Journal of Pharmaceutical Sciences (J PHARM SCI-US )

Publisher: American Pharmaceutical Association; American Pharmacists Association; Fédération internationale pharmaceutique, John Wiley and Sons

Description

The Journal of Pharmaceutical Sciences will publish original research papers original research notes invited topical reviews (including Minireviews) and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals including crystallization lyophilization chemical stability of drugs pharmacokinetics biopharmaceutics pharmacodynamics pro-drug developments metabolic disposition of bioactive agents dosage form design protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology and targeted drug delivery.

Impact factor 3.01

  • Hide impact factor history
     
    Impact factor
  • 5-year impact
    3.39
  • Cited half-life
    9.20
  • Immediacy index
    0.60
  • Eigenfactor
    0.03
  • Article influence
    0.82
  • Website
    Journal of Pharmaceutical Sciences website
  • Other titles
    Journal of pharmaceutical sciences
  • ISSN
    0022-3549
  • OCLC
    1754726
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

John Wiley and Sons

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • On personal web site or secure external website at authors institution
    • Deposit in institutional repositories is not allowed
    • JASIST authors may deposit in an institutional repository
    • Non-commercial
    • Pre-print must be accompanied with set phrase (see individual journal copyright transfer agreements)
    • Published source must be acknowledged with set phrase (see individual journal copyright transfer agreements)
    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'John Wiley and Sons' is an imprint of 'Wiley'
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Drug delivery carriers stabilize drugs and control their release, expanding the therapeutic window, and avoiding side effects of otherwise freely diffusing drugs in the human body. Materials used as carrier vehicles have to be biocompatible, biodegradable, nontoxic, and nonimmunogenic. Previously, particles made of the recombinant spider silk protein eADF4(C16) could be effectively loaded with positively and neutrally charged model substances. Here, a new positively charged variant thereof, named eADF4(κ16), has been engineered. Its particle formation is indistinguishable to that of polyanionic eADF4(C16), but in contrast polycationic eADF4(κ16) allows incorporation of negatively charged substances. Both high-molecular-weight substances, such as nucleic acids, and low-molecular-weight substances could be efficiently loaded onto eADF4(κ16) particles, and release of nucleic acids was shown to be well controlled. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
    Journal of Pharmaceutical Sciences 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although PEGylation of biologics is currently the gold standard for half-life extension, the technology has a number of limitations, most importantly the non-biodegradability of PEG and the extremely high viscosity at high concentrations. HESylation is a promising alternative based on coupling to the biodegradable polymer hydroxyethyl starch (HES). In this study, we are comparing HESylation with PEGylation regarding the effect on the protein's physicochemical properties, as well as on formulation at high concentrations, where protein stability and viscosity can be compromised. For this purpose, the model protein anakinra is coupled to HES or PEG by reductive amination. Results show that coupling of HES or PEG had practically no effect on the protein's secondary structure, and that it reduced protein affinity by one order of magnitude, with HESylated anakinra more affine than the PEGylated protein. The viscosity of HESylated anakinra at protein concentrations up to 75 mg/mL was approximately 40% lower than that of PEG-anakinra. Both conjugates increased the apparent melting temperature of anakinra in concentrated solutions. Finally, HESylated anakinra was superior to PEG-anakinra regarding monomer recovery after 8 weeks of storage at 40°C. These results show that HESylating anakinra offers formulation advantages compared with PEGylation, especially for concentrated protein solutions. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
    Journal of Pharmaceutical Sciences 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lapatinib (LPT) could sensitize human epidermal growth factor receptor-2 (HER-2) positive breast cancer to paclitaxel (PTX) and induce synergetic action with PTX in preclinical test and phase II/III trial. In this study, LPT-conjugated poly (ethylene glycol) (PEG) and poly (lactic acid) (PLA) (LPT-PEG-PLA) was first synthesized and confirmed with (1) H Nuclear Magnetic Resonance and Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry, which was used for the preparation of a novel PEG-PLA combined micelles of LPT and PTX (PPM-LP). The obtained PPM-LP exhibited uniform, spherical shape with a size of 25.80 ± 0.47 nm and zeta potential of -3.17 ± 0.15 mv. PTX existed in molecular or amorphous forms in the micelles and superficial LPT could better delay PTX release. The cytotoxicity of PPM-LP with LPT conjugation against SKBr-3 cells (HER-2 positive) was found to be significantly increasing as compared with PPM-PTX, whereas there was no significant difference against MDA-MB-231 cells (HER-2 negative). PPM-LP could escape from endosomes and be distributed into cytoplasm and led to cell arrest in G2/M and G1/S phases simultaneously. Results of nucleus staining and flow cytometry confirmed that LPT could remarkably increase antineoplastic effect of PTX against SKBr-3 cells. All these results demonstrated that PPM-LP may be a promising drug delivery system for HER-2 positive breast cancer. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
    Journal of Pharmaceutical Sciences 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An experimental technique is presented to determine independently shrinkage and cracking in lyophilized amorphous cakes based on photographic imaging of their top surface. An inverse correlation between cake shrinkage and cracking during freeze-drying is seen. Shrinkage relaxes the drying tension and gives little cracking, whereas if shrinkage is restrained then more cracking occurs. A lower shrinkage and greater cracking with higher disaccharide concentration correlates with change in cake hardness and brittleness. Adhesion of the cake to the inside vial wall could not be identified as a determining factor for shrinkage. Shrinkage is non-uniform across the cake's surface and is manifested largely in the peripheral region. A correlation between shrinkage and wg ' for different disaccharides suggests that drying tension develops as non-frozen water is lost from the porous solid after sublimation of the ice phase has exposed the solid/gas interface. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
    Journal of Pharmaceutical Sciences 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Asymmetrical flow field-flow fractionation (afFFF) was used to investigate the properties of a plant-produced anthrax toxin protective antigen, pp-PA83. The afFFF fractogram consisted of two main peaks with molar masses similar to the molecular mass of pp-PA83 monomer. afFFF carrier solutions strongly influenced the ratio and the intensity of the two main peaks. These differences indicate that conformation changes in the pp-PA83 molecule occurred during the afFFF analysis. Similar fractograms were obtained for different pp-PA83 formulations when the afFFF carrier solution and the protein formulation were the same (or very similar). The data show that in specific cases, afFFF could be used to study protein conformation and document the importance of studying the influence of the carrier solution on afFFF. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
    Journal of Pharmaceutical Sciences 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
    Journal of Pharmaceutical Sciences 11/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the last decade, various magnetic nanomaterials have been developed as magnetic resonance imaging (MRI) contrast agents; the greatest challenges encountered for clinical application have been insufficient stability. In this paper, a lyophilization method for 2, 3-dimercaptosuccinic acid-modified iron oxide (γ-Fe2 O3 @DMSA) nanoparticles was developed to simultaneously overcome two disadvantages; these include insufficient stability and low-magnetic response. After lyophilization, the clusters of γ-Fe2 O3 @DMSA with the size of 156.7 ± 15.3 nm were formed, and the stability of the lyophilized powder (γ-Fe2 O3 @DMSA-LP) increased up to over 3 years. It was also found that rehydrated γ-Fe2 O3 @DMSA-LP could be ingested by RAW264.7 cells in very large quantities. Results of pharmacokinetics and biodistribution studies in vivo indicated that γ-Fe2 O3 @DMSA-LP is a promising liver-targeted material. Furthermore, it also exhibited higher MRI efficiency and longer imaging time in the liver than the well-known product Feridex(®) . Moreover, results of vascular irritation and long-term toxicity experiments demonstrated γ-Fe2 O3 @DMSA-LP could be a nontoxic, biocompatible contrast agent in vivo. Therefore, the proposed γ-Fe2 O3 @DMSA-LP can be used as a potential MRI contrast agent in clinic for hepatic diseases. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 10/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: We evaluated two human immunodeficiency virus (HIV) protease inhibitors, atazanavir (ATV) and darunavir (DRV), for pH-dependent solubility, lipid binding, and drug release from lipid nanoparticles (LNPs). Both ATV and DRV incorporated into LNPs composed of pegylated and non-pegylated phospholipids with nearly 100% efficiency, but only ATV-LNPs formed stable lipid-drug particles and exhibited pH-dependent drug release. DRV-LNPs were unstable and formed mixed micelles at low drug-lipid concentrations, and thus are not suitable for lipid-drug particle development. When ATV-LNPs were prepared with ritonavir (RTV), a metabolic and cellular membrane exporter inhibitor, and tenofovir (TFV), an HIV reverse-transcriptase inhibitor, stable, scalable, and reproducible anti-HIV drug combination LNPs were produced. Drug incorporation efficiencies of 85.5 ± 8.2, 85.1 ± 7.1, and 6.1 ± 0.8% for ATV, RTV, and TFV, respectively, were achieved. Preliminary primate pharmacokinetic studies with these pH-responsive anti-HIV drug combination LNPs administered subcutaneously produced detectable plasma concentrations that lasted for 7 days for all three drugs. These anti-HIV LNPs could be developed as a long-acting targeted antiretroviral therapy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: In hair follicle (Hf) cells, the type-2 5-α-reductase enzyme, implicated in androgenetic alopecia, is selectively inhibited by finasteride (FNS). Because an effective topical formulation to deliver FNS to Hf is currently unavailable, this investigation aimed at evaluating in vitro FNS skin permeation and retention through and into hairless rat and human abdominal skin. Four hydroxypropyl chitosan (HPCH)-based formulations (P-08-012, P-08-016, P-08-063, and P-08-064) and one anhydrous formulation without HPCH (P-10-008) were tested. The pharmacokinetics in plasma and skin after application of P-08-016 or P-10-008 on dorsal rat skin with single and repeated doses was investigated. P-08-016 performed the best in driving FNS to the reticular dermis without producing a high transdermal flux. Neither the in vivo single nor the repeated dose experiments produced plasma levels of FNS and no differences were found between formulations concerning skin retention. No increase in the amount of drug retained in the skin was obtained with the repeated dose experiment. In conclusion, the HPCH-based formulation P-08-016 might represent an alternative to systemic therapy for its ability to promote a cutaneous depot of FNS in the region of hair bulbs, minimizing systemic absorption even after repeated treatments. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The impact of thermal stress on indomethacin (IMC)-nicotinamide (NIC) cocrystal formation with or without neat cogrinding was investigated using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) microspectroscopy, and simultaneous DSC-FTIR microspectroscopy in the solid or liquid state. Different evaporation methods for preparing IMC-NIC cocrystals were also compared. The results indicated that even after cogrinding for 40 min, the FTIR spectra for all IMC-NIC ground mixtures were superimposable on the FTIR spectra of IMC and NIC components, suggesting there was no cocrystal formation between IMC and NIC after cogrinding. However, these IMC-NIC ground mixtures appear to easily undergo cocrystal formation after the application of DSC determination. Under thermal stress induced by DSC, the amount of cocrystal formation increased with increasing cogrinding time. Moreover, simultaneous DSC-FTIR microspectroscopy was a useful one-step technique to induce and clarify the thermal-induced stepwise mechanism of IMC-NIC cocrystal formation from the ground mixture in real time. Different solvent evaporation rates induced by thermal stress significantly influenced IMC-NIC cocrystal formation in the liquid state. In particular, microwave heating may promote IMC-NIC cocrystal formation in a short time. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: An observation of visible particulate matter was made during formulation development of a mAb and investigations initiated to understand the colloidal instability of the formulation. It was observed that there was a loss of polysorbate in the IgG formulation and concurrent hydrolysis of polysorbate 80 (PS80) into fatty acid, polyethylene glycol (PEG), and pegylated sorbitan in the presence of mAb A. This observation was confirmed with two other mAb development programs (mAb B and mAb C) that used PS80 and formed particulate, but was absent in any placebo sample tested. Comparative analysis to acid, base and esterase hydrolysis, and exposure to the oxidation reagents Iron(II) and tert-Butyl hydroperoxide demonstrates that the observed reaction is reproduced by a biologic (enzymatic) mechanism. Monooleates of PS80, including the sorbitan and PEG oleates, are hydrolyzed first, showing a slower reaction with higher-order oleates. This leads to a change in the composition of the formulation over time where PS85 becomes the predominant component of the original surfactant remaining in solution. Data suggest that there is a lipid-specific mechanism rather than a general biologic hydrolysis mechanism that hydrolyzes oleate esters of PS80 increasing the risk that colloidal IgG particles will form in mAb drug product. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, polycaprolactone (PCL). Microspheres were optimized for particle size, structural properties, drug release, and loading properties. In vitro release of Ral was very slow because of the low solubility of the drug and hydrophobic nature of PCL. However, when coloaded with TA, both drugs were released at higher amounts compared with their single forms. Smallest particle sizes were obtained in dual drug-loaded microspheres. In vitro cytotoxicity tests showed biocompatibility of microspheres. In vivo bioefficacy of these microspheres was also examined in adjuvant-induced arthritis model in rats. In vivo histological studies of control groups showed development of RA with high median lesion score (5.0). Compared with control and intra-articular free drug injections, microsphere treatment groups showed lower lesion scores and better healing outcomes in histological evaluations. Results suggest that a controlled delivery system of TA and RAL by a single injection in inflamed joints holds promise for healing and suppressing inflammation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Photoprotective potential and biological consequences (mutagenic potential) of octyl-dimethyl-PABA (ODP), titanium dioxide (TiO2 ), and montmorillonite (MMT) upon ultraviolet B (UVB) irradiation, alone and in different associations [physical mixtures (PMs)], were evaluated using a Saccharomyces cerevisiae ogg1 mutant (deficient) strain. In addition, we developed and characterized a delaminated TiO2 -pillared MMT, called the TiO2 -MMT nanocomposite (NC), which was also investigated in terms of its photoprotective and mutagenic potential. Overall, our results revealed an interesting TiO2 -MMT NC endowed with antimutagenic activity that can be associated to organic sunscreen molecule (ODP) and still maintain its positive effect, whereas its respective PM is unable to grant antimutagenic protection against UVB. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A method for concentration of protein solutions is required for high-dosage protein formulation. Here, we present a precipitation-redissolution method by poly(amino acid) for proteins, including therapeutic enzymes, antibodies, and hormones. The proteins were fully precipitated by the addition of poly-l-lysine or poly-l-glutamic acid at low ionic strength, after which precipitate was dissolved at physiological ionic strength. The activities and secondary structures of redissolved proteins, especially antibodies, were almost identical to the native state. The precipitation-redissolution method is a simple and rapid technique for concentration of protein formulations. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of the present research was to study the feasibility of using near-infrared (NIR) and Fourier transform infrared (FTIR)-based chemometric models in quantifying crystalline and amorphous tacrolimus from its sustained-release amorphous solid dispersion (ASD). ASD contained ethyl cellulose, hydroxypropyl methyl cellulose, and lactose monohydrate as carriers, and amorphous form of tacrolimus in it was confirmed by X-ray powder diffraction. Crystalline physical mixture was mixed with ASD in various proportions to prepare sample matrices containing 0%-100% amorphous/crystalline tacrolimus. NIR and FTIR of the samples were recorded, and data were mathematically pretreated using multiple scattering correction, standard normal variate, or Savitzky-Golay before multivariate analysis, partial-least-square regression (PLSR), and principle component regression (PCR). The PLSR models were more accurate than PCR for NIR and FTIR data as indicated by low value of root-mean-squared error of prediction, standard error of prediction and bias, and high value of R(2) . Additionally, NIR data-based models were more accurate and precise than FTIR data models. In conclusion, NIR chemometric models provide simple and fast method to quantitate crystalline tacrolimus in the ASD formulation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A responsive antioxidant system constituted from quercetin inserted into poly[N,N-dimethylacrylamide-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane] through a semi-imprinted procedure was evaluated. A continuous magnetic field (MF) was used during supramolecular structure preparation. The strength of coupling quercetin was evaluated based on the template release from the polymeric matrices, as well as to what extent quercetin reloaded into the polymer matrix in prescribed conditions-with or without the MF presence-shows antioxidant properties. The antioxidant activity of the complex was investigated by radical inhibitor activity method using 2, 2-diphenyl-l-picrylhydrazyl. The evaluation of the homogeneity distribution of the quercetin inside the polymeric network was made by near-infrared chemical imaging and correspondingly statistical analysis. For in vivo biocompatibility investigation, granuloma test in rats was performed correlated with the activity of enzymes involved in oxidative stress as well as immunologic effects of tested supramolecular complexes that include quercetin as therapeutic agent. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) is a self-assembling polymer, which enables the oral bioavailability of peptide and hydrophobic drugs. In preparation for clinical testing, here we examine GCPQ's synthesis reproducibility, pKa, thermal, and rheological properties. GCPQ was synthesised by acid degradation of glycol chitosan (GC), reaction with palmitic acid N-hydroxysuccinimide (PNS) and methylation. A GC monomer, PNS molar feed ratio of 0.92 together with a gravimetric feed ratio for N-palmitoyl-6-O-glycolchitosan, methyl iodide of 3.3, reproducibly produces GCPQ48 (Mw = 19.9 ± 9.9 kDa, Mn = 13.1 ± 2.4 kDa, mol % palmitoylation = 23 ± 2.7, mol % quaternisation = 10 ± 0.23, n = 56). GCPQ48 decomposes at 218 ± 4.3°C, is glassy at room temperature (Tg = 164.4 ± 8.5°C), is a weak base (pKa = 5.99 ± 0.15), and produces micellar dispersions at neutral pH. Below a concentration of 0.07 g mL(-1) , GCPQ48 dispersions showed Newtonian rheological behaviour but at higher concentrations, the polymer undergoes shear thinning because of the chain disentanglement at high shear rates. GCPQ48 forms a network of micelles and concentrated (0.09 g mL(-1) ) dispersions are viscoelastic, with the storage modulus exceeding the loss modulus at high frequencies. Solid GCPQ48 was stable when stored at room temperature for 18 months. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
    Journal of Pharmaceutical Sciences 06/2014;