Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.

Risk factors for oral antimicrobial consumption in Swiss fattening pig farms - a case-control study.

BACKGROUND: Antimicrobial consumption in veterinary medicine is of great importance. Increased awareness by the public and media has led to demands for decreased use of antimicrobials in pigs. This study aimed to identify risk factors for regular oral antimicrobial consumption in Swiss fattening pig farms, and to quantify the amount of antimicrobial active substances administered orally to pigs at the farm level. RESULTS: A case-control study was performed on 99 fattening farms between May 2014 and January 2015. Seventy-two case farms (with oral group treatment of antimicrobials in at least 50 % of pigs) and 27 control farms (with no regular oral group treatment) were visited once during the study. Data about potential risk factors and antimicrobial consumption were collected by questionnaire. Antimicrobial consumption was recorded and treatment incidence (TI) was calculated for all farms over a one year period. Sulphonamides and tetracyclines were the antimicrobials consumed in the greatest quantity. The median TI for oral antimicrobial use in the case group was 224.7. In the control group, the median TI was 0 for oral antimicrobial use, with values ranging from 0 to 140.1. In a multivariable regression model, seven risk factors associated with regular oral antimicrobial group treatment were identified: mixing pigs from different suppliers within the same pen, absence of a work protocol that ensures treating of healthy pigs before sick pigs, distance to next pig farm < 500 metres, external analysis of production parameters, no availability of dirty visitor boots, the farmer not working on other farms, and no application of homoeopathic agents. CONCLUSIONS: The results of this study point out the importance of increasing farmers' awareness of good farming practices and biosecurity. Important recommendations for decreasing oral antimicrobial consumption identified by this study include avoiding mixing pigs from different suppliers in the same pen and strictly handling sick pigs after healthy ones. Improvements in these areas could enhance the overall health of pigs and thereby reduce the consumption of antimicrobials on pig farms.

EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes.

Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However, little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells, EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore, we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricular myocytes in vitro. In adult rat ventricular myocytes (ARVM), beta-adrenergic receptor (betaAR) stimulation and H(2)O(2) (24 h) each increased EMMPRIN expression as assessed by immunoblotting. Pretreatment with a catalase/superoxide dismutase mimetic or adenoviral-mediated expression of catalase or a dominant-negative c-jun N-terminal kinase-1 (JNK) mutant inhibited the betaAR- and H(2)O(2)-stimulated increases in EMMPRIN expression suggesting that EMMPRIN expression is regulated via a reactive oxygen species-dependent JNK pathway. To determine whether EMMPRIN expression regulates matrix metalloproteinase (MMP) activity, EMMPRIN activity was inhibited by adenoviral expression of an inhibitory mutant of EMMPRIN. Expression of mutant EMMPRIN inhibited the betaAR-stimulated increases in MMP2 expression and zymographic MMP activity. Thus, in cardiac myocytes betaAR stimulation induces the expression of EMMPRIN via the ROS-dependent activation of JNK. The resulting increase in EMMPRIN activity stimulates MMP expression and activity. These findings suggest that in the myocardium the regulated expression of EMMPRIN is a determinant of MMP activity and may thus play a role in myocardial remodeling.