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Publisher: Springer-Verlag (Total: 2351 journals)

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Showing 1 - 200 of 2351 Journals sorted alphabetically
3D Printing in Medicine     Open Access   (Followers: 2)
3D Research     Hybrid Journal   (Followers: 21, SJR: 0.222, CiteScore: 1)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.825, CiteScore: 1)
AAPS J.     Hybrid Journal   (Followers: 26, SJR: 1.118, CiteScore: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 8, SJR: 0.752, CiteScore: 3)
Abdominal Radiology     Hybrid Journal   (Followers: 17, SJR: 0.866, CiteScore: 2)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 4, SJR: 0.439, CiteScore: 0)
Academic Psychiatry     Full-text available via subscription   (Followers: 29, SJR: 0.53, CiteScore: 1)
Academic Questions     Hybrid Journal   (Followers: 8, SJR: 0.106, CiteScore: 0)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 31, SJR: 0.316, CiteScore: 1)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.359, CiteScore: 1)
Acoustics Australia     Hybrid Journal   (SJR: 0.232, CiteScore: 1)
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.367, CiteScore: 0)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.675, CiteScore: 1)
Acta Biotheoretica     Hybrid Journal   (Followers: 4, SJR: 0.284, CiteScore: 1)
Acta Diabetologica     Hybrid Journal   (Followers: 19, SJR: 1.587, CiteScore: 3)
Acta Endoscopica     Hybrid Journal   (Followers: 1)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.769, CiteScore: 1)
Acta Geochimica     Hybrid Journal   (Followers: 7, SJR: 0.24, CiteScore: 1)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 3, SJR: 0.305, CiteScore: 1)
Acta Geophysica     Hybrid Journal   (Followers: 11, SJR: 0.312, CiteScore: 1)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.588, CiteScore: 3)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.517, CiteScore: 1)
Acta Mathematica     Hybrid Journal   (Followers: 13, SJR: 7.066, CiteScore: 3)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.452, CiteScore: 1)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 6, SJR: 0.379, CiteScore: 1)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.27, CiteScore: 0)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.208, CiteScore: 0)
Acta Mechanica     Hybrid Journal   (Followers: 21, SJR: 1.04, CiteScore: 2)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.607, CiteScore: 2)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7, SJR: 0.576, CiteScore: 2)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.638, CiteScore: 1)
Acta Neurochirurgica     Hybrid Journal   (Followers: 7, SJR: 0.822, CiteScore: 2)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 2, SJR: 0.376, CiteScore: 1)
Acta Neuropathologica     Hybrid Journal   (Followers: 4, SJR: 7.589, CiteScore: 12)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.334, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 3, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 18, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8, SJR: 0.103, CiteScore: 0)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 25, SJR: 0.72, CiteScore: 2)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 18, SJR: 1.005, CiteScore: 2)
Adsorption     Hybrid Journal   (Followers: 5, SJR: 0.703, CiteScore: 2)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 4, SJR: 0.698, CiteScore: 1)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 37, SJR: 0.956, CiteScore: 2)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 20, SJR: 0.812, CiteScore: 1)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 58, SJR: 1.09, CiteScore: 1)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.144, CiteScore: 0)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 32, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 45, SJR: 1.04, CiteScore: 3)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 1.075, CiteScore: 3)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 7)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.517, CiteScore: 1)
Aerobiologia     Hybrid Journal   (Followers: 3, SJR: 0.673, CiteScore: 2)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 11, SJR: 0.825, CiteScore: 1)
African Archaeological Review     Hybrid Journal   (Followers: 21, SJR: 0.862, CiteScore: 1)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.235, CiteScore: 0)
AGE     Hybrid Journal   (Followers: 7)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.39, CiteScore: 1)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.67, CiteScore: 2)
Agricultural Research     Hybrid Journal   (Followers: 6, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Open Access   (Followers: 14, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Open Access   (Followers: 20, SJR: 0.663, CiteScore: 1)
Agronomy for Sustainable Development     Open Access   (Followers: 15, SJR: 1.864, CiteScore: 6)
AI & Society     Hybrid Journal   (Followers: 9, SJR: 0.227, CiteScore: 1)
AIDS and Behavior     Hybrid Journal   (Followers: 14, SJR: 1.792, CiteScore: 3)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 4, SJR: 0.862, CiteScore: 3)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 6, SJR: 0.531, CiteScore: 0)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.583, CiteScore: 1)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 1.095, CiteScore: 1)
Algorithmica     Hybrid Journal   (Followers: 9, SJR: 0.56, CiteScore: 1)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.234, CiteScore: 0)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 5, SJR: 1.11, CiteScore: 3)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
AMBIO     Hybrid Journal   (Followers: 10, SJR: 1.569, CiteScore: 4)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 16, SJR: 0.951, CiteScore: 3)
American J. of Community Psychology     Hybrid Journal   (Followers: 29, SJR: 1.329, CiteScore: 2)
American J. of Criminal Justice     Hybrid Journal   (Followers: 9, SJR: 0.772, CiteScore: 1)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 18, SJR: 0.46, CiteScore: 1)
American J. of Dance Therapy     Hybrid Journal   (Followers: 5, SJR: 0.181, CiteScore: 0)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.611, CiteScore: 1)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 22, SJR: 0.314, CiteScore: 0)
American Sociologist     Hybrid Journal   (Followers: 16, SJR: 0.35, CiteScore: 0)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.135, CiteScore: 3)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 7, SJR: 0.211, CiteScore: 1)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 6, SJR: 0.536, CiteScore: 1)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 6)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 32, SJR: 0.978, CiteScore: 3)
Anatomical Science Intl.     Hybrid Journal   (Followers: 3, SJR: 0.367, CiteScore: 1)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.177, CiteScore: 5)
Animal Cognition     Hybrid Journal   (Followers: 20, SJR: 1.389, CiteScore: 3)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.192, CiteScore: 0)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.097, CiteScore: 2)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4, SJR: 0.438, CiteScore: 0)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.429, CiteScore: 0)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.197, CiteScore: 1)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 17, SJR: 1.042, CiteScore: 3)
Annals of Combinatorics     Hybrid Journal   (Followers: 4, SJR: 0.932, CiteScore: 1)
Annals of Data Science     Hybrid Journal   (Followers: 12)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.85, CiteScore: 2)
Annals of Finance     Hybrid Journal   (Followers: 34, SJR: 0.579, CiteScore: 1)
Annals of Forest Science     Hybrid Journal   (Followers: 7, SJR: 0.986, CiteScore: 2)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.228, CiteScore: 1)
Annals of Hematology     Hybrid Journal   (Followers: 15, SJR: 1.043, CiteScore: 2)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.413, CiteScore: 1)
Annals of Microbiology     Hybrid Journal   (Followers: 11, SJR: 0.479, CiteScore: 2)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 5, SJR: 0.687, CiteScore: 2)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.943, CiteScore: 2)
Annals of Ophthalmology     Hybrid Journal   (Followers: 13)
Annals of Regional Science     Hybrid Journal   (Followers: 8, SJR: 0.614, CiteScore: 1)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 9, SJR: 0.239, CiteScore: 1)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 15, SJR: 1.986, CiteScore: 4)
Annals of Telecommunications     Hybrid Journal   (Followers: 9, SJR: 0.223, CiteScore: 1)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 1.495, CiteScore: 1)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.834, CiteScore: 2)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.22, CiteScore: 3)
APOPTOSIS     Hybrid Journal   (Followers: 9, SJR: 1.424, CiteScore: 4)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.294, CiteScore: 1)
Applications of Mathematics     Hybrid Journal   (Followers: 3, SJR: 0.602, CiteScore: 1)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 44, SJR: 0.571, CiteScore: 2)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 18, SJR: 0.21, CiteScore: 1)
Applied Categorical Structures     Hybrid Journal   (Followers: 4, SJR: 0.49, CiteScore: 0)
Applied Composite Materials     Hybrid Journal   (Followers: 50, SJR: 0.58, CiteScore: 2)
Applied Entomology and Zoology     Partially Free   (Followers: 6, SJR: 0.422, CiteScore: 1)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.733, CiteScore: 3)
Applied Geophysics     Hybrid Journal   (Followers: 9, SJR: 0.488, CiteScore: 1)
Applied Intelligence     Hybrid Journal   (Followers: 15, SJR: 0.6, CiteScore: 2)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.319, CiteScore: 1)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 9, SJR: 0.886, CiteScore: 1)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (Followers: 1, SJR: 0.17, CiteScore: 0)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.461, CiteScore: 1)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 66, SJR: 1.182, CiteScore: 4)
Applied Physics A     Hybrid Journal   (Followers: 10, SJR: 0.481, CiteScore: 2)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 25, SJR: 0.74, CiteScore: 2)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.519, CiteScore: 2)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 12, SJR: 0.316, CiteScore: 1)
Applied Solar Energy     Hybrid Journal   (Followers: 22, SJR: 0.225, CiteScore: 0)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 7, SJR: 0.542, CiteScore: 1)
Aquaculture Intl.     Hybrid Journal   (Followers: 26, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 2)
Aquatic Ecology     Hybrid Journal   (Followers: 37, SJR: 0.656, CiteScore: 2)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.591, CiteScore: 1)
Aquatic Sciences     Hybrid Journal   (Followers: 14, SJR: 1.109, CiteScore: 3)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.303, CiteScore: 1)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 2, SJR: 0.319, CiteScore: 1)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 21, SJR: 1.052, CiteScore: 2)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.224, CiteScore: 0)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.725, CiteScore: 1)
Archival Science     Hybrid Journal   (Followers: 68, SJR: 0.745, CiteScore: 2)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 7, SJR: 0.186, CiteScore: 1)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 3, SJR: 0.909, CiteScore: 1)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 3.93, CiteScore: 3)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 6, SJR: 0.79, CiteScore: 2)
Archives and Museum Informatics     Hybrid Journal   (Followers: 159, SJR: 0.101, CiteScore: 0)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 6, SJR: 1.41, CiteScore: 5)
Archives of Dermatological Research     Hybrid Journal   (Followers: 7, SJR: 1.006, CiteScore: 2)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 14, SJR: 0.773, CiteScore: 2)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 17, SJR: 0.956, CiteScore: 2)
Archives of Microbiology     Hybrid Journal   (Followers: 9, SJR: 0.644, CiteScore: 2)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 9, SJR: 1.146, CiteScore: 2)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 0.71, CiteScore: 2)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 10, SJR: 1.493, CiteScore: 3)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.541, CiteScore: 5)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 0.973, CiteScore: 2)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 17, SJR: 1.274, CiteScore: 3)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 0.946, CiteScore: 3)
ArgoSpine News & J.     Hybrid Journal  
Argumentation     Hybrid Journal   (Followers: 6, SJR: 0.349, CiteScore: 1)
Arid Ecosystems     Hybrid Journal   (Followers: 2, SJR: 0.2, CiteScore: 0)
Arkiv för Matematik     Hybrid Journal   (Followers: 2, SJR: 0.766, CiteScore: 1)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1, SJR: 0.355, CiteScore: 0)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 2, SJR: 0.839, CiteScore: 2)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.131, CiteScore: 0)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 11, SJR: 0.937, CiteScore: 2)
Artificial Intelligence Review     Hybrid Journal   (Followers: 18, SJR: 0.833, CiteScore: 4)
Artificial Life and Robotics     Hybrid Journal   (Followers: 10, SJR: 0.226, CiteScore: 0)
Asia Europe J.     Hybrid Journal   (Followers: 4, SJR: 0.504, CiteScore: 1)
Asia Pacific Education Review     Hybrid Journal   (Followers: 12, SJR: 0.479, CiteScore: 1)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 16, SJR: 1.185, CiteScore: 2)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 13, SJR: 0.353, CiteScore: 1)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 3, SJR: 0.187, CiteScore: 0)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 19, SJR: 0.855, CiteScore: 1)
Asian Business & Management     Hybrid Journal   (Followers: 9, SJR: 0.378, CiteScore: 1)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 11)
Asian J. of Criminology     Hybrid Journal   (Followers: 6, SJR: 0.543, CiteScore: 1)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 4, SJR: 0.548, CiteScore: 1)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.183, CiteScore: 0)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  
Astronomy and Astrophysics Review     Hybrid Journal   (Followers: 22, SJR: 3.385, CiteScore: 5)

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Similar Journals
Journal Cover
AAPS PharmSciTech
Journal Prestige (SJR): 0.752
Citation Impact (citeScore): 3
Number of Followers: 8  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1530-9932
Published by Springer-Verlag Homepage  [2351 journals]
  • Improved Oral Absorption of Poorly Soluble Curcumin via the Concomitant
           Use of Borneol
    • Abstract: In this study, borneol, a natural active compound was applied to improve the bioavailability of curcumin (CUR). In order to increase CUR solubility and dissolution, solid dispersions (SDs) were prepared with the matrix of polyvinylpyrrolidone (PVP) at various ratios by solvent evaporation method. CUR was evidenced to exist as amorphous state in solid dispersion by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Fourier-transform infrared spectroscopy (FT-IR) was utilized to confirm intermolecular hydrogen bonding. The SD at the ratio of 1:3 (CUR:PVP) exhibited the optimal solubility and dissolution rate in various media. The results of ex vivo permeability studies by everted gut sac method showed that the apparent permeability coefficients (Papp) of CUR in SD across the duodenum, jejunum, and ileum had been significantly improved by co-incubation of borneol, and the improvement degree relied on the concentration of borneol. The pharmacokinetic results in rats indicated that the AUC0-t of CUR-SD (40 mg/kg) co-administration of borneol (90 mg/kg) were 2.53-fold higher than CUR-SD alone, and 19.41-fold higher than pure CUR (200 mg/kg) with borneol (90 mg/kg). Therefore, the combination of borneol and solid dispersion strategy provide a potential approach to enhance the oral bioavailability of CUR.
      PubDate: 2019-03-22
  • Utility of Microcrystalline Cellulose for Improving Drug Content
           Uniformity in Tablet Manufacturing Using Direct Powder Compression
    • Abstract: Direct powder compression is the simplest tablet manufacturing method. However, segregation occurs when the drug content is low. It is difficult to assure drug content uniformity in these cases. In this study, we evaluated microcrystalline cellulose (MCC) as a segregation inhibitor in pharmaceutical powders. We assessed the influence of MCC concentration and mixing time on the physical properties of tablets. The tablet formulation comprised acetaminophen, lactose hydrate, cornstarch, MCC (0%, 10%, or 20%), croscarmellose sodium, and magnesium stearate (Mg-St). All powders except Mg-St were premixed for 5, 15, or 25 min. Mg-St was then added and mixed for 5 min to prepare nine pharmaceutical powders. Flowability index and practical angle of internal friction were measured. Tablets were also prepared, and their weight variation, hardness, friability, disintegration time, and drug content variation were evaluated. MCC slightly decreased pharmaceutical powder flowability. Tablet hardness increased and disintegration time decreased with increasing MCC concentration. MCC mixed for ≥ 15 min also significantly lowered drug content variation. A contour plot was prepared to assess the effect of MCC concentration and mixing time on the physical properties of tablets. It was determined that tablets with 50–80 N hardness, ≤ 3.5 min disintegration time, and ≤ 3% drug content variation can be prepared when MCC concentration is 6.5–8.5% and the mixing time is 19–24 min. Therefore, MCC is effective as a segregation inhibitor, and the addition of MCC to tablet formulation improves drug content uniformity.
      PubDate: 2019-03-22
  • Cocrystal of 5-Fluorouracil: Characterization and Evaluation of
           Biopharmaceutical Parameters
    • Abstract: To prepare the cocrystals of 5-fluorouracil (5-FU) with GRAS status coformers via a cocrystallization technique with an aim to improve physicochemical properties as well as bioavailability for colon cancer, breast cancer, and prostate cancer. The mechanochemical method was used in the preparations of three crystals of 5-FU with gentisic acid (5-FUGA), 3,4-dihydroxybenzoic acid (5-FUBA), and 4-aminopyridine (5-FUPN). A thermoanalytical and spectroscopic technique was used for their characterization. Their biological evaluation was done in different cancer cell lines. The new solid pure crystal forms were characterized by DSC, FTIR, and PXRD. The crystal structure was determined from single crystal and PXRD that exposed the existence of the monoclinic and triclinic crystal system with P21/n and P-1 space groups. The dermatokinetic studies on the rat skin revealed two- to threefold improvement in relative bioavailability as compared to pure 5-FU. “MTT assay was performed by varying the concentrations of the drug from 1 to 50 μg mL−1. After 24 h, the cell viability dropped to 70.67%, 74.05%, and 76.37% in MCF-7, Hela, and Caco-2 cell lines when the concentration of 5-FU was 50 μg mL−1”, while it dropped dramatically in cocrystals 5-FUGA (22.06%, 24.63%, and 25.61%), 5-FUBA (31.22%, 29.46%, and 32.81%), and 5-FUPN (21.65%, 32.64%, and 21.46%). All the results indicated that 5-FU cocrystals possess better antitumor efficacy than free drug. Thus, cocrystallization expands the extent of the existing pre-formulation options ahead of pure API form to ameliorate the bioavailability and permeability.
      PubDate: 2019-03-22
  • Performance Characteristics of a Novel Vibration Technique for the
           Densification of a Powder Bed within a Die of a Rotary Tablet Press — a
           Proof of Concept
    • Abstract: The aim of this study was to investigate the concept of lower punch vibration as a possible approach to densify the powder bed within the die of a rotary tablet press. Therefore, a laboratory vibration equipment was developed to obtain a better understanding of the performance characteristics and effects of a pneumatically generated vibration system on pharmaceutical powders. For this purpose, two widely used pharmaceutical powders, basic magnesium carbonate (Pharmagnesia MC Type F) and microcrystalline cellulose (Ceolus® KG1000), both with different physical properties, were investigated. The powders were characterized by laser diffraction, scanning electron microscopy, helium pycnometry, ring shear testing, gas adsorption, and by determination of the powder flowability. Furthermore, the extent of densification within the die during vibration was visualized by a high-speed camera system and analyzed by an image-analyzing software. It was observed that lower punch vibration was able to densify the powder bed to a sufficient extent and within an adequate time period. Consequently, the presented results revealed that lower punch vibration may be a promising technique to remove entrapped air from powder beds, thus obtaining a denser powder bed within the die, which might potentially improve the tableting process and prevent complications during tablet manufacture.
      PubDate: 2019-03-20
  • A Thermoelectric Device for Coupling Fluid Temperature Regulation During
           Continuous Skin Sonoporation or Sonophoresis
    • Abstract: During skin sonoporation and sonophoresis, time-consuming duty cycles or fluid replacement is often required to mitigate coupling fluid temperature increases. This study demonstrates an alternative method for temperature regulation: a circulating, thermoelectric system. Porcine skin samples were sonoporated continuously for 10 min at one of three intensities (23.8, 34.2, 39.4 W/m2). A caffeine solution was then applied to the skin and left to diffuse for 20 h. During sonoporation, the system was able to maintain the temperature between 10 and 16°C regardless of the intensity. No increase in transdermal transport was achieved with an intensity of 23.8 W/m2. Intensities of 34.2 and 39.4 W/m2 resulted in 3.5-fold (p < 0.05) and 3.7-fold (p < 0.05) increases in mean transport, relative to a control case with no ultrasound. From these results, it is concluded that a significant transport increase can be achieved with a system that circulates and cools the coupling fluid during ultrasound application. Relative to the previous methods of temperature control (duty cycles and fluid replacement), use of this circulation system will lead to significant time savings in future experimental studies.
      PubDate: 2019-03-18
  • Stability and Bioavailability Enhancement of Telmisartan Ternary Solid
           Dispersions: the Synergistic Effect of Polymers and Drug-Polymer(s)
    • Abstract: The purpose of this study was to investigate the synergistic effect of polymers and drug-polymer(s) interactions on the improved stability and bioavailability of telmisartan (TEL) ternary solid dispersions. As a water-insoluble drug, 40 and 160 mg doses of TEL tablets exhibited bioavailabilities of 42% and 58%, respectively. Through polymer screening, PVP K30 and/or Soluplus were selected and used at different concentrations to prepare TEL amorphous solid dispersions by solvent evaporation. Compared to pure TEL and TEL-PVP K30/Soluplus binary solid dispersions, TEL-PVP K30–Soluplus ternary solid dispersions demonstrated significant advantages, including higher dissolution (over 90% release at 60 min), better amorphous stability (physically stable in 90 days), and improved oral bioavailability (Cmax of 5535.819 ± 325.67 ng/mL and tmax of 1 h). These advantages were related to the complementarity of PVP K30 and Soluplus on TEL. PVP K30 had a better activity to solubilize TEL and achieved a high TEL initial concentration in dissolution media. Simultaneously, the ability of Soluplus to assist in the maintenance of supersaturation played an important role. PVP K30 and Soluplus together inhibited crystallization of the drug at different stages. The existence and intensity of drug-polymer interactions were also determined by DSC (Tg determination) and FT-IR. At the molecular level, a hypothesis was also proposed that the enhancements resulted from the contribution of the synergistic effect between PVP K30 and Soluplus. These results suggested that two polymers, in a combination and via a synergistic effect, could further enhance the bioavailability and amorphous stability of ternary solid dispersions.
      PubDate: 2019-03-18
  • Preparation, Characterization, and In vitro Evaluation of Curcumin- and
           Resveratrol-Loaded Solid Lipid Nanoparticles
    • Abstract: Curcumin and resveratrol are natural compounds with significant anticancer activity; however, their bioavailability is limited due to poor solubility. This study aimed to overcome the solubility problem by means of solid lipid nanoparticles (SLN). 2-Hydroxypropyl β-cyclodextrin (HPβCD) was selected from a range of polymers based on miscibility and molecular interactions. SLNs were obtained by probe sonication and freeze-drying curcumin-resveratrol with/without HPβCD incorporated in gelucire 50/13. SLNs were characterized by dynamic light scattering (DLS), zeta potential, powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and physical stability. The in vitro release of drugs from the SLNs was performed by the direct dispersion method and analyzed using a validated UV-visible method. In vitro efficacy was tested using a colorectal cancer cell line. Curcumin-resveratrol-gelucire 50/13-HPβCD (CRG-CD) and curcumin-resveratrol-gelucire 50/13(CRG) SLNs showed a particle size from 100 to 150 nm and were not in the crystalline state per PXRD results. MDSC results complimented PXRD results by the absence of melting endotherm of curcumin; TGA showed no weight loss, confirming the absence of organic solvent residual, and the shape of the SLNs was confirmed as spherical by SEM. CRG SLNs were stable for 21 days with respect to particle size and zeta potential. MTT assay indicated better IC50 value for CRG as compared to CRG-CD. Hence, novel SLNs of curcumin and resveratrol incorporated in gelucire 50/13 and HPβCD were prepared and characterized to improve their bioavailability and anticancer activity.
      PubDate: 2019-03-18
  • Thermally Induced Denaturing Energetics of Human Blood Plasma Albumin by
           Differential Scanning Calorimetry (DSC) as an Indicator for Breast Cancer
           Diagnosis in Female Patients
    • Abstract: Cancerous invasion yields unusual metabolisms providing a significant amount of peptide albuminomes that modulate albumin stability via binding. The study aimed at the investigation of the thermal stability of human plasma albumin with breast cancer of various stages by means of differential scanning calorimetry (DSC). Blood plasma was drawn from 11 female breast cancer patients and 50 healthy volunteers of homogeneous demographics. Plasma samples and their albumin-enriched fractions were subjected to DSC scanning between 37 and 90°C at 5°C/min rate. For normal blood plasma, a characteristic signature of DSC tracing was observed. And, the deconvolution of DSC thermograms revealed the recognition of thermal transition of albumin. It was found that denaturing temperature of albumin increased with increasing breast cancer staging which implied the increase in albuminome/peptide abundance produced by cancerous invasion. The analysis of albumin denaturing energetics based on rational approximation of the simple Lumry-Eyring model demonstrated that thermal transition of free albumin and albuminome-bound form attained energetic levels expressed as apparent activation energy (Eapp ± s.e.) of 132.68 ± 14.21 and 46.76 ± 8.42 Kcal/mol corresponded to the schemes dominated by irreversible alteration and by reversible unfolding, respectively. Thus, Eapp value may indicate the degrees of cancerous invasion. It was proposed that Eapp may be used as an indicator to diagnose and assess the prognosis of breast cancer.
      PubDate: 2019-03-18
  • Highly Soluble Glimepiride and Irbesartan Co-amorphous Formulation with
           Potential Application in Combination Therapy
    • Abstract: One-third of the population of the USA suffers from metabolic syndrome (MetS). Treatment of patients with MetS regularly includes drugs prescribed simultaneously to treat diabetes and cardiovascular diseases. Therefore, the development of novel multidrug formulations is recommended. However, the main problem with these drugs is their low solubility. The use of binary co-amorphous systems emerges as a promising strategy to increase drug solubility. In the present study, irbesartan (IBS) and glimepiride (GMP), class II active pharmaceutical ingredients (API), widely used in the treatment of arterial hypertension and diabetes, were selected to develop a novel binary co-amorphous system with remarkable enhancement in the dissolution of both APIs. The phase diagram of IBS–GMP was constructed and co-amorphous systems were prepared by melt-quench, in a wide range of compositions. Dissolution profile (studied at pH 1.2 and 37°C for mole fractions 0.01, 0.1, and 0.5) demonstrated that the xGMP = 0.01 formulation presents the highest enhancement in its dissolution. GMP went from being practically insoluble to reach 3.9 ± 0.9 μg/mL, and IBS showed a 12-fold increment with respect to the dissolution of its crystalline form. Infrared studies showed that the increase in the dissolution profile is related to the intermolecular interactions (hydrogen bonds), which were dependent of composition. Results of structural and thermal characterization performed by XRD and DSC showed that samples have remained in amorphous state for more than 10 months of storage. This work contributes to the development of a highly soluble co-amorphous drugs with potential used in the treatment of MetS.
      PubDate: 2019-03-18
  • Release Adjustment of Two Drugs with Different Solubility Combined in a
           Matrix Tablet
    • Abstract: The objective of this study was to modify the release of two drugs having different solubility in a combined matrix tablet as a fixed-dose combination for extended release. Propranolol HCl (freely soluble) and carbamazepine (very slightly soluble) were used as model drugs, water-soluble hydroxypropyl methylcellulose (HPMC) and water-insoluble ethylcellulose (EC) were used as matrix-forming polymers. Tablets were prepared by direct compression of powder blends, or propranolol HCl was first granulated with one of the matrix-forming polymers (1:1) followed by compression with carbamazepine and matrix former. Propranolol HCl release from directly compressed tablets was faster than carbamazepine because of its higher solubility. The release of both drugs was fast when HPMC-propranolol HCl granules were compressed with carbamazepine into EC matrix tablet. Conversely, the release of both drugs was decreased when HPMC-propranolol HCl granules and carbamazepine were compressed into HPMC matrices. The desired release of both drugs was approached when EC-propranolol HCl granules were compressed with carbamazepine into HPMC matrix. Erosion of the HPMC matrix and, therefore, drug release were adjusted by varying the molecular weight of HPMC. A burst release of propranolol HCl decreased when it was granulated with EC in a fluidized bed coater followed by compression with carbamazepine into HPMC matrix.
      PubDate: 2019-03-14
  • Development and Characterization of Microstructured, Spray-Dried
           Co-Amorphous Mixture of Antidiabetic Agents Stabilized by Silicate
    • Abstract: In the present work, co-amorphous mixture (COAM) of poorly soluble nateglinide (NT) and highly soluble Metformin hydrochloride (MT) was prepared by spray drying method to improve the dissolution rate of NT and the processability of COAM. Binary spray-dried COAM of NT and MT (120 mg: 500 mg) was prepared in its clinical dose ratio whereas 20% Neusilin®US2 (NS) was added to prepare non-sticky, free flowing ternary COAM. Solubility studies of binary and ternary COAM exhibited sevenfold and tenfold rise in the solubility of NT. Complete amorphization of NT was revealed in XRPD and DSC studies of both COAM and hydrogen-bonding interactions were reflected in FTIR-spectra. SEM microphotographs illustrated round-shaped microparticles in ternary COAM against the irregular particles in binary COAM. In vitro dissolution of NT was significantly improved in ternary COAM > binary COAM > NT irrespective of dissolution medium. On contrary, MT has partially transformed to the amorphous form in COAM without altering the solubility. In accelerated stability studies, NT and MT devitrification was not observed in XRPD of ternary COAM in contrast to binary COAM. Therefore, enhanced dissolution of NT, stabilization of spray-dried dispersion, and its improved processability can be achieved by preparing ternary COAM of NT:MT:NS.
      PubDate: 2019-03-13
  • Pharmaceutical “New Prior Knowledge”: Twenty-First Century Assurance
           of Therapeutic Equivalence
    • Abstract: Facilitating utility of prior knowledge to accelerate evidence-based new drug development is a focus of several communities of knowledge, such as clinical pharmacology. For example, progress has been made via modeling and simulation of pharmacokinetic and pharmacodynamic relationships in the more effective use of “End of Phase 2” regulatory meetings for a New Drug Application (NDA). Facilitating utility of prior “Chemistry, Manufacturing, and Controls” (CMC) knowledge to accelerate new drug development and regulatory review process is also a topic of significant interest. This paper focuses on facilitating the utility of prior pharmaceutical formulation knowledge to accelerate drug product development and regulatory review of generic and biosimilar products. This knowledge is described as New Prior Knowledge (NPK) because research is often needed to fill ontological (i.e., the domain of connectivity between concepts and phenomena), epistemological (i.e., distinguishing knowledge or justified belief from the opinion), and methodological gaps in information derived a decade or so ago. The corporate economic advantages of such knowledge are derived, in part, when significant portions remain a trade secret. The proposed NPK seeks to generate knowledge about critical aspects of pharmaceutical quality and failure modes to place it in the public domain and to facilitate accelerated and more confident development and regulatory review of generic products. The paradoxical combination of “new” and “prior knowledge” is chosen deliberately to highlight both a distinction from proprietary and trade secret information and to acknowledge certain historical dogmas inherent in the current practices. Considerations for operationalizing NPK are also summarized.
      PubDate: 2019-03-12
  • Formulation of Cinnarizine for Stabilization of Its Physiologically
           Generated Supersaturation
    • Abstract: Physiologically generated supersaturation and subsequent crystallization of a weakly basic drug in the small intestine leads to compromised bioavailability. In this study, the pH-induced crystallization of cinnarizine (CNZ) in the presence of different polymers was investigated. Inhibitory effect of Eudragit L100 (Eu) on crystallization of CNZ at varying supersaturation ratios was examined. The effect of Eu on the dissolution behavior of CNZ from CNZ/Eu physical mixtures (PMs) and solid dispersions (SDs) was assessed. Results showed that both Eu and hydroxypropyl methylcellulose (HPMC) have a considerable maintenance effect on supersaturation of CNZ but Eu was more effective than HPMC. When Eudragit was used the phenomenon of liquid-liquid phase separation (formation of colloidal phase) was observed at supersaturation ratio of 20 times above the solubility of the drug. PMs showed a higher area under the dissolution curve (AUDC) compared with plain CNZ. In contrast, SDs showed a lower AUDC than plain CNZ. For SDs, the AUDC was limited by the slow release of the drug from Eu in acidic pH which in turn hindered the creation of CNZ supersaturation following the transition of acidic to neutral pH. From these findings, it can be concluded that the ability of the formulation to generate supersaturation state and also maintain the supersaturation is vital for improving the dissolution of CNZ.
      PubDate: 2019-03-11
  • Application of the Modified Tangential Spray-Fluidized Bed to Produce
           Nonpareils from Primary Crystals
    • Abstract: Coating of fine primary drug particles by a fluidized bed processor has been reported to be potentially challenging. This work aimed to develop a spray layering process to produce nonpareils by a side spray fluid bed with swirling air flow. The first part examined the effects of various parameters for producing lactose nonpareils by using Box-Behnken design. The factors considered were atomizing air pressure, spray rate, and fluidizing air temperature. This was followed by an in-depth investigation on the effects of inlet airflow rate, air temperature, and spray rate on properties of the product, in addition to process optimization. The results indicated a negative correlation between atomizing air pressure and D90 (particle size at 90th percentile in the cumulative undersize plot) as well as span (size distribution). Temperature had a positive correlation with D90 and span while spray rate affected span. Both atomizing air pressure and temperature correlated negatively with span. It was also found that spray rate negatively affected roundness at different coat weight gain levels across the study design space. Inlet airflow rate was found to correlate negatively with roundness at 15%, w/w coat weight gain. The mean useful yield of the optimized runs was about 91%. In the second part of this study, the metformin hydrochloride crystals as starter seeds were converted into nearly spherical shaped spheroids with 1:1 crystals to coat weight deposition over a processing time of about 3.5 h. The processor studied shows promise for direct spheronization of crystals into spherical seeds.
      PubDate: 2019-03-11
  • Design of Inhalable Solid Dosage Forms of Budesonide and Theophylline for
           Pulmonary Combination Therapy
    • Abstract: Corticosteroid resistance poses a major challenge to effective treatment of chronic obstructive pulmonary diseases. However, corticosteroid resistance can be overcome by co-administration of theophylline. The aim of this study was to formulate the corticosteroid budesonide with theophylline into inhalable dry powders intended for pulmonary combination therapy. Four types of spray-dried powders were prepared: (i) budesonide and theophylline co-dissolved and processed using a 2-fluid nozzle spray drier, (ii) budesonide nanocrystals and dissolved theophylline co-dispersed and processed using a 2-fluid nozzle spray drier, (iii) dissolved budesonide and dissolved theophylline processed using a 3-fluid nozzle spray drier, and (iv) budesonide nanocrystals and dissolved theophylline processed using a 3-fluid nozzle spray drier. Spray drying from the solutions resulted in co-amorphous (i) and partially amorphous powders (iii), whereas spray drying of the nanosuspensions resulted in crystalline products (ii and iv). Even though budesonide was amorphous in (i) and (iii), it failed to exhibit any dissolution advantage over the unprocessed budesonide. In contrast, the dissolution of budesonide from its nanocrystalline formulations, i.e., (ii) and (iv), was significantly higher compared to a physical mixture or unprocessed budesonide. Furthermore, the spray-dried powders obtained from the 2-fluid nozzle spray drier, i.e., (i) and (ii), exhibited co-deposition of budesonide and theophylline at the same weight ratio in the aerodynamic assessment using the New Generation Impactor. In contrast, the depositions of budesonide and theophylline deviated from the starting weight ratio in the aerodynamic assessment of spray-dried powders obtained from the 3-fluid nozzle spray drier, i.e., (iii) and (iv). Based on these results, the powders spray-dried from the suspension by using the 2-fluid nozzle spray drier, i.e., (ii), offered the best formulation properties given the physically stable crystalline solid-state properties and the co-deposition profile.
      PubDate: 2019-03-07
  • Antifungal and Mucoadhesive Properties of an Orally Administered
           Chitosan-Coated Amphotericin B Nanostructured Lipid Carrier (NLC)
    • Abstract: Surface-modified nanostructured lipid carriers (NLC) represent a promising mode of drug delivery used to enhance retention of drugs at absorption site. Formulated chitosan-coated amphotericin-B-loaded NLC (ChiAmp NLC) had a size of 394.4 ± 6.4 nm, encapsulation and loading efficiencies of 86.0 ± 3% and 11.0 ± 0.1% respectively. Amphotericin-B release from NLCs was biphasic with no changes in physical properties upon exposure to simulated gastrointestinal conditions. Antifungal properties of Amphotericin-B and ChiAmpB NLC were comparable but ChiAmpB NLC was twice less toxic to red blood cells and ten times safer on HT-29 cell lines. In vitro mucoadhesion data were observed ex vivo, where ChiAmpB NLC resulted in higher retention within the small intestine compared to the uncoated formulation. The data strongly offers the possibility of orally administering a non-toxic, yet effective Amphotericin-B nanoformulation for the treatment of systemic fungal infections.
      PubDate: 2019-03-05
  • Buspirone Hydrochloride Loaded In Situ Nanovesicular Gel as an Anxiolytic
           Nasal Drug Delivery System: In Vitro and Animal Studies
    • Abstract: Nasal nanovesicular gels of buspirone hydrochloride (BH) were prepared and characterized aiming for sustained delivery and enhancing bioavailability. Buspirone hydrochloride has low bioavailability of about 4% after oral administration due to first pass metabolism. Buspirone hydrochloride nanovesicles were formulated by thin film hydration method (TFH). The selected nanovesicular formulation was incorporated into two types of in situ gels (pH-induced and thermoreversible) using carbopol 974P and poloxamer 407 (P407), respectively, together with different mucoadhesive polymers. The in situ gels were examined for pH, gelling capability, viscosity, content uniformity, mucoadhesiveness, and in vitro drug release. The ex vivo permeation performance of the in situ gel formulations that showed the most sustained release was also assessed. The in vivo study was done by the determination of BH blood level in albino rabbits after nasal administration. Results revealed that nanovesicles prepared using Span 60 and cholesterol in a ratio of 80:20 showed the highest EE% (70.57 ± 1.00%). The ex vivo permeation data confirmed higher permeability figures for carbopol formulation in comparison to poloxamer formulations. The in vivo study data showed an increase of 3.26 times in BH bioavailability when formulated into the carbopol nanovesicular in situ gel relative to control (nasal drug solution).
      PubDate: 2019-03-04
  • Erlotinib-Valproic Acid Liquisolid Formulation: Evaluating Oral
           Bioavailability and Cytotoxicity in Erlotinib-Resistant Non-small Cell
           Lung Cancer Cells
    • Abstract: Lung cancer patients develop acquired resistance to tyrosine kinase inhibitors including erlotinib (ERL) after few months of primary treatment. Evidently, new chemotherapy strategies to delay or overcome the resistance are urgently needed to improve the clinical outcome in non-small cell lung cancer (NSCLC) patients. In this paper, we have investigated the cytotoxic interaction of ERL and valproic acid (VA) in ERL-resistant NSCLC cells and developed a liquisolid formulation of ERL-VA for improving oral bioavailability of ERL. ERL is weakly basic, biopharmaceutical classification system (BCS) class II drug with extremely poor aqueous solubility while VA is a branched chain fatty acid. Ionic interaction between ERL and VA (1:2 M ratio) resulted in significant enhancement in saturation solubility of ERL at different pH range. Liquisolid formulation of ERL-VA (EVLF) developed using PEG 400 and mesoporous calcium silicate was characterized for solid state and in vitro dissolution in biorelevant dissolution medium (FaSSIF and FeSSIF). Cytotoxicity of ERL was enhanced by 2–5 folds on co-incubation with VA in HCC827/ERL cell line. Flow cytometry analysis using AnnexinV-FITC assay demonstrated that VA and ERL alone have poor apoptotic effect on HCC827/ERL cells while combination showed around 69% apoptotic cells. Western blot analysis confirmed the role of survivin in overcoming resistance. In vivo pharmacokinetic studies of EVLF in rats demonstrated a 199% relative bioavailability compared to ERL suspension. Thus, EVLF could be a promising alternative to current ERL formulations in the treatment of NSCLC.
      PubDate: 2019-03-04
  • Optimization of Chitosan-α-casein Nanoparticles for Improved Gene
           Delivery: Characterization, Stability, and Transfection Efficiency
    • Abstract: Among non-viral vectors, the cationic polymer chitosan has gained attention as a gene delivery system. We hypothesized that the addition of casein into the nanoparticle’s structure would facilitate a proper gene transfer. The work herein presented aimed to optimize the production method of chitosan-casein nanoparticles (ChiCas NPs) and to test their ability as a gene delivery system. ChiCas NPs formulation optimization was carried out by analyzing several characteristics such as NP size, zeta potential, and chitosan and casein incorporation efficacy. The best formulation developed presented small and homogenous particle size (around 335 nm) and positive zeta potential (≈ + 38 mV), and showed to be stable for 34 weeks both, at 4°C and 20°C. The particles were further used to entrap or to adsorb DNA and form NPs-DNA complexes. In vitro transfection studies, carried out in COS-7 cells, suggested a low transfection efficiency of the different NPs:DNA ratios tested, comparatively to the positive control. Nonetheless, we could observe that the complexes with larger sizes presented better transfection results than those with smaller diameters. To conclude, ChiCas NPs have great technological potential since the preparation process is very simple, and the DNA incorporation efficacy is very high and shows to be physically very stable. The NPs:DNA ratio still needs to be optimized with the aim of achieving better transfection results and being able to anticipate a high gene expression on DNA-based vaccination studies.
      PubDate: 2019-02-28
  • Preparation and Evaluation of Irinotecan Poly(Lactic-co-Glycolic Acid)
           Nanoparticles for Enhanced Anti-tumor Therapy
    • Abstract: Irinotecan (IRT), the pro-drug of SN-38, has exhibited potent cytotoxicity against various tumors. In order to enhance the anti-tumor effect of IRT, we prepared IRT-loaded PLGA nanoparticles (IRT-PLGA-NPs) by emulsion-solvent evaporation method. Firstly, IRT-PLGA-NPs were characterized through drug loading (DL), entrapment efficiency (EE), particle size, zeta potential, transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). We next studied the in vitro release characteristics of IRT-PLGA-NPs. Finally, the pharmacokinetics and pharmacodynamics profiles of IRT-PLGA-NPs were investigated. The results revealed that IRT-PLGA-NPs were spherical with an average size of (169.97 ± 6.29) nm and its EE and DL were (52.22 ± 2.41)% and (4.75 ± 0.22)%, respectively. IRT-PLGA-NPs could continuously release drug for 14 days in vitro. In pharmacokinetics studies, for pro-drug IRT, the t1/2β of IRT-PLGA-NPs was extended from 0.483 to 3.327 h compared with irinotecan solution (IRT-Sol), and for its active metabolite SN-38, the t1/2β was extended from 1.889 to 4.811 h, which indicated that IRT-PLGA-NPs could prolong the retention times of both IRT and SN-38. The pharmacodynamics results revealed that the tumor doubling time, growth inhibition rate, and specific growth rate of IRT-PLGA-NPs were 2.13-, 1.30-, and 0.47-fold those of IRT-Sol, respectively, which demonstrated that IRT-PLGA-NPs could significantly inhibit the growth of tumor. In summary, IRT-PLGA-NPs, which exhibited excellent therapeutic effect against tumors, might be used as a potential carrier for tumor treatment in clinic.
      PubDate: 2019-02-28
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
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