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Journal: International journal of pharmaceutics


Recent advances in nanotechnology and material science have re-ignited interest in drug delivery research. Arguably, however, hardly any of the systems developed and strategies proposed are really relevant for shaping the future (clinical) face of the nanomedicine field. Consequently, as outlined in this commentary, instead of making ever more carrier materials, and making nanomedicine both science-fiction and fiction-science, we should try to come up with rational and realistic concepts to make nanomedicines work, in particular in patients.

Concepts: Pharmacology, Future, Thermodynamics, Nanomaterials, Materials science, Metaphysics, Science fiction, Nanomedicine


Silver nanoparticle (Ag NP)-loaded chitosan composites have numerous biomedical applications; however, fabricating uniform composite microparticles remains challenging. This paper presents a novel microfluidic approach for single-step and in situ synthesis of Ag NP-loaded chitosan microparticles. This proposed approach enables obtaining uniform and monodisperse Ag NP-loaded chitosan microparticles measuring several hundred micrometers. In addition, the diameter of the composites can be tuned by adjusting the flow on the microfluidic chip. The composite particles containing Ag NPs were characterized using UV-vis spectra and scanning electron microscopy-energy dispersive X-ray spectrometry data. The characteristic peaks of Ag NPs in the UV-vis spectra and the element mapping or pattern revealed the formation of nanosized silver particles. The results of antibacterial tests indicated that both chitosan and composite particles showed antibacterial ability, and Ag NPs could enhance the inhibition rate and exhibited dose-dependent antibacterial ability. Because of the properties of Ag NPs and chitosan, the synthesized composite microparticles can be used in several future potential applications, such as bactericidal agents for water disinfection, antipathogens, and surface plasma resonance enhancers.

Concepts: Synthesis, Composite material, Silver, In situ, Microfluidics, Composite video, Aramid, Kevlar


Powder flow of mixtures is complex and not properly understood. The selection of drug-excipient blends with inadequate powder flow can lead to quality issues of the final dosage form. Therefore, this work aims at a better understanding of how changes in powder flow of binary blends can lead to weight variability in pharmaceutical capsule filling. We used image-analysis-based powder avalanching and shear cell testing to study blends of paracetamol and microcrystalline cellulose. A pilot-scale machine with dosator principle was employed for encapsulation. As a result, the powder flow properties improved generally with rising amounts of microcrystalline cellulose. However, a negative correlation was observed between avalanche angle and angle of internal friction. Results were discussed and percolation theory was considered to explain abrupt changes in the observed flow properties. This was particularly helpful for analysis of the capsule-filling data, since capsule weight variability displayed a threshold behavior as a function of the mixture fraction. The capsule weight variability correlated with the angle of internal friction as well as with the angle and the energy of avalanches. Based on the results we proposed a strategy of how to design minimal weight variability into powder-filled capsules.

Concepts: Understanding, Mass, Force, Knowledge, Explanation, Normal force, Avalanche, Avalanches


Rhizoma paridis steroidal saponins (RPS) have been prepared and identified as the active compounds for antitumor activity in our previous study. However, the low oral bioavailability of the steroidal saponins restricted its using. In the present research, solid dispersion (SD) and phytosome (PHY) formulation of RPS were prepared, and the physicochemical parameters as well as the intestinal absorption in rat everted gut sac model were investigated. Seven agents were selected as the carriers of SD, and poloxamer 407 (P 407) was the most suitable one. SD reduced the particle size of saponins in the water solution, enhanced the solubility of the saponins by about 3.5 folds, and significantly improved the absorption transport of saponins from 48 to 104μg in everted gut sac of the rat system. PHY significantly enhanced the hydrophilic of saponins but showed little effect on the absorption in small intestine. Jejunum and ileum part absorbed more absolute contents of total saponins than duodenum parts. Six saponins, the main contents of RPS, used as the index of comparing the three forms, were also further investigated in the physico-chemical properties and the absorption tests. n-Octanol/water partition coefficients of the six saponins ordered in RPS, SD and PHY were Chonglouoside H>Dioscin>Polyphyllin D>Gracillin>Paris-VII>Formosanin C. All the saponins possessed the higher absorptive characteristics in SD formulation. The absorption rate of diosgenyl saponins in intestine was more than the pennogenyl saponins.

Concepts: Digestive system, Solubility, Intestine, Small intestine, Pharmacokinetics, Biopharmaceutics Classification System, Digestion, Duodenum


In this study, nano sensitively fabricated metallic micro device was combined with conventional micromolding technique in order to assemble polymeric micro needle arrays. We describe the polymer selection and optimization of the fabrication parameters for dissolvable, swellable, and biodegradable polymeric microneedle arrays. Sodium alginate (SA), hydroxypropyl cellulose (H and M grades), cross-linked polyvinyl alcohol with gelatin, chitosan, and polylactic-co-glycolic acid (PLGA) polymers were used to microfabricate solid, out-of-plane, polymeric microneedles from pyramidal male master templates of the following dimensions: 900-μm height, 250-μm needle base width, 500-μm interneedle base spacing. The dimensions of theoretical and measured microarrays were found to be similar. With regard to height, PLGA microneedle fabrication was 10 and 5 times more precise than chitosan and SA microneedle fabrication, respectively. Mechanical failure of SA and PLGA polymeric microneedles was investigated. The fracture forces were approximately 5 times less for SA microneedles than for PLGA microneedles.

Concepts: Polymer, Cell wall, Polysaccharide, Excipients, Polyethylene terephthalate, Microfabrication, Polymers, Polyvinyl butyral


The purpose of the study was to investigate and identify the interactions within solid dispersions of cationic drugs and anionic polymers processed by hot-melt extrusion (HME) technique. Propranolol HCl (PRP) and diphenhydramine HCl (DPD) were used as model cationic active substances while pH sensitive anionic methacrylic acid based methyl methacrylate copolymers Eudragit L100® (L100) and ethyl acrylate copolymer Eudragit L100-55 (Acryl EZE) (L100-55) were used as polymeric carriers. The extrudates were further characterized using various physicochemical characterization techniques to determine the morphology, the drug state within the polymer matrices and the type of drug - polymer interactions. Molecular modelling predicted the existence of two possible H-bonding types while the X - ray photon spectroscopy (XPS) advanced surface analysis of the extrudates revealed intermolecular ionic interactions between the API amino functional groups and the polymer carboxylic groups through the formation of hydrogen bonding. The magnitude of the intermolecular interactions varied according to the drug - polymer miscibility.

Concepts: Protein, Functional group, Hydrogen, Polymer, Copolymer, Polymer chemistry, Functional groups, Carboxylic acid


Sticking is a serious problem during the manufacturing process of tablets. In order to prevent this, we used alloying techniques to prepare metal hardening (MH) and electron beam processing infinite product (EIP) punches with rougher asperity of surfaces than a hard chrome plated (HCr) punch. This study evaluated the anti-sticking properties of the MH and EIP punches compared to the HCr punch, using quantitative scraper force measurements and visual observation, for the manufacture of ibuprofen (Ibu) tablets. The anti-sticking property mechanism of the MH and EIP punches was also confirmed. The amount of Ibu adhering to the punch surface was 66% lower for the MH and EIP punches than for the HCr punch, suggesting a superior anti-sticking property of the MH and EIP punches. The scraper force of the HCr punch was 2.60-4.28N, while that for the MH and EIP punches was 0.54-1.64N and 0.42-1.33N, respectively. The result of X-ray photoelectron spectroscopy suggested that the anti-sticking property of the EIP punch was attributed by the rough asperity as well as existence of low friction substance carbon fluoride on the punch surface. In conclusion, this study provides new evidence for the mechanisms behind the superior anti-sticking property of the MH and EIP punches.

Concepts: Electron, Spectroscopy, X-ray, X-ray photoelectron spectroscopy, Friction, Roughness, Electroplating, Chrome plating


Nanostructured lipid carriers (NLC)-based gel was developed as potential topical system for flurbiprofen (FP) topical delivery. The characterizations of the prepared semisolid formulation for topical application on skin were assessed by means of particle size distribution, zeta potential analysis, X-ray analysis, in vitro percutaneous penetration, rheological study, skin irritation test, in vivo pharmacodynamic evaluation and in vivo pharmacokinetic study. The NLC remained within the colloidal range and it was uniformly dispersed after suitably gelled by carbopol preparation. It was indicated in vitro permeation studies through rat skin that FP-NLC-gel had a more pronounced permeation profile compared with that of FP-loaded common gel. Pseudoplastic flows with thixotropy were obtained for all NLC-gels after storage at three different temperatures. No oedema and erythema were observed after administration of FP-NLC-gel on the rabbit skin, and the ovalbumin induced rat paw edema could be inhibited by the gel. The maximum concentration in plasma was 29.44μg/ml and 2.49μg/ml after oral and topical administration, respectively. While the amount of drug accumulated in skin after topical application was much higher than oral application. In conclusion, NLC-based gel could be a promising vehicle for topical delivery of FP.

Concepts: In vivo, Colloid, In vitro, Particle size distribution, Topical


For the purpose of brain delivery upon intravenous injection, formulations of camptothecin-loaded solid lipid nanoparticles (SLN), prepared by hot high pressure homogenisation, were designed. Incorporation of camptothecin in the hydrophobic and acidic environment of SLN matrix was chosen to stabilise the lactone ring, which is essential for its antitumour activity, and for avoiding premature loss of drug on the way to target camptothecin to the brain. A multivariate approach was used to assess the influence of the qualitative and quantitative composition on the physicochemical properties of camptothecin-loaded SLN in comparison to plain SLN. Mean particle sizes of ≤200nm, homogenous size distributions and high encapsulation efficiencies (>90%) were achieved for the most suitable formulations. In vitro release studies in plasma, showed a prolonged release profile of camptothecin from SLN, confirming the physical stability of the particles under physiological pH. A higher affinity of the SLN to the porcine brain capillary endothelial cells (BCEC) was shown in comparison to macrophages. MTT studies in BCEC revealed a moderate decrease in the cell viability of camptothecin, when incorporated in SLN compared to free camptothecin in solution. In vivo studies in rats showed that fluorescently labelled SLN were detected in the brain after i.v. administration. This study indicates that the camptothecin-loaded SLN are a promising drug brain delivery system worth to explore further for brain tumour therapy.

Concepts: Blood vessel, Brain tumor, In vivo, Intravenous therapy, PH, In vitro, Qualitative research, Pharmaceutical formulation


Pharmaceutical development and manufacturing process optimization work was undertaken in order to propose a potential paediatric rectal formulation of azithromycin as an alternative to existing oral or injectable formulations. The target product profile was to be easy-to-use, cheap and stable in tropical conditions, with bioavailability comparable to oral forms, rapidly achieving and maintaining bactericidal concentrations. PEG solid solution suppositories were characterized in vitro using visual, HPLC, DSC, FTIR and XRD analyses. In vitro drug release and in vivo bioavailability were assessed; a study in rabbits compared the bioavailability of the optimized solid solution suppository to rectal solution and intra-venous product (as reference) and to the previous, non-optimized formulation (suspended azithromycin suppository). The bioavailability of azithromycin administered as solid solution suppositories relative to intra-venous was 43%, which compared well to the target of 38% (oral product in humans). The results of three month preliminary stability and feasibility studies were consistent with industrial production scale-up. This product has potential both as a classical antibiotic and as a product for use in severely ill children in rural areas. Industrial partners for further development are being sought.

Concepts: Pharmacology, Medicine, In vivo, In vitro, Pharmaceutical drug, Rectum, Dosage forms, Suppository