Improved achiral and chiral hplc-uv analysis of ruxolitinib in two different drug formulations

In this paper, two new reversed-phase (RP) HPLC-UV methods enabling the quantitative achiral and chiral analysis of ruxolitinib in commercial tablets (containing 20 mg of active pharmaceutical ingredient, API) and not commercially available galenic capsules (with 5 mg of API) are described. For the achiral method based on the use of a water/acetonitrile [70:30, v/v; with 0.1% (v) formic acid] eluent, a “research validation” study was performed mostly following the “International Council for Harmonization” guidelines. All the system suitability parameters were within the acceptance criteria: tailing factor, between 1.7 and 2.0; retention factor, 2.2; number of theoretical plates, >9000. The linearity curve showed R2 = 0.99 (Rxv2 = 0.99), while trueness (expressed as recovery) was between 96.3 and 106.3%. Coefficient of variations (CVs) (repeatability: CVw and intermediate precision: CVIP ) did not exceed 1.3% and 2.9%, respectively. Moreover, the use of the enantiomeric Whelk-O1 chiral stationary phases operated under similar RP eluent conditions as for the achiral analyses, and the “inverted chirality columns approach (ICCA)” allowed us to establish that the enantiomeric purity of ruxolitinib is retained upon reformulation from tablets to capsules. The two developed methods can allow accurate determinations of ruxolitinib in drug formulations for medical use

Leaves and fruits preparations of Pistacia lentiscus L.: A review on the ethnopharmacological uses and implications in inflammation and infection

There is an increasing interest in revisiting plants for drug discovery, proving scientifically their role as remedies. The aim of this review was to give an overview of the ethnopharmacological uses of Pistacia lentiscus L. (PlL) leaves and fruits, expanding the search for the scientific discovery of their chemistry, anti-inflammatory, antioxidative and antimicrobial activities. PlL is a wild-growing shrub rich in terpenoids and polyphenols, the oil and extracts of which have been widely used against inflammation and infections, and as wound healing agents. The more recurrent components in PlL essential oil (EO) are represented by α-pinene, terpinene, caryophyllene, limonene and myrcene, with high variability in concentration depending on the Mediterranean country. The anti-inflammatory activity of the oil mainly occurs due to the inhibition of pro-inflammatory cytokines and the arachidonic acid cascade. Interestingly, the capacity against COX-2 and LOX indicates PlL EO as a dual inhibitory compound. The high content of polyphenols enriching the extracts provide explanations for the known biological properties of the plant. The protective effect against reactive oxygen species is of wide interest. In particular, their anthocyanins content greatly clarifies their antioxidative capacity. Further, the antimicrobial activity of PlL oil and extracts includes the inhibition of Staphylococcus aureus, Escherichia coli, periodontal bacteria and Candida spp. In conclusion, the relevant scientific properties indicate PlL as a nutraceutical and also as a therapeutic agent against a wide range of diseases based on inflammation and infections

Biodegradable composite porous poly(dl-lactide-co-glycolide) scaffold supports mesenchymal stem cell differentiation and calcium phosphate deposition

In recent decades, tissue engineering strategies have been proposed for the treatment of musculoskeletal diseases and bone fractures to overcome the limitations of the traditional surgical approaches based on allografts and autografts. In this work we report the development of a composite porous poly(dl-lactide-co-glycolide) scaffold suitable for bone regeneration. Scaffolds were produced by thermal sintering of porous microparticles. Next, in order to improve cell adhesion to the scaffold and subsequent proliferation, the scaffolds were coated with the osteoconductive biopolymers chitosan and sodium alginate, in a process that exploited electrostatic interactions between the positively charged biopolymers and the negatively charged PLGA scaffold. The resulting scaffolds were characterized in terms of porosity, degradation rate, mechanical properties, biocompatibility and suitability for bone regeneration. They were found to have an overall porosity of 3c85% and a degradation half time of 3c2\u2009weeks, considered suitable to support de novo bone matrix deposition from mesenchymal stem cells. Histology confirmed the ability of the scaffold to sustain adipose-derived mesenchymal stem cell adhesion, infiltration, proliferation and osteo-differentiation. Histological staining of calcium and microanalysis confirmed the presence of calcium phosphate in the scaffold sections

Effect of agitation regimen on the in vitro release of leuprolide from poly(lactic-co-glycolic) acid microparticles

Because of the importance of in vitro release tests in establishing batch-to-batch reproducibility and in vitroin vivo correlation, this study investigated the influence of agitation regimen on the in vitro release behavior of leuprolide from poly(lactic-co-glycolic) acid microparticles. Leuprolide-loaded microspheres were prepared using Resomer (R) RG502H and RG503H as polymers. Leuprolide in vitro release was performed in phosphate buffer solution under continuous or once-a-week agitation. At predetermined intervals, leuprolide release, polymer mass loss, and degree of hydration were investigated. Leuprolide release and polymer mass loss were higher under continuous agitation with respect to that under intermittent agitation. Using a modified version of Koizumi equation, it was possible to fit leuprolide release profiles. Similarity factor comparison showed a high level of similarity between experimental and modeled data in the case of once-a-week agitation regimen. This work highlights the importance of the in vitro release conditions on peptide release behavior from polyester microparticles. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:12121220, 201

Powder, capsule and device: An imperative m\ue9nage \ue0 trois for respirable dry powders

Objectives: The development of inhaled products to treat or to prevent lung infection is a very active research field in drug delivery. The pulmonary route is extremely attractive but very challenging. This paper reports the study of excipient, capsule brand and device influence on the aerodynamic behavior of dry powder formulations to treat tuberculosis.Methods: A capreomycin hydrophobic salt was powdered using spray-drying and formulated using lactose (added after spray-drying, external excipient) or L-leucine (added before spray-drying, internal excipient). Aerosolization performances were investigated loading the formulations in 2 different capsule brands and aerosolizing them with 3 different devices.Results: Capreomycin oleate and capreomycin oleate/L-leucine powders were produced with a yield around 70%. Capreomycin oleate 'powder was composed of particles with an irregular surface. Particles of capreomycin oleate/L-leucine were roundish and wrinkled on the surface. Capreomycin oleate/L-leucine formulation gave the highest values of respirable fraction in all cases. Statistical analysis asserted the significant effect on the respirable fraction of the powder (p < 0.001), the capsule brand (p < 0.01) and the device (p < 0.05).Conclusions: The use of L-leucine as internal excipient allows one to avoid the use of lactose, obtaining a carrier-free formulation. Even though differences are not very large, to obtain the highest RFE, the best choice between capsule and device is Quali-V (R) and model 8. (C) 2015 Elsevier B.V. All rights reserved

Nanoparticles in biomedicine: New insights from plant viruses

In recent years there has been an outburst of interest regarding the employment of nanoparticles for biomedical applications. Among the different types, such as metallic, organic, biological and hybrid systems, virus based nanoparticles have become a popular field of research. Viruses are able to form organized structures by molecular self assembly of repetitive building blocks, which implies non covalent interactions of protein monomers to form the quaternary structure of viral capsids. Plant virus based systems, in particular, are among the most advanced and exploited for their potential use as bioinspired structured nanomaterials and nanovectors. Plant viruses have a size particularly suitable for nanoscale applications and can offer several advantages. In fact, they are structurally uniform, robust, biodegradable and easy to produce. Moreover, many are the examples regarding functionalization of plant virus based nanoparticles by means of modification of their external surface and by loading cargo molecules into their internal cavity. This plasticity in terms of nanoparticles engineering is the ground on which multivalency, payload containment and targeted delivery can be fully exploited. This review aims primarily to summarize the most important plant virus based nanoparticles systems through their recent applications in biomedicine, such as epitope display for vaccine development and targeted delivery for diagnosis or therapy. In addition, their production in the most commonly used plant propagation and expression systems will be also reviewed

Lipid nanoparticles for drug delivery to the brain: In vivo veritas

The present article is not aimed at extensively reviewing the literature on lipid nanoparticles, already described in monographs of recent redaction, but will provide a compilation of in vivo evidences supporting their potentiality in overcoming the blood-brain barrier problem. The advantages of using lipid over polymer carriers will be also discussed

Simple and scalable method for peptide inhalable powder production

The aim of this work was to produce capreomycin dry powder and capreomycin loaded PLGA microparticles intended for tuberculosis inhalation therapy, using simple and scalable methods. Capreomycin physico-chemical characteristics have been modified by hydrophobic ion pairing with oleate. The powder Suspension was processed by high pressure homogenization and spray-dried. Spray-drying was also used to prepare capreomycin oleate (CO) loaded PLGA microparticles. CO powder was suspended in the organic phase containing PLGA and the suspension was spray-dried. Particle dimensions were determined using photon correlation spectroscopy and Accusizer C770. Morphology was investigated by scanning electron microscopy (SEM) and capreomycin content by spectrophotometry. Capreomycin properties were modified to increase polymeric microparticle content and obtain respirable CO powder. High pressure homogenization allowed to reduce CO particle dimensions obtaining a population in the micrometric (6.18 mu m) and one in the nanometric (similar to 317 nm) range. SEM pictures showed not perfectly spherical particles with a wrinkled Surface, generally suitable for inhalation. PLGA particles were characterized by a high encapsulation efficiency (about 90%) and dimensions (similar to 6.69 mu m) suitable for inhalation. Concluding, two different formulations were successfully developed for capreomycin pulmonary delivery. The hydrophobic ion pair strategy led to a noticeable drug content increase. (C) 2009 Elsevier B.V. All rights reserved