Rapidly-Disintegrating Laminar Extrudates: Preliminary Experiments upon an Age Appropriate Pediatric Formulation

The aim of the present investigation is to produce rapidly disintegrating laminar extrudates for delivering ibuprofen in the mouth of paediatric patients. This laminar shape is particularly convenient for drug delivering in the mouth and can be easily cut in cut in different sizes allowing for a convenient adjustment of the drug dose depending on the age of the patient. Due to the fact that in paediatric formulations, the selection of the excipients is always a challenging issue and the reduction of their amount is always highly desirable, in this study to select the most appropriate composition to achieve a rapid disintegration and simultaneously permit a high amount of ibuprofen in the system, an experimental design for mixtures was employed and the disintegration time in simulated saliva was used as experimental response. In addition, after solid state analyses to check possible insurgence of drug-excipients interactions, laminar extrudates were characterised in terms of mechanical properties and in vitro dissolution performances. Extrudates with the desired uniform laminar shape, constant thickness (2 mm) and a very high content of drug (82% wt) were produced. These products exhibited a short disintegration time. The dose for a patient of 6-12 years corresponded to a length of extrudate between 1-1.5 cm, perfectly compatible with a formulation orodispersible thin laminar extrudate intended for a paediatric patient (Figure 1)

Foam-Mat Freeze-Drying of Blueberry Juice by Using Trehalose-β-Lactoglobulin and Trehalose-Bovine Serum Albumin as Matrices

This study aimed to evaluate the effect of pure protein compounds and trehalose incorporated into blueberry juice for foam-mat freeze-drying on the foam and powder properties. Foam-mat freeze-drying (FMFD) of blueberry juice was tested at − 55 °C for 24 h. Matrices used were trehalose + β-lactoglobulin (T3BL1) and trehalose + bovine serum albumin (T3A1) and compared with maltodextrin + whey protein isolate (M3W1). Physicochemical properties of foam and powder, e.g., foam stability, foam density, moisture, rehydration time, color, particle morphology, total phenolic, and anthocyanins (total and individuals), were investigated. T3BL1 and T3A1 had more stable foam than M3W1. However, overrun of T3BL1 and T3A1 foamed were inferior to the M3W1 sample. The M3W1 sample recovered 79% powder (dry weight) and was superior to others. Rehydration time of powdered T3BL1 and T3A1, with bulk densities of 0.55–0.60 g cm−3, was the fastest (34–36 s). The blueberry powders of M3W1 showed more irregular particle size and shape, while the samples with trehalose and pure proteins generated particles of more uniform size with obvious pores. T3BL1 and T3A1 showed less redness (a*) values than the M3W1 product. All samples were considered pure red due to hue values < 90. M3W1 was superior in total phenolic content (TPC) and total monomeric anthocyanins (TMA) compared with both samples made with trehalose + β-lactoglobulin and trehalose+bovine serum albumin. Delphinidin-3-glucoside (Del3Gl) concentration was found to be higher in M3W1. Also, M3W1 had higher cyanidin-3-glucoside (Cyn3Gl) and malvidin-3-glucoside (Mal3Gl) concentration. M3W1 also prevented the degradation of these bioactive compounds better than the other FMFD samples. The use of pure proteins and trehalose as matrices in the FMFD process had little advantage compared with maltodextrin/whey protein isolate. Thus, maltodextrin/whey protein isolate seems an ideal matrix for the manufacture of FMFD blueberry

Well-Defined Generalized Stochastic Petri Nets: A Net-Level Method to Specify Priorities

Generalized stochastic Petri nets (GSPN), with immediate transitions, are extensively used to model concurrent systems in a wide range of application domains, particularly including software and hardware aspects of computer systems, and their interactions. These models are typically used for system specification, logical and performance analysis, or automatic code generation. In order to keep modeling separate from the analysis and to gain in efficiency and robustness of the modeling process, the complete specification of the stochastic process underlying a model should be guaranteed at the net level, without requiring the generation and exploration of the state space. In this paper, we propose a net-level method that guides the modeler in the task of defining the priorities (and weights) of immediate transitions in a GSPN model, to deal with confusion and conflict problems. The application of this method ensures well-definition without reducing modeling flexibility or expressiveness

Comparative evaluation of the effect of permeation enhancers, lipid nanoparticles and colloidal silica on in vivo human skin penetration of quercetin

Background: The aim of this study was to evaluate emulsions containing a penetration enhancer, lipid nanoparticles (LNs) or colloidal silica, as systems to improve the topical delivery of the flavonoid, quercetin. Methods: The skin penetration of quercetin was investigated in vivo, on human volunteers by tape stripping. Quercetin-loaded LNs were prepared using hot high pressure homogenization and characterized by means of dynamic light scattering and release studies. The location of the silica nanoparticles in the skin was determined by inductively coupled plasma mass spectrometry assay of silicon in the stratum corneum strips. Results and Conclusions: The penetration enhancer, diethylene glycol monoethyl ether did not produce any significant increase in the fraction of applied quercetin dose permeated in vivo into human stratum corneum (17.1 ± 3.2%), as compared to the control emulsion (18.1 ± 2.3 %). A greater, but not statistically significant, accumulation of the flavonoid in the human horny layer (21.2 ± 2.9% of the applied dose) was measured following topical application of quercetin-loaded LNs (mean particle size, 527 nm). On the other hand, the addition of colloidal silica (average particle diameter, 486 nm) to the emulsion (2%, w/w), significantly increased the in vivo uptake of quercetin by the human stratum corneum, to 26.7± 4.1% of the applied dose, the enhancing effect on permeation being more marked in the deepest horny layer strips. The measured in vivo skin penetration profile of colloidal silica showed that silica particles diffused down to the intermediate region of human horny layer and hence could act as carrier for quercetin