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Publisher: Springer-Verlag (Total: 2351 journals)

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Showing 1 - 200 of 2351 Journals sorted alphabetically
3D Printing in Medicine     Open Access   (Followers: 1)
3D Research     Hybrid Journal   (Followers: 21, SJR: 0.222, CiteScore: 1)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.825, CiteScore: 1)
AAPS J.     Hybrid Journal   (Followers: 22, SJR: 1.118, CiteScore: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 7, SJR: 0.752, CiteScore: 3)
Abdominal Imaging     Hybrid Journal   (Followers: 15, SJR: 0.866, CiteScore: 2)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 4, SJR: 0.439, CiteScore: 0)
Academic Psychiatry     Full-text available via subscription   (Followers: 26, SJR: 0.53, CiteScore: 1)
Academic Questions     Hybrid Journal   (Followers: 8, SJR: 0.106, CiteScore: 0)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 27, SJR: 0.316, CiteScore: 1)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.359, CiteScore: 1)
Acoustics Australia     Hybrid Journal   (SJR: 0.232, CiteScore: 1)
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.367, CiteScore: 0)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.675, CiteScore: 1)
Acta Biotheoretica     Hybrid Journal   (Followers: 4, SJR: 0.284, CiteScore: 1)
Acta Diabetologica     Hybrid Journal   (Followers: 18, SJR: 1.587, CiteScore: 3)
Acta Endoscopica     Hybrid Journal   (Followers: 1)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.769, CiteScore: 1)
Acta Geochimica     Hybrid Journal   (Followers: 7, SJR: 0.24, CiteScore: 1)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 2, SJR: 0.305, CiteScore: 1)
Acta Geophysica     Hybrid Journal   (Followers: 10, SJR: 0.312, CiteScore: 1)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.588, CiteScore: 3)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.517, CiteScore: 1)
Acta Mathematica     Hybrid Journal   (Followers: 12, SJR: 7.066, CiteScore: 3)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.452, CiteScore: 1)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 6, SJR: 0.379, CiteScore: 1)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.27, CiteScore: 0)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.208, CiteScore: 0)
Acta Mechanica     Hybrid Journal   (Followers: 21, SJR: 1.04, CiteScore: 2)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.607, CiteScore: 2)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7, SJR: 0.576, CiteScore: 2)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.638, CiteScore: 1)
Acta Neurochirurgica     Hybrid Journal   (Followers: 6, SJR: 0.822, CiteScore: 2)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 1, SJR: 0.376, CiteScore: 1)
Acta Neuropathologica     Hybrid Journal   (Followers: 4, SJR: 7.589, CiteScore: 12)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.334, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 15, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8, SJR: 0.103, CiteScore: 0)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 23, SJR: 0.72, CiteScore: 2)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 16, SJR: 1.005, CiteScore: 2)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.703, CiteScore: 2)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 4, SJR: 0.698, CiteScore: 1)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 37, SJR: 0.956, CiteScore: 2)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 19, SJR: 0.812, CiteScore: 1)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 55, SJR: 1.09, CiteScore: 1)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.144, CiteScore: 0)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 28, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 4, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 45, SJR: 1.04, CiteScore: 3)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 1.075, CiteScore: 3)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 6)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.517, CiteScore: 1)
Aerobiologia     Hybrid Journal   (Followers: 3, SJR: 0.673, CiteScore: 2)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 9, SJR: 0.825, CiteScore: 1)
African Archaeological Review     Hybrid Journal   (Followers: 18, SJR: 0.862, CiteScore: 1)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.235, CiteScore: 0)
AGE     Hybrid Journal   (Followers: 7)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.39, CiteScore: 1)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.67, CiteScore: 2)
Agricultural Research     Hybrid Journal   (Followers: 6, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Hybrid Journal   (Followers: 20, SJR: 0.663, CiteScore: 1)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 12, SJR: 1.864, CiteScore: 6)
AI & Society     Hybrid Journal   (Followers: 8, SJR: 0.227, CiteScore: 1)
AIDS and Behavior     Hybrid Journal   (Followers: 14, SJR: 1.792, CiteScore: 3)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 4, SJR: 0.862, CiteScore: 3)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 6, SJR: 0.531, CiteScore: 0)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.583, CiteScore: 1)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 1.095, CiteScore: 1)
Algorithmica     Hybrid Journal   (Followers: 9, SJR: 0.56, CiteScore: 1)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.234, CiteScore: 0)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 5, SJR: 1.11, CiteScore: 3)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
AMBIO     Hybrid Journal   (Followers: 10, SJR: 1.569, CiteScore: 4)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 16, SJR: 0.951, CiteScore: 3)
American J. of Community Psychology     Hybrid Journal   (Followers: 29, SJR: 1.329, CiteScore: 2)
American J. of Criminal Justice     Hybrid Journal   (Followers: 8, SJR: 0.772, CiteScore: 1)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 16, SJR: 0.46, CiteScore: 1)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.181, CiteScore: 0)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.611, CiteScore: 1)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 21, SJR: 0.314, CiteScore: 0)
American Sociologist     Hybrid Journal   (Followers: 13, SJR: 0.35, CiteScore: 0)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.135, CiteScore: 3)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 7, SJR: 0.211, CiteScore: 1)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 5, SJR: 0.536, CiteScore: 1)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 5)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 32, SJR: 0.978, CiteScore: 3)
Anatomical Science Intl.     Hybrid Journal   (Followers: 3, SJR: 0.367, CiteScore: 1)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.177, CiteScore: 5)
Animal Cognition     Hybrid Journal   (Followers: 19, SJR: 1.389, CiteScore: 3)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.192, CiteScore: 0)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.097, CiteScore: 2)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4, SJR: 0.438, CiteScore: 0)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.429, CiteScore: 0)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.197, CiteScore: 1)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18, SJR: 1.042, CiteScore: 3)
Annals of Combinatorics     Hybrid Journal   (Followers: 4, SJR: 0.932, CiteScore: 1)
Annals of Data Science     Hybrid Journal   (Followers: 12)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.85, CiteScore: 2)
Annals of Finance     Hybrid Journal   (Followers: 30, SJR: 0.579, CiteScore: 1)
Annals of Forest Science     Hybrid Journal   (Followers: 7, SJR: 0.986, CiteScore: 2)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.228, CiteScore: 1)
Annals of Hematology     Hybrid Journal   (Followers: 15, SJR: 1.043, CiteScore: 2)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 13, SJR: 0.413, CiteScore: 1)
Annals of Microbiology     Hybrid Journal   (Followers: 11, SJR: 0.479, CiteScore: 2)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 4, SJR: 0.687, CiteScore: 2)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.943, CiteScore: 2)
Annals of Ophthalmology     Hybrid Journal   (Followers: 12)
Annals of Regional Science     Hybrid Journal   (Followers: 7, SJR: 0.614, CiteScore: 1)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 9, SJR: 0.239, CiteScore: 1)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 13, SJR: 1.986, CiteScore: 4)
Annals of Telecommunications     Hybrid Journal   (Followers: 9, SJR: 0.223, CiteScore: 1)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 1.495, CiteScore: 1)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.834, CiteScore: 2)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.22, CiteScore: 3)
APOPTOSIS     Hybrid Journal   (Followers: 8, SJR: 1.424, CiteScore: 4)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 2, SJR: 0.294, CiteScore: 1)
Applications of Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.602, CiteScore: 1)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 43, SJR: 0.571, CiteScore: 2)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17, SJR: 0.21, CiteScore: 1)
Applied Cancer Research     Open Access  
Applied Categorical Structures     Hybrid Journal   (Followers: 2, SJR: 0.49, CiteScore: 0)
Applied Composite Materials     Hybrid Journal   (Followers: 49, SJR: 0.58, CiteScore: 2)
Applied Entomology and Zoology     Partially Free   (Followers: 4, SJR: 0.422, CiteScore: 1)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.733, CiteScore: 3)
Applied Geophysics     Hybrid Journal   (Followers: 8, SJR: 0.488, CiteScore: 1)
Applied Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.6, CiteScore: 2)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.319, CiteScore: 1)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 9, SJR: 0.886, CiteScore: 1)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.17, CiteScore: 0)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.461, CiteScore: 1)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 65, SJR: 1.182, CiteScore: 4)
Applied Physics A     Hybrid Journal   (Followers: 10, SJR: 0.481, CiteScore: 2)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 24, SJR: 0.74, CiteScore: 2)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.519, CiteScore: 2)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 12, SJR: 0.316, CiteScore: 1)
Applied Solar Energy     Hybrid Journal   (Followers: 18, SJR: 0.225, CiteScore: 0)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 5, SJR: 0.542, CiteScore: 1)
Aquaculture Intl.     Hybrid Journal   (Followers: 24, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 2)
Aquatic Ecology     Hybrid Journal   (Followers: 34, SJR: 0.656, CiteScore: 2)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.591, CiteScore: 1)
Aquatic Sciences     Hybrid Journal   (Followers: 13, SJR: 1.109, CiteScore: 3)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.303, CiteScore: 1)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 2, SJR: 0.319, CiteScore: 1)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 21, SJR: 1.052, CiteScore: 2)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.224, CiteScore: 0)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.725, CiteScore: 1)
Archival Science     Hybrid Journal   (Followers: 62, SJR: 0.745, CiteScore: 2)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 7, SJR: 0.186, CiteScore: 1)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 3, SJR: 0.909, CiteScore: 1)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 3.93, CiteScore: 3)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Archives and Museum Informatics     Hybrid Journal   (Followers: 143, SJR: 0.101, CiteScore: 0)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 5, SJR: 1.41, CiteScore: 5)
Archives of Dermatological Research     Hybrid Journal   (Followers: 7, SJR: 1.006, CiteScore: 2)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 14, SJR: 0.773, CiteScore: 2)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 16, SJR: 0.956, CiteScore: 2)
Archives of Microbiology     Hybrid Journal   (Followers: 8, SJR: 0.644, CiteScore: 2)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 8, SJR: 1.146, CiteScore: 2)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 0.71, CiteScore: 2)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 10, SJR: 1.493, CiteScore: 3)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.541, CiteScore: 5)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 0.973, CiteScore: 2)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 14, SJR: 1.274, CiteScore: 3)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 0.946, CiteScore: 3)
ArgoSpine News & J.     Hybrid Journal  
Argumentation     Hybrid Journal   (Followers: 6, SJR: 0.349, CiteScore: 1)
Arid Ecosystems     Hybrid Journal   (Followers: 2, SJR: 0.2, CiteScore: 0)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.766, CiteScore: 1)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1, SJR: 0.355, CiteScore: 0)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 2, SJR: 0.839, CiteScore: 2)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.131, CiteScore: 0)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 11, SJR: 0.937, CiteScore: 2)
Artificial Intelligence Review     Hybrid Journal   (Followers: 16, SJR: 0.833, CiteScore: 4)
Artificial Life and Robotics     Hybrid Journal   (Followers: 9, SJR: 0.226, CiteScore: 0)
Asia Europe J.     Hybrid Journal   (Followers: 5, SJR: 0.504, CiteScore: 1)
Asia Pacific Education Review     Hybrid Journal   (Followers: 12, SJR: 0.479, CiteScore: 1)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 16, SJR: 1.185, CiteScore: 2)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 12, SJR: 0.353, CiteScore: 1)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.187, CiteScore: 0)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 19, SJR: 0.855, CiteScore: 1)
Asian Business & Management     Hybrid Journal   (Followers: 9, SJR: 0.378, CiteScore: 1)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 9)
Asian J. of Criminology     Hybrid Journal   (Followers: 6, SJR: 0.543, CiteScore: 1)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 3, SJR: 0.548, CiteScore: 1)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.183, CiteScore: 0)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  

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Journal Cover
AAPS PharmSciTech
Journal Prestige (SJR): 0.752
Citation Impact (citeScore): 3
Number of Followers: 7  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1530-9932
Published by Springer-Verlag Homepage  [2351 journals]
  • The Sensitivity of In Vitro Permeation Tests to Chemical Penetration
           Enhancer Concentration Changes in Fentanyl Transdermal Delivery Systems
    • Authors: Soo Hyeon Shin; Jukkarin Srivilai; Sarah A. Ibrahim; Caroline Strasinger; Dana C. Hammell; Hazem E. Hassan; Audra L. Stinchcomb
      Pages: 2778 - 2786
      Abstract: Chemical penetration enhancers (CPEs) are frequently incorporated into transdermal delivery systems (TDSs) to improve drug delivery and to reduce the required drug load in formulations. However, the minimum detectable effect of formulation changes to CPE-containing TDSs using in vitro permeation tests (IVPT), a widely used method to characterize permeation of topically applied drug products, remains unclear. The objective of the current exploratory study was to investigate the sensitivity of IVPT in assessing permeation changes with CPE concentration modifications and subsequently the feasibility of IVPT’s use for support of quality control related to relative CPE concentration variation in a given formulation. A series of drug-in-adhesive (DIA) fentanyl TDSs with different amounts of CPEs were prepared, and IVPT studies utilizing porcine and human skin were performed. Although IVPT could discern TDSs with different amounts of CPE by significant differences in flux profiles, maximum flux (Jmax) values, and total permeation amounts, the magnitudes of the CPE increment needed to see such significant differences were very high (43–300%) indicating that IVPT may have limitations in detecting small changes in CPE amounts in some TDSs. Possible reasons for such limitations include formulation polymer and/or other excipients, type of CPE, variability associated with IVPT, skin type used, and disrupted stratum corneum (SC) barrier effects caused by CPEs.
      PubDate: 2018-10-01
      DOI: 10.1208/s12249-018-1130-0
      Issue No: Vol. 19, No. 7 (2018)
  • Influence of Postprandial Intragastric Pressures on Drug Release from
           Gastroretentive Dosage Forms
    • Authors: Felix Schneider; Melanie Hoppe; Mirko Koziolek; Werner Weitschies
      Pages: 2843 - 2850
      Abstract: Despite extensive research in the field of gastroretentive dosage forms, this “holy grail” of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.
      PubDate: 2018-10-01
      DOI: 10.1208/s12249-018-1022-3
      Issue No: Vol. 19, No. 7 (2018)
  • Physiologically Based Absorption Modeling of Salts of Weak Bases Based on
           Data in Hypochlorhydric and Achlorhydric Biorelevant Media
    • Authors: Filippos Kesisoglou; Maria Vertzoni; Christos Reppas
      Pages: 2851 - 2858
      Abstract: Physiologically based absorption modeling has been attracting increased attention to study the interactions of weakly basic drug compounds with acid-reducing agents like proton-pump inhibitors and H2 blockers. Recently, standardized gastric and intestinal biorelevant media to simulate the achlorhydric and hypochlorhydric stomach were proposed and solubility and dissolution data for two model compounds were generated. In the current manuscript, for the first time, we report the utility of these recently proposed biorelevant media as input into physiologically based absorption modeling. Where needed, data collected with the biorelevant gastrointestinal transfer (BioGIT) system were used for informing the simulations in regard to the precipitation kinetics. Using two model compounds, a HCl salt and a semi-fumarate co-crystal which as expected dissolve to a greater extent in these media (and in gastric and intestinal human aspirates) compared to what the pH–solubility profile of the free form would suggest, we demonstrate successful description of the plasma concentration profiles and correctly predicted the lack of significant interaction after administration with pantoprazole or famotidine, respectively. Thus, the data reported in this manuscript represent an initial step towards defining biorelevant input for such simulations on interactions with acid-reducing agents.
      PubDate: 2018-10-01
      DOI: 10.1208/s12249-018-1059-3
      Issue No: Vol. 19, No. 7 (2018)
  • Characterization of Inclusion Complex of Coenzyme Q10 with the New Carrier
           CD-MOF-1 Prepared by Solvent Evaporation
    • Authors: Yutaka Inoue; Ayumi Nanri; Isamu Murata; Ikuo Kanamoto
      Pages: 3048 - 3056
      Abstract: The aim of the current study was to evaluate the physicochemical properties of a solid dispersion of coenzyme Q10 (CoQ10)/cyclodextrin metal organic frameworks-1 (CD-MOF-1). As a result of the powder X-ray diffraction (PXRD), it was confirmed that the CD-MOF-1 was changed from the α form to the β form by evaporation (EVP). A diffraction peak due to melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). The structure of this complex is presumed to be similar to the β form of CD-MOF-1. As a result of the differential scanning calorimetry (DSC), the endothermic peak due to the melting of CoQ10 disappeared the EVP (CoQ10/CD-MOF-1 = 1/2). As a result of the near-infrared (NIR) absorption spectroscopy, findings suggested the hydrogen bond in formation between the CH group in the isoprene side chains of CoQ10 and the OH group of CD-MOF-1. Therefore, the formation of crystal solid dispersion in CoQ10/CD-MOF-1 was suggested. As a result of the dissolution test in distilled water, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in comparison to CoQ10 alone. Furthermore, also in fasted state simulated intestinal fluid (FaSSIF) in vivo, the EVP (CoQ10/CD-MOF-1 = 1/2) had better dissolution in the human body than CoQ10 alone. From the results of 2D-nuclear overhauser effect spectroscopy (NOESY) NMR spectroscopy, CD-MOF-1 could not include the benzoquinone ring of CoQ10. It was confirmed that the isoprene side chain was included. Therefore, it was suggested that CD-MOF-1 useful as a novel drug carrier for CoQ10.
      PubDate: 2018-10-01
      DOI: 10.1208/s12249-018-1136-7
      Issue No: Vol. 19, No. 7 (2018)
  • Correction to: Promising Antibacterial Effects of Silver
           Nanoparticle-Loaded Tea Tree Oil Nanoemulsion: a Synergistic Combination
           Against Resistance Threat
    • Authors: Roqya Najafi-taher; Behnaz Ghaemi; Sharmin Kharrazi; Samira Rasoulikoohi; Amir Amani
      Pages: 3322 - 3322
      Abstract: With regrets, there is an error in the name of one of the authors which has only been noticed after publication.
      PubDate: 2018-10-01
      DOI: 10.1208/s12249-018-0950-2
      Issue No: Vol. 19, No. 7 (2018)
  • Correction to: Preparation of Controlled-Release Particles Based on
           Spherical Porous Silica Used as the Drug Carrier by the Dry Coating Method
    • Authors: Shohei Nakamura; Shihoko Kondo; Ayaka Mohri; Takatoshi Sakamoto; Hiroshi Yuasa
      Pages: 3323 - 3323
      Abstract: In the present notation, the formula names and the formulas (page 7, left column, lines 20–21) do not correspond to each other. It is a completely incorrect description, due to a typesetting mistake by the publisher. See below for details. The original article has been corrected.
      PubDate: 2018-10-01
      DOI: 10.1208/s12249-018-0981-8
      Issue No: Vol. 19, No. 7 (2018)
  • Novel Random Triblock Copolymers for Sustained Delivery of Macromolecules
           for the Treatment of Ocular Diseases
    • Authors: Mary Joseph Ngatuni; Hoang M. Trinh; Dhananjay Pal; Ashim K. Mitra
      Abstract: The objective of this study is to design, develop, and synthesize novel random triblock (RTB) copolymers for sustained delivery of macromolecules. RTB copolymers have not been utilized for the delivery of macromolecules for ocular diseases. RTB copolymers comprising of polyethylene glycol, glycolide, and ɛ-caprolactone blocks were synthesized and assessed for their molecular weights and purity using 1H-NMR spectroscopy, gel permeation chromatography, FTIR (functionality), and XRD (crystallinity). No toxicity was observed when ocular cell lines were treated with RTB copolymers. These materials were applied for encapsulation of peptides and proteins (catalase, IgG, BSA, IgG Fab fragment, lysozyme, insulin, and octreotide) in nanoparticles. Particle size ranged from 202.41 ± 2.45 to 300.1 ± 3.11 nm depending on the molecular size and geometry of proteins/peptides. Polydispersity indices were between 0.26 ± 0.02 and 0.46 ± 0.07 respectively. Percentage entrapment efficiency and drug loading ranged from 83.44 ± 2.24 to 45.35 ± 5.53 and 21.56 ± 0.46 to 13.08 ± 1.35 respectively depending on molecular weights of peptides or proteins. A sustained in vitro release of macromolecule was observed over 3-month period. These results suggest that RTB copolymers may be suitable for sustained delivery systems for various macromolecules for different diseases including ocular diseases.
      PubDate: 2018-10-10
      DOI: 10.1208/s12249-018-1172-3
  • Lipomers (Lipid-polymer Hybrid Particles) of Vardenafil Hydrochloride: a
           Promising Dual Platform for Modifying the Drug Release Rate and Enhancing
           Its Oral Bioavailability
    • Authors: Mai Ahmed Tawfik; Mina Ibrahim Tadros; Magdy Ibrahim Mohamed
      Abstract: Vardenafil hydrochloride is commonly used for the curing of erectile dysfunction. VAR suffers certain limitations: (i) short elimination half-life (4–5 h), (ii) low aqueous solubility (0.11 mg/mL), (iii) susceptibility to extensive first-pass metabolism and drug efflux transporters (p-glycoprotein), and (iv) limited (15%) oral bioavailability. The current study focused on the development of VAR lipomers as promising modified release systems able to enhance oral bioavailability. VAR-lipomers (lipid-polymer complexes) were successfully developed by a modified precipitation technique employing a lipid (polyglyceryl-6-distearate or glyceryl tristearate) and an amphiphilic polymer (Gantrez®). Three VAR:lipid ratios [1:1, 1:2, and 1:3] and three VAR:Gantrez® ratios [4:1, 2:1, and 1:1] were investigated. Solid-state characterization studies involved differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy. The systems were assessed for particle size, polydispersity index (PDI), zeta-potential, VAR entrapment-efficiency (EE%), morphology, and VAR released % after 2 h (Q2h) and 8 h (Q8h). The best-achieved system (the highest desirability) was promoted for pharmacokinetic studies in fasted rabbits. Statistical analysis of data revealed that L9 system (PGDS, VAR, and Gantrez®; 3:1:1, respectively) had the highest desirability (0.85) with respect to spherical particle size (622.15 nm), PDI (0.11), zeta-potential (−27.90 mV), EE% (62.80%), Q2h (43.45%), and Q8h (77.40%). With respect to Levitra® tablets, the significantly higher relative bioavailability (170%), delayed Tmax, and extended MRT(0–∞) clarified the dual ability of L9 system. Lipomers are emerging systems capable of modifying the rate of VAR release and promoting its oral bioavailability.
      PubDate: 2018-10-05
      DOI: 10.1208/s12249-018-1191-0
  • Radiolabeling of Preformed Niosomes with [ 99m Tc]: In Vitro Stability,
           Biodistribution, and In Vivo Performance
    • Authors: Ameneh Almasi; Soraya Shahhosseini; Azadeh Haeri; Fariba Johari Daha; Parham Geramifar; Simin Dadashzadeh
      Abstract: Nanocarriers radiolabeled with [99mTc] can be used for diagnostic imaging and radionuclide therapy, as well as tracking their pharmacokinetic and biodistribution characteristics. Due to the advantages of niosomes as an ideal drug delivery system, in this study, the radiolabeling procedure of niosomes by [99mTc]-HMPAO complexes was investigated and optimized. Glutathione (GSH)-loaded niosomes were prepared using a thin-film hydration method. To label the niosomes with [99mTc], the preformed GSH-loaded niosomes were incubated with the [99mTc]-HMPAO complex and were characterized for particle size, size distribution, zeta potential, morphology, and radiolabeling efficiency (RE). The effects of GSH concentration, incubation time, incubation temperature, and niosomal composition on RE were investigated. The biodistribution profile and in vivo SPECT/CT imaging of the niosomes and free [99mTc]-HMPAO were also studied. Based on the results, all vesicles had nano-sized structure (160–235 nm) and negative surface charge. Among the different experimental conditions that were tested, including various incubation times, incubation temperatures, and GSH concentrations, the optimum condition that resulted in a RE of 92% was 200-mM GSH and 15-min incubation at 40°C. The in vitro release study in plasma showed that about 20% of radioactivity was released after 24 h, indicating an acceptable radiolabeling stability in plasma. The biodistribution of niosomes was clearly different from the free radiolabel. Niosomes carrying radionuclide were successfully used for tracking the in vivo disposition of these carriers and SPECT/CT imaging in rats. Furthermore, biodistribution studies in tumor-bearing mice revealed higher tumor accumulation of the niosomal formulation as compared with [99mTc]-HMPAO.
      PubDate: 2018-10-05
      DOI: 10.1208/s12249-018-1182-1
  • Enhanced Oral Bioavailability of Chlormadinone Acetate through a
    • Authors: Jia Zeng; Jianxing Chen; Liangkang Chen; Wei Zheng; Yunfeng Cao; Ting Huang
      Abstract: Chlormadinone acetate (CMA) is a derivative of the naturally secreted hormone progesterone and exhibits reliable contraceptive and non-contraceptive benefits. Although the marketed product of CMA as oral tablets under the trade name Belara® has been highly successful, there is still room for further improvements in oral bioavailability and a reduction in the clinical dose to decrease related adverse effects. In the current study, a CMA-based self-microemulsifying drug delivery system (SMEDDS) was developed using 32% ethyl oleate as an oil phase, 40% Tween-80 as a surfactant, and 12% Transcutol P combined with 16% PEG400 as a cosurfactant, resulting in spherical droplets with a z-average particle size of 38.92 nm and an average zeta potential of − 3.18 mv. The in vitro release rate of CMA from CMA-SMEDDS in different media (distilled water, HCl solution at pH 1.2, phosphate buffers at pH 4.5 and pH 6.8) was significantly faster than that from Belara® in the first 15 min. A pharmacokinetic study in rats showed that the Cmax and AUC of CMA-SMEDDS were significantly higher (P < 0.01) than those of Belara®, with a 1.98-fold increase in oral bioavailability. In comparison with Belara®, the developed CMA-SMEDDS showed promising release profiles both in vitro and in vivo, which could potentially be useful in enhancing oral bioavailability and reducing the clinical dose of CMA.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1193-y
  • Nanocarrier-Based Combination Chemotherapy for Resistant Tumor:
           Development, Characterization, and Ex Vivo Cytotoxicity Assessment
    • Authors: Sarjana Raikwar; Sonal Vyas; Rajeev Sharma; Nishi Mody; Surbhi Dubey; Suresh P. Vyas
      Abstract: A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found to be 196 ± 2.5 nm, 0.214 ± 0.04, +23.4 ± 0.3 mV and 88.3 ± 0.2% (PTX), and 89.6 ± 0.5% (DOX) respectively. In vitro drug release study of optimized formulation was carried out using dialysis tube method. FA-conjugated PTX-DOX-loaded NLCs showed 75.6 and 78.4% (cumulative drug release) of PTX and DOX respectively in 72 h in PBS (pH 7.4)/methanol (7:3), while in the case of FA-conjugated PTX-DOX-loaded NLCs, cumulative drug release recorded was 80.4 and 82.8% of PTX and DOX respectively in 72 h in PBS (pH 4.0)/methanol (7:3). Further, the formulation(s) were evaluated for ex vivo cytotoxicity study. The cytotoxicity assay in doxorubicin-resistant human breast cancer MCF-7/ADR cell lines revealed lowest GI50 value of FA-D-P NLCs which was 1.04 ± 0.012 μg/ml, followed by D-P NLCs and D-P solution with GI50 values of 3.12 ± 0.023 and 3.89 ± 0.007 μg/ml, respectively. Findings indicated that the folic acid-conjugated PTX and DOX co-loaded NLCs exhibited lower GI50 values as compared to unconjugated PTX and DOX co-loaded NLCs; thus, they have relatively potential anticancer efficacy against resistant tumor.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1185-y
  • Intratumoral Injection Administration of Irinotecan-Loaded Microspheres:
           In Vitro and In Vivo Evaluation
    • Authors: Shengjun Zhu; Mingjin Dou; Guihua Huang
      Abstract: To reduce the toxic and side effects of intravenous chemotherapeutic drugs on the tumor-patients, the aims of this study were to design and study intratumor-administrated irinotecan-loaded PLGA microspheres (CPT-11-PLGA-MS) in vitro and in vivo according to the structure characteristics of CPT-11. PLGA microspheres containing irinotecan were prepared by emulsion solvent evaporation method and evaluated in terms of their morphology, particle size analysis, in vitro drug release, drug retention and leakage studies in vivo, and pharmacodynamics studies. The CPT-11-PLGA-MS were spherical with mean size of 9.29 ± 0.02 μm, and average encapsulation efficiency were measured of 77.97 ± 1.26% along with the average drug loading of 7.08 ± 0.11%. DSC results indicated that the drug existed in the phase of uncrystallization in the microspheres. The formulation of CPT-11-PLGA-MS could prolong the in vitro drug release to 16 days following Weibull equation. In CPT-11-PLGA-MS after intratumor injection administration was significantly improved. The results demonstrated that the slow-sustained release of CPT-11-PLGA-MS in tumor tissue after intratumor injection of microspheres can reduce the drug leakage to the circulation system, maintain the drug retention, and improve the therapeutic effect, which could become a promising drug delivery system for CPT-11 and could maintain the most effective concentration at the target site to maximum limit.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1167-0
  • Comparing a Statistical Model and Bayesian Approach to Establish the
           Design Space for the Coating of Ciprofloxacin HCl Beads at Different
           Scales of Production
    • Authors: Bhaveshkumar H. Kothari; Raafat Fahmy; H. Gregg Claycamp; Christine M. V. Moore; Sharmista Chatterjee; Stephen W. Hoag
      Abstract: The primary objective of this study was to compare two methods for establishing a design space for critical process parameters that affect ethylcellulose film coating of multiparticulate beads and assess this design space validity across manufacturing scales. While there are many factors that can affect film coating, this study will focus on the effects processing conditions have on the quality and extent of film formation, as evaluated by their impact coating yield and drug release. Ciprofloxacin HCl layered beads were utilized as an active substrate core, ethylcellulose aqueous dispersion as a controlled release polymer, and triethyl citrate as a plasticizer. Thirty experiments were conducted using a central composite design to optimize the coating process and map the response surface to build a design space using either statistical least squares or a Bayesian approach. The response surface was fitted using a linear two-factor interaction model with spraying temperature, curing temperature, and curing time as significant model terms. The design spaces established by the two approaches were in close agreement with the statistical least squares approach being more conservative than the Bayesian approach. The design space established for the critical process parameters using small-scale batches was tested using scale-up batches and found to be scale-independent. The robustness of the design space was confirmed across scales and was successfully utilized to establish process signature for the coating process.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1116-y
  • In-Line Film Coating Thickness Estimation of Minitablets in a Fluid-Bed
           Coating Equipment
    • Authors: Gregor Podrekar; Domen Kitak; Andraž Mehle; Zoran Lavrič; Boštjan Likar; Dejan Tomaževič; Rok Dreu
      Abstract: Film coating thickness of minitablets was estimated in-line during coating in a fluid-bed equipment by means of visual imaging. An existing, commercially available image acquisition system was used for image acquisition, while dedicated image analysis and data analysis methods were developed for this purpose. The methods were first tested against simulated minitablet’s images and after that examined on a laboratory-scale fluid-bed Wurster coating process. An observation window cleaning mechanism was developed for this purpose. Six batches of minitablets were coated in total, using two different dispersions, where for the second dispersion coating endpoint was determined based on the in-line measurement. Coating thickness estimates were calculated from the increasing size distributions of the minitablet’s major and minor lengths, assessed from the acquired images. Information on both the minitablet’s average band and average cap coating thicknesses was obtained. The in-line coating thickness estimates were compared to the coating thickness weight gain calculations and the optical microscope measurements as a reference method. Average band coating thickness estimate was found the most accurate in comparison to microscope measurements, with root mean square error of 1.30 μm. The window cleaning mechanism was crucial for the accuracy of the in-line measurements as was evident from the corresponding decrease of the root mean square error (9.52 μm, band coating thickness). The presented visual imaging approach exhibits accuracy of at least 2 μm and is not susceptible to coating formulation or color variations. It presents a promising alternative to other existing techniques for the in-line coating thickness estimation.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1186-x
  • Interactions Between Biological Products and Product Packaging and
           Potential Approaches to Overcome Them
    • Authors: Minjia Wang; Yusheng Li; Priyanka Srinivasan; Zhiqing Hu; Rui Wang; Anggrida Saragih; M. A. Repka; S. N. Murthy
      Abstract: Biological products such as protein-based biopharmaceuticals are playing an important role in the healthcare and pharmaceutical industry. The interaction between biological products and packaging materials has become the focus of many studies since it can reduce the effectiveness of biological products. These interactions are heavily influenced by the surface properties and physicochemical nature of the therapeutic agents and the packaging materials. Therefore, it is critical to understand the interactions between packaging materials and biological products in order to design biocompatible packaging materials and develop approaches to minimize adverse interactions. We describe the interactions that occur when using several common packaging materials, including glass and polymer. We discuss the interaction between these materials and biological products such as blood, blood derivatives, recombinant proteins, monoclonal antibodies, and gene therapeutics. We also summarize approaches for overcoming these interactions. Understanding the interactions between biological materials and packaging materials is critical for the development of novel packaging materials that improve the safety of pharmaceutical products.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1184-z
  • Nano-lipid Complex of Rutin: Development, Characterisation and In Vivo
           Investigation of Hepatoprotective, Antioxidant Activity and
           Bioavailability Study in Rats
    • Authors: G. S. Ravi; R. Narayana Charyulu; Akhilesh Dubey; Prabhakara Prabhu; Srinivas Hebbar; Avril Candida Mathias
      Abstract: The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent (t-butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. The properties of the nano-complexes such as complexation, thermal behaviour, surface morphology, molecular crystallinity, particle size, zeta potential, drug content, solubility, in vitro stability study, in vitro drug release, in vitro and in vivo antioxidant study, in vivo hepatoprotective activity and oral bioavailability/pharmacokinetic studies were investigated. Rutin nano-complexes were developed successfully via the lyophilisation method and found to be in nanometric range. Rutin nano-complexes significantly improved the solubility and in vitro drug release, and kinetic studies confirmed the diffusion-controlled release of the drug from the formulation. The nano-complex showed better antioxidant activity in vitro and exhibited well in vitro stability in different pH media. The in vivo study showed better hepatoprotective activity of the formulation compared to pure rutin at the same dose levels with improved oral bioavailability. Carbon tetrachloride (CCl4)-treated animals (group II) failed to restore the normal levels of serum hepatic marker enzymes and liver antioxidant enzyme compared to the nano-complex-treated animals. The results obtained from solubility, hepatoprotective activity and oral bioavailability studies proved the better efficacy of the nano-complex compared to the pure drug.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1195-9
  • Aggregate Elasticity and Tabletability of Molecular Solids: a Validation
           and Application of Powder Brillouin Light Scattering
    • Authors: Dherya Bahl; Aditya B. Singaraju; Lewis L. Stevens
      Abstract: Describing the elastic deformation of single-crystal molecular solids under stress requires a comprehensive determination of the fourth-rank stiffness tensor (Cijkl). Single crystals are, however, rarely utilized in industrial applications, and thus averaging techniques (e.g., the Voigt or Reuss approach) are employed to reduce the Cijkl (or its inverse Sijkl) to polycrystalline aggregate mechanical moduli. With increasing elastic anisotropy, the Voigt and Reuss-averaged aggregate moduli can diverge dramatically and, provided that drug molecules almost exclusively crystallize into low-symmetry space groups, warrants a significant need for accurate aggregate mechanical moduli. This elasticity data, which currently is largely absent for pharmaceutical materials, is expected to aid understanding how materials respond to direct compression and tablet formation. Powder Brillouin light scattering (p-BLS) has recently demonstrated facile access to porosity-independent, aggregate mechanical moduli. In this study, we extend our previous p-BLS model for obtaining mechanical properties and validate our approach against a broad library of molecular solids with diverse intermolecular interaction topologies and with previously determined Cijkl which permits benchmarking our results. Our Young’s and shear moduli determined with p-BLS strongly correlate, with limited bias (i.e., a near 1:1 relation), with the Voigt-averaged Young’s and shear moduli determined using the Cijkl. Through follow-on tabletability studies, we introduce initial classifications of tabletability behavior based on the results of our p-BLS studies and the apparent elastic anisotropy. With further development, this approach represents a robust and novel method to potentially identify materials for optimum tabletability at early developmental stages.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1194-x
  • Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid
           Carriers (MOS-SMNLCs) for Treatment of Reflux Diseases: In vitro
           Optimization, Pharmacodynamics, and Pharmacokinetic Studies
    • Authors: Reham Waheed Hammad; Rania Abdel Baset Sanad; Nevine Shawky Abdelmalk; Randa Latif Aziz; Faisal A. Torad
      Abstract: Gastroesophageal reflux disease (GERD) is an esophageal injury occurred when the stomach contents reflux abnormally into the esophagus. GERD complications include esophageal adenocarcinoma. Mosapride (MOS) is a safe prokinetic agent potentially used to treat GERD. Yet, its low solubility and bioavailability due to extensive first-pass metabolism limits its applications. This study aimed to formulate MOS nanostructured lipid carriers (MOS-NLCs) via the intranasal route to improve its bioavailability. Melt–emulsification low temperature–solidification technique using 23 full factorial design was adopted to formulate MOS-NLCs. Eight formulae were prepared and assessed in terms of entrapment efficiency (%EE), particle size, and in vitro release. Glycerol addition significantly reduced the particle sizes and improved %EE and %drug released. Surface modification using chitosan was applied. The optimized MOS surface-modified nanostructured lipid carriers (MOS-SMNLCs-F7)(stearic acid, 4% glycerol, 0.5% LuterolF127, 0.5% chitosan) showed low particle size 413.8 nm ± 11.46 nm and high %EE 90.19% ± 0.06% and a threefold increase in permeation of MOS with respect to the drug suspension. MOS-SMNLCs (F7) was also evaluated for its bioavailability compared with drug suspension and commercial product. Statistical analysis revealed a significant increase in gastric emptying rate to be 21.54 ± 1.88 contractions/min compared with10.02 ± 0.62 contractions/min and 8.9 ± 0.72 contractions/min for drug suspension and oral marketed product respectively. Pharmacokinetic studies showed 2.44-fold rise in bioavailability as compared to MOS suspension and 4.54-fold as compared to the oral marketed product. In vitro/in vivo studies proven to level A correlation between in vitro permeation through sheep nasal mucosa and in vivo absorption. Therefore, MOS-SMNLCs could be considered a step forward towards enhancing the clinical efficacy of Mosapride.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1142-9
  • Investigating a Novel Hot Melt Extrusion-Based Drying Technique to
           Solidify an Amorphous Nanosuspension Using Design of Experiment
    • Authors: Bhavin Y. Gajera; Dhaval A. Shah; Rutesh H. Dave
      Abstract: The hot melt extrusion (HME) technology was explored and optimized to solidify an amorphous nanosuspension using Quality by Design (QbD) methodology. A design of experiments (DoE) approach was used to perform a set of 15 experiments, varying independent variables (feed rate, input temperature, and screw speed) within a design space. Redispersibility index (RDI), moisture content, and process yield constituted the critical quality attributes (CQAs) of the experimental design. Regression analysis and ANOVA were employed to identify and estimate significant main effects and two-way interactions, and model the process of HME drying for predictive purposes. The optimized HME-dried end product was characterized for physicochemical properties using differential scanning calorimetry (DSC), X-ray powder diffractions (XRPD), polarized light microscopy (PLM), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. The statistical analysis reveals feed rate and input temperature as significant independent variables, critically influencing RDI and moisture content of solidified end product. The model developed for process yield was insignificant at a p-value of 0.05. The API retained its amorphous nature after the extrusion process which was confirmed using DSC and XRPD techniques. PLM was unsuitable to differentiate and determine crystallinity of drug moiety in the presence of a semi-crystalline bulking agent, microcrystalline cellulose (MCC). In vitro dissolution study depicted solubility and dissolution enhancement for HME-dried amorphous nanosuspension in both the dissolution media which can be attributed to amorphous nature of nanosized drug particles. A well-designed study implemented by DoE aided in developing a robust and novel HME technique to dry aqueous nanosuspension.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1189-7
  • Preparation and Characterization of an Oral Vaccine Formulation Using
           Electrosprayed Chitosan Microparticles
    • Authors: Jorge Alberto S. Moreno; Danai-Anastasia Panou; Karen Stephansen; Ioannis S. Chronakis; Anja Boisen; Ana C. Mendes; Line Hagner Nielsen
      Abstract: Chitosan particles loaded with the antigen ovalbumin (OVA) and the adjuvant Quil-A were produced by electrospray, using mixtures of water/ethanol/acetic acid as a solvent. Three different chitosans designed as HMC+70, HMC+85, and HMC+90 (called as 705010, 855010, and 905010) were tested and its efficacy to be used in oral vaccine delivery applications was investigated. The morphology, size, and zeta potential of the produced particles were investigated, together with the encapsulation efficiency and release of OVA from the three chitosan formulations. Moreover, the mucoadhesion and cytotoxicity of the chitosan microparticles was examined. All the three formulations with OVA and Quil-A were in the micrometer size range and had a positive zeta potential between 46 and 75 mV. Furthermore, all the three formulations displayed encapsulation efficiencies above 80% and the release of OVA over a period of 80 h was observed to be between 38 and 47%. None of the developed formulations exhibited high mucoadhesive properties, either cytotoxicity. The formulation prepared with HMC+70, OVA, and Quil-A had the highest stability within 2 h in buffer solution, as measured by dynamic light scattering. The electrosprayed formulation consisting of HMC+70 with OVA and Quil-A showed to be the most promising as an oral vaccine system.
      PubDate: 2018-10-02
      DOI: 10.1208/s12249-018-1190-1
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Heriot-Watt University
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