EU-LIFEHAB: Expanding the discussion on the life cycles of harmful algae

Versión del edito

From Bitter to Sweet: a preliminary study towards a patient-friendly Praziquantel dosage form

Praziquantel (PZQ) is an antihelmintic drug used worldwide against Schistosomiasis, despite its low solubility, bioavailability and the disgusting taste. This research represents a preliminary screening of 6 selected sweeteners in terms of their aptitude to be ground with PZQ, towards the development of a patient-friendly dosage form, capable of overcoming both dissolution and taste drawbacks. A vibrational mill was used to process equimolar mixtures of PZQ and each sweetener, and the dispersions were characterized by means of Differential Scanning Calorimetry, Powder X-ray Diffraction, Fourier Transform-Infrared Spectrometry, water solubility and Intrinsic Dissolution Rate. Physical stability of the coground systems was checked over a period of 1 year. The grinding for a short period (such as 30 min) of PZQ and selected sweeteners led to several very interesting products, with prevalent amorphous character, enhanced solubility and Intrinsic Dissolution Rate comparing to the raw drug. Peculiar behavior was found in the case of xylitol:PZQ ground mixtures where the appearance of traces of PZQ anhydrous Form B was noticed. Therefore, this research highlights the possibility of using binary premixes of PZQ and sweeteners in order to obtain an increase in the biopharmaceutical and organoleptic properties of the anthelmintic drug, underlining also the need for a careful screening of sweetener to design a PZQ patient-friendly dosage form

Rapidly-Disintegrating Laminar Extrudates: Preliminary Experiments upon an Age Appropriate Pediatric Formulation

The aim of the present investigation is to produce rapidly disintegrating laminar extrudates for delivering ibuprofen in the mouth of paediatric patients. This laminar shape is particularly convenient for drug delivering in the mouth and can be easily cut in cut in different sizes allowing for a convenient adjustment of the drug dose depending on the age of the patient. Due to the fact that in paediatric formulations, the selection of the excipients is always a challenging issue and the reduction of their amount is always highly desirable, in this study to select the most appropriate composition to achieve a rapid disintegration and simultaneously permit a high amount of ibuprofen in the system, an experimental design for mixtures was employed and the disintegration time in simulated saliva was used as experimental response. In addition, after solid state analyses to check possible insurgence of drug-excipients interactions, laminar extrudates were characterised in terms of mechanical properties and in vitro dissolution performances. Extrudates with the desired uniform laminar shape, constant thickness (2 mm) and a very high content of drug (82% wt) were produced. These products exhibited a short disintegration time. The dose for a patient of 6-12 years corresponded to a length of extrudate between 1-1.5 cm, perfectly compatible with a formulation orodispersible thin laminar extrudate intended for a paediatric patient (Figure 1)

Competitive Mechanochemical Solvate Formation of Theophylline in the Presence of Miscible Liquid Mixtures

In this study, we investigated the mechanochemical competitive solvate formation of polymorphic Form II of theophylline in the presence of two solvate/hydrate-forming miscible liquids, namely, water and 2-pyrrolidone. It is known that theophylline transforms into a monohydrate in the presence of water, while 2-pyrrolidone gives a monosolvate or a sesquisolvate, depending on the experimental conditions. Different theophylline-to-liquid molar ratios and several water:2-pyrrolidone mixtures were used to understand the competitive formation and/or transformation between these solvates. Interconversion studies between hydrate/monosolvate/sesquisolvate forms were also conducted. The obtained results suggest that water:2-pyrrolidone mixtures have a detrimental effect on the formation of multicomponent phases, as they dramatically reduce the efficiency of incorporation of both liquids in the crystal. In fact, all milling experiments performed in the presence of water:2-pyrrolidone mixtures suggested that a higher stoichiometric ratio is needed to obtain a pure form of a specific solvate. Importantly, additional competitive milling experiments revealed a preferential inclusion of 2-pyrrolidone over water. Based on several experimental datasets performed, we conclude that the propensity of solvate formation in the presence of liquid mixtures is a consequence of a complex interplaying of physicochemical and kinetic factors

P216 Comparative Assessment C-reactive Protein Between a Point-of-Care Testing and Current Standard of Care (Immunonephelometric testing)

Abstract Background C-reactive protein (CRP) is widely used as a biomarker of inflammatory disease activity in hospitalized and non-hospitalized patients. In particular, CRP is commonly used in patients suspected to have an inflammatory bowel disease (IBD) or with a confirmed diagnosis of IBD diagnosis in order to drive the diagnostic approach, to monitor disease activity and to guide therapeutic adjustments. However, standard laboratory CRP testing (Immunonephelometric assays) present some drawbacks, including a turnaround time of 1–2 hours, and the need of specialized equipment, offices and laboratory personnel. Because of that, point-of care testing (POCT) was recently developed in order to provide results within 2 minutes from blood collection, enabling a rapid response to clinical condition. Aim To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) using capillary whole blood and the comparative Immunonephelometric assay using serum samples. Methods From October to November 2020, consecutive patients hospitalized at Gastroenterology Unit, Padua University Hospital, aged > 18 years and with clinical evidence of active inflammatory disease or infection, who underwent to a standard of care CRP test (Dimension Vista – Siemens Healthineers) were included in the study (range 2.9–340 g/L). Within 1 hour from blood collection, in each patient, CRP quantitation from capillary whole blood collected by finger stick was performed using the ProciseDx CRP assay, with reportable range between 3.6–100 g/L. A Deming regression test was used to identify the correlation between the two methods. Results Eighty-three patients were enrolled (62.5% males with mean age ± SD: 60±18). The most common indications for hospitalisation were liver disease (34.9%), pancreatic disturbance (27.7%) and suspicious or recurrence of IBD (16.7%). ProciseDx POCT with finger prick samples required a turnaround time of 2±0.2 minutes, whereas serum samples analyzed in clinical laboratory with the reference method required a turnaround time of about 180±15 minutes (p<0.001). Overall, the correlation between the two tests was high (R squared of 0.899 (95% CI 0.916–0.968)). In particular, the correlation between the methods was even higher with CRP values between 0–100 g/L with R squared of 0.961 (95% CI 0.958–0.986). Conclusion The ProciseDx POCT allows a more rapid and comparable accuracy of CRP assessment in hospitalized patients as compared to the standard laboratory measurement. Moreover, the ProciseDx POCT does not require specialised personnel to be performed. The use of ProciseDx POCT may improve and accelerate the decision-making approach, further reducing the resources required for CRP assessment

A specific microbiota signature is associated to various degrees of ulcerative colitis as assessed by a machine learning approach

Ulcerative colitis (UC) is a complex immune-mediated disease in which the gut microbiota plays a central role, and may determine prognosis and disease progression. We aimed to assess whether a specific microbiota profile, as measured by a machine learning approach, can be associated with disease severity in patients with UC. In this prospective pilot study, consecutive patients with active or inactive UC and healthy controls (HCs) were enrolled. Stool samples were collected for fecal microbiota assessment analysis by 16S rRNA gene sequencing approach. A machine learning approach was used to predict the groups’ separation. Thirty-six HCs and forty-six patients with UC (20 active and 26 inactive) were enrolled. Alpha diversity was significantly different between the three groups (Shannon index: p-values: active UC vs HCs = 0.0005; active UC vs inactive UC = 0.0273; HCs vs inactive UC = 0.0260). In particular, patients with active UC showed the lowest values, followed by patients with inactive UC, and HCs. At species level, we found high levels of Bifidobacterium adolescentis and Haemophilus parainfluenzae in inactive UC and active UC, respectively. A specific microbiota profile was found for each group and was confirmed with sparse partial least squares discriminant analysis, a machine learning-supervised approach. The latter allowed us to observe a perfect class prediction and group separation using the complete information (full Operational Taxonomic Unit table), with a minimal loss in performance when using only 5% of features. A machine learning approach to 16S rRNA data identifies a bacterial signature characterizing different degrees of disease activity in UC. Follow-up studies will clarify whether such microbiota profiling are useful for diagnosis and management

Sarcopenia, severe anxiety and increased C-reactive protein are associated with severe fatigue in patients with inflammatory bowel diseases

Patients with inflammatory bowel disease (IBD) report fatigue more frequently than healthy population, but the precise mechanisms underlying its presence are unknown. This study aimed to evaluate the prevalence of fatigue in IBD and its relation with potential causative factors. A survey on fatigue, depression, anxiety, sleep disorders, and the presence of sarcopenia and malnutrition, was sent by email to 244 IBD outpatients of the Gastroenterology Unit of Academic Hospital of Padua. Demographics and clinical data, including the levels of fecal calprotectin (FC) and C-reactive protein (CRP), and current pharmacological treatments were obtained from patients’ medical records. Ninety-nine (40.5%) subjects answered the survey. Ninety-two (92.9%) patients reported fatigue, with sixty-six having mild to moderate fatigue and twenty-six severe fatigue. Multivariate analysis showed that abnormal values of CRP (OR 5.1), severe anxiety (OR 3.7) and sarcopenia (OR 4.4) were the factors independently associated with severe fatigue. Fatigue has a high prevalence in subject affected by IBD. Subjects with altered CRP, sarcopenia and severe anxiety appear more at risk of severe fatigue

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility

Irritable bowel syndrome with diarrhoea (IBS-D) and functional diarrhoea (FDr) are the two major functional bowel disorders characterized by diarrhoea. In spite of their high prevalence, IBS-D and FDr are associated with major uncertainties, especially regarding their optimal diagnostic work-up and management. A Delphi consensus was performed with experts from 10 European countries who conducted a literature summary and voting process on 31 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus (defined as >80% agreement) was reached for all the statements. The panel agreed with the potential overlapping of IBS-D and FDr. In terms of diagnosis, the consensus supports a symptom-based approach also with the exclusion of alarm symptoms, recommending the evaluation of full blood count, C-reactive protein, serology for coeliac disease, and faecal calprotectin, and consideration of diagnosing bile acid diarrhoea. Colonoscopy with random biopsies in both the right and left colon is recommended in patients older than 50 years and in presence of alarm features. Regarding treatment, a strong consensus was achieved for the use of a diet low fermentable oligo-, di-, monosaccharides and polyols, gut-directed psychological therapies, rifaximin, loperamide, and eluxadoline. A weak or conditional recommendation was achieved for antispasmodics, probiotics, tryciclic antidepressants, bile acid sequestrants, 5-hydroxytryptamine-3 antagonists (i.e. alosetron, ondansetron, or ramosetron). A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of IBS-D and FDr

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD