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Publisher: Springer-Verlag   (Total: 2329 journals)

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Showing 1 - 200 of 2329 Journals sorted alphabetically
3D Research     Hybrid Journal   (Followers: 19, SJR: 0.214, h-index: 10)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 9, SJR: 1.073, h-index: 25)
AAPS J.     Hybrid Journal   (Followers: 18, SJR: 1.192, h-index: 74)
AAPS PharmSciTech     Hybrid Journal   (Followers: 5, SJR: 0.718, h-index: 54)
Abdominal Imaging     Hybrid Journal   (Followers: 14, SJR: 0.723, h-index: 60)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 2, SJR: 0.447, h-index: 12)
Academic Psychiatry     Full-text available via subscription   (Followers: 22, SJR: 0.492, h-index: 32)
Academic Questions     Hybrid Journal   (Followers: 7, SJR: 0.135, h-index: 6)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 26, SJR: 0.378, h-index: 30)
Acoustical Physics     Hybrid Journal   (Followers: 10, SJR: 0.355, h-index: 20)
Acoustics Australia     Hybrid Journal  
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.387, h-index: 6)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.624, h-index: 34)
Acta Biotheoretica     Hybrid Journal   (Followers: 5, SJR: 0.419, h-index: 25)
Acta Diabetologica     Hybrid Journal   (Followers: 14, SJR: 1.318, h-index: 46)
Acta Endoscopica     Hybrid Journal   (Followers: 1, SJR: 0.113, h-index: 8)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.465, h-index: 23)
Acta Geochimica     Hybrid Journal   (Followers: 3)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 1, SJR: 0.294, h-index: 13)
Acta Geotechnica     Hybrid Journal   (Followers: 6, SJR: 1.818, h-index: 22)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.524, h-index: 32)
Acta Mathematica     Hybrid Journal   (Followers: 10, SJR: 8.021, h-index: 47)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.53, h-index: 29)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 5, SJR: 0.406, h-index: 30)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.451, h-index: 5)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.22, h-index: 20)
Acta Mechanica     Hybrid Journal   (Followers: 18, SJR: 0.898, h-index: 52)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 4, SJR: 0.426, h-index: 29)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 5, SJR: 0.525, h-index: 18)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.524, h-index: 14)
Acta Neurochirurgica     Hybrid Journal   (Followers: 6, SJR: 0.833, h-index: 73)
Acta Neurologica Belgica     Hybrid Journal   (SJR: 0.348, h-index: 27)
Acta Neuropathologica     Hybrid Journal   (Followers: 3, SJR: 6.61, h-index: 117)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 17)
Acta Parasitologica     Hybrid Journal   (Followers: 9, SJR: 0.581, h-index: 28)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.551, h-index: 39)
Acta Politica     Hybrid Journal   (Followers: 13, SJR: 0.658, h-index: 20)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 5, SJR: 0.103, h-index: 4)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 20, SJR: 0.871, h-index: 15)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 7)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 14, SJR: 0.795, h-index: 40)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.774, h-index: 52)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 3, SJR: 0.319, h-index: 15)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 34, SJR: 0.959, h-index: 44)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 15, SJR: 1.255, h-index: 44)
Advances in Contraception     Hybrid Journal   (Followers: 2)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 53, SJR: 1.113, h-index: 14)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.141, h-index: 3)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 23, SJR: 1.397, h-index: 42)
Advances in Manufacturing     Hybrid Journal   (Followers: 3, SJR: 0.2, h-index: 4)
Advances in Polymer Science     Hybrid Journal   (Followers: 40, SJR: 0.637, h-index: 89)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 0.79, h-index: 44)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 7)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.882, h-index: 23)
Aerobiologia     Hybrid Journal   (Followers: 1, SJR: 0.511, h-index: 36)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 8, SJR: 0.821, h-index: 49)
African Archaeological Review     Hybrid Journal   (Followers: 14, SJR: 0.612, h-index: 24)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.248, h-index: 6)
AGE     Hybrid Journal   (Followers: 7, SJR: 1.358, h-index: 33)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.337, h-index: 10)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.529, h-index: 55)
Agricultural Research     Hybrid Journal   (Followers: 3)
Agriculture and Human Values     Hybrid Journal   (Followers: 12, SJR: 1.197, h-index: 49)
Agroforestry Systems     Hybrid Journal   (Followers: 20, SJR: 0.64, h-index: 56)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 10, SJR: 1.732, h-index: 59)
AI & Society     Hybrid Journal   (Followers: 7, SJR: 0.171, h-index: 19)
AIDS and Behavior     Hybrid Journal   (Followers: 13, SJR: 2.006, h-index: 71)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 3, SJR: 0.706, h-index: 19)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 2, SJR: 0.566, h-index: 18)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.388, h-index: 22)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 0.868, h-index: 20)
Algorithmica     Hybrid Journal   (Followers: 7, SJR: 0.898, h-index: 56)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.183, h-index: 20)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 4, SJR: 0.729, h-index: 20)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3, SJR: 1.392, h-index: 32)
AMBIO     Hybrid Journal   (Followers: 14, SJR: 1.094, h-index: 87)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 10, SJR: 0.864, h-index: 39)
American J. of Community Psychology     Hybrid Journal   (Followers: 24, SJR: 1.237, h-index: 83)
American J. of Criminal Justice     Hybrid Journal   (Followers: 7, SJR: 0.634, h-index: 13)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 11, SJR: 0.283, h-index: 3)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.175, h-index: 13)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.558, h-index: 35)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 21, SJR: 0.293, h-index: 13)
American Sociologist     Hybrid Journal   (Followers: 11, SJR: 0.18, h-index: 13)
Amino Acids     Hybrid Journal   (Followers: 7, SJR: 1.362, h-index: 83)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 5, SJR: 0.21, h-index: 37)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 4, SJR: 0.665, h-index: 7)
Analysis in Theory and Applications     Hybrid Journal  
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 4)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 28, SJR: 1.096, h-index: 123)
Anatomical Science Intl.     Hybrid Journal   (Followers: 2, SJR: 0.301, h-index: 26)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.212, h-index: 69)
Animal Cognition     Hybrid Journal   (Followers: 15, SJR: 1.122, h-index: 55)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.156, h-index: 4)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.377, h-index: 32)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.504, h-index: 14)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.167, h-index: 26)
Annals of Behavioral Medicine     Hybrid Journal   (Followers: 12, SJR: 2.112, h-index: 98)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18, SJR: 1.182, h-index: 94)
Annals of Combinatorics     Hybrid Journal   (Followers: 3, SJR: 0.849, h-index: 15)
Annals of Data Science     Hybrid Journal   (Followers: 8)
Annals of Dyslexia     Hybrid Journal   (Followers: 9, SJR: 0.857, h-index: 40)
Annals of Finance     Hybrid Journal   (Followers: 28, SJR: 0.686, h-index: 14)
Annals of Forest Science     Hybrid Journal   (Followers: 4, SJR: 0.929, h-index: 57)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.136, h-index: 23)
Annals of Hematology     Hybrid Journal   (Followers: 13, SJR: 1.117, h-index: 62)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 6, SJR: 0.593, h-index: 42)
Annals of Microbiology     Hybrid Journal   (Followers: 9, SJR: 0.402, h-index: 26)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 5, SJR: 0.68, h-index: 45)
Annals of Operations Research     Hybrid Journal   (Followers: 8, SJR: 1.186, h-index: 78)
Annals of Regional Science     Hybrid Journal   (Followers: 7, SJR: 0.405, h-index: 42)
Annals of Software Engineering     Hybrid Journal   (Followers: 12)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 10, SJR: 0.553, h-index: 8)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 11, SJR: 1.902, h-index: 127)
Annals of Telecommunications     Hybrid Journal   (Followers: 7, SJR: 0.315, h-index: 25)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.931, h-index: 31)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.992, h-index: 87)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.14, h-index: 57)
APOPTOSIS     Hybrid Journal   (Followers: 8, SJR: 1.554, h-index: 87)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.354, h-index: 27)
Applications of Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.274, h-index: 20)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 44, SJR: 0.575, h-index: 80)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17, SJR: 0.267, h-index: 26)
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.361, h-index: 21)
Applied Composite Materials     Hybrid Journal   (Followers: 46, SJR: 0.705, h-index: 35)
Applied Entomology and Zoology     Partially Free   (Followers: 2, SJR: 0.554, h-index: 34)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.323, h-index: 9)
Applied Geophysics     Hybrid Journal   (Followers: 7, SJR: 0.541, h-index: 13)
Applied Intelligence     Hybrid Journal   (Followers: 14, SJR: 0.777, h-index: 43)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 3, SJR: 0.358, h-index: 34)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 4, SJR: 0.955, h-index: 33)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.275, h-index: 8)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 4, SJR: 0.37, h-index: 26)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 61, SJR: 1.262, h-index: 161)
Applied Physics A     Hybrid Journal   (Followers: 7, SJR: 0.535, h-index: 121)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 23, SJR: 0.983, h-index: 104)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 7, SJR: 0.677, h-index: 47)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 10, SJR: 0.288, h-index: 15)
Applied Solar Energy     Hybrid Journal   (Followers: 15, SJR: 0.251, h-index: 6)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 4, SJR: 0.351, h-index: 9)
Aquaculture Intl.     Hybrid Journal   (Followers: 22, SJR: 0.613, h-index: 40)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 1)
Aquatic Ecology     Hybrid Journal   (Followers: 30, SJR: 0.646, h-index: 44)
Aquatic Geochemistry     Hybrid Journal   (Followers: 3, SJR: 0.764, h-index: 39)
Aquatic Sciences     Hybrid Journal   (Followers: 12, SJR: 1.172, h-index: 53)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.345, h-index: 20)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 1, SJR: 0.417, h-index: 16)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 21, SJR: 1.056, h-index: 15)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.397, h-index: 13)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.597, h-index: 29)
Archival Science     Hybrid Journal   (Followers: 52, SJR: 0.804, h-index: 22)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 7, SJR: 0.28, h-index: 15)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 1, SJR: 0.946, h-index: 23)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 4.091, h-index: 66)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 4, SJR: 0.865, h-index: 40)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 4, SJR: 2.841, h-index: 40)
Archives of Dermatological Research     Hybrid Journal   (Followers: 6, SJR: 0.9, h-index: 65)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 10, SJR: 0.846, h-index: 84)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 16, SJR: 0.695, h-index: 47)
Archives of Microbiology     Hybrid Journal   (Followers: 8, SJR: 0.702, h-index: 85)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 8, SJR: 1.039, h-index: 56)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 1.092, h-index: 13)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 9, SJR: 1.198, h-index: 74)
Archives of Toxicology     Hybrid Journal   (Followers: 16, SJR: 1.595, h-index: 76)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 1.086, h-index: 90)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 13, SJR: 1.264, h-index: 50)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 1.2, h-index: 42)
ArgoSpine News & J.     Hybrid Journal   (SJR: 0.102, h-index: 3)
Argumentation     Hybrid Journal   (Followers: 5, SJR: 0.295, h-index: 18)
Arid Ecosystems     Hybrid Journal   (Followers: 3)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.948, h-index: 22)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 1, SJR: 0.797, h-index: 17)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.145, h-index: 8)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 10, SJR: 0.288, h-index: 25)
Artificial Intelligence Review     Hybrid Journal   (Followers: 15, SJR: 0.948, h-index: 48)
Artificial Life and Robotics     Hybrid Journal   (Followers: 8, SJR: 0.231, h-index: 14)
Asia Europe J.     Hybrid Journal   (Followers: 4, SJR: 0.247, h-index: 9)
Asia Pacific Education Review     Hybrid Journal   (Followers: 9, SJR: 0.371, h-index: 17)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 11, SJR: 1.676, h-index: 50)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 11, SJR: 0.353, h-index: 13)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.19, h-index: 15)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 20, SJR: 1.006, h-index: 14)
Asian Business & Management     Hybrid Journal   (Followers: 7, SJR: 0.41, h-index: 10)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 7)
Asian J. of Criminology     Hybrid Journal   (Followers: 5, SJR: 0.263, h-index: 8)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 2, SJR: 0.681, h-index: 15)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.195, h-index: 5)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  
Astronomy and Astrophysics Review     Hybrid Journal   (Followers: 21, SJR: 4.511, h-index: 44)
Astronomy Letters     Hybrid Journal   (Followers: 19, SJR: 0.58, h-index: 30)
Astronomy Reports     Hybrid Journal   (Followers: 12, SJR: 0.473, h-index: 23)
Astrophysical Bulletin     Hybrid Journal   (Followers: 2, SJR: 0.469, h-index: 11)

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Journal Cover AAPS PharmSciTech
  [SJR: 0.718]   [H-I: 54]   [5 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1530-9932
   Published by Springer-Verlag Homepage  [2329 journals]
  • Simultaneous Comparison of Two Roller Compaction Techniques and Two
           Particle Size Analysis Methods
    • Authors: Tuomas Saarinen; Osmo Antikainen; Jouko Yliruusi
      Abstract: A new dry granulation technique, gas-assisted roller compaction (GARC), was compared with conventional roller compaction (CRC) by manufacturing 34 granulation batches. The process variables studied were roll pressure, roll speed, and sieve size of the conical mill. The main quality attributes measured were granule size and flow characteristics. Within granulations also the real applicability of two particle size analysis techniques, sieve analysis (SA) and fast imaging technique (Flashsizer, FS), was tested. All granules obtained were acceptable. In general, the particle size of GARC granules was slightly larger than that of CRC granules. In addition, the GARC granules had better flowability. For example, the tablet weight variation of GARC granules was close to 2%, indicating good flowing and packing characteristics. The comparison of the two particle size analysis techniques showed that SA was more accurate in determining wide and bimodal size distributions while FS showed narrower and mono-modal distributions. However, both techniques gave good estimates for mean granule sizes. Overall, SA was a time-consuming but accurate technique that provided reliable information for the entire granule size distribution. By contrast, FS oversimplified the shape of the size distribution, but nevertheless yielded acceptable estimates for mean particle size. In general, FS was two to three orders of magnitude faster than SA.
      PubDate: 2017-05-24
      DOI: 10.1208/s12249-017-0778-1
  • Exploration of alginates as potential stabilizers of nanosuspension
    • Authors: Jian Guan; Yeli Zhang; Qiaoyu Liu; Xin Zhang; Rina Chokshi; Shirui Mao
      Abstract: The objective of this study was to explore the feasibility of using alginate as a potential stabilizer of nanosuspension and elaborate the corresponding stabilization mechanism. Using lovastatin as a Biopharmaceutics Classification System (BCS) II drug model, alginate-stabilized nanosuspension was fabricated by the high-pressure homogenization method. The particle size, zeta potential, short-term stability, and dissolution behavior of the nanosuspension were characterized. Thereafter, the surface morphology, crystallinity, redispersability, and stability of the spray-dried nanosuspension were investigated. The spray-dried powder was further compressed into tablets via direct compression, and stressing test was carried out to investigate the stability of nanocrystal loaded tablets. It was demonstrated that alginate could stabilize nanocrystals by providing both electrostatic and steric stabilization, and the effective concentration was much lower than that of the commonly used stabilizers. Good redispersability was achieved after spray drying of the nanosuspension, and the existing state of lovastatin was not changed as indicated by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) studies. The stress test indicated that nanocrystal-loaded tablets possessed a favorable stability. In conclusion, alginate could be used as a potential stabilizer of nanosuspension with preferable stabilizing ability at a very low concentration either in liquid or in solid state.
      PubDate: 2017-05-23
      DOI: 10.1208/s12249-017-0801-6
  • Development and Evaluation of a Family of Human Face and Upper Airway
           Models for the Laboratory Testing of Orally Inhaled Products
    • Authors: Mark W. Nagel; Jason A. Suggett; Dominic P. Coppolo; Jolyon P. Mitchell
      Abstract: ABSTRACT Many orally inhaled products are supplied with a facemask instead of a mouthpiece, enabling aerosolized medication to be transferred from the inhaler to the lungs when the user lacks the capability to use a mouthpiece. Until recently, laboratory evaluation of an orally inhaled product-facemask was frequently undertaken by removing the facemask, treating the facemask adapter as being equivalent to a mouthpiece. Measurements of delivered drug mass were therefore subject to bias arising from the absence of dead volume, had the facemask been present. We have described the development of the Aerosol Delivery to an Anatomic Model (ADAM) infant, small child, and adult faces and upper airways, and their subsequent evaluation. Each model possesses physical features of appropriate size, and the soft tissues are also simulated. Rudimentary underlying bony structure is also present, because its purpose is only to provide support, enabling the mechanical response of the facial soft tissues when a facemask is applied to be realized. A realistic upper airway (nasopharynx for the infant model, naso- and oropharynx for the child and oropharynx for the adult models) is also incorporated, so that each model can be used to determine the mass of inhaled medication likely to penetrate as far as the lungs where therapy is intended to be applied. Measurements of the mass of pressurized metered-dose inhaler-delivered salbutamol at a filter distal to the upper airway of each model, simulating age-appropriate tidal breathing, were remarkably consistent, almost all being in the range 0.3 to 1.0 μg/kg across the model age ranges, when expressed as a fraction of body weight.
      PubDate: 2017-05-23
      DOI: 10.1208/s12249-017-0802-5
  • Formulation and In Vitro Characterization of Bioactive Mesoporous Silica
           with Doxorubicin and Metronidazole Intended for Bone Treatment and
    • Authors: Katarzyna Czarnobaj; Magdalena Prokopowicz; Wiesław Sawicki
      Abstract: ABSTRACT The purpose of this study was to evaluate the surface mineralization activity and in vitro drug behavior potential of two forms of mesoporous silica: powder and granulate. Ordered mesoporous SiO2 powder was synthesized by surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. The granulate was prepared using silica powder and ethyl cellulose as a binding agent. Metronidazole (MT)—an anti-inflammatory substance and doxorubicin hydrochloride (ChD)—an anti-cancer drug were chosen as drug models for delivery studies. The results of structural characteristic studies, utilizing transmission electron microscope (TEM) and scanning electron microscope (SEM) images, powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and nitrogen adsorption–desorption (BET) measurements, show that obtained materials have two-dimensional hexagonal p6mm symmetry, high specific surface area, narrow pore size, and a satisfactory mineralization behavior in the simulated body solution (SBF, pH = 7.4). The release rate of drugs depends upon the structural features of the drug molecules and the form of the carrier material. Of both the drugs analyzed, faster release was observed for small MT molecules characterized by weaker interactions with the carrier. In addition, the slower drug release was observed with granulate form due to increased diffusion barrier for drugs. Obtained results prove that the MT/ChD-loaded silica formulations could be attractive materials for filling bone defects and for local delivery systems.
      PubDate: 2017-05-22
      DOI: 10.1208/s12249-017-0804-3
  • Formulation and Evaluation of Naringenin Nanosuspensions for
           Bioavailability Enhancement
    • Authors: Sonia Gera; Sreekanth Talluri; Nagarjun Rangaraj; Sunitha Sampathi
      Abstract: The clinical potential of naringenin (NRG) is compromised due to its poor aqueous solubility and low oral bioavailability. The study is aimed at addressing these issues by means of naringenin nanosuspensions (NRG-NS) formulated using polyvinylpyrrolidone (PVP K-90) as stabiliser via antisolvent sonoprecipitation method. Optimisation of sonication time, drug concentration and stabilisers was done based on particle size. Characterisation of pure NRG and NRG-NS was carried out by scanning electron microscopy, differential scanning calorimetry (DSC), x-ray powder diffractometry (XRD) and Fourier transform infrared spectroscopy (FTIR). In vitro dissolution, intestinal absorption by non-everted rat intestinal sac model and in situ single pass intestinal perfusion techniques were performed for further investigation. Nanosuspensions prepared using PVP K-90 lead to minimum particle size (117 ± 5 nm) with zeta potential of −14.6 ± 5.6 mV. The particle size was affected by increasing sonication time, concentration of stabiliser and drug. Nanosizing process converted the crystalline drug into amorphous form as predicted from DSC and XRD patterns. FTIR demonstrated the formation of hydrogen bonds between drug and polymer. NRG-NS displayed a higher dissolution amount (91 ± 4.4% during 60 min) compared to NRG powder (42 ± 0.41%). The apparent and effective permeability of NRG-NS was increased as compared to the pure NRG. The in vivo pharmacokinetics demonstrated that the C max and AUC0–24 h values of NRG-NS were approximately 2- and 1.8-fold superior than the pure drug. Hence, overall results confirmed nanosuspensions as promising approach for NRG delivery with high absorption in gastrointestinal tract, improved dissolution and oral bioavailability.
      PubDate: 2017-05-22
      DOI: 10.1208/s12249-017-0790-5
  • Adsorption onto Mesoporous Silica Using Supercritical Fluid Technology
           Improves Dissolution Rate of Carbamazepine—a Poorly Soluble Compound
    • Authors: Aditya V. Gandhi; Priyanka Thipsay; Bharat Kirthivasan; Emilio Squillante
      Abstract: The purpose of this research was to design and characterize an immediate-release formulation of carbamazepine (CBZ), a poorly soluble anti-epileptic drug, using a porous silica carrier. Carbon dioxide in its supercritical state (2000 psi, 30–35°C) was used as an anti-solvent to precipitate CBZ onto two particle size variants of silica. Adsorption isotherms were used as a pre-formulation strategy to select optimum ratios of silica and CBZ. The obtained drug-silica formulations were characterized by dissolution studies, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). This formulation strategy resulted in a 2.4-fold improvement in dissolution rate when compared to pure drug after 30 min of dissolution testing. PXRD and DSC confirmed the amorphous nature of CBZ in the formulations as well as the differences in polymorphic forms of commercial and supercritical fluid-processed CBZ. Additionally, solid-state NMR spectroscopy showed that the spin-lattice relaxation time for bulk drug (without silica) was ∼7.5 times greater than that for silica-confined CBZ, implying that when CBZ was adsorbed onto mesoporous silica, it is structurally disordered and had higher structural mobility, a characteristic of amorphous solids. The mesoporous silica matrix prevented CBZ crystal growth by imposing spatial constraint on CBZ nuclei and hence resulted in faster dissolution compared to bulk solid drug. Adsorption onto mesoporous silica using supercritical fluid technology may be used as a novel formulation strategy for amorphization of poorly soluble compounds, in turn improving their dissolution rate.
      PubDate: 2017-05-22
      DOI: 10.1208/s12249-017-0784-3
  • Implementation of Quality by Design for Formulation of Rebamipide
           Gastro-retentive Tablet
    • Authors: Jung-Myung Ha; Jeong-Woong Seo; Su-Hyeon Kim; Ju-Young Kim; Chun-Woong Park; Yun-Seok Rhee; Eun-Seok Park
      Abstract: Abstract The purpose of the present study was to develop a rebamipide (RBM) gastro-retentive (GR) tablet by implementing quality by design (QbD). RBM GR tablets were prepared using a sublimation method. Quality target product profile (QTPP) and critical quality attributes (CQAs) of the RBM GR tablets were defined according to the preliminary studies. Factors affecting the CQAs were prioritized using failure mode and effects analysis (FMEA). Design space and optimum formulation were established through a mixture design. The validity of the design space was confirmed using runs within the area. The QTPP of the RBM GR tablets was the orally administered GR tablet containing 300 mg of RBM taken once daily. Based on the QTPP, dissolution rate, tablet friability, and floating property were chosen as CQAs. According to the risk assessment, the amount of sustained-release agent, sublimating material, and diluent showed high-risk priority number (RPN) values above 40. Based on the RPN, these factors were further investigated using mixture design methodology. Design space of formulations was depicted as an overlaid contour plot and the optimum formulation to satisfy the desired responses was obtained by determining the expected value of each response. The similarity factor (f2) of the release profile between predicted response and experimental response was 89.463, suggesting that two release profiles are similar. The validity of the design space was also confirmed. Consequently, we were able to develop the RBM GR tablets by implementing the QbD concept. These results provide useful information for development of tablet formulations using the QbD.
      PubDate: 2017-05-19
      DOI: 10.1208/s12249-017-0797-y
  • Synthesis, Comparison, and Optimization of a Humic Acid-Quat10
           Polyelectrolyte Complex by Complexation-Precipitation versus
    • Authors: Margaret Siyawamwaya; Yahya E. Choonara; Pradeep Kumar; Pierre P. D. Kondiah; Lisa C. du Toit; Viness Pillay
      Abstract: Abstract A novel humic acid and polyquaternium-10 polyelectrolyte complex (PEC) was synthesized utilizing two methods and the solubility and permeability of efavirenz (EFV) were established. Complexation-precipitation and extrusion-spheronization were used to synthesize and compare the drug-loaded PECs. The chemical integrity, thermo-mechanical differences, and morphology between the drug-loaded PECs produced by the two methods were assessed by attenuated total reflectance-Fourier transform infrared, differential scanning calorimetry, and SEM. The extent of drug solubilization was determined using the saturation solubility test while the biocompatibility of both PECs was confirmed by cytotoxicity studies on human adenocarcinoma cells (caco2). Bio-relevant media was used for the solubility and permeability analysis of the optimized PEC formulations for accurate assessment of formulation performance. Ritonavir (RTV) was loaded into the optimized formulation to further corroborate the impact of the PEC on the solubility and permeability properties of a poorly soluble and poorly permeable drug. The optimized EFV-loaded PEC and the RTV-loaded PEC exhibited 14.16 ± 2.81% and 4.39 ± 0.57% increase in solubility, respectively. Both PECs were compared to currently marketed formulations. Intestinal permeation results revealed an enhancement of 61.24 ± 6.92% for EFV and 38.78 ± 0.50% for RTV. Although both fabrication methods produced PECs that enhanced the solubility and permeability of the model Biopharmaceutics Classification System Class II and IV drugs, extrusion-spheronization was selected as most optimal based on the higher solubility and permeability improvement and the impact on caco2 cell viability.
      PubDate: 2017-05-18
      DOI: 10.1208/s12249-017-0803-4
  • Co-spray Drying with HPMC as a Platform to Improve Direct Compaction
           Properties of Various Tablet Fillers
    • Authors: JinZhi Li; LiJie Zhao; Xiao Lin; Lan Shen; Yi Feng
      Abstract: Abstract Many commonly used tablet fillers are not suitable for direct compaction process due to insufficient properties, mainly of flowability and compactability. This work therefore aimed to use co-spray drying with HPMC as a platform to improve direct compaction properties of various tablet fillers. Starch, calcium hydrogen phosphate dihydrate (DCPD), and mannitol were chosen as a representative of three types of commonly used fillers (i.e. organic macromolecules, water-insoluble inorganic salts, and water-soluble small molecular carbohydrates), respectively. The five-level central composite design-response surface methodology was used (i) to investigate the effects of HPMC level and solid content of the feed on various powder, tableting, and tablet properties of composite excipients, and (ii) to optimize the composition. The results showed that the impacts of the two factors on various properties of composite excipients showed great similarity, despite of significantly different primary properties of the parent fillers, and the HPMC level was the main contributor to the majority of the impacts. An increase in HPMC level significantly improved tablet tensile strength and various tableting parameters. For all the three fillers, their optimized composite excipients provided by the established models showed excellent performances as predicted. The platform suggested is confirmed to be effective and promising.
      PubDate: 2017-05-18
      DOI: 10.1208/s12249-017-0794-1
  • Preparation of Essential Oil-Based Microemulsions for Improving the
           Solubility, pH Stability, Photostability, and Skin Permeation of Quercetin
    • Authors: Xia Lv; Tiantian Liu; Huipeng Ma; Yan Tian; Lei Li; Zhen Li; Meng Gao; Jianbin Zhang; Zeyao Tang
      Abstract: Abstract Quercetin can bring many benefits to skin based on its various bioactivities. However, the therapeutic effect of quercetin is limited due to the poor water solubility, pH instability, light instability, and skin permeation. The aim of the present work was applying essential oil-based microemulsions to improve the solubility, pH stability, photostability, and skin permeation of quercetin for topical application. Peppermint oil (PO-ME), clove oil (CO-ME), and rosemary oil (RMO-ME) were selected as model essential oils. Microemulsions composed of Cremophor EL/1,2-propanediol/essential oils (47:23:30, w/w) were selected as model formulations, based on the pseudo-ternary phase diagram and the characterizations. In the solubility study, the solubility of quercetin was improved dozens of times by microemulsions. Quercetin was found instable under alkaline condition, with 50% degraded in the solution of pH 13. However, PO-ME, CO-ME, and RMO-ME could protect quercetin from the hydroxide ions, with 47, 9, and 12% of quercetin degraded. In the photostability study, the essential oil-based microemulsions showed the capability of protecting quercetin from degradation under UV radiation. Where more than 67% of quercetin was degraded in aqueous solution, while less than 7% of quercetin degraded in microemulsions. At last, the in vitro skin permeation study showed that the essential oil-based microemulsions could enhance the permeation capacity of quercetin by 2.5–3 times compared to the aqueous solution. Hence, the prepared essential oil microemulsions could improve the solubility, pH stability, photostability, and skin permeation of quercetin, which will be beneficial for its topical application.
      PubDate: 2017-05-17
      DOI: 10.1208/s12249-017-0798-x
  • Optimized Mucoadhesive Coated Niosomes as a Sustained Oral Delivery System
           of Famotidine
    • Authors: AL-Zahraa M. Khalifa; Bazigha K. Abdul Rasool
      Abstract: Abstract The objective of this study is to develop an oral formulation of famotidine niosomes coated with a mucoadhesive polymer, chitosan. Famotidine (FMT) has low oral bioavailability of 40–45% and short half-life between 2.5 to 4 h. Famotidine is classified as class IV in BCS because of its low aqueous solubility (0.1% w/v) and low permeability. Thus, FMT was loaded to the bioadhesive coated niosomes to improve its solubility, enhance its oral bioavailability, and sustain FMT release pattern. Different formulations were prepared by thin-film hydration method and characterized in terms of entrapment efficiency, morphological features, vesicle size, and zeta potential. In vitro release and ex vivo permeability of famotidine from the formulations were evaluated. The optimized formula was coated with chitosan and its mucoadhesion and stability in bile salt was tested. The optimized formula showed a high entrapment efficiency of 74%, as well sustained the in vitro release of FMT in the simulated gastric medium and enhanced its permeation through an excised goat’s intestinal membrane by 1.4 fold in comparison to FMT control suspension. The mucoadhesive coated formula exhibited a significantly higher (p < 0.05) mucoadhesive efficiency and more stability in the bile salt as compared to the uncoated formula. Therefore, it could be considered as an efficient delivery system to maintain the prolonged release of FMT and improve its oral bioavailability.
      PubDate: 2017-05-17
      DOI: 10.1208/s12249-017-0780-7
  • Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization,
           and Hepatoprotective and Toxicity Evaluation
    • Authors: Amira E. El-Nahas; Ahmed N. Allam; Doaa A. Abdelmonsif; Amal H. El-Kamel
      Abstract: Abstract The objectives of this study were to formulate, characterize silymarin-loaded Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic effects after oral administration. SNPs were prepared by nanoprecipitation technique and were evaluated for particle size, entrapment efficiency, TEM, solid-state characterization, and in vitro drug release. The hepatoprotective activity was evaluated after oral administration of selected SNPs in carbon tetrachloride-intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed. The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after 12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state and absence of chemical interaction. The hepatoprotective evaluation of the selected SNPs in CCl4-intoxicated rats revealed significant improvement in the activities of different biochemical parameters (P ≤ 0.01) compared to the marketed product. The histopathological studies suggested that the selected SNPs produced better hepatoprotective effect in CCl4-intoxicated rats compared with the commercially marketed product. Toxicity study revealed no evident toxic effect for blank or silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The obtained results suggested that the selected SNPs were safe and potentially offered enhancement in the pharmacological hepatoprotective properties of silymarin.
      PubDate: 2017-05-17
      DOI: 10.1208/s12249-017-0799-9
  • Optimization of Adhesive Pastes for Dental Caries Prevention
    • Authors: Patteera Sodata; Apa Juntavee; Niwut Juntavee; Jomjai Peerapattana
      Abstract: Abstract Dental caries prevention products available on the market contain only remineralizing agents or antibacterial agents. This study aimed to develop adhesive pastes containing calcium phosphate and α-mangostin for dental caries prevention using the optimization technique. Calcium phosphate was used as a remineralizing agent, and extracted α-mangostin was used as an antibacterial agent. The effect of the independent variables, which were fumed silica, Eudragit® EPO, polyethylene glycol, and ethyl alcohol, on the responses was investigated. The drying time, erosion rate, calcium release rate, and α-mangostin release rate were established as the measured responses. An equation and a model of the relationship were constructed. An optimal formulation was obtained, and its effect on dental caries prevention was investigated using the pH-cycling model. The quadratic equation revealed that the drying time, calcium release rate, and α-mangostin release rate tended to decrease when increasing the fumed silica and decreasing other factors. The erosion rate tended to increase when decreasing Eudragit® EPO and increasing other factors. The observed responses of the optimal adhesive pastes were not significantly different from the predicted responses. This result demonstrated that optimization is an efficient technique in the formulation development of the adhesive pastes. In addition, the optimal adhesive pastes could enhance acid resistance activity to the tooth enamel.
      PubDate: 2017-05-17
      DOI: 10.1208/s12249-017-0750-0
  • Self-emulsification of Lipidic Drug Delivery System in Pure Water and in
           Concentrated Glycerol Solution
    • Authors: Carole Planchette; Annalisa Mercuri; Lorenzo Arcangeli; Manfred Kriechbaum; Peter Laggner
      Abstract: Abstract Self-emulsifying drug delivery systems (SEDDS), often intended for oral delivery, are normally explored in biorelevant aqueous media. The high complexity of these multi-component systems leaves the understanding of self-emulsification poor, hindering formulation rationalization. In this work, we aimed to fill this gap by studying the effects of glycerol on the self-emulsification of a ternary component formulation made of 20% w/w Tween 80, 15% w/w Span 80, and 65% w/w Captex 300 Low C6. The behavior of SEDDS in pure water and a binary mixture of water and glycerol (58.8% w/w) were investigated by optical microscopy, SAXS (small angle X-ray scattering), dynamic light scattering, and surface tension measurements. The presence of glycerol, at 58.8% w/w, altered the self-emulsification behavior by suppressing the formation of lamellar structures observed in the presence of water, reducing the droplet mean diameter from 0.2 to 0.1 μm and changing the mechanism of self-emulsification. As co-surfactant, glycerol may intercalate within the polyoxyethylene chains of the surfactant at the palisade layer, increasing the interface flexibility and expanding it. Since no free water is available at the investigated glycerol concentration, glycerol, which is also a co-solvent, may additionally modify long-range interactions by reducing Van-der-Waals attractions or giving rise to repulsive surface-solvent mediated forces of entropic origin. These effects could be exploited to rationalize SEDDS formulations, widening their use within the pharmaceutical industry.
      PubDate: 2017-05-17
      DOI: 10.1208/s12249-017-0785-2
  • Development and Characterization of Magnetite/Poly(butylcyanoacrylate)
           Nanoparticles for Magnetic Targeted Delivery of Cancer Drugs
    • Authors: Margarita López-Viota; Mazen M. El-Hammadi; Laura Cabeza; José Prados; Consolación Melguizo; M. Adolfina Ruiz Martinez; José L. Arias; Ángel V. Delgado
      Abstract: Abstract A great attention is presently paid to the design of drug delivery vehicles based on surface-modified magnetic nanoparticles. They can, in principle, be directed to a desired target area for releasing their drug payload, a process triggered by pH, temperature, radiation, or even magnetic field. To this, the possibility of forming part of diagnostic tools by enhanced magnetic resonance imaging or that of further treatment by magnetic hyperthermia can be added. Bare particles are rapidly eliminated from the bloodstream by the phagocyte mononuclear system, leading to short biological half-life. It is hence required to coat them in order to increase their biocompatibility and facilitate the drug incorporation. In this work, magnetite nanoparticles were coated with poly(butylcyanoacrylate) (PBCA) manufactured and characterized with regard to their physical properties and their suitability as a platform for magnetically controlled drug delivery. The average diameter of magnetite and core–shell nanoparticles was 97 ± 19 and 140 ± 20 nm, respectively. Infrared analysis, electrophoretic mobility, surface thermodynamics analysis, and X-ray diffraction all confirmed that the magnetic particles were sufficiently covered by the polymer in the composite nanoparticles. In addition, assays using normal (CCD-18 and MCF-10A) and tumoral (T-84 and MCF-7) cell lines derived from colon and breast tissue, respectively, demonstrated that nanocomposites have low or negligible cytotoxicity. It is concluded that PBCA-coated magnetite core–shell nanoparticles represent a remarkable promise as a platform for magnetically controlled drug delivery.
      PubDate: 2017-05-15
      DOI: 10.1208/s12249-017-0792-3
  • Hydroxyurea-Lactose Interaction Study: In Silico and In Vitro Evaluation
    • Authors: Kunal B. Bachchhao; R. R. Patil; C. R. Patil; Dipak D Patil
      Abstract: Abstract The Maillard reaction between hydroxyurea (a primary amine-containing drug) and lactose (used as an excipient) was explored. The adduct of these compounds was synthesized by heating hydroxyurea with lactose monohydrate at 60 °C in borate buffer (pH 9.2) for 12 h. Synthesis of the adduct was confirmed using UV–visible spectroscopy and Fourier transform infrared, differential scanning calorimetry, high-pressure liquid chromatography, and liquid chromatography-mass spectrometry studies. An in silico investigation of how the adduct formation affected the interactions of hydroxyurea with its biological target oxyhemoglobin, to which it binds to generate nitric oxide and regulates fetal hemoglobin synthesis, was carried out. The in silico evaluations were complemented by an in vitro assay of the anti-sickling activity. Co-incubation of hydroxyurea with deoxygenated blood samples reduced the percentage of sickled cells from 38% to 12 ± 1.6%, whereas the percentage of sickled cells in samples treated with the adduct was 17 ± 1.2%. This indicated loss of anti-sickling activity in the case of the adduct. This study confirmed that hydroxyurea can participate in a Maillard reaction if lactose is used as a diluent. Although an extended study at environmentally feasible temperatures was not carried out in the present investigation, the partial loss of the anti-sickling activity of hydroxyurea was investigated along with the in silico drug–target interactions. The results indicated that the use of lactose in hydroxyurea formulations needs urgent reconsideration and that lactose must be replaced by other diluents that do not form Maillard adducts.
      PubDate: 2017-05-12
      DOI: 10.1208/s12249-017-0791-4
  • In Vivo Anticancer Efficacy and Toxicity Studies of a Novel Polymer
           Conjugate N -Acetyl Glucosamine (NAG)–PEG–Doxorubicin for Targeted
           Cancer Therapy
    • Authors: Smita Pawar; Ketan Mahajan; Pradeep Vavia
      Abstract: Abstract A novel polymer–drug conjugate, polyethylene glycol–N-(acetyl)-glucosamine–doxorubicin (PEG-NAG-DOX) was evaluated in this study for its in vivo potential for treatment of tumours demonstrating improved efficacy and reduced toxicity. The proposed polymer–drug conjugate comprised of polyethylene glycol–maleimide (mPEG-MAL, 30000 Da) as a carrier, doxorubicin (DOX) as an anticancer drug and N-acetyl glucosamine (NAG) as a targeting moiety as well as penetration enhancer. Doxorubicin has a potent and promising anticancer activity; however, severe cardiotoxicity limits its application in cancer treatment. By modifying DOX in PEG-NAG-DOX prodrug conjugate, we aimed to eliminate this limitation. In vivo anticancer efficacy of the conjugate was evaluated using BDF mice-induced skin melanoma model by i.v. administration of DOX conjugates. Anticancer efficacy studies were done by comparing tumour volume, body weight, organ index and percent survival rate of the animals. Tumour suppression achieved by PEG-NAG-DOX at the cumulative dose of 7.5 mg/kg was two-fold better than that achieved by DOX solution. Also, the survival rate for PEG-NAG-DOX conjugate was >70% as compared to <50% survival rate for DOX solution. In addition, toxicity studies and histopathological studies revealed that while maintaining its cytotoxicity towards tumour cells, PEG-NAG-DOX conjugate showed no toxicities to major organs. Therefore, PEG-NAG-DOX conjugate can be suggested as a desirable candidate for targeted cancer therapy.
      PubDate: 2017-05-11
      DOI: 10.1208/s12249-017-0787-0
  • Dual-Prevention for UV-Induced Skin Damage: Incorporation of
           Melatonin-Loaded Elastic Niosomes into Octyl Methoxycinnamate Pickering
    • Authors: Gulcin Arslan Azizoglu; Sakine Tuncay Tanriverdi; Fadime Aydin Kose; Petek Ballar Kirmizibayrak; Ozgen Ozer
      Abstract: Abstract Incorporation of antioxidants into sunscreens is a logical approach, yet co-delivery of them with UV filters is a challenge. Here, we purposed a combination therapy, in which the chemical UV filter, octyl methoxycinnamate, was accumulated on upper skin while the antioxidant, melatonin, can penetrate deeper layers to show its effects. Melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion were prepared separately. Lyophilized elastic niosomes were dispersed into the Pickering emulsion to prepare the proposed combination formulation. The characterization studies of the formulations revealed that elastic niosomes can be prepared with tunable nanometer sizes, whereas Pickering emulsions can encapsulate the UV filter in micrometer-sized droplets. Melatonin-loaded elastic niosomes prepared with Tween80/Span80 mixture were 146 nm with a PI of 0.438, and 58.42% entrapment efficiency was achieved. The mean diameter size of the combination formulation was 27.8 μm. Ex vivo permeation studies revealed that 7.40% of octyl methoxycinnamate and 58% of melatonin were permeated through the rat skin while 27.6% octyl methoxycinnamate and 37% of melatonin accumulated in the skin after 24 h. Cell culture studies with real-time cell analyzer showed that the proposed formulation consist of melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion had no negative effect on the cell proliferation and viability. According to α,α-diphenyl-β-picrylhydrazyl free radical scavenging method, the proposed formulation showed as high antioxidant activity as melatonin itself. It is concluded that the proposed formulation would be a promising dual therapy for UV-induced skin damage with co-delivery strategy.
      PubDate: 2017-05-10
      DOI: 10.1208/s12249-017-0786-1
  • Efavirenz Dissolution Enhancement IV—Antisolvent Nanocrystallization by
           Sonication, Physical Stability, and Dissolution
    • Authors: Gabriela Julianelly Sartori; Livia Deris Prado; Helvécio Vinícius Antunes Rocha
      Abstract: Abstract Efavirenz is a fundamental drug in the HIV therapy; however, it has a low bioavailability due to low water solubility. Particle nanonization should enhance its dissolution and therefore its bioavailability. Nanocrystallization is a promising technique for preparing drug nanocrystals. A solution containing efavirenz (EFV) and methanol was added to an aqueous solution of particle stabilizers, under sonication. The adequate polymer stabilizer and its concentration and drug load were evaluated. Particle size and zeta potential of suspensions were measured. Nanosuspensions were freeze-dried and the resulting powder was characterized by some techniques, with special attention to dissolution. Particle size and zeta potential analysis showed that HMPC and PVP were the most suitable polymers. All samples prepared with these stabilizers had nanosized particles and proper zeta potential; however, sedimentation and particle growth were detected with Turbiscan™. Time-related destabilization occurred when the lowest polymer concentration of 20% was used. SEM analysis of the dried powder shows film formation for suspensions with 40% of polymer and particle aggregation in samples with less polymer. Dissolution profiles of samples were higher than EFV raw material, although the lower the polymer concentration, the higher the dissolution.
      PubDate: 2017-05-10
      DOI: 10.1208/s12249-017-0781-6
  • Bio-shielding In Situ Forming Gels (BSIFG) Loaded With Lipospheres for
           Depot Injection of Quetiapine Fumarate: In Vitro and In Vivo Evaluation
    • Authors: Mustafa M. Abo Elela; Nermeen A. ElKasabgy; Emad B. Basalious
      Abstract: Abstract Quetiapine fumarate (QF), an anti-schizophrenic drug, suffers from rapid elimination and poor bioavailability due to extensive first-pass effect. Intramuscularly (IM) injected lipospheres were designed to enhance the drug’s bioavailability and extend its release. A central composite design was applied to optimize the liposphere preparation by a melt dispersion technique using Compritol® 888 ATO or glyceryl tristearate as lipid component and polyvinyl alcohol as surfactant. Lipospheres were evaluated for their particle size, entrapment efficiency, and in vitro release. The optimized QF lipospheres were prepared using a Compritol® 888 ATO fraction of 18.88% in the drug/lipid mixture under a stirring rate of 3979 rpm. The optimized lipospheres were loaded into a thermoresponsive in situ forming gel (TRIFG) and a liquid crystalline in situ forming gel (LCIFG) to prevent in vivo degradation by lipases. The loaded gels were re-evaluated for their in vitro release and injectability. Bioavailability of QF from liposphere suspension and bio-shielding in situ gels loaded with QF lipospheres were assessed in rabbits compared to drug suspension. Results revealed that the AUC0–72 obtained from the liposphere-loaded TRIFG was ∼3-fold higher than that obtained from the aqueous drug suspension indicating the bio-shielding effect of Poloxamer® 407 gel to inhibit the biodegradation of the lipospheres prolonging the residence of the drug in the muscle for higher absorption. Our results propose that bio-shielding in situ Poloxamer® 407 gels loaded with lipospheres is promising for the development of IM depot injection of drugs having extensive first-pass metabolism and rapid elimination.
      PubDate: 2017-05-10
      DOI: 10.1208/s12249-017-0789-y
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