European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V Impact Factor & Information

Publisher: Elsevier

Journal description

Current impact factor: 4.25

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 4.245
2012 Impact Factor 3.826
2011 Impact Factor 4.269
2010 Impact Factor 4.304
2009 Impact Factor 3.151
2008 Impact Factor 3.344
2007 Impact Factor 2.611
2006 Impact Factor 3.185
2005 Impact Factor 2.525
2004 Impact Factor 1.877
2003 Impact Factor 1.393
2002 Impact Factor 2.064
2001 Impact Factor 1.503
2000 Impact Factor 1.077
1999 Impact Factor 0.616
1998 Impact Factor 0.969

Impact factor over time

Impact factor
Year

Additional details

5-year impact 0.00
Cited half-life 5.00
Immediacy index 0.87
Eigenfactor 0.02
Article influence 0.87
ISSN 1873-3441

Publisher details

Elsevier

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    • Publisher last contacted on 18/10/2013
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nano lipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2015; DOI:10.1016/j.ejpb.2015.06.020
  • Markus Riehl, Meike Harms, Rea Hanefeld, Karsten Mäder
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    ABSTRACT: Quantification of stabilizer content in microparticles and other products is of great importance for formulation development, drug product quality control as well as for reproducible manufacturing. A fast and sensitive HPLC method with evaporative light scattering detection (ELSD) capable of detecting docusate sodium (DOSS), poly (lactic-co-glycolic acid (PLGA; Resomer RG 503H) and R-1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) in a single run was successfully developed. In contrast to previously described methods, hydrolysis of PLGA as pretreatment is not necessary, thereby enabling accurate quantification of stabilizer next to the intact matrix polymer. This method was used to investigate the impact of washing procedures of polymeric microparticles manufactured either with anionic stabilizer DOSS or cationic stabilizer DOTAP. High amounts of DOSS were detected in the washing water. This finding was consistent with the result that no DOSS could be detected in the washed and dried microparticles (< limit of detection). In contrast, DOTAP was hardly measurable in the washing water during all washing cycles. However, DOTAP could be quantified in dried particles. The ratio of DOTAP to dry particle mass was approx. 1:10. This is most probably due to the different polymer surfactant interactions (e.g. charge) and the different hydrophilicity of the stabilizers used. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2015; DOI:10.1016/j.ejpb.2015.06.025
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    ABSTRACT: Percolation theory has been used for several years in the design of HPMC hydrophilic matrices. This theory predicts that a minimum threshold content of polymer is required to provide extended release of drug, and that matrices with a lower polymer content will exhibit more rapid drug release as a result of percolation pathways facilitating the faster penetration of the aqueous medium. At present, percolation thresholds in HPMC matrices have been estimated solely through the mathematical modelling of dissolution data. This paper examines if they can be also identified in a novel way: through the use of confocal laser scanning fluorescence microscopy (CLSM) to observe the morphology of the emerging gel layer during the initial period of polymer hydration and early gel formation at the matrix surface. In this study, matrices have been prepared with a polymer content of 5% to 30% w/w HPMC 2208 (Methocel K4M), with a mix of other excipients (a soluble drug (caffeine), lactose, microcrystalline cellulose and magnesium stearate) to provide a typical industrially realistic formulation. Dissolution studies, undertaken in water using USP apparatus 2 (paddle) at 50 rpm, provided data for the calculation of the percolation threshold through relating dissolution kinetic parameters to the excipient volumetric fraction of the dry matrix. The HPMC percolation threshold estimated this way was found to be 12.8% v/v, which was equivalent to a matrix polymer content of 11.5% w/w. The pattern of polymer hydration and gel layer growth during early gel layer formation was examined by confocal laser scanning fluorescence microscopy (CLSM). Clear differences in gel layer formation were observed. At polymer contents above the estimated threshold a continuous gel layer was formed within 15 minutes, whereas matrices with polymer contents below the threshold were characterised by irregular gel layer formation with little evidence of HPMC particle coalescence. According to percolation theory, this implies that a continuous cluster of HPMC particles was not formed. The images provide the first direct evidence of how the percolation threshold may be related to the success or failure of early gel layer development in HPMC matrices. It also shows how extended release characteristics are founded on the successful coalescence of hydrated polymer particles to form a continuous coherent diffusion barrier, which can then inhibit further percolation of the hydration medium. The correlation between percolation thresholds estimated from dissolution and imaging techniques suggests that confocal imaging may provide a more rapid method for estimating the percolation thresholds, facilitating the rational design of HPMC extended release matrices at lower polymer contents with minimal risk of dose dumping. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2015; DOI:10.1016/j.ejpb.2015.06.019
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    ABSTRACT: Novel raft forming systems incorporating curcumin-Eudragit(®) EPO solid dispersions were developed to prolong the gastric residence time and provide for a controlled release therapy of curcumin to treat gastric ulcers. The solid dispersions of curcumin with Eudragit(®) EPO were prepared by the solvent evaporation method at various ratios to improve the solubility and the dissolution of curcumin. The optimum weight ratio of 1:5 for curcumin to Eudragit(®) EPO was used to incorporate into the raft forming systems. The raft forming formulations were composed of curcumin-Eudragit(®) EPO solid dispersions, sodium alginate as a gelling polymer and calcium carbonate for generating divalent Ca(++) ions and carbon dioxide to form a floating raft. All formulations formed a gelled raft in 1 min and sustained buoyancy on the 0.1N hydrochloric acid (pH1.2) surface with a 60-85% release of curcumin within 8 h. The curative effect on the acetic acid-induced chronic gastric ulcer in rats was determined. The curcumin raft forming formulations at 40 mg/kg once daily showed a superior curative effect on the gastric ulcer in terms of the ulcer index and healing index than the standard antisecretory agent: lansoprazole (1 mg/kg, twice daily) and a curcumin suspension (40 mg/kg, twice daily). These studies demonstrated that the new raft forming systems containing curcumin solid dispersions are promising carriers for a stomach-specific delivery of poorly soluble lipophilic compounds. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2015; DOI:10.1016/j.ejpb.2015.06.024
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    ABSTRACT: The influence of critical operating parameters on the Flash Nanoprecipitation (FNP) and resulting material properties of curcumin (CUR) nanoparticles has been evaluated using a confined impinging jets-with-dilution mixer (CIJ-D-M). It has been shown that the mixing rate, molecular weight of polymeric stabilizer (i.e., polyethylene glycol-b-poly (DL-lactide) di-block copolymer; PEG-PLA) and drug-to-copolymer mass ratio all exert a significant impact on the particle size and stability of the generated nanosuspensions. The attainable mean particle size and span of the nanoparticles through optimization of these process parameters were approximately 70 nm and 0.85 respectively. However, the optimized nanosuspension was only stable for about two hours after preparation. Co-formulation with polyvinylpyrrolidone (PVP) substantially extended the product lifespan to 5 days at ambient conditions and two weeks at 4˚C. Results from zeta potential measurement and X-ray photoelectron spectroscopy (XPS) suggested that the enhanced stability is probably due to the formation of an additional protective barrier by PVP around the particle surface, thereby suppressing the dissociation of PEG-PLA from the particles and preventing CUR leakage from inside. Long-term storage stability (>1 year) could be achieved by lyophilization of the optimized nanosuspension with Kleptose (hydroxypropyl-β-cyclodextrin), which was shown to be the only effective lyoprotectant among all the ones tested for the CUR nanoparticles. At an optimal concentration of Kleptose (1.25% w/v), the redispersibility (Sf/Si; ratio of the final and initial particle sizes) and encapsulation efficiency of lyophilized CUR nanoparticles were about 1.22 and 94%, respectively. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2015; DOI:10.1016/j.ejpb.2015.06.022
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    ABSTRACT: Small interfering RNA (siRNA)-mediated gene silencing represents a promising strategy for treating diseases such as cancer; however, specific gene silencing requires an effective delivery system to overcome the instability and low transfection efficiency of siRNAs. To address this issue, a polysorbitol-based transporter (PSOT) was prepared by low molecular-weight branched polyethylenimine (bPEI) crosslinked with sorbitol diacrylate (SDA). Osteopontin (OPN) gene, which is highly associated with non-small cell lung cancer (NSCLC) was targeted by siRNA therapy using siRNA targeting OPN (siOPN). Characterization study confirmed that PSOT formed compact complexes with siOPN and protected siOPN against degradation by RNase. PSOT/siOPN complexes demonstrated low cytotoxicity and enhanced transfection efficiency in vitro, suggesting that this carrier may be suitable for gene silencing. In the A549 and H460 lung cancer cell lines, PSOT/siOPN complexes demonstrated significant silencing efficiency at both RNA and protein levels. To study in vivo tumor growth suppression, two lung cancer cell-xenograft mouse models were prepared and PSOT/siOPN complexes were delivered into the mice through intravenous injection. The siOPN- treated groups demonstrated significantly reduced OPN expression at both the RNA and protein levels as well as suppression of tumor volume and weight. Taken together, siOPN delivery using PSOT may present an effective and novel therapeutic system for lung cancer treatment. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.017
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    ABSTRACT: Curcumin (CM) has been reported as a potential anticancer agent. However, its pharmaceutical applications as therapeutic agent are hampered because of its poor aqueous solubility. The present study explores the advantages of polymeric micelles composed of block copolymers of methoxypoly(ethylene glycol) (mPEG) and N-(2-hydroxypropyl) methacrylamide (HPMA) modified with monolactate, dilactate and benzoyl side groups to enhance CM solubility and inhibitory activity against cancer cells. Amphiphilic block copolymers, ω-methoxypoly(ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (PEG-HPMA-Bz) were synthesized and characterized by (1)H-NMR and GPC. One polymer with a molecular weight of 28000 Da was used to formulate CM and compared with other aromatic substituted polymers. CM was loaded by a fast heating method (PEG-HPMA-DL and PEG-HPMA-Bz-L) and a nanoprecipitation method (PEG-HPMA-Bz). Physicochemical characteristics and cytotoxicity/cytocompatibility of CM loaded polymeric micelles were evaluated. It was found that HPMA-based polymeric micelles significantly enhanced the solubility of CM. The PEG-HPMA-Bz micelles showed the best solubilization properties. CM loaded polymeric micelles showed sustained release of the loading CM for more than 20 days. All of CM loaded polymeric micelles formulations showed a significantly potent cytotoxic effect against three cancer cell lines. HPMA-based polymeric micelles are therefore promising nanodelivery systems of CM for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.010
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    ABSTRACT: To reduce the effort required to penetrate the skin and optimize drug release profiles, bioceramic microneedle arrays with higher-aspect-ratio needles and a flexible and self-swelling substrate have been developed. Swelling of the substrate can assist in separating it from the needles and leave them in the skin as a drug depot. The preparation procedures for this bioceramic microneedle are described in the paper. Clonidine hydrochloride, the model drug, was released in a controlled manner by the microneedle device in vitro. Results showed that the microneedle array with a flexible and self-swelling substrate released the drug content faster than the array with a rigid substrate. Disintegration of the needle material and diffusion of the drug molecules are believed as the main control mechanisms of the drug release from these microneedle arrays. Ex vivo skin penetration showed that they can effectively penetrate the stratum corneum without an extra device. This work represents a progression in the improvement of bioceramic microneedles for transdermal drug delivery. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.016
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    ABSTRACT: Modern subunit vaccines have many benefits compared to live vaccines like convenient and competitive large scale production, better reproducibility and safety. However, the poor immunogenicity of subunit vaccines usually requires the addition of potent adjuvants or drug delivery vehicles. Accordingly, researchers are investigating different adjuvants and particulate vaccine delivery vehicles to boost the immunogenicity of subunit vaccines. Despite the rapidly growing knowledge in this field, a comparison of different adjuvants is sparsely found. Until today, little is known about efficient combinations of the different adjuvants and particulate vaccine delivery vehicles. In this study we compared three adjuvants with respect to their immune stimulatory potential and combined them with different particulate vaccine delivery vehicles. For this reason, we investigated two types of polyI:C and a CL264 base analogue and combined these adjuvants with differently sized and shaped particulate vaccine delivery vehicles. A high molecular weight polyI:C combined with a spherical nano-sized particulate vaccine delivery vehicle promoted the strongest dendritic cells activation. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.015
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    ABSTRACT: We have previously demonstrated that peptide fragments (PFs) of the human serum albumin could be developed as potential renal targeting carriers, in particular, the peptide fragment, PF-A299-585 (A299-585 representing the amino acid sequence of the human serum albumin). In this paper, we conjugated triptolide (TP), the anti-inflammatory Chinese traditional medicine, to PF-A299-585 via a succinic acid spacer to give TPS-PF-A299-585 (TP loading 2.2% w/w). Compared with the free TP, TPS-PF-A299-585 exhibited comparable anti-inflammatory activity in the lipopolysaccharide stimulated MDCK cells, but was significantly less cytotoxic than the free drug. Accumulation of TPS-PF-A299-585 in the MDCK cells in vitro and in rodent kidneys in vivo was demonstrated using FITC-labelled TPS-PF-A299-585. Renal targeting was confirmed in vivo in a membranous nephropathic (MN) rodent model, where optical imaging and analyses of biochemical markers combined to show that TPS-PF-A299-585 was capable of alleviating the characteristic symptoms of MN. The collective data affirms PF-A299-585 to be a useful carrier for targeting TP to the kidney. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; 94. DOI:10.1016/j.ejpb.2015.06.012
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    ABSTRACT: Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit(®) NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5 h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8 h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8 h to 24 h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24 h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.014
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    ABSTRACT: To date the effectiveness of antibiotics is undermined by microbial resistance, threatening public health worldwide. Enhancing the efficacy of the current antibiotic arsenal is an alternative strategy. The administration of antimicrobials encapsulated in nanocarriers, such as liposomes, is considered a viable option, though with some drawbacks related to limited affinity between conventional liposomes and bacterial membranes. Here we propose a novel "top-down" procedure to prepare unconventional liposomes from the membranes of prokaryotes (PD-liposomes). These vectors, being obtained from bacteria with limited growth requirements, also represent low-cost systems for scalable biotechnology production. In depth physico-chemical characterization, carried out with dynamic light scattering (DLS) and Small Angle X-ray Scattering (SAXS), indicated that PD-liposomes can be suitable for the employment as antibiotic vectors. Specifically, DLS showed that the mean diameter of loaded liposomes was ∼ 200-300 nm, while SAXS showed that the structure was similar to conventional liposomes, thus allowing a direct comparison with more standard liposomal formulations. Compared to free penicillin G, PD-liposomes loaded with penicillin G showed minimal inhibitory concentrations against E. coli that were up to 16-times lower. Noteworthy, the extent of the bacterial growth inhibition was found to depend on the microorganisms from which liposomes were derived. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.013
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    ABSTRACT: Amorphous formulations of APIs in polymers tend to absorb water from the atmosphere. This absorption of water can induce API recrystallization, leading to reduced long-term stability during storage. In this work, the phase behavior of different formulations was investigated as a function of relative humidity. Indomethacin and naproxen were chosen as model APIs and poly(vinyl pyrrolidone) (PVP) and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA64) as excipients. The formulations were prepared by spray drying. The water sorption in pure polymers and in formulations was measured at 25°C and at different values of relative humidity (RH = 25%, 50% and 75%). Most water was absorbed in PVP-containing systems, and water sorption was decreasing with increasing API content. These trends could also be predicted in good agreement with the experimental data using the thermodynamic model PC-SAFT. Furthermore, the effect of absorbed water on API solubility in the polymer and on the glass-transition temperature of the formulations was predicted with PC-SAFT and the Gordon-Taylor equation, respectively. The absorbed water was found to significantly decrease the API solubility in the polymer as well as the glass-transition temperature of the formulation. Based on a quantitative modeling of the API/polymer phase diagrams as function of relative humidity, appropriate API/polymer compositions can now be selected to ensure long-term stable amorphous formulations at given storage conditions. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; 94. DOI:10.1016/j.ejpb.2015.06.009
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    ABSTRACT: This study reports the potential of different polymers and polymer incorporation methods to inhibit crystallisation and maintain supersaturation of amorphous indomethacin (IND) in aqueous suspensions during storage. Three different polymers (poly(vinyl pyrrolidone) (PVP), hydroxypropyl methyl cellulose (HPMC) and Soluplus® (SP)) were used and included in the suspensions either as a solid dispersion (SD) with IND or dissolved in the suspension medium prior to the addition of amorphous IND. The total concentrations of both IND and the polymer in the suspensions were kept the same for both methods of polymer incorporation. All the polymers (with both incorporation methods) inhibited crystallisation of the amorphous IND. The SDs were better than the predissolved polymer solutions at inhibiting crystallisation. The SDs were also better at maintaining drug supersaturation. SP showed a higher IND crystallisation inhibition and supersaturation potential than the other polymers. However, this depended on the method of addition. IND in SD with SP did not crystallise, nor did the SD generate any drug supersaturation, whereas IND in the corresponding predissolved SP solution crystallised (into the recently characterised η polymorphic form of the drug) but also led to a more than 20-fold higher IND solution concentration than that observed for crystalline IND. The ranking of the polymers with respect to crystallisation inhibition potential in SDs was SP≫PVP>HPMC. Overall, this study showed that both polymer type and polymer incorporation method strongly impact amorphous form stability and drug supersaturation in aqueous suspensions. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.005
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    ABSTRACT: Formulation of sublingual tablets of drugs with limited permeability poses a great challenge due their poor absorption. In this study, bioenhanced sublingual tablets (BESTs) of zolmitriptan were prepared using novel surfactant binder (Pluronic®p123/Syloid® mixture) to enhance tablet disintegration and dissolution. Microencapsulated polysorbate 80 (Sepitrap(TM)80) were included in the composition of BESTs to enhance the drug transport through the sublingual mucosa. Tablets were evaluated for in vitro / in vivo disintegration, in vitro dissolution and ex vivo permeation. Solubility studies confirmed that phosphate buffer; pH 6.8 could be used as dissolution medium for sublingual tablets of zolmitriptan. BEST-5 containing Pluronic® p123/Syloid® mixture and Sepitrap(TM) 80 exhibited the shortest in vitro / in vivo disintegration times (<30s), the highest dissolution at early time dissolution points and the highest enhancement of drug transport through mucosal membrane. The in vivo pharmacokinetic study using human volunteers showed a significant increase in the rate and extent of sublingual absorption with less variations of Tmax after sublingual administration of both BEST-5 and Zomig-ZMT ODT. Our results proposed that Pluronic® p123/ Syloid® mixture and Sepitrap(TM) 80 could be promising for development of sublingual tablets for rapid onset of action of drugs with limited permeability. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.006
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    ABSTRACT: Drug nanoparticles in suspensions can form aggregates leading to physical instability, which is traditionally mitigated using soluble polymers and surfactants. The aim of this paper is to explore common superdisintegrants, i.e., sodium starch glycolate (SSG), croscarmellose sodium (CCS), and crospovidone (CP), as novel class of dispersants for enhanced stabilization of fenofibrate (FNB), a model BCS Class II drug, suspensions. FNB was wet-milled with superdisintegrants along with hydroxypropyl methylcellulose (HPMC), a soluble adsorbing polymer, in a stirred media mill. For comparison, FNB was also milled in the presence of HPMC and/or SDS (sodium dodecyl sulfate) without superdisintegrants. Laser diffraction, scanning electron microscopy, viscometry, differential scanning calorimetry, and powder x-ray diffraction were used to characterize the suspensions. The results show that 2% HPMC along with 1% SSG or 1% CCS mitigated the aggregation of FNB nanoparticles significantly similarly to the use of either 5% HPMC or 1% HPMC-0.075% SDS, whereas CP was not effective due to its low swelling capacity. CCS/SSG enhanced steric-kinetic stabilization of the FNB suspensions owing to their high swelling capacity, viscosity enhancement, and physical barrier action. Overall, this study provides a mechanistic basis for a novel method of formulating surfactant-free drug nanosuspensions with co-milled superdisintegrants. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.05.028
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    ABSTRACT: Gellan gum, kappa-Carragenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use. To achieve this purpose different proportion of the biopolymers were analyzed using a mixture experimental design evaluating their transparency, mechanical properties and bioadhesion in absence and presence of simulated tear fluid. Tear induces a rapid sol-to-gel phase transition in the mixtures forming a consistent hydrogel. The solution composed by 80% of Gellan Gum and 20% kappa-Carrageenan showed the best mechanical and mucoadhesive properties. This mixture was evaluated for rheological behavior, microstructure, cytotoxicity, acute corneal irritancy, ex-vivo and in vivo ocular toxicity and in vivo corneal contact time using Magnetic Resonance Images (MRI) techniques. Result indicates that the system is safe at ophthalmic level and produces an extensive ocular permanence higher than 6 hours. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.003
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    ABSTRACT: In a former publication the authors showed that low amounts of amorphous content (LOQ of0.5%) in a hydrophobic model API (Ciclesonide) can be measured with an individually adjusted one-step dynamic organic vapor sorption (DVS). In this investigation the applicability is tested on various APIs which differ in lipophilicity (poor water solubility) and hygroscopicity (absorption of water). The vapor sorption method proved to be applicable in almost all cases. Moisture sorption isotherms were determined for all five investigated crystalline and amorphous APIs. However, it was necessary to select the parameters individually for each API. The used solvents (water, methanol, isopropanol and methylene chloride) and the humidity-levels (0.05 p/p0 until 0.5 p/p0) were chosen carefully because otherwise the amorphous amounts switch to their crystalline counterparts and are not detectable. The production of fully amorphous samples (absence of crystalline material measured by DSC, mDSC and XRPD) was optimized over several trials. As successfully methods proved ball-milling, freeze-drying, spray-drying and / or quench cooling. In the next step these fully amorphous amounts were blended with crystalline starting material to calibration curves (Turbula blender, influence of electrostatic charge to homogeneity) for the calculation of amorphous content. In summary, the following presented methods were used to determine and quantify low amorphous amounts (between 1.5% and 17.0%) in jet-milled powders (grinding pressure of 8bar, 1 to 3 grinding cycles), respectively. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.004