Texture analysis as a tool to study the kinetics of wet agglomeration processes

In this work wet granulation experiments were carried out in a planetary mixer with the aim to develop a novel analytical tool based on surface texture analysis. The evolution of a simple formulation (300 g of microcrystalline cellulose with a solid binders pre-dispersed in water) was monitored from the very beginning up to the end point and information on the kinetics of granulation as well as on the effect of liquid binder amount were collected. Agreement between texture analysis and granules particle size distribution obtained by sieving analysis was always found. The method proved to be robust enough to easily monitor the process and its use for more refined analyses on the different rate processes occurring during granulation is also suggested

Influence of process variables on the properties of simvastatin self-emulsifying granules obtained through high shear wet granulation

Improvements of the oral bioavailability of lipophilic drugs can be obtained using lipidic formulations such as the self-emulsifying drug delivery systems. The high shear wet granulation (HSWG), using microemulsions as binder, is a viable process to produce self-emulsifying granules. However only few information are present in the literature on the effect of process variables on the properties of the granules obtained with these binders. Consequently, this article compares the effects of some relevant experimental variables (impeller speed and massing time) on thefinal technological and pharmaceutical properties of the granules produced using simple water, or alternatively, a microemulsion as binder and containing simvastatin (SV) as model drug. The effects of the variables were determined by evaluating the granule median diameter, their particle size distribution, roundness, disintegration time and dissolution rate of SV. Results clearly demonstrated that the microemulsion-based process was less sensitive tooperating conditions than the water-based process. With microemulsion the nucleation process and growth regimes were more difficult to control, resulting in products with broader PSDs. At the same operatingconditions microemulsion-based granules were more brittle but rounder and showed smaller median diameter compared to water-based granules. The dissolution rate of simvastatin was not significantly affected by the operating conditions

A New ELISA Using the ANANAS Technology Showing High Sensitivity to diagnose the Bovine Rhinotracheitis from Individual Sera to Pooled Milk

Diagnostic tests for veterinary surveillance programs should be efficient, easy to use and, possibly, economical. In this context, classic Enzyme linked ImmunoSorbent Assay (ELISA) remains the most common analytical platform employed for serological analyses. The analysis of pooled samples instead of individual ones is a common procedure that permits to certify, with one single test, entire herds as "disease-free". However, diagnostic tests for pooled samples need to be particularly sensitive, especially when the levels of disease markers are low, as in the case of anti-BoHV1 antibodies in milk as markers of Infectious Bovine Rhinotracheitis (IBR) disease. The avidin-nucleic-acid-nanoassembly (ANANAS) is a novel kind of signal amplification platform for immunodiagnostics based on colloidal poly-avidin nanoparticles that, using model analytes, was shown to strongly increase ELISA test performance as compared to monomeric avidin. Here, for the first time, we applied the ANANAS reagent integration in a real diagnostic context. The monoclonal 1G10 anti-bovine IgG1 antibody was biotinylated and integrated with the ANANAS reagents for indirect IBR diagnosis from pooled milk mimicking tank samples from herds with IBR prevalence between 1 to 8%. The sensitivity and specificity of the ANANAS integrated method was compared to that of a classic test based on the same 1G10 antibody directly linked to horseradish peroxidase, and a commercial IDEXX kit recently introduced in the market. ANANAS integration increased by 5-fold the sensitivity of the 1G10 mAb-based conventional ELISA without loosing specificity. When compared to the commercial kit, the 1G10-ANANAS integrated method was capable to detect the presence of anti-BHV1 antibodies from bulk milk of gE antibody positive animals with 2-fold higher sensitivity and similar specificity. The results demonstrate the potentials of this new amplification technology, which permits improving current classic ELISA sensitivity limits without the need for new hardware investments

Sublingual Administration of Sildenafil Oro-dispersible Film: New Profiles of Drug Tolerability and Pharmacokinetics for PDE5 Inhibitors

Objective: Type 5 phosphodiesterase inhibitors (PDE5i) are efficient drugs used for treatment of erectile dysfunction (ED); however, a large discontinuation rate due to major side effects is reported. The aim of this study was to evaluate the possible improvement of sildenafil (Sild) pharmacokinetics associated to the sublingual administration of the new available oro-dispersible film (ODF), compared to both the oro-dispersible tablet (ODT) and the film-coated tablet (FCT) as original per os formulation.Methods:In vitro disaggregation test, dissolution test, and permeation test in specific devices to estimate the trans-mucosal absorption. In vivo analysis of serum Sild levels, by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), was performed in 20 patients with psychogenic ED receiving alternatively per os FCT or sublingual ODT or ODF, at an equal dosage (50 mg). Pharmacokinetic parameters of Sild and adverse drug reactions experienced after the dosing of each formulation were compared.Results:In vitro, ODF showed the highest time to disaggregation and an increased rate of permeation compared to both ODT and FCT (P = 0.017 and P = 0.008, respectively). In vivo, compared to both FCT and ODT, ODF showed a faster increase of serum Sild levels (serum levels at 15 min from dosing, respectively: 2.24 ± 1.4 ng/ml FCT, 0.5 ± 0.3 ng/ml ODT, and 13.5 ± 9.1 ng/ml ODF; P < 0.01 and P < 0.05 vs. ODF) together with a higher drug bioavailability within 60 min from dosing (relative AUC60min vs. FCT, respectively: 100.0 ± 44.9% FCT, 183.8 ± 75.4% ODT, and 304.2 ± 156.0% ODF). A trend toward lower peak serum levels was observed for ODF. Finally, ODF showed a lower prevalence of headache compared to FCT (1 vs. 35%; P < 0.05) and improved pattern of flushing and nasal congestion.Conclusion: Sublingual Sild ODF improves the drug tolerability through a likely modified pharmacokinetic, suggesting a possible implication also in the clinical efficacy profile. Sublingual administration of oro-dispersible formulations may represent a strategy to ameliorate the adherence to therapy with PDE5i, particularly in patients discouraged by side effects

Early Evaluation of Copper Radioisotope Production at ISOLPHARM

The ISOLPHARM (ISOL technique for radioPHARMaceuticals) project is dedicated to the development of high purity radiopharmaceuticals exploiting the radionuclides producible with the future Selective Production of Exotic Species (SPES) Isotope Separation On-Line (ISOL) facility at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (INFN-LNL). At SPES, a proton beam (up to 70 MeV) extracted from a cyclotron will directly impinge a primary target, where the produced isotopes are released thanks to the high working temperatures (2000 \ub0C), ionized, extracted and accelerated, and finally, after mass separation, only the desired nuclei are collected on a secondary target, free from isotopic contaminants that decrease their specific activity. A case study for such project is the evaluation of the feasibility of the ISOL production of 64Cu and 67Cu using a zirconium germanide target, currently under development. The producible activities of 64Cu and 67Cu were calculated by means of the Monte Carlo code FLUKA, whereas dedicated off-line tests with stable beams were performed at LNL to evaluate the capability to ionize and recover isotopically pure copper

Promuovere la salute in et\ue0 pediatrica \u2026 Ma sono originator, generici, genericati o equivalenti?

Qualit\ue0, Sicurezza ed Efficacia dei medicinali equivalenti alla luce della attuale normativa europea sul medicinale, con particolare riferimento all'uso pediatrico. Sono descritte le caratteristiche tecnologiche del medicinale generico \u2013 equivalente, in particolare sotto l\u2019aspetto della Qualit\ue0 facendo riferimento alle norme europee introdotte con il Codice comunitario del medicinale ed evidenziando l\u2019impatto della vigilanza dell\u2019AIFA sul medicinale generico dalla produzione al post-marketing. Sviluppo degli studi di bioequivalenza alla luce delle pi\uf9 recenti indicazioni scientifiche. Sonodescritte le caratteristiche di efficacia e sicurezza del medicinale generico \u2013 equivalente facendo riferimento alle norme europee in merito alla definizione degli studi di bioequivalenza sottesi alla Autorizzazione all\u2019immissione in commercio nonch\ue9 alla loro valenza in termini di efficacia del medicinale