International Journal of Pharmaceutics

Publisher: Elsevier

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 Papers not sufficiently substantiated by experimental detail will not be published.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 If accepted, the manuscript shall not be published elsewhere in the same form, in either the same or another language, without the consent of the Editors and Publisher.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.

Publisher details

Elsevier

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    • Publisher last contacted on 18/10/2013
  • Classification
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The study of controlled release and drug release devices has been dominated by considerations of the bulk or average properties of material or devices. Yet the outermost surface atoms play a central role in their performance. The objective of this article has been to characterize the surface of hydrophilic matrix tablets using the contact angle (CA) method to ascertain the surface free energy, and atomic force microscopy (AFM) and confocal microscopy (CM) for the physical characterization of the surface of the hydrophilic matrix. The surface free energy results obtained show that hydroxypropylmethylcellulose K15M hinders the spreading of water on the surface of the tablet, and so as the concentration of HPMC K15M increases the reaction rate of the hydrophobic interactions between the chains of HPMC K15M increases with respect to the rate of penetration of water into the tablet. In this study, we developed a new method to characterize the swelling of the tablets and established a relationship between the new method based on microswelling and the swelling ratio parameter. The surface texture parameters have been determined and the morphology of the tablets of the different formulations and the evolution of the surface morphology after interacting with the water, swelling and forming a gel layer were characterized. This work represents significant progress in the characterization of matrix tablets. Copyright © 2014. Published by Elsevier B.V.
    International Journal of Pharmaceutics 01/2015; 478:328-340.
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    ABSTRACT: Pentamidine is an effective antiparasitic agent and approved drug for the treatment of African trypanosomiasis (sleeping sickness). However, pentamidine suffers from poor orally bioavailability and lacks central nervous system (CNS) delivery. Therefore its applicability is limited to intravenous or intramuscular treatment of the first stage of the African trypanosomiasis. For this reason, several new pentamidine pro-drugs have been developed with the aim of providing improved orally availability and CNS penetration.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: Curcumin (CM) has demonstrated safety and efficacy as a drug, but its pharmaceutical role is restricted as a result of extremely low aqueous solubility, rapid systemic elimination, inadequate tissue absorption and degradation at alkaline pH; properties that severely curtail its bioavailability. To address this issue, CM was encapsulated within pH responsive amphiphilic chitosan, resulting in the formation of 100 nm spontaneously self-assembled polymeric micelles in water. The amphiphilic chitosan, namely N-benzyl-N,O-succinyl chitosan (BSCS), was prepared by reductive N-benzylation and N,O-succinylation. The stability of micelles after being re-dispersed in water was investigated using glycine as a cryoprotectant, and the average sizes were shown to be maintained at a level lower than 200 nm for up to 4 months, at temperatures of 4 °C and 25 °C. In vitro drug release results showed that CM was slowly released from the micelles without any burst effect in the intestine (pH 5.5–7.4), with limited release in the stomach (pH 1.2). Cytotoxicity assays indicated that CM loaded micelles showed half maximal inhibitory concentrations (IC50) 4.7-, 3.6-, and 12.2-fold lower than that of free CM in HeLa, SiHa and C33a cervical cell lines, respectively. Cellular uptake of micelles was confirmed by confocal laser scanning microscopy and flow cytometry, with a 6-fold significant increase in the amount of CM loaded micelles compared to free CM in all cervical cancer cells. Notably, CM loaded micelles promoted an increase (30–55%) in the percentage of early apoptosis of HeLa, SiHa and C33a cells, compared to free CM. These results suggest that BSCS micelles may be a promising carrier for effective oral delivery of CM.
    International Journal of Pharmaceutics 12/2014; 477(1-2):261–272.
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    ABSTRACT: This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin–phospholipid complex at different levels (0, 2.5 and 10% w/w), were readily dispersed in water to form nanoemulsions of 35 nm and vesicles of 300 nm. The association efficiency of non-complexed insulin in the dispersed SNEDDS was 18.6%, and was increased to 73.1% for insulin–phospholipid complex (at 10% loading level). The morphology of the dispersed SNEDDS changed from nanoemulsion droplets to vesicular structures with increasing complex loading levels. A pH-dependent insulin release profile was observed for SNEDDS filled into capsules coated with the enteric polymer, Eudragit® L100. Using a Caco-2 cell model, it was observed that the transport of insulin was enhanced by factors of 7.7- and 9.3- for SNEDDS loaded with 2.5 and 10% complex, respectively. In healthy fasted rats, administration of SNEDDS (10% complex) filled in enteric-coated capsules produced a 2.7-fold and 3.4-fold enhancement in the relative bioavailability and glucose reduction, respectively. This study shows the effectiveness of combining SNEDDS (loaded with insulin–phospholipid complex) with enteric-coated capsules for enhancing the oral absorption and efficacy of insulin.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: The purpose of the research was to investigate the effect of moisture content of cellulose on the degradation of a drug in binary mixtures with cellulose. Physical mixtures of acetylsalicylic acid and two forms of cellulose, either microcrystalline cellulose or low crystalline cellulose, in the proportion 1:1 were stored at 50 °C at a series of relative humidities (0–90%) for up to 175 days.The degradation rate constant of the drug increased with increased cellulose moisture content in a bi-regional fashion, with a low and a high degradation rate region. The shift from region 1 to 2 occurred at higher moisture content for the low crystalline cellulose. The relationships between rate constant and the temperature of maximum endothermic value overlapped for the two celluloses. It is proposed that the amount of water available for degradation of a solid drug is controlled by the water presenting capacity of cellulose which is dependent of the mechanism of sorption of water in cellulose. The water sorption of water can for cellulose satisfactorily be described by a two-site residence model with cellulose crystallinity as the structural correlate to the distribution between the two residence sites.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: Although, adhesion at the interface of bilayer tablets is critical for their design it is difficult to characterize this adhesion between layers. In view of this, a new test with an easy implementation was proposed for the characterization of the interface of bilayer tablets. This work is presented as a proof-of-concept study to investigate the reliability of this new test with regard to the effects of some critical process parameters (e.g., compaction pressure applied on each layer) and material attributes (e.g., elasticity of the layered materials) on the interfacial adhesion of bilayer tablets. This was investigated using a design of experiment approach and the results obtained were in good accordance with those obtained with other tests and thus, confirms the potential of such a method for the measurement of the interfacial adhesion of bilayer tablets.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: The purpose of this study was to prepare and optimize ophiopogon polysaccharide liposome (OPL), and to improve the immune-enhancing activity of ophiopogon polysaccharide (OP). OPL was prepared and optimized using the methods of reverse-phase evaporation and response surface methodology. The property was evaluated with particle size, zeta potential, and morphology. The results showed that the optimum preparation conditions were: soybean phosphatide to OP ratio of 9.5:1, soybean phospholipid to cholesterol ratio of 8:1, and chloroform to phosphate-buffered saline ratio of 3:1. Subsequently, the immune-enhancing activity of OPL on Kupffer cells (KCs) was performed. The results showed that OPL could significantly promote the phagocytosis of KCs, induce the secretion of nitric oxide, induced nitric oxide synthase, IL-6 and IL-12, and improve the expression of CD80 and CD86 compared with OP at 125–7.813 μg mL−1. These results indicated that the immune-enhancing activity of OP was significantly improved after encapsulated with liposome. Therefore, liposome would be expected to exploit into a new-type preparation of OP.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: Infection still present as one of common complications after total hip replacement (∼2.5%), which may cause serious outcomes. For preventing such risk, loading antibiotics onto implants for increasing local drug concentration at targeted sites could be a solution. This study aims at modifying the surface of hydroxyapatite (HA) coated titanium hip implant material (Ti–HA) with polymer of cyclodextrin (polyCD) for loading antibiotics, to achieve a sustained local drug delivery. Two widely applied antibiotics (tobramycin and rifampicin) in orthopedic surgery were loaded alone or in combination. The drug adsorption isotherm, drug release kinetics and drug’s efficacy were thoroughly investigated. The results proved that polyCD coating significantly improved the affinity of both drugs to Ti–HA surface, while the mechanism of drug–polyCD interaction varies from the nature of drug, courtesy of the structural complex of polyCD. The advantage of dual-drug loading was highlighted by its strong efficacy against both Staphylococcus aureus and Enterobacter cloacae, which overcomes the limitation of mono-drug loading for an effective treatment against both bacterial strains. The prolonged antibacterial activity of antibiotic loaded Ti–HA-polyCD samples confirmed that polyCD could be a promising drug-delivery system, for sustained antibiotics release or other potential applications e.g., antimitotic agent release.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: Nonwoven scaffolds consisting of poly-ε-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) and polidocanol (PD), and loaded with lysozyme crystals were prepared by electrospinning. The composition of the matrix was varied and the effect of PD content in binary mixtures, and of PD and PLGA content in ternary mixtures regarding processability, fiber morphology, water sorption, swelling and drug release was investigated. Binary PCL/PD blend nonwovens showed a PD-dependent increase in swelling of up to 30% and of lysozyme burst release of up to 45% associated with changes of the fiber morphology. Furthermore, addition of free PD to the release medium resulted in a significant increase of lysozyme burst release from pure PCL nonwovens from approximately 2–35%. Using ternary PCL/PD/PLGA blends, matrix degradation could be significantly improved over PCL/PD blends, resulting in a biphasic release of lysozyme with constant release over 9 weeks, followed by constant release with a reduced rate over additional 4 weeks. Based on these results, protein release from PCL scaffolds is improved by blending with PD due to improved lysozyme desorption from the polymer surface and PD-dependent matrix swelling.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: Camptothecin (CPT) nanosuspension was prepared by anti-solvent precipitation with TPGS as stabilizer to improve the solubility, stability and antitumor activity of CPT. And an increased solubility, stability and dissolution rate was achieved after nanosuspension being prepared. While, enhanced intracellular accumulation and cellular cytotoxicity was also observed for CPT nanosuspension than that of CPT solution.In addition, nanosuspension could increase bioavailability and intratumor accumulation of CPT in vivo after intravenous administration, and then produced a much higher antitumor effect and biocompatibility than that of CPT solution. Meanwhile, an enhanced cellular CPT uptake in hypoxic or acid conditions could also be observed for nanosuspension. As a result, nanosuspension represents a potentially feasible formation for insoluble drug in antitumor research.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: The principal aim of this work was to study the formulation of a ternary complex comprising salmon calcitonin (sCT), hyaluronate (HA), and chitosan (CS) in a nanoparticle (NP) format. As interactions between the constituents are possible, their presence and component mass mixing ratio (MMR) and charge mixing ratio (CMR) were investigated to tune the properties of NPs.Intermolecular interactions between sCT and HA as well as sCT and CS were studied by infrared spectroscopy (FTIR) and dynamic viscosity. The impact of MMR, CMR, and HA molecular weight on the sCT loading capacity in NPs and in vitro release properties was determined.sCT complexes to HA via electrostatic interactions and a support for hydrophobic interactions between sCT and HA as well as sCT and CS was found by FTIR. The sCT/HA complex is soluble but, depending on the mass mixing ratio between sCT and HA, NPs and microparticles were also formed indicative of associative phase separation between HA and sCT. The negatively charged HA/CS/sCT NPs were characterized by very high values (above 90%) of peptide association for the systems tested. Also, high sCT loading up to 50% were achieved. The peptide loading capacity and in vitro release properties were dependent on the NP composition. The zeta potential of the NPs without sCT was negative and ranging from −136 to −36 mV, but increased to −84 to −19 mV when the peptide was loaded. The particle size was found to be smaller and ranging 150–230 nm for sCT/NPs in comparison to NPs without sCT (170–260 nm). Short-term storage studies in liquid dispersions showed that the colloidal stability of NPs was acceptable and no release of sCT was observed for up to 3 days.In conclusion, a range of NP systems comprising sCT, HA, and CS was successfully developed and characterized. Such NPs may be considered as a suitable nanoparticulate format for the delivery of sCT.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: Smart nanoparticles based on the mechanisms of asialoglycoprotein (ASGP)-mediated endocytosis and pH-induced drug release were developed for the efficient treatment of hepatoma using a newly developed copolymer, methoxy-polyethylene glycols (PEG)-b-poly (d-galactopyranose) (MPEG-b-PMaIPG). The particles exhibited spherical shapes, uniform particle size distribution (100 ± 4.43 nm), negative zeta potential (−32.8 ± 0.23 mV), high drug loading (24.77 ± 2.68%) and encapsulation efficiency (66.12 ± 9.44%). The in vitro drug release was also investigated, resulting that the release of drug from particles depended on different pH value. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the MPEG-b-PMaIPG nanoparticles. Anticancer activity showed that DOX-loaded MPEG-b-PMaIPG nanoparticles exhibited a high antitumor activity toward HepG2 cells, which was similar to free DOX, while blank MPEG-b-PMaIPG nanoparticles were non-toxic up to a tested concentration of 1.0 mg/mL. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) were used to verify the targeting efficiency of d-galactopyranose-modified nanoparticles. The results clearly demonstrated that d-galactopyranose-modified nanoparticles were taken up quickly by the HepG2 cells, which suggests that MPEG-b-PMaIPG nanoparticles with good biocompatibility and non-toxic for normal cells may be used as an effective cancer-targeting drug delivery system for chemotherapy.
    International Journal of Pharmaceutics 12/2014; 477(1).
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    ABSTRACT: The therapeutic efficacy of repaglinide (RPG) is limited by the low and variable oral bioavailability owing to its limited aqueous solubility. In our present study, the development and evaluation of inclusion complex applying hydroxypropyl-β-cyclodextrin (HP-β-CD) for the improvement of oral bioavailability of repaglinide was investigated systematically. The inclusion complex of repaglinide was prepared by lyophilization technique using drug: hydroxypropyl-β-cyclodextrin (1:15 mole). The prepared complexation was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), NMR spectroscopy and evaluated by dissolution studies. The 1H NMR was used in the structure study of repaglinide-HP-β-CD (RPG-HP-β-CD) inclusion complex. The analysis proved the higher probability of the repaglinide A-ring into the narrow rim of the β-cyclodextrin molecule. All the characterization information confirmed the formation of RPG-HP-β-CD inclusion complex. The in vivo pharmacokinetics of RPG-HP-β-CD and their physical mixture were performed in beagle dogs. For the first time, a simple, rapid, and sensitive LC–MS/MS method for determination of RPG in beagle dog plasma was developed. The Cmax and AUC0−t of RPG-HP-β-CD were 2.5 and 2 times higher than that of the physical mixture. These results suggested that the interaction of repaglinide with HP-β-CD could notably improve the dissolution rate and bioavailability of repaglinide comparing with its physical mixture.
    International Journal of Pharmaceutics 12/2014; 477(1).