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R Kamel, H Abbas
To avoid frequent drug administration, PLGA-based monolithic filament-shaped implants were prepared. In this study, the effect of different formulation variables was studied, namely: type of PLGA (PLGA 502 and PLGA 503), type of drug (the lipophilic Prednisolone acetate, PA and the hydrophilic Propranolol Hydrochloride, PH) and drug loading (10 and 30% w/w). PLGA 503-based implants showed a lower water uptake, lower mass loss and erosion, slower drug release, and better mechanical properties and elasticity (P<0...
November 13, 2017: Annales Pharmaceutiques Françaises
Aide Macias-Muñoz, Kyle J McCulloch, Adriana D Briscoe
Vertebrate (CRALBP) and Drosophila (PINTA) proteins with a CRAL-TRIO domain transport retinal-based chromophores that bind to opsin proteins and are necessary for phototransduction. The CRAL-TRIO domain gene family is composed of genes that encode proteins with a common N-terminal structural domain. While there is an expansion of this gene family in Lepidoptera, there is no lepidopteran ortholog of pinta. Further, the function of these genes in lepidopterans has not yet been established. Here we explored the molecular evolution and expression of CRAL-TRIO domain genes in the butterfly Heliconius melpomene in order to identify a member of this gene family as a candidate chromophore transporter...
November 9, 2017: Genome Biology and Evolution
Brodie Sutcliffe, Anthony A Chariton, Andrew J Harford, Grant C Hose, Sarah Stephenson, Paul Greenfield, David J Midgley, Ian T Paulsen
Elevated uranium dose (4 g kg(-1)) causes a shift in billabong sediment communities that result in the enrichment of five bacterial species. These taxa include Geobacter, Geothrix and Dyella species, as well as a novel-potentially predatory-Bacteroidetes species, and a new member of class Anaerolineae (Chloroflexi). Additionally, a population of methanogenic Methanocella species was also identified. Genomic reconstruction and metabolic examination of these taxa reveal a host of divergent life strategies and putative niche partitioning...
November 11, 2017: Microbial Ecology
Yongcheng Li, Ming Lu, Chuanbin Wu
The purpose of this study was to explore poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) as a novel release-modifier to tailor the drug release from ethylcellulose (EC)-based mini-matrices prepared via hot melt extrusion (HME). Quetiapine fumarate (QF) was selected as model drug. QF/EC/PVP VA64 mini-matrices were extruded with 30% drug loading. The physical state of QF in extruded mini-matrices was characterized using differential scanning calorimetry, X-ray powder diffraction, and confocal Raman microscopy...
November 10, 2017: Drug Delivery and Translational Research
Yuchan Li, Jian Wang, Zhigang Wang, Jingyan Tang, Tingting Yu
BACKGROUND: Hereditary multiple exostoses (HME) is a rare autosomal dominant skeletal disorder that can cause a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of HME by using a scoring system and correlate the genotypes with different clinical phenotypes in Chinese patients. METHODS: Forty-six patients from different families were prospectively enrolled. The mutations were identified by direct sequencing of PCR-amplified genomic DNA or by multiplex ligation-dependent probe amplification (MLPA)...
November 10, 2017: BMC Medical Genetics
Vibha Puri, David Brancazio, Eranda Harinath, Alexander R Martinez, Parind M Desai, Keith D Jensen, Jung-Hoon Chun, Richard D Braatz, Allan S Myerson, Bernhardt L Trout
We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300 μm...
November 4, 2017: International Journal of Pharmaceutics
Michael A Repka, Suresh Bandari, Venkata Raman Kallakunta, Anh Q Vo, Haley McFall, Manjeet B Pimparade, Ajinkya M Bhagurkar
Over the last few decades, hot melt extrusion (HME) has emerged as a successful technology for a broad spectrum of applications in the pharmaceutical industry. As indicated by multiple publications and patents, HME is mainly used for the enhancement of solubility and bioavailability of poorly soluble drugs. This review is focused on the recent reports on the solubility enhancement via HME and provides an update for the manufacturing/scaling up aspects of melt extrusion. In addition, drug characterization methods and dissolution studies are discussed...
November 2, 2017: International Journal of Pharmaceutics
Anne Q Phan, Maurizio Pacifici, Jeffrey D Esko
Multiple hereditary exostoses (MHE) is an autosomal dominant disorder that affects about 1 in 50,000 children worldwide. MHE, also known as hereditary multiple exostoses (HME) or multiple osteochondromas (MO), is characterized by cartilage-capped outgrowths called osteochondromas that develop adjacent to the growth plates of skeletal elements in young patients. These benign tumors can affect growth plate function, leading to skeletal growth retardation, or deformations, and can encroach on nerves, tendons, muscles, and other surrounding tissues and cause motion impairment, chronic pain, and early onset osteoarthritis...
November 3, 2017: Connective Tissue Research
Yulong Xia, Meng Yuan, Yueyang Deng, Xue Ke, Tianyuan Ci
The purpose of this work was to investigate the effect on the dissolution behavior when silica was added in different ways. The solid dispersion was prepared by hot-melt extrusion (HME) using indomethacin (IND) as a model drug and Kollidon VA64 as a carrier. In order to change the dissolution behavior, the silica was added during or after the HME respectively, to obtain the corresponding silica internal-added solid dispersion (InSD) and silica external-added solid dispersion (ExSD). According to the results, the internal-added silicon dioxide could reduce the dissolution rate from 66...
October 24, 2017: International Journal of Pharmaceutics
Hwee Jing Ong, Rodolfo Pinal
A formulation/processing combination approach for increasing the solubility of poorly-soluble drugs using solid dispersions (SDs) is presented, whereby the API retains its crystalline state. The approach utilizes a biopolymer naturally produced as dendrimeric nanoparticles that has been surface-modified to act as a solubilizing agent. The solubilizing agent is enabled by hot melt extrusion to produce the SDs. Four APIs, phenytoin (PHT), griseofulvin (GSF), ibuprofen (IBU) and loratadine (LOR) were used as model compounds to evaluate solubility enhancement...
October 23, 2017: Journal of Pharmaceutical Sciences
Sarah Beaudin, JoEllen Welsh
Genomic profiling has identified a subset of metabolic genes that are altered by 1,25-dihydroxyvitamin D (1,25D) in breast cells including GLUL, the gene that encodes glutamine synthetase (GS). Here, we explored the relevance of vitamin D modulation of GLUL and other metabolic genes in the context of glutamine utilization and dependence. We show that exposure of breast epithelial cells to glutamine deprivation or a GS inhibitor reduced growth and these effects were exacerbated by co-treatment with 1,25D. 1,25D down-regulation of GLUL was sufficient to reduce abundance and activity of GS...
September 28, 2017: Endocrinology
Theodoros Avgerinos, Nikolaos Kantiranis, Athanasia Panagopoulou, Stavros Malamataris, Kyriakos Kachrimanis, Ioannis Nikolakakis
Objective/significance: To elucidate the role of plasticizers in different mini matrices and correlate mechanical properties with drug release. METHODS: Cylindrical pellets were prepared by hot-melt extrusion (HME) and mini tablets by hot (HC) and ambient compression (AC). Venlafaxine HCl was the model drug, Eudragit(®) RSPO the matrix former and citric acid or Lutrol(®) F127 the plasticizers. The matrices were characterized for morphology, crystallinity, and mechanical properties. The influence of plasticizer's type and content on the extrusion pressure (Pe) during HME and ejection during tableting was examined and the mechanical properties were correlated with drug release parameters...
October 26, 2017: Drug Development and Industrial Pharmacy
Natalja Genina, Johan Peter Boetker, Stefano Colombo, Necati Harmankaya, Jukka Rantanen, Adam Bohr
The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion (HME) of the drug-containing filaments...
October 6, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Gabriela Moya, Zheng-Fei Yan, Kyung-Hwa Won, Jung-Eun Yang, Moo-Chang Kook, Tae-Hoo Yi
A Gram-stain-negative, aerobic, non-motile, yellow and rod-shaped bacterial strain was isolated from forest mud located at Kyung Hee University, South Korea. Strain THG-AG6.4(T) grew at 10-35 °C, pH 6.0-9.5 and in the presence of 0-1.5 % (w/v) NaCl. Phylogenetic analysis, based on 16S rRNA gene sequencing, showed that strain THG-AG6.4(T) was most closely related to Flavobacterium gyeonganense HME 7524(T) (97.66 %), Flavobacterium defluvii EMB 117(T) (96.93 %) and Flavobacterium arsenitoxidans S2-3H(T) (96...
October 6, 2017: International Journal of Systematic and Evolutionary Microbiology
Jiaxiang Zhang, Weiwei Yang, Anh Q Vo, Xin Feng, Xingyou Ye, Dong Wuk Kim, Michael A Repka
The objective of this study was to develop a new approach for fabrication of zero order release of active pharmaceutical ingredients (APIs) using hot-melt extrusion (HME) and 3D printing technology to generate tablets with specific 3D structures. By correlating the geometry of the 3D printed tablets with their dissolution and drug release rates, mathematical models that have been developed to describe drug release mechanisms were also studied. Acetaminophen was used as a model drug, and Benecel™ hydroxypropyl methylcellulose (HPMC) E5 and Soluplus(®) were used to formulate nine fuse depositional 3D-printed tablets with different inner core fill densities and outside shell thicknesses...
December 1, 2017: Carbohydrate Polymers
Parker W Lee, João Maia, Jonathan K Pokorski
Polymeric systems for the immobilization and delivery of proteins have been extensively used for therapeutic and catalytic applications. While most devices have been created via solution based methods, hot melt extrusion (HME) has emerged as an alternative due to the high encapsulation efficiencies and solvent-free nature of the process. HME requires high temperatures and mechanical stresses that can result in protein aggregation and denaturation, but additives and chemical modifications have been explored to mitigate these effects...
November 25, 2017: International Journal of Pharmaceutics
Noel M Gately, James E Kennedy
Hot melt extrusion (HME) is considered an efficient technique in developing solid molecular dispersions, and has been demonstrated to provide sustained, modified and targeted drug delivery resulting in improved bioavailability. However, most commercial enteric or pH-responsive polymers are relatively difficult to process or have high Glass Transition Temperature (Tg) values, making their use with temperature-sensitive drugs, probiotics or biologics not viable. Shellac is a natural thermoplastic, and after a review of current literature on the pharmaceutical HME process, a possible gap in the knowledge of the use of shellac to produce dosage forms by means of HME was identified...
September 22, 2017: Pharmaceutics
Ahmad B Albadarin, Catherine B Potter, Mark T Davis, Javed Iqbal, Sachin Korde, Sudhir Pagire, Anant Paradkar, Gavin Walker
The aim of this study was to evaluate a novel combination of hydroxypropyl methylcellulose phthalate (HPMCP-HP-50) and Soluplus(®) polymers for enhanced physicochemical stability and solubility of the produced amorphous solid dispersions (ASDs). This was achieved using hot melt extrusion (HME) to convert the crystalline active pharmaceutical ingredient (API) into a more soluble amorphous form within the ternary systems. Itraconazole (ITZ), a Biopharmaceutics Classification System class II (BCS II) API, was selected as the model drug...
September 18, 2017: International Journal of Pharmaceutics
Dipen Desai, Harpreet Sandhu, Navnit Shah, Waseem Malick, Hossein Zia, Wantanee Phuapradit, Siva Ram Kiran Vaka
The objective of the study was to select solid-state plasticizers for hot-melt extrusion (HME) process. The physical and mechanical properties of plasticizers, in selected binary (polymer:plasticizer) and ternary (active pharmaceutical ingredient:polymer:plasticizer) systems, were evaluated to assess their effectiveness as processing aids for HME process. Indomethacin and Eudragit(®) E PO were selected as model active pharmaceutical ingredient and polymer, respectively. Solubility parameters, thermal analysis, and rheological evaluation were used as assessment tools...
September 18, 2017: Journal of Pharmaceutical Sciences
Karel Medek, Jiří Zeman, Tomáš Honzík, Hana Hansíková, Štěpánka Švecová, Kamila Beránková, Vendula Kučerová Vidrová, Miloslav Kuklík, Jiří Chomiak, Markéta Tesařová
Hereditary multiple exostoses (HME) represents a heterogeneous group of diseases often associated with progressive skeletal deformities. Most frequently, mutations in EXT1 and EXT2 genes with autosomal dominant inheritance are responsible for HME. In our group of 9 families with HME we evaluated the clinical course of the disease and analysed molecular background using Sanger sequencing and MLPA in EXT1 and EXT2 genes. The mean age in our group of patients, when the first exostosis was recognised was 4.5 years (range 2-10 years) and the number of exostoses per one patient documented on X-ray ranged from 2 to 54...
2017: Prague Medical Report
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