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Journal of Pharmaceutical Sciences

Hui Ping Goh, Paul Wan Sia Heng, Celine Valeria Liew
Die filling is a critical process step during tablet production as it defines the tablet weight. Achieving die fill consistency during production of mini-tablets, tablets with diameters ≤ 6 mm, is considerably more challenging. While die filling in rotary presses had been studied in relation to feed paddle design, paddle speed and turret speed, it is unclear how these process variables could impact mini-tablet production and product properties. In this study, 1.8 and 3 mm mini-tablets were prepared using a rotary press with multiple-tip tooling using different process configurations...
September 17, 2018: Journal of Pharmaceutical Sciences
Saki Yoneda, Bertram Niederleitner, Michael Wiggenhorn, Hiroki Koga, Shinichiro Totoki, Elena Krayukhina, Wolfgang Friess, Susumu Uchiyama
In the past, analysis of micron-sized (>1.0 μm) aggregates of therapeutic proteins has been limited to light obscuration (LO), and appropriate quantitative methods of evaluating protein aggregates need to be developed. Recently, novel methods with enhanced reliability and sensitivity, such as nano-particle tracking (NTA), resonant mass measurement (RMM) and flow imaging (FI), have emerged. We have found that quantitative laser diffraction (qLD) is also effective for quantitative evaluation of protein aggregates over a wide size range...
September 17, 2018: Journal of Pharmaceutical Sciences
Patrick Poulin, Severine H Collet, Nicolas Atrux-Tallau, Jean-Michel Linget, Laurent Hennequin, Claire E Wilson
The minipig continues to build a reputation as a viable alternative large animal model to predict human in dermatology and toxicology studies. Therefore, it is essential to describe and predict the pharmacokinetics (PK) in that species to speed-up the clinical candidate selection. A key parameter in whole-body physiologically-based pharmacokinetic (PBPK) models is the tissue-to-plasma partition coefficients (Kp-tissue ) and the resulting volume of distribution at steady-state (Vss ). Mechanistic in vitro- and/or in silico-based models used for predicting these parameters of tissue distribution of drugs refer to the tissue composition-based model (TCM)...
September 14, 2018: Journal of Pharmaceutical Sciences
Breno Maurício Marson, Guilherme Picheth, Thatiane Kuczera Pereira, Diogo Henrique Kita, Glaucio Valdameri, Leociley Rocha Alencar Menezes, Giovana Gioppo Nunes, Rilton Alves de Freitas, Roberto Pontarolo
Perillyl alcohol (POH) is a natural compound that has attracted a significant interest due to its potent antitumor activity. However, clinical trials have exhibited poor tolerance by oral administration, mainly due to gastrointestinal side effects. We propose the entrapment of POH into poly(D,L-lactic acid)-block-poly(ethylene glycol) (PLA-b-PEG) as delivery platform (entrapment efficiency of 63 - 68%). The influence of different concentrations of the tensoactives poly(vinyl alcohol) (PVAl) and sodium cholate (SC) on shear strength and morphology was evaluated by confocal laser scanning microscopy and interfacial tension studies...
September 14, 2018: Journal of Pharmaceutical Sciences
Andrea Arsiccio, Andrea Paladini, Franco Pattarino, Roberto Pisano
Biopharmaceuticals are often stored in a lyophilized form. However, stresses due to both the freezing and the drying steps of the lyophilization process can be harmful to protein stability, and appropriate excipients must be added to minimize detrimental effects. In this work, Molecular Dynamics (MD) was used to provide insight into the mechanisms of protein stabilization by different osmolytes, using lactate dehydrogenase (LDH) as model protein. Our simulations indicate that good cryoprotectants are not always equally good as lyoprotectants, suggesting that synergistic effects may arise when different excipients are combined...
September 14, 2018: Journal of Pharmaceutical Sciences
Donna A Volpe, Yun Xu, Chandrahas G Sahajwalla, Islam R Younis, Vikram Patel
Methadone is utilized for the treatment of individuals with opiate dependence. Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, CYP2C9 and CYP2C8. In vivo, polymorphism effects on methadone systemic exposure have been noted for CYP2B6, CYP3A4 and CYP2D6. Clinical drug interaction studies with antiviral drugs in methadone maintenance treatment patients yield varying results on methadone pharmacokinetics and pharmacodynamics. In general, CYP inhibitors altered methadone exposure with no adverse effects...
September 8, 2018: Journal of Pharmaceutical Sciences
Linfeng Wu, Wu Chen, Feng Li, Brian R Morrow, Franklin Garcia-Godoy, Liang Hong
It is important to address the periodontitis-associated bacteria in the residual sub-gingival plaque after scaling and root planing (SRP) to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca2+ , and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to SRP. Minocycline-calcium-dextran sulfate (Mino-Ca-DS) complex microparticles were synthesized from minocycline, CaCl2, and dextran sulfate...
September 7, 2018: Journal of Pharmaceutical Sciences
Natalia Osiecka, Mirosław Gałązka, Monika Marzec, Wojciech Zając, Maria Massalska-Arodź
Polymorphism and molecular dynamics of ethosuximide with molecules of left- and right-handed chirality have been studied in detail using dielectric spectroscopy. Density functional theory calculations of molecular conformations and dimer formation were performed to aid the interpretation of measurements. Moving window correlation analysis of the imaginary part of dielectric permittivity spectra allowed us to complete the monotropic system of phases found by the differential scanning calorimetry method. Extra transition connected with freezing-in/activation of slow molecular motions was identified in partially ordered crystal CrI phase...
September 7, 2018: Journal of Pharmaceutical Sciences
Sanjida Mahjabeen, Manolya Kukut Hatipoglu, Doris M Benbrook, Lucila Garcia-Contreras
SHetA2 is a novel compound with strong potential to treat cervical dysplasia, but its low aqueous solubility limits its oral bioavailability. A vaginal suppository achieved SHetA2 cervix concentrations that were several fold above the predicted therapeutic levels. Thus, we aimed to determine the minimum dose that would achieve SHetA2 therapeutic levels while reducing cyclin D1 levels, the pharmacodynamic endpoint. The disposition of SHetA2 after vaginal administration of escalating SHetA2 doses and the corresponding reduction in cyclin D1 levels was compared to that after the conventional oral treatment...
September 6, 2018: Journal of Pharmaceutical Sciences
Tsutomu Ueda, Koji Nakamura, Yoshihiko Abe, John F Carpenter
To reduce the risk of immunogenicity that may be caused by therapeutic protein products, it is important to properly characterize subvisible particles and to develop strategies to reduce the levels of particles delivered to patients. In the current study, by employing state-of-the-art methods to quantify particle levels, we found that the Factor VIII product, Kogenate FS, contained relatively high levels of protein particles and silicone oil droplets; the vast majority of which were submicron in size. In a test of effects of product mishandling, the Kogenate FS vial was shaken instead of swirled during reconstitution...
September 6, 2018: Journal of Pharmaceutical Sciences
Leo Manley, Jon Hilden, Pablo Valero, Tim Kramer
The modern rotary pharmaceutical tablet press is capable of accepting or rejecting individual tablets based on the measured compression force of the tablet. Because during steady operation, each tablet is compressed to the same thickness, a larger compression force implies a heavier tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured compression force thus becomes an important input to the overall control strategy, and variability in the compression force from one tablet to the next corresponds directly with the uniformity of dosage units...
September 6, 2018: Journal of Pharmaceutical Sciences
Sara Ottoboni, Chris J Price, Christopher Steven, Elizabeth Meehan, Alastair Barton, Paul Firth, Andy Mitchell, Furqan Tahir
The lack of a commercial laboratory, pilot and small manufacturing scale dead end continuous filtration and drying unit it is a significant gap in the development of continuous pharmaceutical manufacturing processes for new active pharmaceutical ingredients (APIs). To move small-scale pharmaceutical isolation forward from traditional batch Nutsche filtration to continuous processing a continuous filter dryer prototype unit (CFD20) was developed in collaboration with Alconbury Weston Ltd. The performance of the prototype was evaluated by comparison with manual best practice exemplified using a modified Biotage VacMaster unit to gather data and process understanding for API filtration and washing...
September 6, 2018: Journal of Pharmaceutical Sciences
Naby Hadilou, Ali Navid Khoshgenab, Mitra Amoli-Diva, Rasoul Sadighi-Bonabi
Three magneto-plasmonic nanohybrids were synthesized using Au and Ag-coated Fe3 O4 nanoparticles (NPs) modified dual pH- and temperature-responsive triblock copolymer of poly (butyl methacrylate-co-acrylamide-co-methacrylic acid) to serve as drug carriers with potential of using in both photothermal and controlled/targeted chemo-therapies. The internal superparamagnetic core gives the carriers targeted-delivery characteristics and surface plasmon resonance (SPR)-based noble metallic Au/Ag shells give them on-demand photothermal and photo-triggering release properties...
September 5, 2018: Journal of Pharmaceutical Sciences
Yun Seob Jung, Dongwoo Chae, Kyungsoo Park
Pegylated interferon alfa-2a (PEG-IFN alfa-2a), which was developed to overcome the disadvantages of conventional formulations, is widely prescribed for hepatitis B or C virus infection. It is characterized by pharmacokinetic (PK) and pharmacodynamic (PD) properties much different from those of conventional forms. The present study developed a population PK-PD model of subcutaneous PEG-IFN α-2a in a Korean population. For PK, IFN alfa-2a concentrations were described by a one compartment model with first order absorption, preceded by skin-to-depot first order input...
September 1, 2018: Journal of Pharmaceutical Sciences
D Andrew James, Manon J Fradin, Artur Pedyczak, Bruce W Carpick
HSV529 is a replication defective HSV-2 viral vaccine candidate in clinical development. An engineered cell line is required to support production of HSV529 by transgenic expression of the HSV-1 transcription factors UL5 (HELI) and UL29 (DNBI). These two genes have been deleted from the vaccine candidate to ensure replication deficiency, and the transgene products are thus impurities that must be monitored in the final product. Multiple reaction monitoring (MRM) is a mass spectrometry (MS) workflow that can be used to quickly develop targeted protein detection and quantitation methods...
August 31, 2018: Journal of Pharmaceutical Sciences
Adam D Grabarek, Daniel Weinbuch, Wim Jiskoot, Andrea Hawe
The objective was to evaluate performance, strengths and limitations of the microfluidic resistive pulse sensing (MRPS) technique for the characterization of particles in the size range from about 50 to 2000 nm. MRPS, resonant mass measurement (RMM), nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) were compared for the analysis of nanometer-sized polystyrene (PS) beads, liposomes, bacteria and protein aggregates. An electrical conductivity of at least 3 mS/cm (equivalent to 25 mM NaCl) was determined as a key requirement for reliable analysis with MRPS...
August 31, 2018: Journal of Pharmaceutical Sciences
Ashaben Patel, Vineet Gupta, John Hickey, Nancy S Nightlinger, Richard S Rogers, Christine Siska, Sangeeta B Joshi, Michael S Seaman, David B Volkin, Bruce A Kerwin
In this study, we investigated analytical challenges associated with the formulation of two broadly neutralizing anti-HIV monoclonal antibodies (bnAbs), 3BNC117 and PGT121, both separately at 100 mg/mL and together at 50 mg/mL each. The bnAb formulations were characterized for relative solubility and conformational stability followed by accelerated and real-time stability studies. While the bnAbs were stable during 4o C storage, incubation at 40o C differentiated their stability profiles. Specific concentration dependent aggregation rates at 30o C and 40o C were measured by size exclusion chromatography for the individual bnAbs with the mixture showing intermediate behavior...
August 31, 2018: Journal of Pharmaceutical Sciences
Esra'a Albarahmieh, Muthaffer Albarahmieh, Bashar A Alkhalidi
The landscape of thin films is continuously evolving as an attractive self-administration mean to drive patient compliance. This work reports incorporation of drugs into various polymeric compositions using spin coating technology to screen amorphous solid dispersion film formation for buccal applications. Polarized light microscopy and differential scanning calorimetry were used for characterization. Physical stability was assessed after films storage at 0%RH/25◦C for 6months. Chlorpheniramine maleate, Theophylline and Famotidine were used as model drugs and mixed with Opadry amb II® or Kollicoat IR®...
August 31, 2018: Journal of Pharmaceutical Sciences
Haley Shelley, Roxanne M Rodriguez-Galarza, Sue H Duran, Eva M Abarca, R Jayachandra Babu
Nepafenac is a water insoluble nonsteroidal anti-inflammatory drug that is available as an ophthalmic suspension (Nevanac®). Suspensions are undesirable for two reasons: they tend to cause foreign body sensation and lacrimation, which could limit residence time and drug bioavailability. This decreases the amount of time the drug has to reach the site of action, the cornea. Previously, we improved the solubility and ocular permeability of nepafenac by complexing the drug with hydroxypropyl-β-cyclodextrin. In this study, we utilized the complex to formulate an ion-activated in-situ gel system using sodium alginate, Protanal PH 1033, to increase the residence time and to reduce repeat eye drop instillation...
August 28, 2018: Journal of Pharmaceutical Sciences
S Kevin Li, Doungdaw Chantasart
The effectiveness of skin penetration enhancers and the enhancer concentration required for effective skin permeation enhancement are difficult to predict. A quantitative structure enhancement relationship (QSER) of chemical penetration enhancers for skin permeation is not currently available. The present study (a) investigated the relationship between skin permeation enhancement and chemical enhancer concentration and (b) examined a simple QSER relationship for predicting skin permeation enhancement to guide enhancer formulation development...
August 27, 2018: Journal of Pharmaceutical Sciences
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