Redispersible lipidic nanoparticles obtained by Fluid Bed Drying

Abstract Formulation of aqueous dispersions of lipidic nanoparticles is an elegant way to enhance and control drug bioavailability, ameliorate stability, and mask bitterness of some drugs. They are interesting vectors for oral delivery of lipophilic and, to a certain extent, hydrophilic substances. Their production can be done without the use of organic solvents, this make this kind of formulation ideal for pediatric use. [1] Therfore, these systems can present some instability phenomena, in order to prevent eventual issues, lipidic nanoparticles are classicaly dryed by spray-drying or lyophilisation technics into reconstitutable powders, the commun of these technics is their highly cost witch limited their use at large scale in cosmetic and pharmaceutical industries. [2], A comparison between Fluid Bed Drying and classical drying methods (lyophilization and spray drying) was performed, the comparison took into consideration quality of the obtained powder and its redipersibility, drug stability during the process and the effect of the drying method on particle size, the benefit of each method was highlighted

Comparison of Three Processes for Parenteral Nanoemulsion Production: Ultrasounds, Microfluidizer, and Premix Membrane Emulsification

International audienceNanoemulsions are of great interest for pharmaceutical applications, including parenteral dosage forms. However, their production is still limited and requires more efficient and adaptive technologies. The more common systems are high-shear homogenization like microfludizers (MF) at industrial scale and ultrasounds at research scale, both based on high energy limiting their application for sensitive drugs. Recently, a process based on premix membrane emulsification (PME) was developed to produce nanoemulsions. These three processes have been compared for the production of a model parenteral nanoemulsion containing all-trans-retinoic acid, a thermolabile molecule which is used in the treatment of acute promyelocytic leukemia in a parenteral form. Droplet size and active integrity were studied because of their major interest for efficacy and safety assessment. Regarding droplet size, PME produced monodispersed droplets of 335 nm compared to the other processes which produced nanoemulsions of around 150 nm but with the presence of micron size droplets detected by laser diffraction and optical microscopy. No real difference between the three processes was observed on active degradation during emulsifcation. However, regarding stability, especially at 40 o C nanoemulsions obtained with the microfluidizer showed a greater molecule degradation and unstable nanoemulsion with a 4 times droplet size increase under stress conditions

Vitamin E encapsulation within pharmaceutical drug-carriers prepared using membrane contactors

Vitamin E encapsulation within pharmaceutical drug-carriers prepared using membrane contactor

Preparation of liposomes: a novel application of microengineered membranes

Liposomes with a mean size of 59–308 nm suitable for pulmonary drug delivery were prepared by the ethanol injection method using nickel microengineered flat disc membranes with a uniform pore size of 5–40 μm and a pore spacing of 80 or 200 μm. An ethanolic phase containing 20–50 mg ml−1 phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or Lipoid® E80), 5–12.5 mg ml−1 stabilizer (cholesterol, stearic acid or cocoa butter), and 0 or 5 mg ml−1 vitamin E was injected through the membrane into an agitated aqueous phase at a controlled flux of 142–355 l m−2 h−1 and a shear stress on the membrane surface of 0.80–16 Pa. The mean particle size obtained under optimal conditions was 84 and 59 nm for Lipoid E80 and POPC liposomes, respectively. The particle size of the prepared liposomes increased with an increase in the pore size of the membrane and decreased with an increase in the pore spacing. Lipoid E80 liposomes stabilized by cholesterol or stearic acid maintained their initial size within 3 months. A high entrapment efficiency of 99.87% was achieved when Lipoid E80 liposomes were loaded with vitamin E. Transmission electron microscopy images revealed spherical multi-lamellar structure of vesicles. The reproducibility of the developed fabrication method was high

Preparation of liposomes: a novel application of microengineered membranes-from laboratory scale to large scale

A novel ethanol injection method using microengineered nickel membrane was employed to produce POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and Lipoid® E80 liposomes at different production scales. A stirred cell device was used to produce 73 ml of the liposomal suspension and the product volume was then increased by a factor of 8 at the same transmembrane flux (140 l m−2 h−1), volume ratio of the aqueous to organic phase (4.5) and peak shear stress on the membrane surface (2.7 Pa). Two different strategies for shear control on the membrane surface have been used in the scaled-up versions of the process: a cross flow recirculation of the aqueous phase across the membrane surface and low frequency oscillation of the membrane surface (∼40 Hz) in a direction normal to the flow of the injected organic phase. Using the same membrane with a pore size of 5 μm and pore spacing of 200 μm in all devices, the size of the POPC liposomes produced in all three membrane systems was highly consistent (80–86 nm) and the coefficient of variation ranged between 26 and 36%. The smallest and most uniform liposomal nanoparticles were produced in a novel oscillating membrane system. The mean vesicle size increased with increasing the pore size of the membrane and the injection time. An increase in the vesicle size over time was caused by deposition of newly formed phospholipid fragments onto the surface of the vesicles already formed in the suspension and this increase was most pronounced for the cross flow system, due to long recirculation time. The final vesicle size in all membrane systems was suitable for their use as drug carriers in pharmaceutical formulations

Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating

The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of manoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant. However, in the case of the cationic Eudragit E, protonation of the tertiary amine groups by acidification of the aqueous phase was necessary to improve the emulsion stability in the absence of surfactant and subsequently to prevent droplet coalescence during evaporation. In addition, a pseudolatex of Eudragit E was used to validate the coating properties of the formulation for solid dosage forms. Film-coated tablets of quinidine sulfate showed a transparent glossy continuous film that was firmly attached to the tablet. The dissolution profile of quinidine sulfate from the tablets coated with the Eudragit E pseudolatex was comparable to that of tablets coated with an acetonic solution of Eudragit E. Furthermore, both types of coating ensured similar taste masking. The emulsification-evaporation method used was shown to be appropriate for the preparation of surfactant-free colloidal dispersions of the 3 types of preformed methacrylic acid copolymers; the dispersions can subsequently be used for film coating of solid dosage form

Production of liposomes using microengineered membrane and co-flow microfluidic device

Two modified ethanol injection methods have been used to produce Lipoid® E80 and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) liposomes: (i) injection of the organic phase through a microengineered nickel membrane kept under controlled shear conditions and (ii) injection of the organic phase through a tapered-end glass capillary into co-flowing aqueous stream using coaxial assemblies of glass capillaries. The organic phase was composed of 20 mg ml−1 of phospholipids and 5 mg ml−1 of cholesterol dissolved in ethanol and the aqueous phase was ultra-pure water. Self-assembly of phospholipid molecules into multiple concentric bilayers via phospolipid bilayered fragments was initiated by interpenetration of the two miscible solvents. The mean vesicle size in the membrane method was 80 ± 3 nm and consistent across all of the devices (stirred cell, cross-flow module and oscillating membrane system), indicating that local or temporal variations of the shear stress on the membrane surface had no effect on the vesicle size, on the condition that a maximum shear stress was kept constant. The mean vesicle size in co-flow microfludic device decreased from 131 to 73 nm when the orifice diameter in the injection capillary was reduced from 209 to 42 μm at the aqueous and organic phase flow rate of 25 and 5.55 ml h−1, respectively. The vesicle size was significantly affected by the mixing efficiency, which was controlled by the orifice size and liquid flow rates. The smallest vesicle size was obtained under conditions that promote the highest mixing rate. Computational Fluid Dynamics (CFD) simulations were performed to study the mixing process in the vicinity of the orifice

pH-sensitive micelles for targeted drug delivery prepared using a novel membrane contactor method

A novel membrane contactor method was used to produce size-controlled poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of diblock copolymers with different average molecular weights, Mn (9200 or 10 400 Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m–2 h–1 of the organic phase (a 1 mg mL–1 solution of PEG-PCL in tetrahydrofuran) through a microengineered nickel membrane with a hexagonal pore array and 200 μm pore spacing into deionized water agitated at 700 rpm, the micelle size linearly increased from 92 nm for a 5-μm pore size to 165 nm for a 40-μm pore size. The micelle size was finely tuned by the agitation rate, transmembrane flux and aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug loading of 75% (w/w) were achieved when a hydrophobic drug (vitamin E) was entrapped within the micelles, as determined by ultracentrifugation method. The drug-loaded micelles had a mean size of 146 ± 7 nm, a polydispersity index of 0.09 ± 0.01, and a ζ potential of −19.5 ± 0.2 mV. When drug-loaded micelles where stored for 50 h, a pH sensitive drug release was achieved and a maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH-sensitive hydrazone bond was incorporated between PEG and PCL blocks, no significant change in micelle size was observed at the same micellization conditions

Topical co-delivery of indomethacin and nigella sativa L. essential oil in poly-cappa-caprolactone nanoparticles: in vitro study of anti-inflammatory activity

Indomethacin is a potent, nonselective Non-steroidal Antiinflammatory Drug (NSAID) but its low water-solubility precludes its use as topical dosage form. As with other NSAIDs, the systemic delivery is associated with high risk of serious gastrointestinal adverse events including bleeding, ulceration and perforation of stomach and intestines. Here we demonstrate a safer way of administration i.e via topical demonstrating synergistic effects when co-delivered with Nigella sativa L. seeds essential oil (NSSEO) in the form of coencapsulated particles (~200 nm) of poly--caprolactone. The particles showed penetrability across stratum corneum to dermis layer in ex-vivo human skin. Further study in the xyline-induced ear edema in mice was performed, and co-encapsulated particles demonstrated highest antiinflammatory effect compared to indomethacin particles and indomethacin gels. Despite slower onset compared to indomethacin gels, the inflamed ear continued to show reduction in thickness over 8 hours of observation demonstrating synergistic and pro-longed effect contributed by NSSEO. In immunohistochemistry study of CD45+, the mice ears treated with co-encapsulated particles showed considerable reduction in lesions, epidermal-dermal separation and inflammatory cells (lymphocytes and neutrophils) infiltration as compared to other formulation. Based on microscopic evaluation, the anti-inflammatory inhibition effect of co-encapsulated particles is the highest (90%) followed by indomethacin particles (79%) and indomethacin gel (49%). The findings suggest not only skin permeability of indomethacin significantly improved but also the therapeutic effects, all provided by the presence of NSSEO in the particles. This study paves the way to more co-encapsulation of any other contemporary medicines in combination with this wholesome natural oil, NSSEO

Degradação e estabilização do diclofenaco em nanocápsulas poliméricas

I den tidigare gjorda kunskapsöversikten fann vi “hål” i forskningen gällande elevers upplevelser om kooperativt lärande. Denna studie undersöker därför elevers upplevelser och erfarenheter om kamratrespons i matematikämnet. Lundgren, Säljö och Liberg (2014, s.308) menar på att kunskap är någonting som växer fram i interaktion mellan elever. Lärandet ses alltså som en del av den mänskliga gemenskapen där skolans uppgift är att involvera människor i samhällets kollektiva kunskaper. Fohlin et al. (2017 s.13) menar i sin tur på att det samhället vi lever i idag är demokratiskt och förväntas därför ha sammanlänkande roller. Varför speglas då inte undervisningen av ett hjälpande beteende. Läroplanen för grundskolan, förskoleklassen och fritidshemmet 2011 (Lgr11, s. 9) slår fast att skolan ska sträva efter att vara en levande och social gemenskap som ska bidra till vilja, trygghet samt lust att lära. Den ska även sträva efter att skapa de ultimata förutsättningarna för elevernas kunskapsutveckling, bildning och tänkande. Varje enskild elev i skolan har rätt att få utvecklas, få en ökad glädje, få möjlighet till att uppleva tillfredsställelse som ges vid framsteg och klara av de svårigheter som kan uppstå. Syftet med studien är därför att undersöka yngre elevers upplevelser och erfarenheter av arbetssättet kamratrespons inom matematikämnet. Vilka är elevernas upplevelser om kamratrespons och hur arbetar eleverna med kamratrespons och varför gör de det? För att finna svar på studiens syfte och frågeställningar har en kvalitativ metod använts, genom fokusgruppsdiskussioner. Resultatet i studien indikerar i huvudsak på att eleverna har en positiv inställning och upplevelse till arbetssättet kamratrespons. Det framgår även att eleverna inte endast tränar ämnesinnehåll utan även sociala förmågor då lärandet sker i en social kontext. Resultatet visar att kamratrespons har positiv inverkan på elevers kunskapsutveckling, uthållighet och motivation. Men förmågan att ge varandra gynnsam respons kräver övning där elevernas ansvarskänsla behöver utvecklas, både för sitt eget men också för gruppens lärande. För att kunna genomföra kamratrespons på korrekt sätt krävs det prioritering från läraren under en längre period. Läraren behöver också ha en förståelse för att arbetssättet inte passar alla elever. Men då forskningen belyser goda effekter när det gäller kooperativt lärande får läraren stöd i sitt didaktiska beslut att arbeta med kamratrespons