Introduction: Single inhaler triple therapy (SITT) is used as maintenance therapy in servereCOPD. SITT is available as dry-powder inhalers (DPIs) and pressured metered-dose inhalers(pMDIs). pMDIs have a more harmful impact on the climate compared to DPIs. Aim: To map changes in the prescription of SITT in Sweden and to compare regionaldifferences regarding the climate impact of the treatments. Methods: A mapping of recommended SITT DPIs (ATC-code: R03AL08) and pMDIs (R03AL09,R03AL11) in all 21 regions. Changes in SITT prescriptions between 2018 and 2022 were retrieved from the national statistical database and used for the climate impact calculations.The regional drug committees were interviewed to discuss factors influencing theprescription of inhalers. Results: Ninety percent of the regions (n=19/21) recommended DPI as the first choice SITT. The use of pMDIs increased from 0.6 to 3.3 patients per 1,000 inhabitants and DPIs from 0.3to 2.2 patients per 1,000 inhabitants during the same period. The climate impact from SITT was significantly higher in 2022 than in 2018. The climate impact for DPIs increased from 9,370 kg CO2e in 2018 to 84,297 kg CO2e in 2022. The climate impact for pMDIs increased from 291,630 kg CO2e in 2018 to 2,765,651 kg CO2e in 2022. Increased recognition of SITT and annual treatment recommendation updates were factors influencing the SITT prescriptions found in the interviews.Conclusion: The SITT use in Sweden has increased since 2018. DPIs are widelyrecommended but pMDIs are more common. There are large regional differences in theprescription and climate impact, and most of the climate impact originates from the pMDIs. Follow-up of the SITT prescriptions at a regional level is proposed to reduce the climateimpact.

<p dir="ltr">Pharmaceutical manufacturing of solid oral dosage forms is undergoing a significant evolution with the introduction of continuous manufacturing and advanced manufacturing technologies such as three-dimensional printing (3DP). Pharmaceutical manufacturing requires new approaches to ensure the quality of excipients and new ways to design and formulate advanced solid oral dosage forms. One example of a raw material that has quality issues is magnesium stearate, the most commonly used excipient in solid oral dosage forms. The complicated physicochemical nature of magnesium stearate introduces variability to the performance of tablet lubrication and dissolution. The lack of understanding on this variability can cause product loss or failure of quality assessments. In addition, new manufacturing methods such as 3DP binder-jet printing of pharmaceuticals have poorly understood quality challenges that need to be explored.</p><p dir="ltr">The specific aims of this project are as follows: [1] To determine the susceptibility of the disordered form to form interconversion and disproportionation when used to make a tablet. The comparison of lab synthesized samples to the more relevant forms that appear in commercial products such as the monohydrate and dihydrate forms of magnesium stearate are included. 13C labeled magnesium stearate of all forms will be prepared to determine which causes the greatest extent of disproportionation.</p><p dir="ltr">[2] To determine if a newly investigated form of magnesium stearate, named the disordered form, is viable for pharmaceutical use. The disordered form must minimize risk impacting dissolution while being an effective lubricant, thereby reducing batch and continuous manufacturing failures.</p><p dir="ltr">[3] To evaluate how 3DP printed tablet manufacturing methods impact critical quality attributes. This work will identify the importance of attributes such as weight; binder composition; excipients; compatible drugs; software; hardware change as a function of raw material attributes (API, powder character, and binder) and critical process parameters.</p>

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Background: Attentiveness is a fundamental function of the brain. Deficits in attentional performance is a major cause for individual and societal burden. An important region involved in attention is striatum, inside of which there is dopamine: a key neurotransmitter in the regulation of attention. The dopamine transporter (DAT) is abundant in dorsal striatum (DS) and ventral striatum (VS) and DAT acts as a modulator of dopamine signaling. Abnormal DAT expression is identified as one of the causes of attentional dysfunction in several neuropsychiatric diseases. This project aimed to parse the relationship between DAT expression and attentional performance in a sustained visual attention task, as well as DAT’s relationship to amphetamine (AMPH) sensitivity. Methods: To test for attention 15 male Sprague-Dawley rats were trained and tested in a signal detection task (SDT) to gather attentional data and to measure change in performance after AMPH administration. To quantify DAT in striatum, this project used immunohistochemistry to measure fluorescent intensity, a measurement representing the corresponding DAT expression level. To support findings, the project used drift diffusion models (DDMs) to enhance our understanding of the decision-making process affected by DAT expression. Results: The results showed non-significant correlations between DAT density in DS and VS and premature responses and accuracy in the SDT. The data also showed that the DAT DS:VS expression ratio significantly correlates to AMPH sensitivity. Conclusion: We concluded that increased DAT expression in striatum can predict worse accuracy and increased premature response times during a SDT. The project also found that the ratio of DAT expression in dorsal and ventral striatum can predict changes in accuracy after AMPH administration.