Injectable Long-acting Human Immunodeficiency Virus Antiretroviral Prodrugs with Improved Pharmacokinetic Profiles
Publication date: Available online 8 October 2018Source: International Journal of PharmaceuticsAuthor(s): Sai Archana Krovi, Matthew D. Gallovic, Austin M. Keller, Menakshi Bhat, Pamela Tiet, Naihan Chen, Michael A. Collier, Elizabeth G. Gurysh, Erica N. Pino, Monica M. Johnson, M. Shamim Hasan Zahid, Mackenzie L. Cottrell, Jason R. Pirone, Angela D. Kashuba, Jesse J. Kwiek, Eric M. Bachelder, Kristy M. AinslieAbstractWhile highly active antiretroviral therapy (HAART) has significantly reduced mortality rates in patients with human immunodeficiency virus type 1 (HIV-1), its efficacy may be impeded by emergence of drug resi...
Source: International Journal of Pharmaceutics - October 8, 2018 Category: Drugs & Pharmacology Source Type: research

Methodology to estimate the break force of pharmaceutical tablets with curved faces under diametrical compression
Publication date: Available online 8 October 2018Source: International Journal of PharmaceuticsAuthor(s): M. Al-Sabbagh, P. Polak, R.J. Roberts, G.K. Reynolds, I.C. SinkaAbstractThis paper develops a methodology to estimate the break force of curved faced tablets under diametrical compression. Common excipients used in pharmaceutical tablet formulations, including microcrystalline cellulose, calcium phosphate and mannitol as well as their mixtures were characterised. Compacts of different densities were manufactured and their compressive and tensile strength was measured. The break force of curved face tablets having a com...
Source: International Journal of Pharmaceutics - October 8, 2018 Category: Drugs & Pharmacology Source Type: research

Antitumor Effect of a Liposome-Encapsulated β1,4-Galactosyltransferase Inhibitor
In this study, 612 was introduced into a cationic liposome (LP) delivery system, and the anti-proliferative effects of both free and the LP-incorporated 612 (612-LP) were investigated in A549 lung cancer cells, which actively express anionic sialic acid moieties on the surfaces of cells. The anti-proliferative effects were evaluated via MTT assays. The results revealed that free 612 and empty LP impose neither anti-proliferative nor apoptotic effects on cancer cells at low doses, whereas the 612-LP system inhibited cancer cell growth at a concentration as low as 0.1 μg/mL after 3 days of incubation, suggesting that this...
Source: International Journal of Pharmaceutics - October 7, 2018 Category: Drugs & Pharmacology Source Type: research

Analysis of Pin Milling of Pharmaceutical Materials
Publication date: Available online 6 October 2018Source: International Journal of PharmaceuticsAuthor(s): Tina Bonakdar, Mojtaba GhadiriAbstractMilling is an important process for tailoring the particle size distribution for enhanced dissolution, content uniformity, tableting, etc., specially for active pharmaceutical ingredients and excipient in pharmaceutical industries. Milling performance of particulate solids depends on the equipment operating conditions (geometry, process conditions and input energy etc.) as well as material properties (particle size, shape, and mechanical properties, such as Young's modulus, hardnes...
Source: International Journal of Pharmaceutics - October 7, 2018 Category: Drugs & Pharmacology Source Type: research

Polysaccharide-based film loaded with vitamin C and propolis: A promising device to accelerate diabetic wound healing
Publication date: Available online 6 October 2018Source: International Journal of PharmaceuticsAuthor(s): Guilherme T. Voss, Matheus S. Gularte, Ane G. Vogt, Janice L. Giongo, Rodrigo A. Vaucher, Joanna V.Z. Echenique, Mauro P. Soares, Cristiane Luchese, Ethel A. Wilhelm, André R. FajardoAbstractWound healing can be a painful and time-consuming process in patients with diabetes mellitus. In light of this, the use of wound healing devices could help to accelerate this process. Here, cellulose-based films loaded with vitamin C (VitC) and/or propolis (Prop), two natural compounds with attractive properties were enginee...
Source: International Journal of Pharmaceutics - October 7, 2018 Category: Drugs & Pharmacology Source Type: research

Polysorbate degradation in biotherapeutic formulations: Identification and discussion of current root causes
Publication date: Available online 6 October 2018Source: International Journal of PharmaceuticsAuthor(s): Mridula Dwivedi, Michaela Blech, Ingo Presser, Patrick GaridelAbstractBiotherapeutic protein formulations are often high concentration liquid protein solutions, which are required to be stable under pharmaceutically relevant storage conditions and presence of external stress. Non-ionic detergents like polysorbate have been the most commonly used excipient to maintain formulation stability. Recently, particle formation in polysorbate containing biotherapeutic formulations has arisen as a major quality concern and potent...
Source: International Journal of Pharmaceutics - October 7, 2018 Category: Drugs & Pharmacology Source Type: research

Improved oral bioavailability of notoginsenoside R1 with sodium glycocholate-mediated liposomes: preparation by supercritical fluid technology and evaluation in vitro and in vivo
Publication date: Available online 4 October 2018Source: International Journal of PharmaceuticsAuthor(s): Qiangyuan Fan, Yongtai Zhang, Xuefeng Hou, Zhe Li, Kai Zhang, Qun Shao, Nianping FengAbstractThe chief objective of this research was to appraise liposomes embodying a bile salt, sodium glycocholate (SGC), as oral nanoscale drug delivery system to strengthen the bioavailability of a water-soluble and weakly penetrable pharmaceutical, notoginsenoside R1 (NGR1). NGR1-loaded liposomes were prepared with the improved supercritical reverse evaporation (ISCRPE) method and the preparation conditions were optimized with respon...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

An Application of Deep Learning to Detect Process Upset during Pharmaceutical Manufacturing using Passive Acoustic Emissions
Publication date: Available online 22 September 2018Source: International Journal of PharmaceuticsAuthor(s): Allan Carter, Lauren BriensAbstractThe multivariate nature of a fluidized bed system creates process complexity that increases the risk of production upset. This research explores the use of passive acoustic emissions monitoring paired with an artificial neural network to detect fluidized bed distributor plate blockage. In many cases, early process failure detection can allow for immediate intervention, thus lowering operation costs. Blockages were simulated by actively covering portions of a top-spray fluidized bed...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Physicochemical and Biopharmaceutical Characterization of Celecoxib Nanoparticle: Avoidance of Delayed Oral Absorption Caused by Impaired Gastric Motility
Publication date: Available online 22 September 2018Source: International Journal of PharmaceuticsAuthor(s): Keisuke Yakushiji, Mizuki Ogino, Hiroki Suzuki, Yoshiki Seto, Hideyuki Sato, Satomi OnoueAbstractThe present study aimed to develop a celecoxib (CEL) nanoparticle with improved dissolution/dispersion and consistent absorption even in the presence of impaired gastric motility. CEL was pulverized by a wet-milling with hydroxypropyl cellulose (HPC), and the prepared nanoparticles were physicochemically characterized after freeze-drying. CEL nanoparticle with HPC-SSL (NP/CEL) exhibited better dissolution/dispersion beha...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

A stent film of paclitaxel presenting extreme accumulation of paclitaxel in tumor tissue and excellent antitumor efficacy after implantation beneath the subcutaneous tumor xenograft in mice
Publication date: Available online 26 September 2018Source: International Journal of PharmaceuticsAuthor(s): Keqin Wu, Jieying Liu, Lei lei, Yuanyuan Shen, Shengrong GuoAbstractAnti-tumor drug/stent combinations play a dual role of stent and local chemotherapy to cancer. Herein, a series of paclitaxel (PTX) loaded polylactic acid (PLA) stent films were studied on drug release characteristics and in vivo antitumor effects. The film was implanted beneath and released drug towards the subcutaneous PC-3 tumor xenograft in mice, which consisted of a PTX-loaded layer and a drug-free backing layer. The concentrations of PTX were ...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Development and evaluation of topical formulations for a novel skin whitening agent (AP736) using Hansen solubility parameters and PEG-PCL polymers
In this study, we aimed to develop a new topical delivery system in which AP736 is not only physically stable, but also suitably delivered to the skin. By calculating each HSP (Hansen Solubility Parameters), ethylenedioxy moiety-containing compounds could be easily selected for the formulation ingredients of AP736. Although the highest solubility of AP736 in diethylene glycol monoethyl ether make AP736-incorporated water in oil emulsions well formed, the recrystallization of AP736 was observed in oil in water emulsions. Therefore, we fabricated polymeric nanoparticles (PNPs) in order to encapsulate AP736. Three different P...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Controlled Drug Delivery from 3D Printed Two-Photon Polymerized Poly(Ethylene Glycol) Dimethacrylate Devices
Publication date: Available online 27 September 2018Source: International Journal of PharmaceuticsAuthor(s): Anh-Vu Do, Kristan Worthington, Budd Tucker, Aliasger K. SalemAbstractControlled drug delivery systems have been utilized to enhance the therapeutic effects of many drugs by delivering drugs in a time-dependent and sustained manner. Here, with the aid of 3D printing technology, drug delivery devices were fabricated and tested using a model drug (fluorophore: rhodamine B). Poly(ethylene glycol) dimethacrylate (PEGDMA) devices were fabricated using a two-photon polymerization (TPP) system and rhodamine B was homogenou...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Mucus-penetrating phage-displayed peptides for improved transport across a mucus-like model
The objective of this work is to use phage display libraries as a screening tool to identify peptides that facilitate transport across the mucus barrier. Mucus is a complex selective barrier to particles and molecules, limiting penetration to the epithelial surface of mucosal tissues. In mucus-associated diseases such as cystic fibrosis (CF), mucus has increased viscoelasticity and a higher concentration of covalent and non-covalent physical entanglements compared to healthy tissues, which greatly hinders permeability and transport of drugs and particles across the mucosae for therapeutic delivery. Treatment of CF lung dis...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Detailed Modeling and Process Design of an Advanced Continuous Powder Mixer
Publication date: Available online 27 September 2018Source: International Journal of PharmaceuticsAuthor(s): Peter Toson, Eva Siegmann, Martina Trogrlic, Hermann Kureck, Johannes Khinast, Dalibor Jajcevic, Pankaj Doshi, Daniel Blackwood, Alexandre Bonnassieux, Patrick D Daugherity, Mary T. am EndeAbstractA vertical in-line continuous powder mixing device (CMT – Continuous Mixing Technology) has been modelled with the discrete element method (DEM) utilizing a calibrated cohesive contact model. The vertical design of the mixing device allows independent control of mean residence time (MRT) and shear rate. The hold-up m...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Enhanced dissolution of naproxen from pure-drug, crystalline nanoparticles: A case study formulated into spray-dried granules and compressed tablets
Publication date: Available online 29 September 2018Source: International Journal of PharmaceuticsAuthor(s): Veronika Braig, Christoph Konnerth, Wolfgang Peukert, Geoffrey LeeAbstractThis is a case study of the use of rapidly-dissolving naproxen crystalline nanoparticles to prepare compressed tablets. The dissolution rates of different formulations were determined: the crystalline pure-drug nanodispersion, a pure-drug microsuspension, a granule prepared by spray drying the nanodispersion with mannitol, and a tablet prepared by compressing the granule with a bulking agent and a disintegrant. The goal was to determine the in...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

AgCa-PLGA submicron particles inhibit the growth and colonization of E. faecalis and P. gingivalis on dentin through infiltration into dentinal tubules
Publication date: Available online 29 September 2018Source: International Journal of PharmaceuticsAuthor(s): Wei Fan, Danfeng Liu, Yanyun Li, Qing Sun, Bing FanAbstractEliminating the infection from root canals and periodontal tissues of human teeth as well as the repair of infected periodontal bone has been a great challenge. Poly(lactide-co-glycolide) (PLGA) particles have been used for drug delivery due to their biodegradability, sustained drug release and nontoxic properties. As silver ions (Ag+) exhibit strong antibacterial ability and calcium ions (Ca2+) are essential for hard tissue regeneration, the Ag+ and Ca2+ we...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Influence of preparation technique on co-amorphization of carvedilol with acidic amino acids
In this study the basic drug carvedilol (CAR) and the two acidic AAs, glutamic acid and aspartic acid, were used to explore the possibilities of producing co-amorphous formulations using BM, SD and liquid assisted grinding (LAG). X-ray powder diffraction, thermal analysis and Fourier-transform infrared spectroscopy were used to determine the solid state form of the various CAR-AA mixtures prepared. BM the CAR-AA mixtures for 60 min did not result in co-amorphization as XRPD revealed remaining crystallinity of both CAR and the AA. On the other hand, successful co-amorphous salt formation was obtained for all SD samples. Dif...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Novel ultra-small micelles based on rebaudioside A: A potential nanoplatform for ocular drug delivery
Publication date: Available online 3 October 2018Source: International Journal of PharmaceuticsAuthor(s): Kaichao Song, Meng Xin, Hongxia Yu, Zhou Zheng, Jun Li, Mengshuang Li, Huimin Guo, Youlan Tan, Xianggen WuAbstractWe investigated if the self-assembled micelles of rebaudioside A (RA) could potentially be utilized as an ocular drug-delivery system in this investigation. RA self-assembled into micelles with ultra-small particle sizes (
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

A Poloxamer-407 modified liposome encapsulating epigallocatechin-3-gallate in the presence of magnesium: characterization and protective effect against oxidative damage
In conclusion, the results demonstrated that the produced formulation enhances the efficacy of EGCG under stress conditions, thus representing a potential formulation for the intracellular delivery of EGCG in diseases caused by oxidative damage.Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

A novel antibacterial agent based on AgNPs and Fe3O4 loaded chitin microspheres with peroxidase-like activity for synergistic antibacterial activity and wound-healing
In this study, a novel antibacterial agent was developed based on chitin nanofibrous microspheres loaded with AgNPs and Fe3O4 nanoparticles (Ag-Fe3O4-NMs) for synergistic antibacterial activity and wound healing. Ag-Fe3O4-NMs was prepared via an in situ synthetic method which showed an excellent porosity and wettability. Moreover, Ag-Fe3O4-NMs were capable of sustained release of Ag+ and catalysed the decomposition of low H2O2 concentrations to generate hydroxyl radical (·OH). The ·OH radicals and Ag+ showed higher antibacterial activity and exhibited the toxicity with high dose of AgNPs and H2O2. In vitro bi...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Prevention of rat liver fibrosis by selective targeting of hepatic stellate cells using hesperidin carriers
In conclusion, this newly developed carrier represents a potentially beneficial approach for HSCs specific targeting of hesperidin in a rat model with liver fibrosis.Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Smart pH Responsive Drug Delivery System Based on poly(HEMA-co-DMAEMA) Nanohydrogel
Publication date: Available online 3 October 2018Source: International Journal of PharmaceuticsAuthor(s): Amir Roointan, Javad Farzanfar, Soliman Mohammadi-Samani, Abbas Behzad-Behbahani, Fatemeh FarjadianAbstractThe advent of smart nanohydrogel has revealed new opportunities for scientists to develop the most efficient anti-cancer vehicles with safe and biocompatible profile. In this experiment, using reversible addition–fragmentation chain transfer polymerization method as a novel, safe and smart pH responsive formulation of poly (hydroxyethyl methacrylate-co-N, N-dimethylaminoethyl methacrylate) and poly (ethylene...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Towards a better understanding of dry binder functionality
Publication date: Available online 4 October 2018Source: International Journal of PharmaceuticsAuthor(s): Oscar-Rupert Arndt, Peter KleinebuddeAbstractIt is of great importance to get a deeper understanding of the binding behaviour and functionality of different types of dry binders, since dry binders are crucial to ensure appropriate properties of dry granules and tablets. Based on previous studies, the most effective dry bindersof chemically different types have been chosen to apply a new approach analysing the compressibility of tablets made from pure dry binders. Therefore, tablets were compressed at different tabletin...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Editorial Board
Publication date: 15 November 2018Source: International Journal of Pharmaceutics, Volume 551, Issues 1–2Author(s): (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Utilizing glutathione-triggered nanoparticles to enhance chemotherapy of lung cancer by reprograming the tumor microenvironment
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Tao Cui, Xiaohong Li, Yaqian Shu, Xianzhou Huang, Yan Wang, Wenli ZhangAbstractIn the present study, we have developed the robust nanoparticles (MGC-GNP/PTX), which are TAMs and tumor cells-dual recognizable, for targeting cancer therapy. Of great importance, the developed nano-platforms are glutathione (GSH)-activable, which means it remains structure intact under normal physiological condition and can be disrupted when exposed to certain concentration of GSH. As demonstrated by the drug release assay in...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Soluplus micelles for acyclovir ocular delivery: Formulation and cornea and sclera permeability
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Angela Varela-Garcia, Angel Concheiro, Carmen Alvarez-LorenzoAbstractNearly 20% of people affected by the herpes simplex virus (HSV) suffer from vision problems. The virus can infect all layers of the cornea or cause inflammatory diseases of the sclera. The aim of this work was to test whether encapsulation of acyclovir in Soluplus or Solutol polymeric micelles increases its solubility, corneal permeability and sclera penetration. The aqueous solubility of acyclovir is known to be low, and therefore appro...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Binding and structure-kinetic relationship analysis of selective TLR4-targeted immunosuppressive self-assembling heparin nanoparticles
In conclusion, the present study characterizes the immunosuppressive effect of aliphatic heparin derivatives and provides a promising strategy to develop selective immunosuppressants for acute and chronic inflammatory disorders.Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

In vitro effect of mPEG2k-PCLx micelles on rat liver cytochrome P450 enzymes
In conclusion, mPEG2k-PCLx micelles can interfere with the normal metabolic function of CYP450s in vitro, indicating polymeric micelles as promising drug nano-carriers might cause micelle–drug interaction and the in vivo interaction deserves further investigation.Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

A preclinical evaluation of cytarabine prodrug nanofibers assembled from cytarabine-lauric acid conjugate toward solid tumors
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Ruiling Liu, Yue Jiang, Xu Hu, Jilian Wu, Wei Jiang, Guoxia Jin, Yuxia LuanAbstractCytarabine (Ara-C) has become cornerstones for the treatment of hatmatological malignancies for several decades; however, it still faces serious challenges in clinical applications due to its side effects such as hand foot syndrome (HFS) and stomatitis. Therefore, considerable researchers have devoted to looking for the new derivative with desirable activity and low toxicity. A new prodrug based on the conjugation of cytara...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Comparison of different chemometric methods to extract chemical and physical information from Raman images of homogeneous and heterogeneous semi-solid pharmaceutical formulations
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Hery Mitsutake, Simone R. Castro, Eneida de Paula, Ronei J. Poppi, Douglas N. Rutledge, Márcia C. BreitkreitzAbstractIn formulations of nanostructured lipid carriers, lipid solid dispersions and self-emulsifying drug delivery systems, it is common that a solid or semi-solid lipid excipient is mixed with a liquid solvent or liquid lipid. Even when the excipients are visually miscible upon melting, they might have microscopic non-homogeneities which could lead to instability over time and future phas...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Novel combination proliposomes containing tobramycin and clarithromycin effective against Pseudomonas aeruginosa biofilms
In conclusion, the core-carrier method coupled with spray-drying provided a novel approach for the preparation of combination antibiotics proliposomes.Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

A systematic evaluation of dual functionality of sodium lauryl sulfate as a tablet lubricant and wetting enhancer
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Jiangnan Dun, Frederick Osei-Yeboah, Pierre Boulas, Yiqing Lin, Changquan Calvin SunAbstractAppropriate lubrication is important in tablet manufacturing as it lowers punch sticking propensity and protects tooling by reducing friction between die wall and tablet during tablet manufacturing. Most commercial lubricants negatively impact tabletability and dissolution. A delicate balance is usually attained by trial and error to identify the optimal level of lubricant in a tablet formulation. In this work, we ...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Ketoprofen and MicroRNA-124 Co-loaded poly (lactic-co-glycolic acid) microspheres inhibit progression of Adjuvant-induced arthritis in rats
In this study, in an effort to improve the therapeutic effect for rheumatoid arthritis (RA), microRNA-124 (miR-124), a promising new therapeutic agent for RA, was co-loaded with ketoprofen into poly (lactic-co-glycolic acid) (PLGA) microspheres and administrated to adjuvant-induced arthritis rats. PLGA microspheres loaded with ketoprofen and miR-124 were prepared by a modified multiple emulsion–solvent evaporation method. In vivo pharmacodynamics experimental results indicated ketoprofen in co-loaded microspheres could significantly reduce inflammation of the joints and miR-124 in the microspheres could reduce bone d...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Preparation of lapatinib ditosylate solid dispersions using solvent rotary evaporation and hot melt extrusion for solubility and dissolution enhancement
This study provided the insight of introducing theoretical models to guide SD formulation/process development and illustrating the potential of bioavailability enhancement for LB-DT.Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Unexplored benefits of controlled ice nucleation: Lyophilization of a highly concentrated monoclonal antibody solution
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Shubhadra N. Singh, Swati Kumar, Valeriy Bondar, Ning Wang, Rachel Forcino, James Colandene, Doug NestaAbstractThe study explores new benefits of controlled ice nucleation during lyophilization. A highly concentrated monoclonal antibody product was lyophilized using conventional (uncontrolled) and controlled ice nucleation freezing and the processes were compared for their impact on process performance, reconstitution time, and product quality attributes. Glass fogging was observed during the conventional...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Polymorphism of spironolactone: An unprecedented case of monotropy turning to enantiotropy with a huge difference in the melting temperatures
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Ivo B. Rietveld, Maria Barrio, Pol Lloveras, René Céolin, Josep-Lluis TamaritAbstractSpironolactone form I melts at about 70 degrees lower than form II, which is very unusual for two co-existing polymorphs. The phase relationships involving this unprecedented case of dimorphism have been investigated by constructing a topological pressure-temperature phase diagram. The transition from polymorph I to polymorph II is unambiguously exothermic while it is accompanied with an increase in the spec...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

Commentary: New perspectives on protein aggregation during Biopharmaceutical development
Publication date: 1 December 2018Source: International Journal of Pharmaceutics, Volume 552, Issues 1–2Author(s): Maryam ShahAbstractThe occurrence of protein aggregation during bioprocessing steps such as purification, formulation and fill-finish, impacts yield and production costs, and must be controlled throughout the manufacturing process. Understanding aggregation mechanisms and developing mitigating strategies are imperative to ensure the clinical efficacy of the protein drug product and to reduce costs. This commentary reflects on recent progress made in the field of monoclonal antibody (mAb) aggregation with ...
Source: International Journal of Pharmaceutics - October 5, 2018 Category: Drugs & Pharmacology Source Type: research

A study on the role of cholesterol and phosphatidylcholine in various features of liposomal doxorubicin: from liposomal preparation to therapy
Publication date: Available online 20 September 2018Source: International Journal of PharmaceuticsAuthor(s): Hamidreza Farzaneh, Maryam Ebrahimi Nik, Mohammad Mashreghi, Zahra Saberi, Mahmoud Reza Jaafari, Manouchehr TeymouriAbstractThe lipid membrane composition defines the physical and pharmacological characteristics of liposomal drugs, and it can be tailored to meet the desired drug delivery needs. The current study is aimed to provide a sharper understanding of the lipid composition effect on doxorubicin (DOX) delivery kinetics, using cholesterol and phosphatidylcholine lipids (PCs) with different acyl chains in liposo...
Source: International Journal of Pharmaceutics - September 21, 2018 Category: Drugs & Pharmacology Source Type: research

Direct imaging of the dissolution of salt forms of a carboxylic acid drug
Publication date: Available online 20 September 2018Source: International Journal of PharmaceuticsAuthor(s): Kofi Asare-Addo, Karl Walton, Adam Ward, Ana-Maria Totea, Sadaf Taheri, Maen Alshafiee, Nihad Mawla, Antony Bondi, William Evans, Adeola Adebisi, Barbara R. Conway, Peter TimminsAbstractThe optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses a...
Source: International Journal of Pharmaceutics - September 21, 2018 Category: Drugs & Pharmacology Source Type: research

Non-viral vectors based on cationic niosomes as efficient gene delivery vehicles to central nervous system cells into the brain
Publication date: Available online 19 September 2018Source: International Journal of PharmaceuticsAuthor(s): Mohamed Mashal, Noha Attia, Cristina Soto-Sánchez, Gema Martínez-Navarrete, Eduardo Fernández, Gustavo Puras, José Luis PedrazAbstractDevelopment of safe and efficient non-viral vectors to deliver DNA into the CNS represents a huge challenge to face many neurological disorders. We elaborated niosomes based on DOTMA cationic lipid, lycopene “helper” lipid and polysorbate 60 as non-ionic surfactants for gene delivery to the CNS. Niosomes, and their corresponding nioplexes obtain...
Source: International Journal of Pharmaceutics - September 20, 2018 Category: Drugs & Pharmacology Source Type: research

Theranostic Polymeric Nanoparticles for NIR Imaging and Photodynamic Therapy
Publication date: Available online 19 September 2018Source: International Journal of PharmaceuticsAuthor(s): E. Tugce Sarcan, Mine Silindir-Gunay, A. Yekta OzerAbstractNear-Infrared (NIR) dyes forming some of the photosensitizer agents show imaging and therapy features by themselves. NIR dyes show photodynamic therapy by formation of reactive oxygen species and imaging by NIR Fluorescence light. Photodynamic therapy occurs from irradiation of laser or light to photosensitizer matters and following by the formation of reactive oxygen species diseased tissues or cells can be killed effectively. NIR dyes have advantages such ...
Source: International Journal of Pharmaceutics - September 20, 2018 Category: Drugs & Pharmacology Source Type: research

3D printing and coating to fabricate a hollow bullet-shaped implant with porous surface for controlled cytoxan release
Publication date: Available online 19 September 2018Source: International Journal of PharmaceuticsAuthor(s): Ning Yang, Huanfei Chen, Huijie Han, Yuanyuan Shen, Song Gu, Yong He, Shengrong GuoAbstractIntratumoral implants have aroused great interests for local chemotherapy of cancer, however, how to efficiently control drug release from implants is still a great challenge. Herein, we designed and prepared a new hollow bullet-shaped implant with porous surface by 3D printing, loaded chemotherapeutic agent cytoxan (CTX) with tetradecyl alcohol or lecithin as matrix and coated it with poly (lactic acid) to obtain a CTX implan...
Source: International Journal of Pharmaceutics - September 20, 2018 Category: Drugs & Pharmacology Source Type: research

Using Two-Fluid Nozzle for Spray Freeze Drying to Produce Porous Powder Formulation of Naked siRNA for Inhalation
In this study, we reported the use of two-fluid nozzle to produce spray freeze dried powder of small interfering RNA (siRNA). The effect of atomization gas flow rate and liquid feed rate were inspected initially using herring sperm DNA (hsDNA) as nucleic acid model. The atomization gas flow rate was found to have a major impact on the aerosol properties. The higher the atomization gas flow rate, the smaller the particle size, the higher the fine particle fraction (FPF). In contrast, the liquid feed rate had very minor effect. Subsequently, spray freeze dried siRNA powder was produced at various atomization gas flow rates. ...
Source: International Journal of Pharmaceutics - September 20, 2018 Category: Drugs & Pharmacology Source Type: research

Mechanistic study of the adjuvant effect of chitosan-aluminum nanoparticles
Publication date: Available online 19 September 2018Source: International Journal of PharmaceuticsAuthor(s): F. Lebre, M.C. Pedroso de Lima, Ed C. Lavelle, O. BorgesAbstractThe use of tailored particle-based adjuvants constitutes a promising way to enhance antigen-specific humoral and cellular immune responses. However, a thorough understanding of the mechanisms underlying their adjuvanticity is crucial to generate more effective vaccines. We studied the ability of chitosan-aluminum nanoparticles (CH-Al NPs), which combine the immunostimulatory effects of chitosan and aluminum salts, to promote dendritic cell activation, a...
Source: International Journal of Pharmaceutics - September 20, 2018 Category: Drugs & Pharmacology Source Type: research

Optimized acriflavine-loaded lipid nanocapsules as a safe and effective delivery system to treat breast cancer
Publication date: Available online 17 September 2018Source: International Journal of PharmaceuticsAuthor(s): Yoann Montigaud, Bernard Ucakar, Balaji Krishnamachary, Zaver M Bhujwalla, Olivier Feron, Véronique Préat, Fabienne Danhier, Bernard Gallez, Pierre DanhierAbstractAcriflavine (ACF) hydrochloride is currently repurposed as multimodal drug, inhibiting hypoxia-inducible factors (HIF) pathways and exerting cytotoxic properties. The aim of this study was to encapsulate ACF in reverse micelles and to incorporate this suspension in lipid nanocapsules (LNC). Designs of experiments were used to work under quali...
Source: International Journal of Pharmaceutics - September 18, 2018 Category: Drugs & Pharmacology Source Type: research

Freeze drying of polyelectrolyte complex nanoparticles: effect of nanoparticle composition and cryoprotectant selection
Publication date: Available online 17 September 2018Source: International Journal of PharmaceuticsAuthor(s): Anita Umerska, Krzysztof J. Paluch, Maria-Jose Santos Martinez, Owen I. Corrigan, Carlos Medina, Lidia TajberAbstractThis work investigates the impact of nanoparticle (NP) composition and effectiveness of cryo-/lyo-protectants in a freeze drying process, which was employed to convert liquid dispersions of polyelectrolyte complex (PEC) NPs into completely redispersible powders. PEC NPs, with and without peptide, were produced by complex coacervation. The cryo-/lyo-protectants investigated were mannitol, trehalose (TR...
Source: International Journal of Pharmaceutics - September 18, 2018 Category: Drugs & Pharmacology Source Type: research

Investigating the effects of amphipathic gastrointestinal compounds on the solution behaviour of salt and free base forms of clofazimine: an in vitro evaluation
In this study, it is demonstrated that amphipathic compounds present in the gastric and intestinal systems can overcome the instability experienced by CFZ at these pH values. This is done by encapsulation of the hydrophobic drug in mixed bile salt phospholipid micelles in both the gastric and intestinal fluid, and by the drug actively binding with the digestive enzyme pepsin in the gastric system. Pepsin binds and solubilises the drug at even relatively low concentration (0.1 mg/mL). When pepsin concentration is increased in the gastric media, a corresponding increase in the solution stability of CFZ is observed.Graphical ...
Source: International Journal of Pharmaceutics - September 18, 2018 Category: Drugs & Pharmacology Source Type: research

2D materials for next generation healthcare applications
Publication date: Available online 18 September 2018Source: International Journal of PharmaceuticsAuthor(s): Ashtami Jayakumar, Anju Surendranath, Mohanan PVAbstract2 dimensional (2D) materials are budding new class of materials with exciting potential in optical, electrical, chemical and biomedical applications. Inspired by the attractive properties of graphene attributing to its 2D structure has stimulated researchers to hunt for new 2D materials. Unique characteristics like high surface-volume ratio, shape, surface charge, anisotropic nature and tunable functionalities of 2D structures opens up its application scope fur...
Source: International Journal of Pharmaceutics - September 18, 2018 Category: Drugs & Pharmacology Source Type: research

Designing an ADME Liquid Formulation with Matching Exposures to an Amorphous Dosage Form
Publication date: Available online 18 September 2018Source: International Journal of PharmaceuticsAuthor(s): Hanmi Xi, Zhen Yang, Aditya Tatavarti, Wei Xu, Joy Fuerst, James OrmesAbstractAmorphous Solid Dispersion (ASD) based formulations have been frequently used to improve the bioavailability of poorly water soluble drugs, however, common processes to produce ASDs are not feasible for Absorption, Distribution, Metabolism and Excretion (ADME) studies with radio-labeled Active Pharmaceutical Ingredients (API) due to the complications associated with radioactive material handling. Liquid formulations are routinely used to s...
Source: International Journal of Pharmaceutics - September 18, 2018 Category: Drugs & Pharmacology Source Type: research

Assessment of HBEC-5i endothelial cell line cultivated in astrocyte conditioned medium as a human blood-brain barrier model for ABC drug transport studies
Publication date: Available online 18 September 2018Source: International Journal of PharmaceuticsAuthor(s): Clémentine Puech, Sophie Hodin, Valérie Forest, Zhiguo He, Patrick Mismetti, Xavier Delavenne, Nathalie PerekAbstractEndothelial cells are main components of the Blood-Brain Barrier (BBB) and form a tight monolayer that regulates the passage of molecules, with the ATP-Binding Cassette (ABC) transporters efflux pumps. We have developed a human in vitro model of HBEC-5i endothelial cells cultivated alone or with human astrocytes conditioned medium on insert. HBEC-5i cells showed a tight monolayer within ...
Source: International Journal of Pharmaceutics - September 18, 2018 Category: Drugs & Pharmacology Source Type: research