability. Formulation optimization for maximized Tg and RHg identified a formulation composed of 26 % w/w insulin, 40 % w/w sucrose, and 34 % w/w PVP, with a predicted Tg of 82 °C and RHg of 60 % RH. The enhanced glass stability of the ternary insulin-sucrose-polymer formulations offers potential advantages for the manufacture, storage and handling of peptide containing oral dosage forms.

The pharmaceutical industry is undergoing a rapid digital transformation. These changes are reshaping drug substance and drug product development and manufacturing, creating both opportunities and challenges that span pharmaceutical sciences, data science, and automation engineering. However, significant skills gaps persist, limiting the sector's ability to fully leverage digital technologies and sustain innovation. This paper explores the shifting digital and data science skills needs within the pharmaceutical industry, with a focus on industrial pharmacy and pharmaceutical sciences in the UK and Europe. We examine the key technological transformations reshaping the sector, the evolution of job roles, and the attributes required of the future workforce. Building on these insights, we propose an integrated approach to skills development that spans the entire career lifecycle - from embedding digital competencies in higher education to supporting lifelong learning through flexible, industry-aligned continuing professional development. Addressing these skills gaps requires coordinated action from academia, industry, and policymakers. By fostering a collaborative, interdisciplinary, and adaptive learning ecosystem, the pharmaceutical sector can equip its workforce to thrive in a rapidly changing landscape and continue improving global health and wellbeing.

GS1-144 is a neurokinin-3 receptor (NK3R) antagonist in development for treating menopausal vasomotor symptoms (VMS). This first-in-human, randomized phase 1 study (NCT06385158) evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GS1-144 in healthy Chinese participants following single and multiple ascending doses (SAD/MAD), and food effect (FE). In Part 1 (SAD), GS1-144 (5-90 mg) or placebo was administered to healthy participants. In Part 2 (FE), GS1-144 30mg was given under fasted and fed conditions in a two-period crossover in healthy participants. In Part 3 (MAD), healthy female participants of childbearing potential and postmenopausal women received GS1-144 (15-120 mg) or placebo once- (q24h) or twice-daily (q12h) fasted for 7 consecutive days. Primary endpoints included safety and tolerability. Secondary and exploratory endpoints included PK, QT/QTc interval changes, and PD (luteinizing hormone [LH] suppression). Overall, 38, 24, and 66 participants were enrolled in Parts 1-3, respectively. GS1-144 was well-tolerated with no serious adverse events (AEs), deaths, or treatment discontinuations. Most AEs were mild and not dose-related. GS1-144 was rapidly absorbed (median T_max 0.5-2.0 hours) with a linear PK profile after single 5-90 mg and multiple 15-120 mg q24h dosing. Mean half-life at steady state was 5.36-5.96 hours, with no dose-dependent changes. Dose-dependent LH reductions were observed across 15-120 mg, with consistent effects between 30mg q12h and 60mg q24h (MAD). GS1-144 could be administered with or without meals with no clinically significant impact on PK exposure. These results support further clinical development of GS1-144 for the treatment of VMS.