International Journal of Pharmaceutics

Publisher: Elsevier

Journal description

The International Journal of Pharmaceutics provides a medium for the publication of innovative papers, reviews, mini-reviews, short communications and notes dealing with physical, chemical, biological, microbiological and engineering studies related to the conception, design, production, characterisation and evaluation of drug delivery systems in vitro and in vivo. "Drug" is defined as any therapeutic or diagnostic entity, including oligonucleotides, gene constructs and radiopharmaceuticals. Areas of particular interest include: physical pharmacy; polymer chemistry and physical chemistry as applied to pharmaceutics; excipient function and characterisation; biopharmaceutics; absorption mechanisms; membrane function and transport; novel routes and modes of delivery; responsive delivery systems, feedback and control mechanisms including biosensors; applications of cell and molecular biology to drug delivery; prodrug design; bioadhesion (carrier-ligand interactions); and biotechnology (protein and peptide delivery). Editorial Policy The over-riding criteria for publication are originality, high scientific quality and interest to a multidisciplinary audience. Papers not sufficiently substantiated by experimental detail will not be published. Any technical queries will be referred back to the author, although the Editors reserve the right to make alterations in the text without altering the technical content. Manuscripts submitted under multiple authorship are reviewed on the assumption that all listed authors concur with the submission and that a copy of the final manuscript has been approved by all authors and tacitly or explicitly by the responsible authorities in the laboratories where the work was carried out. If accepted, the manuscript shall not be published elsewhere in the same form, in either the same or another language, without the consent of the Editors and Publisher. Authors must state in a covering letter when submitting papers for publication the novelty embodied in their work or in the approach taken in their research. Routine bioequivalence studies are unlikely to find favour. No paper will be published which does not disclose fully the nature of the formulation used or details of materials which are key to the performance of a product, drug or excipient. Work which is predictable in outcome, for example the inclusion of another drug in a cyclodextrin to yield enhanced dissolution, will not be published unless it provides new insight into fundamental principles.

Current impact factor: 3.65

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.65
2013 Impact Factor 3.785
2012 Impact Factor 3.458
2011 Impact Factor 3.35
2010 Impact Factor 3.607
2009 Impact Factor 2.962
2008 Impact Factor 3.061
2007 Impact Factor 2.408
2006 Impact Factor 2.212
2005 Impact Factor 2.156
2004 Impact Factor 2.039
2003 Impact Factor 1.539
2002 Impact Factor 1.495
2001 Impact Factor 1.419
2000 Impact Factor 1.024
1999 Impact Factor 0.952
1998 Impact Factor 0.978
1997 Impact Factor 0.898

Impact factor over time

Impact factor

Additional details

5-year impact 4.01
Cited half-life 7.30
Immediacy index 0.53
Eigenfactor 0.04
Article influence 0.77
Website International Journal of Pharmaceutics website
ISSN 1873-3476

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Authors pre-print on any website, including arXiv and RePEC
    • Author's post-print on author's personal website immediately
    • Author's post-print on open access repository after an embargo period of between 12 months and 48 months
    • Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months
    • Author's post-print may be used to update arXiv and RepEC
    • Publisher's version/PDF cannot be used
    • Must link to publisher version with DOI
    • Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives License
    • Publisher last reviewed on 03/06/2015
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Topical chemotherapy is the application of cancer drugs directly onto the skin, which has become a standard treatment for basal cell carcinoma. Due to the promising results in the treatment of skin cancer, topical chemotherapy has recently been applied to breast cancer patients because some breast cancer tissues are only superficial. Hydroxytyrosol, a phenolic compound from olives that is present in high amounts in Hidrox® olive extract, has been shown to have a protective effect on normal cells and selective antitumor activities on cancerous cells. The aims of the present study were to develop an alginate bilayer film containing Hidrox® and to investigate its potential use as a topical chemotherapeutic agent. Alginate films were characterized for swelling and for physical, thermal, rheological, and mechanical properties. Drug content uniformity and in vitro drug release tests were also investigated. The alginate bilayer films containing Hidrox®, HB2, showed controlled release of hydroxytyrosol at a flux of 0.094±0.009mg/cm(2)/h. The results of the cytotoxic assay showed that the HB2 films were dose-dependent and could significantly reduce the growth of breast cancer cells (MCF-7) at 150μg/mL for a cell viability of 29.34 ± 4.64%. In conclusion, an alginate bilayer film containing Hidrox® can be a potential alternative for topical chemotherapeutic agent for skin and breast cancer treatment.
    International Journal of Pharmaceutics 10/2015; DOI:10.1016/j.ijpharm.2015.09.057
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    ABSTRACT: While hot melt extrusion is now established within the pharmaceutical industry, the prediction of miscibility, processability and structural stability remains a pertinent issue, including the issue of whether molecular interaction is necessary for suitable performance. Here we integrate the use of theoretical and experimental drug-polymer interaction assessment with determination of processability and structure of dispersions in two polyvinylpyrrolidone-based polymers (PVP and PVP vinyl acetate, PVPVA). Caffeine and paracetamol were chosen as model drugs on the basis of their differing hydrogen bonding potential with PVP. Solubility parameter and interaction parameter calculations predicted a greater miscibility for paracetamol, while ATR-FTIR confirmed the hydrogen bonding propensity of the paracetamol with both polymers, with little interaction detected for caffeine. PVP was found to exhibit greater interaction and miscibility with paracetamol than did PVPVA. It was noted that lower processing temperatures (circa 40(°)C below the Tg of the polymer alone and Tm of the crystalline drug) and higher drug loadings with associated molecular dispersion up to 50% w/w were possible for the paracetamol dispersions, although molecular dispersion with the non-interactive caffeine was noted at loadings up to 20% w./w. A lower processing temperature was also noted for caffeine-loaded systems despite the absence of detectable interactions. The study has therefore indicated that theoretical and experimental detection of miscibility and drug-polymer interactions may lead to insights into product processing and extrudate structure, with direct molecular interaction representing a helpful but not essential aspect of drug-polymer combination prediction.
    International Journal of Pharmaceutics 10/2015; DOI:10.1016/j.ijpharm.2015.09.063
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    ABSTRACT: In the oral solid dosage form space, material physical properties have a strong impact on the behaviour of the formulation during processing. The ability to identify materials with similar characteristics (and thus expected to exhibit similar behaviour) within the company's portfolio can help accelerate drug development by enabling early assessment and prediction of potential challenges associated with the powder properties of a new active pharmaceutical ingredient. Such developments will aid the production of robust dosage forms, in an efficient manner. Similarity scoring metrics are widely used in a number of scientific fields. This study proposes a practical implementation of this methodology within pharmaceutical development. The developed similarity metrics is based on the Mahalanobis distance. Scanning electron microscopy was used to confirm morphological similarity between the reference material and the closest matches identified by the metrics proposed. The results show that the metrics proposed are able to successfully identify material with similar physical properties.
    International Journal of Pharmaceutics 10/2015; DOI:10.1016/j.ijpharm.2015.09.046
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    ABSTRACT: The purpose of this study was to clarify the mechanism responsible for high-shear wet granulation using time-of-flight secondary ion mass spectrometry (ToF-SIMS), which can be used for surface chemical mapping. A total of 15 kinds of granules, including hydroxypropylcellulose (HPC) as a binder, were obtained in a model formulation using different granulation conditions, such as the amount of sprayed water and the granulation time. Surface chemical mapping of these granules was then performed using a ToF-SIMS analysis, which distinguishes each component by detecting the specific mass-to-charge ratio (m/z). As a result, we found that HPC got to appear on the surface of granule with proceeding wet granulation. By considering this result, we concluded that the distributions of HPC might be closely related to the progress of granule consolidation and growth in wet granulation. Therefore, the progress of granulation can likely be understood by measuring the content of HPC on the granule surface.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.060
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    ABSTRACT: The resistance of Helicobacter pylori to classical antimicrobial treatment has become increasingly common, whereupon biofilms are considered to play an important role in the resistance mechanism. Here 10.2% of amoxicillin (AMX) and a novel anti H. pylori adhesion material pectin sulfate (PECS) loaded lipid polymer nanoparticles (LPN) were prepared, with rhamnolipid and phospholipids as the outer mixed lipids layer (RHL-PC-LPN). The size of RHL-PC-LPNs was around 200nm, was negatively-charged, and showed sustained and complete drug release within 24h. In an in vitro study, H. pylori biofilm models were successfully established. RHL-PC-LPN, superior to PC-LPN (employing phospholipids only as the outer lipid layer), PECS+AMX (mixture of PECS and AMX) and AMX only, was proven to significantly eradicate H. pylori in the biofilm form. In accordance to our previous results, the RHL-PC-LPN group, together with the PC-LPN and PECS+AMX group, inhibited H.pylori from adhering to AGS cells. Investigating the underlying mechanisms contributing to the death of H. pylori caused by RHL-PC-LPNs, we found that LPNs could lower the antibiotic minimal inhibition concentration (MIC) to biofilm form from 125μg/ml to 15.6μg/ml. Furthermore, FITC-ConA labeled extracellular polymeric substances (EPS) were decreased in the RHL-PC-LPN group observed by a laser scanning confocal microscope. Therefore, we conclude that employing the mixed lipids of rhamnolipid and phospholipids as the outer layer of nanoparticles and PECS as the inner core produces a system capable of significantly disrupting H. pylori biofilm by eliminating the EPS as well as inhibiting the adherence and colonization of bacteria.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.055
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    ABSTRACT: To pave the way for technology transfer and scale up of the spherical agglomeration (SA) process for dimethyl fumarate, effects of the US, European and Kawashima type baffles and 0.5, 2.0 and 10 L- sized common stirred tank were studied. It was found that the particle size distribution varied significantly. However, the size-related properties such as dissolution profile and flowability of agglomerates from the same size cut after sieving could remain unchanged. The interior structure-related properties such as particle density and mechanical property of agglomerates upon baffle change and scale up from the same size cut were decayed and the agglomerates could become denser and stronger by prolonged maturation time. To maintain the same size distribution, agglomerates from any batch could have been separated and classified by sieving and then blended back together artificially by the desired weight % of each cut.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.056
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    ABSTRACT: Our recent publication showed that VES-dFdC nanocapsules in pure water could be obtained via the self-assembling of VES-dFdC prodrug synthesized by coupling gemcitabine (dFdC) with vitamin E succinate (VES). To prepare the intravenous injection nanoformulation, we present here a novel strategy to improve the stability and drug concentration of VES-dFdC nanoformulation in PBS or isotonic solution. Particularly, d-α-tocopheryl polyethylene glycol succinate (TPGS), usually used as drug solubilizer and coincidently contains the same VES moiety as VES-dFdC prodrug and PEG chain, is selected to co-assemble with VES-dFdC prodrug. The zeta potentials of all the TPGS/VES-dFdC co-assemblies were close to 0mV, and their particle size measured by dynamic light scattering (DLS) decreased from 113 to 36nm with increasing TPGS/VES-dFdC molar ratios from 0.15 to 1.5. Stable colloidal suspensions were obtained without aggregates in PBS at 4°C in one month or isotonic solution at 37°C in one week, and the weight concentration of VES-dFdC prodrug increased from 7 to 17mg/mL when the molar ratios of TPGS/VES-dFdC ranged from 0.5/1 to 1.5/1. The concentration of VES-dFdC prodrug was high enough to be used as intravenous injection nanoformulation in nude mice. Interestingly, along with the increase of TPGS/VES-dFdC molar ratios from 0.3/1 to 1.5/1, the morphology of TPGS/VES-dFdC co-assemblies changed from loose nanocapsule to compact micelle revealed by transmission electron microscope (TEM). Finally, the co-assembly of TPGS/VES-dFdC (TPGS/VES-dFdC: 1/1) was selected as intravenous injection nanoformulation to evaluate the antitumor activity. Compared with native dFdC, TPGS/VES-dFdC nanoformulation with 0.2 mmol/kg of dosage showed similar low toxicity in vivo, but 4.7 times high of tumor inhibition rate in nude mice with pre-established BxPC-3 tumors.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.030
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    ABSTRACT: A series of 5-fluorouracil (5-FU) loaded core/shell electrospun fibers is reported. The fibers have shells made of Eudragit S100 (ES-100), and drug-loaded cores comprising poly(vinylpyrrolidone), ethyl cellulose, ES-100, or drug alone. Monolithic 5-FU loaded ES-100 fibers were also prepared for comparison. Electron microscopy showed all the fibers to have smooth cylindrical shapes, and clear core-shell structures were visible for all samples except the monolithic fibers. 5-FU was present in the amorphous physical form in all the materials prepared. Dissolution studies showed that the ES-100 shell was not able to prevent drug release at pH 1.0, even though the polymer is completely insoluble at this pH: around 30 to 80 % of the maximum drug release was reached after 2h immersion at pH 1.0. These observations are ascribed to the low molecular weight of 5-FU permitting it to diffuse through pores in the ES-100 coating, and the high acid solubility of the drug providing a thermodynamic impetus for this to happen. In addition, the fibers were observed to be broken or merged following 2h at pH 1.0, providing additional escape routes for the 5-FU.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.044
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    ABSTRACT: In the present study the mechanical properties of microcrystalline cellulose compacts compressed were studied. The resistance to crushing was tested using diametral compression testing and apparent Young's modulus was determined using consecutive uniaxial compression of the full cross-sectional area of single tablets. As non-elastic deformation during the first compression cycle and reverse plasticity were discovered, the loading phase of the second compression cycle was used to determine Young's modulus. The relative standard deviation of 10 consecutive measurements was 3.6%. The results indicate a direct correlation between crushing strength and Young's modulus, which found further support when comparing surface roughness data and radial recovery of the tablets to Young's modulus. The extrapolated elastic modulus at zero-porosity was found to be 1.80 ± 0.08GPa, which is slightly lower than previously reported values, confirming the complexity of measuring the elastic properties of microcrystalline cellulose compacts. The method can be used for non-destructive assessment of mechanical properties of powder compacts for example during storage studies.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.051
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    ABSTRACT: We used surface plasmon resonance (SPR) to measure the affinity and kinetics of the interaction between serum proteins and both conventional and PEGylated liposomes. The effect of the interactions on secretory phospholipase A2 (sPLA2) -induced release of a model drug from liposomes was also assessed. SPR analysis of 12 serum proteins revealed that the mode of interaction between serum proteins and liposomes greatly varies depending on the type of protein. For example, albumin bound to liposomes at slower association/dissociation rates with higher affinity and prevented sPLA2-induced drug release from PEGylated liposomes. Conversely, fibronectin bound at faster association/dissociation rates with lower affinity and demonstrated little impact on the drug release. These results indicate that the effect of serum proteins on sPLA2 phospholipid hydrolysis varies with the mode of interaction between proteins and liposomes. Understanding how the proteins interact with liposomes and impact sPLA2 phospholipid hydrolysis should aid the rational design of therapeutic liposomal formulations.\.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.053
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    ABSTRACT: Multidrug resistance (MDR) is one of the major obstacles to the successful treatment of breast cancer. The overexpression of drug efflux transporters such as P-glycoprotein (P-gp) and of anti-apoptotic proteins like survivin are the major causes of MDR. Here, we developed a gambogic acid (GA)-loaded mixed micelle system made of poly(ethylene glycol)- poly(L-histidine)-poly(D,L-lactide-co-glycolide) (PEG-pHis-PLGA) and D-α-tocopheryl polyethylene glycol 1000 (TPGS) that is potentially useful for overcoming MDR by integrating the beneficial effects of pH-sensitive behavior, P-gp inhibition, and down-regulation of anti-apoptotic proteins. The therapeutic potential and mechanism of action of GA-loaded pH-sensitive mixed micelles were examined in drug-sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. The resulting GA-loaded mixed micelles with an average size of 190.1nm were stable at pH 7.4, but dissociated rapidly in a weakly acidic environment (pH 5.5). The GA-loaded mixed micelles increased the cell cytotoxicity against both MCF-7 and MCF-7/ADR cells, which was associated with enhanced apoptosis. In addition, the GA-loaded mixed micelles down-regulated the expression of the anti-apoptotic proteins survivin and Bcl-2, and inhibited both the expression and activity of P-gp in MCF-7/ADR cells. Our results indicate that this system could overcome drug resistant in breast cancer by targeting distinct mechanisms, which may facilitate the translation of the GA-mediated effects into clinical benefits.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.041
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    ABSTRACT: A novel approach for ultrasound (US) mediated drug delivery - Acoustic Cluster Therapy (ACT) - is proposed, and basic characteristics of the ACT formulation are elucidated. The concept comprises administration of free flowing clusters of negatively charged microbubbles and positively charged microdroplets. The clusters are activated within the target pathology by diagnostic US, undergo an ensuing liquid-to-gas phase shift and transiently deposit 20-30μm large bubbles in the microvasculature, occluding blood flow for ∼ 5-10minutes. Further application of US will induce biomechanical effects that increases the vascular permeability, leading to a locally enhanced extravasation of components from the vascular compartment (e.g. released or co-administered drugs). Methodologies are detailed for determination of vital in-vitro characteristics of the ACT compound; cluster concentration and size distribution. It is shown how these attributes can be engineered through various formulation parameters, and their significance as predictors of biological behaviour, such as deposit characteristics, is demonstrated by US imaging in a dog model. Furthermore, in-vivo properties of the activated ACT bubbles are studied by intravital microscopy in a rat model, confirming the postulated behaviour of the concept.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.047
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    ABSTRACT: A salbutamol sulfate (SS)-Poloxamer bioadhesive hydrogel specially developed for buccal administration was investigated by studying interactions with TR146 human buccal epithelium cells (i.e. cellular toxicity (i) and trans-epithelial SS diffusion (ii)). The assessment of cell viability (MTT, Alamar Blue), membrane integrity (Neutral Red), and apoptosis assay (Hoechst 33342), were performed and associated to Digital Holographic Microscopy analysis. After the treatment of 2h, SS solution induced drastic cellular alterations that were prevented by hydrogels in relation with the concentrations of poloxamer and xanthan gum. The formulation containing P407 19%/P188 1%/Satiaxane 0.1% showed the best tolerance after single and multiple administrations and significantly reduced the trans-epithelial permeability from 5.00±0.29 (×10(3)) (SS solution) to 1.83±0.22cm/h. Digital Holographic Microscopy images in good agreement with the viability data confirmed the great interest of this direct technique. In conclusion, the proposed hydrogels represent a safe and efficient buccal drug delivery platform.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.045
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    ABSTRACT: Novel orally disintegrating system based on multiparticulate form was developed, offering an alternative to encounter major issues in the design of dosage form for pediatric patients, i.e. the difficulty in swallowing large solid dosage form (tablet or capsule), and the requirement to cover a broad range of doses for different age groups. Microcrystalline cellulose-based pellets containing acetaminophen were prepared via extrusion/spheronization followed by freeze-drying. The in vitro disintegration behavior of these pellets was quantitatively measured with a texture analyzer. Mercury intrusion and gas adsorption techniques, scanning electron microscopy of pellet surface and cross-section were performed in order to characterize their internal porous structure. Pellets characteristics such as size distribution, sphericity, friability and drug release were also determined. The developing process was able to produce pellets containing high drug loading (25, 50 and up to 75%, w/w) with good sphericity (aspect ratio ∼1) and low friability. The pellets exhibited an instantaneous disintegration upon contact with water, which was indicated by two parameters: the disintegration onset was approximating to 0, and the disintegration time less than 5seconds. The fast disintegration behavior is correlated with the pellet internal structure characterized by a capillary network with pore diameter varying from 0.1 to 10μm. Such a structure not only ensured a rapid disintegration but it also offers to freeze-dried pellets adequate mechanical properties in comparison with conventional freeze-dried forms. Due to pellet disintegration, fast dissolution of acetaminophen was achieved, i.e. more than 90% of drug released within 15minutes. This novel multiparticulate system offers novel age-appropriate dosage form for pediatric population owing to their facility of administration (fast disintegration) and dosing flexibility (divided and reduced-size solid form).
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.049
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    ABSTRACT: The purpose of present study was to assess the enhancing effect of resveratrol (Res) on the absorption of bestatin and clarify the related molecular mechanism. Res facilitated bestatin absorption by down-regulating both protein and gene levels of multidrug resistance 1 (Mdr1) and Multidrug resistance-associated protein 2 (Mrp2), and up-regulating oligopeptide transporter 1 (Pept1) protein and mRNA expression in rat intestine. In the same manner, Res increased penetration of bestatin via significantly activating mRNA and protein expression of PEPT1 in Caco-2 cells. Conversely, mRNA and protein expression levels of MDR1, MRP2 and phosphorylation level of Insulin-like growth factor 1 receptor (IGF-1R) were inhibited by Res in Caco-2 cells. Moreover, Res also altered the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT). Res enhanced the intracellular concentration of bestatin by down-regulating MDR1 and MRP2 expression through a mechanism that involves IGF-1R/AKT/ERK signaling pathway inhibition in Caco-2 cells. In conclusion, Res enhances bestatin absorption by regulating PEPT1, MDR1 and MRP2 both in vivo and in vitro.
    International Journal of Pharmaceutics 09/2015; DOI:10.1016/j.ijpharm.2015.09.042