The role of specific biomarkers, as predictors of post-operative complications following flexible ureterorenoscopy (FURS), for the treatment of kidney stones: a single-centre observational clinical pilot-study in 37 patients

Abstract: Background: The number of patients diagnosed and subsequently treated for kidney stones is increasing, and as such the number of post-operative complications is likely to increase. At present, little is known about the role of specific biomarkers, following flexible ureterorenoscopy (FURS) for the surgical treatment of kidney stones. The main aim of the study was to evaluate the role of kidney and infection biomarkers, in patients undergoing FURS. Methods: Included were 37 patients (24 males, 13 females), who underwent elective FURS, for the treatment of kidney stones. Venous blood samples were collected from each patient: pre-operatively, and at 30 min, 2 and 4 h post-operatively. Changes to kidney (NGAL, Cystatin-C) and infection (MPO, PCT) biomarkers was quantified by means of ELISA, Biomerieux mini-vidas and Konelab 20 analysers. Results: Four patients developed post-operative complications (3 - UTIs with urinary retention, 1 - urosepsis. NGAL concentration increased significantly following FURS (p = 0.034). Although no significant changes were seen in Cystatin C, MPO and PCT (p ≥ 0.05) some key clinical observation were noted. Limiting factors for this study were the small number of patients recruited and restriction in blood sampling beyond 4 h. Conclusions: Although not confirmative, changes seen to biomarkers such as Cystatin C, NGAL and MPO in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications which can develop following FURS

A holistic multi evidence approach to study the fragmentation behaviour of crystalline mannitol

Mannitol is an essential excipient employed in orally disintegrating tablets due to its high palatability. However its fundamental disadvantage is its fragmentation during direct compression, producing mechanically weak tablets. The primary aim of this study was to assess the fracture behaviour of crystalline mannitol in relation to the energy input during direct compression, utilising ball milling as the method of energy input, whilst assessing tablet characteristics of post-milled powders. Results indicated that crystalline mannitol fractured at the hydrophilic (011) plane, as observed through SEM, alongside a reduction in dispersive surface energy. Disintegration times of post-milled tablets were reduced due to the exposure of the hydrophilic plane, whilst more robust tablets were produced. This was shown through higher tablet hardness and increased plastic deformation profiles of the post-milled powders, as observed with a lower yield pressure through an out-of-die Heckel analysis. Evaluation of crystal state using x-ray diffraction/differential scanning calorimetry showed that mannitol predominantly retained the β-polymorph; however x-ray diffraction provided a novel method to calculate energy input into the powders during ball milling. It can be concluded that particle size reduction is a pragmatic strategy to overcome the current limitation of mannitol fragmentation and provide improvements in tablet properties

Anti-factor Xa levels in obese patients receiving enoxaparin for treatment and prophylaxis indications

Linda Tahaineh,1 Sahar M Edaily,1 Shadi F Gharaibeh2 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology (JUST), Irbid, Jordan; 2Department of Pharmaceutical Sciences, Faculty of Pharmacy, Jerash University, Jerash, Jordan Objectives: To evaluate the degree of anticoagulation achieved with different enoxaparin dosing regimens used in obese and morbidly obese patients in a hospital setting in Jordan.Methods: All obese adult patients who were prescribed enoxaparin for various indications were invited to participate in the study. The anti-factor Xa (anti-Xa) level was checked once after 4–6 hours of the third or fourth dose of enoxaparin (at steady state). Patients were followed daily to evaluate drug efficacy and safety through their hospital course.Results: Enoxaparin daily dose used for prophylaxis indications ranged from 0.3 to 0.85 mg/kg and from 0.31 to 2.25 mg/kg in case of certain treatment indications. Most participants who received enoxaparin for treatment indications (76.9%) were on capping dosing regimens, which was <1 mg/kg twice daily. On the other hand, most patients (88.5%) who received enoxaparin for prophylaxis indications were on a fixed 40 mg/d dose. Among the 52 patients who completed the study, 19 patients (36.5%) had therapeutic anti-Xa levels. The results showed no statistically significant associations between regimens that were used and achieving therapeutic anti-Xa level (p>0.05). No bleeding events or thrombocytopenia were noticed, and there was one case of recurrent thrombosis.Conclusion: Enoxaparin dosing regimens that were used for obese patients varied based on prescribing physicians. Regardless of the regimen used, the majority of participants had nontherapeutic anti-Xa. Individualized dosing regimens based on anti-Xa levels are warranted for obese patients on enoxaparin. Keywords: anti-factor Xa, anticoagulation, enoxaparin, obesit

Co-Processed Excipients for Dispersible Tablets–Part 1: Manufacturability

Co-processed excipients may enhance functionality and reduce drawbacks of traditional excipients for the manufacture of tablets on a commercial scale. The following study aimed to characterise a range of co-processed excipients that may prove suitable for dispersible tablet formulations prepared by direct compression. Co-processed excipients were lubricated and compressed into 10.5-mm convex tablets using a Phoenix compaction simulator. Compression profiles were generated by varying the compression force applied to the formulation and the prepared tablets were characterised for hardness, friability, disintegration and fineness of dispersion. Our data indicates that CombiLac, F-Melt type C and SmartEx QD100 were the top 3 most suitable out of 16 co-processed excipients under the conditions evaluated. They exhibited good flow properties (Carr’s index ˂ 20), excellent tabletability (tensile strength > 3.0 MPa at 0.85 solid fraction), very low friability (< 1% after 15 min), rapid disintegration times (27–49 s) and produced dispersions of ideal fineness (< 250 μm). Other co-processed excipients (including F-Melt type M, Ludiflash, MicroceLac, Pharmaburst 500 and Avicel HFE-102) may be appropriate for dispersible tablets produced by direct compression providing the identified disintegration and dispersion risks were mitigated prior to commercialisation. This indicates that robust dispersible tablets which disintegrate rapidly could be manufactured from a range of co-processed excipients