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Showing 1 - 200 of 2355 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: 20, SJR: 1.192, h-index: 74)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6, 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: 11, 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: 7, SJR: 1.818, h-index: 22)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.524, h-index: 32)
Acta Mathematica     Hybrid Journal   (Followers: 11, 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: 19, SJR: 0.898, h-index: 52)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, 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)
Activitas Nervosa Superior     Hybrid Journal  
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: 15, 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: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 52, SJR: 1.113, h-index: 14)
Advances in Gerontology     Partially Free   (Followers: 9, 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: 9, SJR: 0.821, h-index: 49)
African Archaeological Review     Hybrid Journal   (Followers: 15, 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: 19, 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: 6, 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: 3, 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: 6, 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: 12, SJR: 0.18, h-index: 13)
Amino Acids     Hybrid Journal   (Followers: 8, 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: 3, 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: 16, 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: 11, 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: 14, 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 Ophthalmology     Hybrid Journal   (Followers: 9)
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 Cancer Research     Open Access  
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.361, h-index: 21)
Applied Composite Materials     Hybrid Journal   (Followers: 47, 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: 12, 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: 60, 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: 8, 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: 17, 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: 53, 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 and Museum Informatics     Hybrid Journal   (Followers: 118)
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: 17, 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: 9, SJR: 0.288, h-index: 25)
Artificial Intelligence Review     Hybrid Journal   (Followers: 14, SJR: 0.948, h-index: 48)
Artificial Life and Robotics     Hybrid Journal   (Followers: 7, 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: 12, 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  

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Journal Cover AAPS PharmSciTech
  [SJR: 0.718]   [H-I: 54]   [6 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1530-9932
   Published by Springer-Verlag Homepage  [2355 journals]
  • Study of the Transformations of Micro/Nano-crystalline Acetaminophen
           Polymorphs in Drug-Polymer Binary Mixtures
    • Authors: Mohammed Maniruzzaman; Matthew Lam; Carlos Molina; Ali Nokhodchi
      Pages: 1428 - 1437
      Abstract: This study elucidates the physical properties of sono-crystallised micro/nano-sized acetaminophen/paracetamol (PMOL) and monitors its possible transformation from polymorphic form I (monoclinic) to form II (orthorhombic). Hydrophilic Plasdone® S630 copovidone (S630), N-vinyl-2-pyrrolidone and vinyl acetate copolymer, and methacrylate-based cationic copolymer, Eudragit® EPO (EPO), were used as polymeric carriers to prepare drug/polymer binary mixtures. Commercially available PMOL was crystallised under ultra sound sonication to produce micro/nano-sized (0.2–10 microns) crystals in monoclinic form. Homogeneous binary blends of drug-polymer mixtures at various drug concentrations were obtained via a thorough mixing. The analysis conducted via the single X-ray crystallography determined the detailed structure of the crystallised PMOL in its monoclinic form. The solid state and the morphology analyses of the PMOL in the binary blends evaluated via differential scanning calorimetry (DSC), modulated temperature DSC (MTDSC), scanning electron microscopy (SEM) and hot stage microscopy (HSM) revealed the crystalline existence of the drug within the amorphous polymeric matrices. The application of temperature controlled X-ray diffraction (VTXRPD) to study the polymorphism of PMOL showed that the most stable form I (monoclinic) was altered to its less stable form II (orthorhombic) at high temperature (>112°C) in the binary blends regardless of the drug amount. Thus, VTXRD was used as a useful tool to monitor polymorphic transformations of crystalline drug (e.g. PMOL) to assess their thermal stability in terms of pharmaceutical product development and research.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0596-x
      Issue No: Vol. 18, No. 5 (2017)
  • Development and Optimisation of Spironolactone Nanoparticles for Enhanced
           Dissolution Rates and Stability
    • Authors: H. R. Kelidari; M. Saeedi; J. Akbari; K. Morteza-semnani; H. Valizadeh; Mohammed Maniruzzaman; Ali Farmoudeh; Ali Nokhodchi
      Pages: 1469 - 1474
      Abstract: Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0621-0
      Issue No: Vol. 18, No. 5 (2017)
  • Lidocaine-loaded fish scale-nanocellulose biopolymer composite
    • Authors: Pangkhi Medhi; Ololade Olatunji; Atul Nayak; Chandra Teja Uppuluri; Richard T. Olsson; Buchi N. Nalluri; Diganta B. Das
      Pages: 1488 - 1494
      Abstract: Microneedle (MN) technology has emerged as an effective drug delivery system, and it has tremendous potential as a patient friendly substitute for conventional methods for transdermal drug delivery (TDD). In this paper, we report on the preparation of lidocaine-loaded biodegradable microneedles, which are manufactured from fish scale-derived collagen. Lidocaine, a common tissue numbing anaesthetic, is loaded in these microneedles with an aim of delivering the drug with controlled skin permeation. Evaluation of lidocaine permeation in porcine skin has been successfully performed using Franz diffusion cell (FDC) which has shown that the drug permeation rate increases from 2.5 to 7.5% w/w after 36 h and pseudo steady state profile is observed from 5.0 to 10.0% w/w lidocaine-loaded microneedle. Swelling experiments have suggested that the microneedles have negligible swellability which implies that the patch would stick to the tissue when inserted. The experiments on MN dissolution have depicted that the lidocaine loaded in the patch is lower than the theoretical loading, which is expected as there can be losses of the drug during initial process manufacture.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-017-0758-5
      Issue No: Vol. 18, No. 5 (2017)
  • Preparation and Characterization of the Sulfobutylether-β-Cyclodextrin
           Inclusion Complex of Amiodarone Hydrochloride with Enhanced Oral
           Bioavailability in Fasted State
    • Authors: Dandan Wang; Guoguang Chen; Lili Ren
      Pages: 1526 - 1535
      Abstract: Amiodarone hydrochloride (AMD) is used in the treatment of a wide range of cardiac tachyarrhythmias, including both ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT). The objectives of this study were to improve the solubility and bioavailability in fasted state and to reduce the food effect of AMD by producing its inclusion complex with sulfobutylether-β-cyclodextrin (SBE-β-CD). The complex was prepared through a saturated water solution combined with the freeze-drying method and then characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. The solubilities of AMD and its complex were 0.35 and 68.62 mg/mL, respectively, and the value of the inclusion complex was significantly improved by 196-fold compared with the solubility of free AMD. The dissolution of the AMD-SBE-β-CD inclusion complex in four different dissolution media was larger than that of the commercial product. The cumulative dissolution was more than 85% in water, pH 4.5 NaAc-HAC buffer, and pH 1.2 HCl aqueous solution. Moreover, the pharmacokinetic study found that the C max, AUC(0–t), and AUC(0–∞) of the AMI-SBE-β-CD inclusion complex had no significant difference in fasted and fed state, which indicated that the absorption of the AMI-SBE-β-CD inclusion complex in fasted state was increased and not affected by food.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0646-4
      Issue No: Vol. 18, No. 5 (2017)
  • The Serum-Resistant Transfection Evaluation and Long-Term Stability of
           Gene Delivery Dry Powder Based on Mesoporous Silica Nanoparticles and
           Polyethyleneimine by Freezing-Drying
    • Authors: Xiaoxu Zhang; Jianpan Zhang; Guilan Quan; Pianpian Yang; Xin Pan; Chuanbin Wu
      Pages: 1536 - 1543
      Abstract: Mesoporous silica nanoparticles (MSNs) with large surface area, tunable pore size, and low toxicity can act as suitable vehicles for drug and gene delivery. An MSN/DNA/PEI complex delivery system was prepared by using MSNs to hold plasmid DNA coated with polyethyleneimine (PEI), and the dry powder formulation was produced by freeze-drying with trehalose as lyoprotectant. The MSN/DNA/PEI complexes successfully enhanced the gene expression with about 1.5-fold higher efficiency as compared with the control, and even better effects and lower toxicity were achieved at lower content of PEI. Also, this gene delivery system showed nearly sixfold higher efficiency in the serum-containing condition than the control, so further application of these vehicles in vivo is highly appreciated. Besides, the trehalose containing lyophilized formulation could hold the availability for at least 4 months of storing at room temperature, presenting the potential for industrial production and transportation of gene therapy.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0617-9
      Issue No: Vol. 18, No. 5 (2017)
  • Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release
           Behavior Studied by Imaging and Computational Modeling
    • Authors: María Dolores Campiñez; Isidoro Caraballo; Maxim Puchkov; Martin Kuentz
      Pages: 1544 - 1553
      Abstract: The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0613-0
      Issue No: Vol. 18, No. 5 (2017)
  • Analytical Characterization of an Oil-in-Water Adjuvant Emulsion
    • Authors: Jenny Sun; Richard L. Remmele; Gautam Sanyal
      Pages: 1595 - 1604
      Abstract: Adjuvants are typically used in subunit vaccine formulations to enhance immune responses elicited by individual antigens. Physical chemical characterization of novel adjuvants is an important step in ensuring their effective use in vaccine formulations. This paper reports application of a panel of quantitative assays developed to analyze and characterize an oil-in-water adjuvant emulsion, which contains glucopyranosyl lipid A (GLA) and is a squalene-based emulsion. GLA is a fully synthetic analogue of monophosphoryl lipid A, which is a Toll-like receptor type 4 agonist and an FDA-approved adjuvant. The GLA-stable emulsion (GLA-SE) is currently being used for a respiratory syncytial virus vaccine in a phase 2 clinical trial. GLA was quantitated using reverse-phased high-performance liquid chromatography (RP-HPLC) coupled to a mass spectrometric detector, achieving higher assay sensitivity than the charged aerosol detection routinely used. Quantitation of the excipients of GLA-SE, including squalene, egg phosphatidyl choline, and Poloxamer 188, was achieved using a simple and rapid RP-HPLC method with evaporative light scattering detection, eliminating chemical derivatization typically required for these chromophore-lacking compounds. DL-α-tocopherol, the antioxidant of the GLA-SE, was quantitated using a RP-HPLC method with conventional UV detection. The experimental results compared well with values expected for these compounds based on targeted composition of the adjuvant. The assays were applied to identify degradation of individual components in a GLA-SE sample that degraded into distinct aqueous and oil phases. The methods developed and reported here are effective tools in monitoring physicochemical integrity of the adjuvant, as well as in formulation studies.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0626-8
      Issue No: Vol. 18, No. 5 (2017)
  • Evaluation of the Safety, Cell Migration, and Mucoadhesive Properties of a
           Mucoadhesive Polymer Blend in Human Oral Mucosa
    • Authors: Guiyun Song; Daniel Banov; August S. Bassani; Benigno C. Valdez
      Pages: 1617 - 1623
      Abstract: The efficacy of active pharmaceutical ingredients (API) in compounded medications for oral mucosa greatly depends on the composition of the base. Here, we assessed the safety, facilitation of cell migration, and mucoadhesive properties of a newly developed mucoadhesive polymer blend (MPB) which contains pullulan, tamarindus indica polysaccharide, and sodium hyaluronate. No cell death was observed when human oral keratinocyte (HOK) and fibroblast (HOrF) cells were exposed to 1% MPB for 24 h. Epithelial cells in a 3D buccal tissue model (EpiOral) were unaffected when exposed to 50% MPB for 20 h whereas 1% Triton X-100 killed 93% cells after 4.5 h. The expressions of cytokines IL1α and IL1β and cell proliferation markers PCNA, CYCLIN A, and CYCLIN D1 in EpiOral tissue did not increase suggesting that MPB is neither an irritant nor a mitogen. Markers of apoptosis such as cleavage of CASPASES 8/9, upregulation of pro-apoptosis NOXA protein, and downregulation of anti-apoptosis XIAP protein were observed in Triton X-100-treated cells but not in cells exposed to MPB. The migration of HOK and HOrF cells was stimulated by MPB, and the expression of E-CADHERIN in the EpiOral tissues was unaffected. Moreover, MPB showed stronger mucoadhesion on the human EpiOral tissue model compared with a reference product. We conclude that MPB can safely deliver API within the oral mucosa, facilitate cell migration, and may increase drug efficacy through its strong mucoadhesive property.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0630-z
      Issue No: Vol. 18, No. 5 (2017)
  • Accelerated Stability Modeling for Peptides: a Case Study with Bacitracin
    • Authors: Robin Waterman; Jennifer Lewis; Kenneth C. Waterman
      Pages: 1692 - 1698
      Abstract: The Accelerated Stability Assessment Program (ASAP) was applied for the first time to a peptide, the antibiotic active pharmaceutical ingredient bacitracin. Bacitracin and its complex with zinc were exposed to temperature and relative humidity conditions from 50 to 80°C and from 0 to 63% for up to 21 days. High-performance liquid chromatography was used to analyze the stressed samples for both degradant formation and loss of the active (bacitracin A) and two inactive isoforms, with identities confirmed by mass spectrometry. These data were then analyzed using a humidity-corrected Arrhenius equation and isoconversion approach to create a shelf-life predicting model for typical storage conditions. Model fitting was found to be good with low residuals in both temperature and relative humidity axes for all parameters examined. The generated model’s predictions for both the native and zinc complex of bacitracin for both formation of the major degradation product (F) and loss of the active isoform (A) were consistent with longer-term measured values at 30°C/53%RH and 40°C/75%RH, validating this approach for accelerating the determination of long-term stability of a peptide.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0635-7
      Issue No: Vol. 18, No. 5 (2017)
  • Aerodynamic Droplet Stream Expansion for the Production of Spray
           Freeze-Dried Powders
    • Authors: Stefan Wanning; Richard Süverkrüp; Alf Lamprecht
      Pages: 1760 - 1769
      Abstract: In spray freeze-srying (SFD), a solution is sprayed into a refrigerant medium, frozen, and subsequently sublimation dried, which allows the production of flowable lyophilized powders. SFD allows commonly freeze-dried active pharmaceutical ingredients (e.g., proteins and peptides) to be delivered using new applications such as needle-free injection and nasal or pulmonary drug delivery. In this study, a droplet stream was injected into a vortex of cold gas in order to reduce the risk of droplet collisions and therefore droplet growth before congelation, which adversely affects the particle size distribution. Droplets with initial diameters of about 40–50 μm were frozen quickly in a swirl tube at temperatures around −75°C and volumetric gas flow rates between 17 and 34 L/min. Preliminary studies that were focused on the evaluation of spray cone footprints were performed prior to SFD. A 23 factorial design with a model solution of mannitol (1.5% m/V) and maltodextrin (1.5% m/V) was used to create flowable, low density (0.01–0.03 g/cm3) spherical lyophilisate powders. Mean particle diameter sizes of the highly porous particles ranged between 49.8 ± 6.6 and 88.3 ± 5.5 μm. Under optimal conditions, the mean particle size was reduced from 160 to 50 μm (decrease of volume by 96%) compared to non-expanded streams, whereas the SPAN value did not change significantly. This method is suitable for the production of lyophilized powders with small particle sizes and narrow particle size distributions, which is highly interesting for needle-free injection or nasal delivery of proteins and peptides.
      PubDate: 2017-07-01
      DOI: 10.1208/s12249-016-0648-2
      Issue No: Vol. 18, No. 5 (2017)
  • Enhancing the Solubility of Fenofibrate by Nanocrystal Formation and
    • Authors: Raj Kumar; Prem Felix Siril
      Abstract: Development of techniques to enhance bioavailability of drugs having poor water solubility is a big challenge for pharmaceutical industry. Solubility can be enhanced by particle size reduction and encapsulation using hydrophilic polymers. Fenofibrate (FF) is a drug for regulating lipids. Multi-fold enhancement in solubility of FF has been achieved by nanocrystal formation in the present study. Nanoparticles were prepared by an evaporation-assisted solvent–antisolvent interaction (EASAI) approach. Water-soluble polymers, viz. polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC), were used to encapsulate and thus control the particle size of FF nanocrystals. Spherical particles having average particle size well below 30 nm could be prepared under optimum conditions. Almost complete release of the drug molecules from the polymer-stabilized nanocrystals within 2 h was clearly evident from the in vitro drug release studies. Infrared (FTIR) spectroscopy indicated the absence of solvent impurities and any strong interaction between the drug and stabilizers. The polymorphic form of raw-FF was retained in the nanoparticles as per the X-ray diffraction (XRD) patterns. Lower crystallinity of the nanoformulated samples compared to raw-FF was confirmed by differential scanning calorimetric (DSC) studies.
      PubDate: 2017-07-12
      DOI: 10.1208/s12249-017-0840-z
  • Tamibarotene-Loaded PLGA Microspheres for Intratumoral Injection
           Administration: Preparation and Evaluation
    • Authors: Liu Tian; Jinhua Gao; Zhenlei Yang; Zhihua Zhang; Guihua Huang
      Abstract: Tamibarotene (Am80) has good curative effect on advanced hepatocellular carcinoma (HCC). To improve the therapeutic efficacy furtherly, we prepared tamibarotene-loaded PLGA microspheres (Am80-PLGA-MS) for intratumoral injection. Firstly, Am80-PLGA-MS were prepared by emulsion-solvent evaporation method. Subsequently, microspheres were characterized by particle size analysis, drug loading (DL), and entrapment efficiency (EE). Finally, the drug release characteristics in vitro, pharmacokinetic, and pharmacodynamics were studied separately. According to results obtained, microspheres were spherical with a uniform particle size 7.04 ± 0.03 μm and its EE and DL were 82.23 ± 0.74 and 11.74 ± 0.11%, respectively. In vitro, Am80-PLGA-MS can release drug for 14 days and its release behavior was fitted with the Higuchi equation. In pharmacokinetic studies, the t1/2β, MRT, and AUC of microspheres were 15.43-fold, 8.62-fold, and 9.98-fold those of Am80 solution, respectively, which revealed that the utilization of drug was improved obviously. The pharmacodynamics studies showed that the tumor doubling time, growth inhibition rate, and specific growth rate of tumor of Am80-PLGA-MS were 1.34 times, 2.63 times, and 0.72 times those of drug solution, respectively, indicating that the inhibitory effect on tumor by the microspheres was significantly improved. In summary, Am80-PLGA-MS are promising carrier to enhance the inhibitory effect on tumor, which will provide significantly clinical value for treatment of HCC.
      PubDate: 2017-07-12
      DOI: 10.1208/s12249-017-0827-9
  • Proliposome Powders for the Generation of Liposomes: the Influence of
           Carbohydrate Carrier and Separation Conditions on Crystallinity and
           Entrapment of a Model Antiasthma Steroid
    • Authors: Iftikhar Khan; Sakib Yousaf; Sneha Subramanian; Mohamed Albed Alhnan; Waqar Ahmed; Abdelbary Elhissi
      Abstract: Formulation effects on the entrapment of beclometasone dipropionate (BDP) in liposomes generated by hydration of proliposomes were studied, using the high-density dispersion medium deuterium oxide in comparison to deionized water (DW). Proliposomes incorporating BDP (2 mol% of the lipid phase consisting of soya phosphatidylcholine (SPC) and cholesterol; 1:1) were manufactured, using lactose monohydrate (LMH), sorbitol or d-mannitol as carbohydrate carriers (1:5 w/w lipid to carrier). Following hydration of proliposomes, separation of BDP-entrapped liposomes from the unentrapped (free) BDP at an optimized centrifugation duration of 90 min and a centrifugation force of 15,500g were identified. The dispersion medium was found to have a major influence on separation of BDP-entrapped liposomes from the unentrapped drug. Entrapment efficiency values were higher than 95% as estimated when DW was used. By contrast, the entrapment efficiency was 19.69 ± 5.88, 28.78 ± 4.69 and 34.84 ± 3.62% upon using D2O as a dispersion medium (for LMH-, sorbitol- and d-mannitol-based proliposomes, respectively). The similarity in size of liposomes and BDP crystals was found to be responsible for co-sedimentation of liposomes and free BDP crystals upon centrifugation in DW, giving rise to the falsely high entrapment values estimated. This was remedied by the use of D2O as confirmed by light microscopy, nuclear magnetic resonance (1HNMR), X-ray diffraction (XRD) and entrapment studies. This study showed that carrier type has a significant influence on the entrapment of BDP in liposomes generated from proliposomes, and using D2O is essential for accurate determination of steroid entrapment in the vesicles.
      PubDate: 2017-07-11
      DOI: 10.1208/s12249-017-0793-2
  • Aqueous Polymer Dispersion Coating Used for Osmotic Pump Tablets: Membrane
           Property Investigation and IVIVC Evaluation
    • Authors: Lizhen Cheng; Xiumei Gai; Haoyang Wen; Dandan Liu; Xin Tang; Yanyan Wang; Tuanjie Wang; Weisan Pan; Xinggang Yang
      Abstract: The objective of this study was to investigate the fundamental properties of propranolol hydrochloride osmotic pump tablets coated by aqueous polymer dispersion, simultaneously exploring the in vitro and in vivo correlation of the tablet. The physicochemical properties and parameters of aqueous polymer dispersion membranes (SEM, water uptake, and water vapor transmission coefficient) were investigated. In addition, the release behavior and the in vitro release and in vivo absorption profiles of the tablets coated by aqueous polymer dispersion were investigated by comparing with propranolol hydrochloride osmotic pump tablets coated by an organic solvent. Results showed that the similarity factor (f 2) between cellulose acetate-coated tablet and Eudragit-coated tablet was 78.1, and f 2 between cellulose acetate-coated tablet and Kollicoat-coated tablet was 77.6. The linear IVIVC of Eudragit-coated and Kollicoat-coated osmotic pump tablets was determined, which confirmed excellent correlation between the absorption in vivo and the drug release in vitro. Consequently, the membrane coated by aqueous polymer dispersion or organic solvent has similar in vitro release rates of controlled release. Also, compared with organic solvent coating, aqueous polymer dispersion has numerous advantages, such as reduced toxicity and no environmental damage. Therefore, the aqueous polymer dispersion technology has enormous potential as a replacement of organic solvent coating.
      PubDate: 2017-07-10
      DOI: 10.1208/s12249-017-0837-7
  • Study of the Emitted Dose After Two Separate Inhalations at Different
           Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic
           Characteristics of Indacaterol Onbrez Breezhaler ® 150 and 300 μg
    • Authors: Mohamad Abadelah; Henry Chrystyn; Golshan Bagherisadeghi; Gaballa Abdalla; Hassan Larhrib
      Abstract: Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.
      PubDate: 2017-07-10
      DOI: 10.1208/s12249-017-0841-y
  • Association of Silver Nanoparticles and Curcumin Solid Dispersion:
           Antimicrobial and Antioxidant Properties
    • Authors: Thais Francine Alves; Marco V. Chaud; Denise Grotto; Angela Faustino Jozala; Raksha Pandit; Mahendra Rai; Carolina Alves dos Santos
      Abstract: The last century, more precisely after 1945, was marked by major advances in the treatment of infectious diseases which promoted a decrease in mortality and morbidity. Despite these advances, currently the development of antimicrobial resistance has been growing drastically and therefore there is a pressing need to search for new compounds. Silver nanoparticles (AgNps) have been demonstrating good antimicrobial activity against different bacteria, viruses, and fungi. Curcumin (CUR) extracted from rhizomes of Curcuma longa has a variety of applications including antiinflammatory, antioxidant, and antibacterial agent. The association between silver nanoparticles and curcumin in a formulation can be a good alternative to control infectious diseases due the antimicrobial properties of both compounds. The objective of this work was to develop a formulation composed of a thermoresponsive gel—with antimicrobial and antioxidant properties due to the association of AgNps with PVP and PVA polymers. After AgNp synthesis, these were incorporated together with the previously prepared CUR/P407 (1:2) solid dispersion (SD) into a polymer dispersion of 20% P407 (thermosensitive gel). Our results showed that the association between the AgNps with CUR SD demonstrated good antioxidant activity as compared to the standard compound. Measures of MIC showed more efficacy against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) than for Gram-positive bacteria (Staphylococcus aureus). This association enhances antimicrobial activity against E. coli and P aeruginosa and added antioxidant value in formulations.
      PubDate: 2017-07-05
      DOI: 10.1208/s12249-017-0832-z
  • Enhanced Ungual Permeation of Terbinafine HCl Delivered Through
           Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach
    • Authors: Viral H. Shah; Amee Jobanputra
      Abstract: The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of −26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.
      PubDate: 2017-07-05
      DOI: 10.1208/s12249-017-0831-0
  • Topical Delivery of Coumestrol from Lipid Nanoemulsions Thickened with
           Hydroxyethylcellulose for Antiherpes Treatment
    • Authors: Débora Fretes Argenta; Juliana Bidone; Letícia Scherer Koester; Valquíria Link Bassani; Cláudia Maria Oliveira Simões; Helder Ferreira Teixeira
      Abstract: We have recently shown that coumestrol, an isoflavonoid-like compound naturally occurring in soybeans, alfafa, and red clover, inhibited Herpes Simplex Virus types 1 (HSV-1) and 2 (HSV-2) replication. In this study, we designed coumestrol formulations in an attempt to enable its topical delivery to mucosa tissues. Physicochemical and microscopic examinations suggested that coumestrol was efficiently incorporated in positively-charged nanoemulsions dispersed in a hydroxyethylcellulose gel. The higher coumestrol flux through excised porcine esophageal mucosa was detected from nanoemulsions composed by a fluid phospholipid (dioleylphosphocholine, DOPC) in comparison with that of a rigid one (distearoylphosphocholine, DSPC) in two mucosa conditions (intact and injured). Such results were supported by confocal fluorescence images. Furthermore, the low IC50 values demonstrated an increasement in the antiviral inhibition against HSV-1 and HSV-2 after incorporation of coumestrol into nanoemulsions containing DOPC. Overall, coumestrol-loaded nanoemulsions proved to be beneficial for herpes simplex treatment.
      PubDate: 2017-07-05
      DOI: 10.1208/s12249-017-0828-8
  • Antiproliferative Activity and VEGF Expression Reduction in MCF7 and PC-3
           Cancer Cells by Paclitaxel and Imatinib Co-encapsulation in
           Folate-Targeted Liposomes
    • Authors: Marco Júnio Peres-Filho; Alexandre Pereira dos Santos; Thais Leite Nascimento; Renato Ivan de Ávila; Fabrícia Saba Ferreira; Marize Campos Valadares; Eliana Martins Lima
      Abstract: Co-encapsulation of anticancer drugs paclitaxel and imatinib in nanocarriers is a promising strategy to optimize cancer treatment. Aiming to combine the cytotoxic and antiangiogenic properties of the drugs, a liposome formulation targeted to folate receptor co-encapsulating paclitaxel and imatinib was designed in this work. An efficient method was optimized for the synthesis of the lipid anchor DSPE-PEG(2000)-folic acid (FA). The structure of the obtained product was confirmed by RMN, FT-IR, and ESI-MS techniques. A new analytical method was developed and validated for simultaneous quantification of the drugs by liquid chromatography. Liposomes, composed of phosphatidylcholine, cholesterol, and DSPE-mPEG(2000), were prepared by extrusion. Their surface was modified by post-insertion of DSPE-PEG(2000)-FA. Reaction yield for DSPE-PEG(2000)-FA synthesis was 87%. Liposomes had a mean diameter of 122.85 ± 1.48 nm and polydispersity index of 0.19 ± 0.01. Lyophilized formulations remained stable for 60 days in terms of size and drug loading. FA-targeted liposomes had a higher effect on MCF7 cell viability reduction (p < 0.05) when compared with non-targeted liposomes and free paclitaxel. On PC-3 cells, viability reduction was greater (p < 0.01) when cells were exposed to targeted vesicles co-encapsulating both drugs, compared with the non-targeted formulation. VEGF gene expression was reduced in MCF7 and PC-3 cells (p < 0.0001), with targeted vesicles exhibiting better performance than non-targeted liposomes. Our results demonstrate that multifunctional liposomes associating molecular targeting and multidrug co-encapsulation are an interesting strategy to achieve enhanced internalization and accumulation of drugs in targeted cells, combining multiple antitumor strategies.
      PubDate: 2017-07-05
      DOI: 10.1208/s12249-017-0830-1
  • Preparation of a Sustained-Release Nebulized Aerosol of R -terbutaline
           Hydrochloride Liposome and Evaluation of Its Anti-asthmatic Effects via
           Pulmonary Delivery in Guinea Pigs
    • Authors: Qingrui Li; Shuyao Zhan; Qing Liu; Hao Su; Xi Dai; Hai Wang; Huimin Beng; Wen Tan
      Abstract: An aerosolized liposome formulation for the pulmonary delivery of an anti-asthmatic medication was developed. Asthma treatment usually requires frequent administration of medication for a sustained bronchodilator response. Liposomes are known for their sustained drug release capability and thus would be a suitable delivery system for prolonging the therapeutic effect of anti-asthmatic medication. Liposomes prepared by thin film hydration were loaded with a model drug, R-terbutaline hydrochloride(R-TBH), using an ammonium sulfate-induced transmembrane electrochemical gradient. This technique provided an encapsulation efficiency of up to 71.35% and yielded R-TBH liposomes with a particle size of approximately 145 ± 20 nm. According to stability studies, these R-TBH liposomes should be stored at 4°C before usage. Compared to R-TBH solution, which showed 90.84% release within 8 h, liposomal R-TBH had a cumulative release of 73.53% at 37°C over 192 h. A next generation impactor (NGI) was used to analyze the particle size distribution in the lungs of R-TBH liposome aerosol in vitro at 5°C. The therapeutic efficacy of the nebulized aerosol of the R-TBH liposomes was assessed via pulmonary delivery in guinea pigs. The results showed that, compared to the R-TBH solution group, the R-TBH liposome group had a prolonged anti-asthma effect.
      PubDate: 2017-07-05
      DOI: 10.1208/s12249-017-0816-z
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