Maltodextrins as drying auxiliary agent for the preparation of easily resuspendable nanoparticles

The drying of biodegradable polymeric nanoparticles (NP) is mandatory to improve their physical and chemical stability over time. Spray- or freeze-drying can induce irreversible aggregation of NP and therefore the use of drying auxiliary agents is required. The ability of four grades of maltodextrins differing in dextrose equivalent (DE) (i.e. DE2, DE6, DE12 and DE38) to protect PLGA NP from stresses was studied. High Mw maltodextrins (DE2) was not functional for obtaining an easily resuspendable dried product, since it needs a prolonged time to fully hydrate. Maltodextrins at intermediate DE showed a poor ability to protect NP from irreversible aggregation probably because too sensitive to environmental variation. DE38, which did not alter \u3b6-potential of NP, allowed to obtain an easily resuspendable nanosuspension independently of the drying process. The effectiveness of such material was attributed to the easiness of spray-dry a low viscous solution and to the ability of substitute the water molecules\u2019 hydrogen bonds with NP during freeze-drying

Regulatory aspects and quality controls of polymer-based parenteral long-acting drug products: the challenge of approving copies

To assure the safety and the efficacy of a medicinal product, quality and batch-to-batch reproducibility need to be guaranteed. In the case of parenteral long-acting products, the European Union (EU) and US Regulatory Authorities provide different indications, from the classification to the in vitro release assays related to such products. Despite their relevance, there are few in vitro experimental set-ups enabling researchers to discriminate among products with different in vivo behavior. Consequently, most copies are authorized through hybrid instead of generic applications. Here, we review the actual regulatory frameworks to evaluate the in vitro release tests of polymer-based long-acting parenterals to highlights the directions followed by the Regulatory Agencies in the USA and EU

Preserving the Integrity of Liposomes Prepared by Ethanol Injection upon Freeze-Drying: Insights from Combined Molecular Dynamics Simulations and Experimental Data

The freeze-drying of complex formulations, such as liposomes, is challenging, particularly if dispersions contain residual organic solvents. This work aimed to investigate the effects of possible protectants, namely sucrose, trehalose and/or poly(vinyl pyrrolidone) (PVP), on the main features of the dried product using a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based liposomal dispersion prepared by ethanol injection and containing ethanol up to 6%, as a model. The interactions among vesicles and protectants were preliminary screened by Molecular Dynamics (MD) simulations, which have been proved useful in rationalizing the selection of protectant(s). The freeze-drying protocol was based on calorimetric results. Overall data suggested a stronger cryo-protectant effect of trehalose, compared with sucrose, due to stronger interactions with the DPPC bilayer and the formation of highly ordered clusters around the lipids. The effect further improved in the presence of PVP. Differently from the other tested protectants, the selected trehalose/PVP combination allows to preserve liposome size, even in the presence of 6% ethanol, as demonstrated by Nanoparticle Tracking Analysis (NTA). Nevertheless, it should be also underlined that cakes blew out at an ethanol concentration higher than 1% v/v, probably due to the poor cohesion within the cake and solvent vapour pressure upon sublimation

A new mucoadhesive dosage form for the management of oral lichen planus : formulation study and clinical study

The work aimed at studying a new mucoadhesive prolonged release tablet containing 24\u3bcg clobetasol-17 propionate (CP) suitable for the management of oral lichen planus. Low swellable dosage forms were designed by combining a mucoadhesive polymer, i.e. poly(sodium methacrylate, methylmethacrylate), with hydroxypropylmethylcellulose and MgCl2. This formulation was selected to modify the tablet erosion rate in order to obtain a release of CP over a 6-h period. A double-blind, controlled study was performed using three groups of patient (n=16) who received three applications-a-day over 4weeks of the developed CP tablets (group CP-T), placebo tablets (group CP-P) or commercial CP ointment for cutaneous application (123\u3bcg/application) extemporary mixed with Orabase\u2122 (group CP-O). At the end of the study, pain and ulceration resolved in 13/16 and 11/16 patients of group CP-T and group CP-O, respectively. In the group CP-O, a transient acute hyperaemic candidosis (n=2) and taste alteration (n=4) were also observed. No changes in clinical signs of patients in the group CP-P were evident. The application of mucoadhesive tablet containing 24\u3bcg CP 3 times a day appeared to be effective, avoiding the side effects of the generally used treatment

A successful experimental model for intimal hyperplasia prevention using a resveratrol eluting balloon

Objective: Restenosis due to intimal hyperplasia is a major clinical problem that compromises the success of angioplasty and endovascular surgery. Resveratrol (RSV) has demonstrated a beneficial effect on restenosis from angioplasty. Unfortunately, the physicochemical characteristics of RSV reduce the practicality of its immediate clinical application. This work proposes an experimental model aiming to setup an intravessel, elutable, RSV-containing compound. Methods: A 140 mg/mL RSV sterile injectable solution with a suitable viscosity for intravascular administration by drugdelivery catheter (RSV-c) was prepared. This solution was locally administered in the common iliac artery of adult male New Zealand White rabbits using a dedicated device (Genie; Acrostak, Geneva, Switzerland) after the induction of intimal hyperplasia by traumatic angioplasty. The RSV concentrations in the wall artery were determined, and the thickness of the harvested iliac arteries was measured over a 1-month period. Results: The Genie catheter was applied in rabbit vessels, and the local delivery resulted in an effective reduction in restenosis after plain angioplasty. Notably, RSV-c forced into the artery wall by balloon expansion might accumulate in the interstitial areas or within cells, avoiding the washout of solutions. Magnification micrographs showed intimal proliferation was significantly inhibited when RSV-c was applied. Moreover, no adverse events were documented in in vitro or in vivo studies. Conclusions: RSV can be advantageously administered in the arterial walls by a drug-delivery catheter to reduce the risk of restenosis

Y Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale

The reproduction of reliable in vitro models of human skeletal muscle is made harder by the intrinsic 3D structural complexity of this tissue. Here we coupled engineered hydrogel with 3D structural cues and specific mechanical properties to derive human 3D muscle constructs (“myobundles”) at the scale of single fibers, by using primary myoblasts or myoblasts derived from embryonic stem cells. To this aim, cell culture was performed in confined, laminin-coated micrometric channels obtained inside a 3D hydrogel characterized by the optimal stiffness for skeletal muscle myogenesis. Primary myoblasts cultured in our 3D culture system were able to undergo myotube differentiation and maturation, as demonstrated by the proper expression and localization of key components of the sarcomere and sarcolemma. Such approach allowed the generation of human myobundles of ~10 mm in length and ~120 μm in diameter, showing spontaneous contraction 7 days after cell seeding. Transcriptome analyses showed higher similarity between 3D myobundles and skeletal signature, compared to that found between 2D myotubes and skeletal muscle, mainly resulting from expression in 3D myobundles of categories of genes involved in skeletal muscle maturation, including extracellular matrix organization. Moreover, imaging analyses confirmed that structured 3D culture system was conducive to differentiation/maturation also when using myoblasts derived from embryonic stem cells. In conclusion, our structured 3D model is a promising tool for modelling human skeletal muscle in healthy and diseases conditions

Data on spray-drying processing to optimize the yield of materials sensitive to heat and moisture content

Full dataset used to evaluate the spray-drying process parameters on the preparation of a micronized powder made of maltodextrin (MDX) is herein reported. The process parameters (namely, feed flow rate (FFR); inlet temperature (T in ); nozzle pressure (P N ); noozle diameter (D N ) and difference of pressure between cyclone and chamber (\u394P)) were screened through a Central Composite Design (2 5 121 ; 2 17 5; n C =2) using the following responses: product yield, powder size and size dispersity (span) and the outlet temperature of the exhausted air (T out ). Data indicate that, in the considered range, only the product yield and the powder median diameter were influenced by the process. The product yield progressively increased on increasing inlet temperature and decreasing the amount or the size of droplets to be dried. The powder median diameter was positively influenced only by the nozzle diameter. This data presented in this article completes a wider work related on \u201cMaltodextrins as drying auxiliary agent for the preparation of easily resuspendable nanoparticles\u201

Clinical presentation and management of acromegaly in elderly patients

Background and aim: Acromegaly is a rare disease with a peak of incidence in early adulthood. However, enhanced awareness of this disease, combined with wide availability of magnetic resonance imaging (MRI), has increased the diagnosis of forms with mild presentation, especially in elderly patients. Moreover, due to increased life expectancy and proactive individualized treatment, patients with early-onset acromegaly are today aging. The aim of our study was to describe our cohort of elderly patients with acromegaly. Materials and methods: This is a cross-sectional retrospective study of 96 outpatients. Clinical, endocrine, treatment, and follow-up data were collected using the electronic database of the University Hospital of Padova, Italy. Results: We diagnosed acromegaly in 13 patients, aged 6565\ua0years, presenting with relatively small adenomas and low IGF-1 secretion. Among them, 11 patients were initially treated with medical therapy and half normalized hormonal levels after 6\ua0months without undergoing neurosurgery (TNS). Remission was achieved after TNS in three out of four patients (primary TNS in two); ten patients presented controlled acromegaly at the last visit. Acromegaly-related comorbidities (colon polyps, thyroid cancer, adrenal incidentaloma, hypertension, and bone disease) were more prevalent in patients who had an early diagnosis (31 patients, characterized by a longer follow-up of 24\ua0years) than in those diagnosed aged 6565\ua0years (5\ua0years of follow-up). Conclusions: Elderly acromegalic patients are not uncommon. Primary medical therapy is a reasonable option and is effectively used, while the rate of surgical success is not reduced. A careful cost-benefit balance is suggested. Disease-specific comorbidities are more prevalent in acromegalic patients with a longer follow-up rather than in those diagnosed aged 6565\ua0years