Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Purpose The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. Methods Samples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch. Results The disintegration time (R$^{2}$ = 0.86) and API dissolved after 15 min (R$^{2}$ = 0.96) linearly correlates with the effective refractive index, neff, measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of neff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, αeff, we observed a better correlation with dissolution after 20 min (R$^{2}$ = 0.96) and a weaker correlation with disintegration (R$^{2}$ = 0.83) compared to neff. Conclusion The measurements of neff and αeff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to measure content uniformity and the fact that the method requires no chemometric models this technology shows clear promise to be established as a process analyser to non-destructively predict critical quality attributes of tablets.We would like to thank GlaxoSmithKline for providing the sets of samples and sharing their valuable experience and advice. D.M. and J.A.Z. would like to acknowledge the the U.K. Engineering and Physical Sciences Research Council (EPSRC) for funding (EP/L019922/1). J.S. participated in this study as a undergraduate summer student visiting from the Friedrich-Schiller-University Jena and would like to thank the German Academic Exchange Service (DAAD) RISE Worldwide programme for supporting her visit (GB-PH-1870)

Associations of common mental disorder with alcohol use in the adult general population: a systematic review and meta-analysis

Background and Aims: Research has shown that alcohol use and common mental disorders (CMDs) co-occur; however, little is known about how the global prevalence of alcohol use compares across different CMDs. We aimed to (i) report global associations of alcohol use (alcohol use disorder (AUD), binge drinking and consumption) comparing those with and without a CMD, (ii) examine how this differed among those with and without specific types of CMDs and (iii) examine how results may differ by study characteristics. Methods: We used a systematic review and meta-analysis. Cross-sectional, cohort, prospective, longitudinal and case–control studies reporting the prevalence of alcohol use among those with and without a CMD in the general population were identified using PsycINFO, MEDLINE, PsyARTICLES, PubMed, Scopus and Web of Science until March 2020. Depression, anxiety and phobia were included as a CMD. Studies were included if they used a standardized measure of alcohol use. A random-effects meta-analysis was conducted to generate pooled prevalence and associations of AUD with CMD with 95% confidence intervals (CI). A narrative review is provided for binge drinking and alcohol consumption. Results: A total of 512 full-texts were reviewed, 51 included in our final review and 17 in our meta-analyses (n = 382 201). Individuals with a CMD had a twofold increase in the odds of reporting an AUD [odds ratio (OR) = 2.02, 95% CI = 1.72–2.36]. The odds of having an AUD were similar when stratified by the type of CMD (mood disorder: OR = 2.00, 95% CI = 1.62–2.47; anxiety/phobic disorder: OR = 1.94, 95% CI = 1.35–2.78). An analysis of study characteristics did not reveal any clear explanations for between-study heterogeneity (I2 > 80%). There were no clear patterns for associations between having a CMD and binge drinking or alcohol consumption, respectively. Conclusions: People with common mental disorders (depression, anxiety, phobia) are twice as likely to report an alcohol use disorder than people without common mental disorders

Understanding alcohol use and changes in drinking habits among people with a severe mental illness: a qualitative framework analysis study

Introduction: Individuals with a severe mental illness (SMI) are more likely to drink at harmful levels or abstain. While it is known that drinking patterns change over time, the reasons for this among those with a SMI are unclear. This study aimed to (i) explore the experiences with alcohol, particularly in relation to mental health symptoms, and (ii) how drinking patterns have changed over time, among individuals who have a SMI diagnosis, who either currently drink alcohol or no longer drink. Methods: One-to-one semi-structured telephone interviews were conducted to address the study aims. Current drinkers’ alcohol use was assessed using the Alcohol Use Disorder Identification Test. A framework analysis was used to address the study aims with a specific focus on the differences in the experiences with alcohol use between current and former drinkers. Results: 16 participants were interviewed, and five themes were developed. The analysis highlighted how alcohol was increasingly used to cope with (i) trauma, (ii) SMI-related symptoms, or (iii) stress. Among those with a SMI, non-drinking was facilitated through declines in SMI-related symptoms, previous negative consequences due to alcohol and changing the social environment. Current drinking habits were facilitated through changes in the reasons for drinking and adopting different alcohol moderation techniques. Discussion: Among those with a SMI diagnosis and who either currently drink alcohol or no longer drink, our findings support the self-medication hypothesis and drinking motives model. However, our findings indicate the need for further development of drinking to cope with a focus on symptoms of a SMI and trauma. Our findings also have implications on specialist alcohol and mental health services, the need to improve individuals’ understanding of SMI, and the need to identify reasons for drinking among those with a recent diagnosis of a SMI

Liquid Extraction Surface Analysis (LESA) Electron-Induced Dissociation and Collision-Induced Dissociation Mass Spectrometry of Small Molecule Drug Compounds.

Here, we present liquid extraction surface analysis (LESA) coupled with electron-induced dissociation (EID) mass spectrometry in a Fourier-transform ion cyclotron resonance mass spectrometer for the analysis of small organic pharmaceutical compounds directly from dosed tissue. First, the direct infusion electrospray ionisation EID and collision-induced dissociation (CID) behaviour of erlotinib, moxifloxacin, clozapine and olanzapine standards were compared. EID mass spectra were also compared with experimental or reference electron impact ionisation mass spectra. The results show that (with the exception of erlotinib) EID and CID result in complementary fragment ions. Subsequently, we performed LESA EID MS/MS and LESA CID MS/MS on singly charged ions of moxifloxacin and erlotinib extracted from a thin tissue section of rat kidney from a cassette-dosed animal. Both techniques provided structural information, with the majority of peaks observed for the drug standards also observed for the tissue-extracted species. Overall, these results demonstrate the feasibility of LESA EID MS/MS of drug compounds from dosed tissue and extend the number of molecular structures for which EID behaviour has been determined. Graphical Abstract ᅟ

Human Factors Validation of a Wearable, On-Body Infusor for Subcutaneous Administration of Furosemide

Anthony D Andre,1 John F Mohr,2 Barbara W Cornelius,2 Matthew M Goodwin,2 Carson P Whitaker,1 Bhavini H Patel,2 Jessica A Huckleberry,3 Michael D Hassman2 1Interface Analysis Associates LLC, Saratoga, CA, USA; 2scPharmaceuticals, Inc, Burlington, MA, USA; 3Heart Group of the Eastern Shore, P.C, Fairhope, AL, USACorrespondence: Michael D Hassman, scPharmaceuticals, Inc, 25 Mall Road, Suite 203, Burlington, MA, 01803, USA, Tel +1 781 301 7373, Email [email protected]: Furoscix® (subcutaneous furosemide) is administered using a wearable On-Body Infusor (OBI) and is approved for the treatment of congestion associated with heart failure (HF). The purpose of this study was to assess the safe and effective use of the OBI and Instructions for Use (IFU) by patients with HF, caregivers, and healthcare practitioners (HCPs).Methods: Sixty participants (patients, n=30; caregivers, n=15; HCPs, n=15) were evaluated on completion of OBI use tasks and IFU knowledge tasks in a simulated use environment. Fifteen of the patients received OBI/IFU training before evaluation.Results: Overall, 893/900 (99.2%) use tasks and 2211/2220 (99.6%) knowledge tasks were completed successfully, without differences due to training. The most common (n=6) use error was failure to wipe skin or cartridge tip with an alcohol wipe. Errors were due to forgetfulness/misinterpretation rather than IFU clarity.Conclusion: The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.Keywords: heart failure, furosemide, subcutaneous furosemide, on-body infusor, human factor

Ecology of domestic dogs canis familiaris as an emerging reservoir of Guinea worm dracunculus medinensis infection

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: Data are available at Dryad data repository https://doi.org/10.5061/dryad.vx0k6djnh.Global eradication of human Guinea worm disease (dracunculiasis) has been set back by the emergence of infections in animals, particularly domestic dogs Canis familiaris. The ecology and epidemiology of this reservoir is unknown. We tracked dogs using GPS, inferred diets using stable isotope analysis and analysed correlates of infection in Chad, where numbers of Guinea worm infections are greatest. Dogs had small ranges that varied markedly among villages. Diets consisted largely of human staples and human faeces. A minority of ponds, mostly <200 m from dog-owning households, accounted for most dog exposure to potentially unsafe water. The risk of a dog having had Guinea worm was reduced in dogs living in households providing water for animals but increased with increasing fish consumption by dogs. Provision of safe water might reduce dog exposure to unsafe water, while prioritisation of proactive temephos (Abate) application to the small number of ponds to which dogs have most access is recommended. Fish might have an additional role as transport hosts for Guinea worm, by concentrating copepods infected with worm larvae.Chad Ministry of Public HealthWorld Health OrganizationCarter Cente