DA-SVM, MLR, PLS i OLS modeliranje kumulativnog otpuštanja Tramadola iz formulacija inkapsuliranih s PCL i PVP

This work aimed to model the kinetics of cumulative drug release from formulations based on encapsulation by biodegradable polycaprolactone and polyvinylpyrrolidone polymers. Different ratios of the polymerswere prepared by a solvent evaporation method using Span 20 and Span 80 as surfactants. The cumulative drug release was estimated depending on the formulation component and time. Four models: hybrid model of support vector machine and dragonfly algorithm (DA-SVM), partial least squares (PLS) model, multiple linear regression (MLR) model, and ordinary least squared (OLS) model, were developed and compared. The statistical analysis proved there were no issues in variable inputs. The results showed that the DA-SVM model gave a better result where a determination coefficient was close to one and RMSE error close to zero. A graphical interface was built to calculate the cumulative drug release. This work is licensed under a Creative Commons Attribution 4.0 International License.Cilj ovog rada bio je modeliranje kinetike kumulativnog otpuštanja lijeka iz formulacija inkapsuliranih biorazgradivim polikaprolaktonom i polivinilpirolidonom. Različiti omjeri polimera pripremljeni su isparavanjem otapala uz upotrebu Span 20 i Span 80 kao površinski aktivnih tvari. U modeliranju kinetike primijenjena su četiri pristupa: hibridni pristup kombiniranjem metode potpornih vektora i Dragonfly algoritma (DA-SVM), metoda parcijalnih najmanjih kvadrata (PLS), višestruka linearna regresija (MLR) te metoda najmanjih kvadrata (OLS). Provedena je usporedba kvalitete predviđanja kumulativnog otpuštanja lijeka, ovisno o primijenjenom polimeru i vremenu. Statistička analiza nije ukazala na probleme s odabranim ulaznim varijablama. Rezultati su pokazali superiornost predviđanja DA-SVM modelom uz koeficijent determinacije blizu jedinice te RMSE pogrešku blizu nule. Za izračun kumulativnog otpuštanja lijeka konstruirano je grafičko sučelje. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna

Ethylene-methyl acrylate-glycidyl methacrylate toughened poly(lactic acid) nanocomposites

Poly (lactic acid) (PLA) was melt blended in a twin screw extruder using an ethylene-methyl acrylate-glycidyl methacrylate rubber as a toughener. PLA/rubber blends were immiscible as observed by scanning electron microscopy. Impact strength and ductility of PLA were improved by the addition of the rubber at the expense of strength and stiffness. An organo-montmorillonite (OMMT) was used at 2 wt % to counteract the negative effect of the rubber on modulus, and balanced properties were observed at 10 wt % rubber content. X-ray diffraction and transmission electron microscopy revealed the formation of intercalated/exfoliated structure in the ternary nanocomposites. Thermal behavior analysis indicated that the degree of crystallinity is slightly affected by the clay and the rubber. Both the clay and the rubber decreased the crystallization temperature of PLA and acted as nucleating agents for PLA. The viscosity of the mixtures as measured by melt flow index was highly influenced by the rubber and the OMMT. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 201

Effects of Mixing Protocols on Impact Modified Poly(lactic acid) Layered Silicate Nanocomposites

Poly(lactic acid)/2 wt % organomodified montmorillonite (PLA/OMMT) was toughened by an ethylene-methyl acrylate-glycidyl methacrylate (E-MA-GMA) rubber. The ternary nanocomposites were prepared by melt compounding in a twin screw extruder using four different addition protocols of the components of the nanocomposite and varying the rubber content in the range of 5-20 wt %. It was found that both clay dispersion and morphology were influenced by the blending method as detected by X-ray diffraction (XRD) and observed by TEM and scanning electron microscopy (SEM). The XRD results, which were also confirmed by TEM observations, demonstrated that the OMMT dispersed better in PLA than in E-MA-GMA. All formulations exhibited intercalated/partially exfoliated structure with the best clay dispersion achieved when the clay was first mixed with PLA before the rubber was added. According to SEM, the blends were immiscible and exhibited fine dispersion of the rubber in the PLA with differences in the mean particle sizes that depended on the addition order. Balanced stiffness-toughness was observed at 10 wt % rubber content in the compounds without significant sacrifice of the strength. High impact toughness was attained when PLA was first mixed with the clay before the rubber was added, and the highest tensile toughness was obtained when PLA was first compounded with the rubber, and then clay was incorporated into the mixture. Thermal characterization by DSC confirmed the immiscibility of the blends, but in general, the thermal parameters and the degree of crystallinity of the PLA were not affected by the preparation procedure. Both the clay and the rubber decreased the crystallization temperature of the PLA by acting as nucleating agents. (c) 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41518

An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits

This research was funded by the Government of the Region de Murcia (Spain) by the Fundacion Seneca (project 20950/PI/18). The Fundacion Seneca had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Background: Metformin hydrochloride is a biguanide derivative that has been widely used to treat type 2 diabetes in humans. In veterinary medicine, metformin has shown increasing potential for diabetes treatment in different species, such as equids, dogs, cats and rabbits. It is highly hydrophilic, with incomplete gastrointestinal absorption and very large variability in absolute bioavailability between species, ranging from 4% in equids to 60% in humans. Metformin also shows a short half-life of approximately 2 h in dogs, cats, horses and humans. The objectives of this study were to evaluate a poly (lactic acid) (PLA) metformin microparticle formulation to test in rabbits and conduct a pharmacokinetics study of intravenous ( SIV) and oral solution ( SPO) metformin administration and oral PLA microparticle ( SPLA) administration to rabbits to evaluate the improvement in the metformin pharmacokinetics profile. Results: Metformin-loaded PLA microparticles were characterized by a spherical shape and high encapsulation efficiency. The results from Fourier transform infrared (FTIR) spectroscopy suggested the presence of interactions between metformin and PLA. X-Ray diffraction (XRD) analysis corroborated the results from the differential scanning calorimetry (DSC) studies, showing that metformin is present in an amorphous state within the microparticles. Physicochemical characterization suggested that PLA and metformin hydrochloride interacted within the microparticles via hydrogen bonding interactions. The pharmacokinetic study in rabbits showed sustained-release characteristics from the prepared microparticles with a delay in the time needed to reach the maximum concentration ( Tmax), decreased Cmax and bioavailability, and increased mean residence time (MRT) and half-life compared to the pure drug solution. Conclusions: Metformin-loaded PLA microparticles showed optimal and beneficial properties in terms of their physicochemical characteristics, making them suitable for use in an in vivo pharmacokinetic study. The pharmacokinetic parameters of the metformin microparticles from the in vivo study showed a shorter Tmax, longer MRT and half-life, decreased Cmax and the prolonged/sustained release expected for metformin. However, the unexpected decrease in bioavailability of metformin from the microparticles with respect to the oral solution should be evaluated for microparticle and dose design in future works, especially before being tested in other animal species in veterinary medicine.Government of the Region de Murcia (Spain) by the Fundacion Seneca 20950/PI/1

Polysaccharide-based films of cactus mucilage and agar with antioxidant properties for active food packaging

The production of films derived from renewable resources for food packaging applications is an important research area within the scope of sustainable development. Herein, fully biobased films made from cactus mucilage (CM), extracted from Algerian Opuntia ficus-indica cladodes, and agar (A), extracted from marine red algae, were assembled via solvent film casting method. The effect of agar concentration on the properties of the plasticized CM films (40 wt.% glycerol) was evaluated at three different mass ratios of CM/A, namely 70:30, 60:40 and 50:50. Overall, the results revealed that the polysaccharide-based films exhibited good mechanical properties (Young’s modulus ≥ 135 MPa and tensile strength ≥ 5.3 MPa) and UVlight protection (transmittance ≤ 40% (200–400 nm)), as well as thermal stability up to 140 °C, low water vapor transmission rate (WVTR ≤ 10.6 g  h−1 m−2) and moderate antioxidant activity (DPPH scavenging ≥ 19% and ferric reducing antioxidant power ≥ 1.3 mg AAE per g of film). Following from this, the pliable freestanding CM/A-based films with UV protection, water barrier properties and antioxidant activity can be a low-cost and eco-friendly option for the development of active food packaging materials.publishe

Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.

BACKGROUND: Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. METHODS: 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. FINDINGS: Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05). INTERPRETATION: Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear