Investigation of long-term pressure on primary packaging materials and a biologic drug product for injection with a novel autoinjector concept.

Gerresheimer and Midas Pharma have developed a novel cartridge-based autoinjector concept in which the cartridge as primary packaging is under constant pressure. In this article standard cartridge primary packaging material of five different companies were analyzed for their behavior under long-term pressure. Materials of 3 glass manufacturers and 2 manufacturers for cartridge rubber parts were considered. Within the test program septum stability, septum piercing, glide forces (GF), break-loose forces (BLF), glass breaking as well as a regulatory approved and marketed antibody drug product under pressure were subject to analysis. Under pressure the cartridge septum bulge grew within the first 14 days and then relevantly slowed down. An accelerated study in different atmospheric conditions allowed to extrapolate values for 24 months storage, not showing any signs of decay or problematic septum bulge increase. Pierce forces were in normal ranges and septum rupture could not be observed at the end of 42 days of pressurization. GF and BLF were within acceptable ranges and changes due to pressure could not be observed. Lowest glass breaking pressures at 4922 kPa turned out to be at least 3.5 times higher than pressures used in the autoinjector concept. Degradation of the Adalimumab antibody drug product due to pressure or device fluid pathway could not be observed with size exclusion chromatography, electrophoresis or sub-visible particles tested as a release testing in a GMP setting.

Perfluorodecalin allows resuspension and prevents sediment solidification of extended-release drug formulations in primary packaging.

In this technical note we show with two simple experiments how Perfluorodecalin (PFD), an injectable perfluorocarbon, can be used as an agent for resuspending microparticulate suspensions in primary packaging containers for injection. Furthermore, we explain how this can be a substantial improvement regarding patient compliance in comparison to the commonly used gas headspace for resuspension. Our experiments are conducted with poly(lactic-co-glycolic acid) particles (often used in extended-release pharmaceutical formulations for injection) and in primary packaging that is commonly used in injection devices (glass cartridges). The results show that our method is feasible for resuspension and moreover even sediment solidification/caking is reduced. The differences between the two datasets collected are statistically significant with p < 0.01 in both cases.

Psychological Factors Linked to Intimate Partner Violence and Childhood Maltreatment: On Dissociation as a Possible Bridge Symptom.

Intimate partner violence (IPV) is a serious health concern, occurring worldwide in various forms and settings. Over the past years, multiple sources reported an increase of IPV globally, partly related to COVID-19 restrictions. Childhood maltreatment enhances the risk of IPV, possibly via alterations in emotion regulation, attachment, maladaptive core beliefs, dissociation, and psychopathological symptoms. However, studies investigating these associations simultaneously are still needed. This study aimed to investigate association between IPV, childhood maltreatment severity, maladaptive schemata (mistrust, alienation, enmeshment), attachment anxiety, social support, emotion regulation, dissociation, posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD) symptoms. We further explored the complex interplay of all factors, accounting for their shared associations. An anonymous online survey was posted on international online platforms for people experiencing domestic violence and on research platforms. Regression analyses and graph-theoretical network analysis were used to explore associations between all variables. N = 434 participants (40% in treatment) completed the survey. IPV perpetration and victimization were highly correlated. Both were significantly associated with childhood maltreatment severity, early maladaptive schemata, dissociation, BPD features, and PTSD symptoms. When including all variables in one model, IPV was associated with dissociation, which indirectly linked it to childhood maltreatment experiences, PTSD symptoms, withdrawal, and self-blame. Our findings suggest that IPV perpetration and victimization often co-occur. Dissociation may be an important bridge symptom, linking IPV to childhood maltreatment experiences, PTSD symptoms, and maladaptive coping. Prospective studies are needed to corroborate these findings and to establish psychological mechanisms underlying IPV.

Trait aggressiveness modulates neurophysiological correlates of laboratory-induced reactive aggression in humans.

Reactive aggression following provocation is a frequent form of human social behavior. The neural basis of reactive aggression, especially its control, remains poorly understood, however. We conducted an event-related potential (ERP) study using a competitive reaction time task that elicits aggression through provocation. Participants were selected from a larger sample because of extreme scores in trait aggressiveness, yielding high and low trait aggressive groups. As each trial in the task is separated into a decision phase, during which the punishment level for the opponent is set, and an outcome phase, during which the punishment is applied or received, we were able to disentangle provocation-related and evaluation-related modulations of the ERPs during the aggressive interaction. Specifically, we observed an enhanced frontal negativity during the decision phase under high provocation that was positively correlated with the participants' ability to refrain from retaliation. This held true for high trait aggressive participants only, pointing to a higher need for inhibitory and control processes in these people when provoked. During the outcome phase, we detected a mediofrontal negativity in loss compared to win trials, resembling previous ERP findings to negative feedback stimuli, which have been linked to the evaluation of an outcome's valence. This mediofrontal negativity was differentially pronounced in aggressive and nonaggressive participants: Nonaggressive participants showed only a slightly smaller mediofrontal negativity in win than in loss trials, suggesting that for them punishing the opponent had a similar negative valence as being punished.