Determination of permeation pathways of hydrophilic or hydrophobic dyes through the mammary papilla
Publication date: 10 July 2018 Source:International Journal of Pharmaceutics, Volume 545, Issues 1–2 Author(s): Samantha L. Kurtz, Louise B. Lawson The transport pathways and permeation kinetics of lipophilic and hydrophilic fluorescent dyes through porcine mammary papillae were visualized and quantified. Porcine mammary papillae, removed from full-thickness abdominal tissue, were positioned in a Franz diffusion cell for passive diffusion studies. Solutions containing the fluorescent dyes were applied topically for time periods ranging from 30 min to 48 h. Dye concentrations in tissue and Franz diffusion compart...
Source: International Journal of Pharmaceutics - April 28, 2018 Category: Drugs & Pharmacology Source Type: research

Hydrogels in three-dimensional dendritic cell (MUTZ-3) culture as a scaffold to mimic human immuno competent subcutaneous tissue
The objective of this study was to develop a 3D cell culture model of the human subcutaneous tissue, allowing the prediction of the immunogenicity of subcutaneously injected therapeutic proteins. Several hydrogels were evaluated as scaffolds to mimic the human subcutaneous tissue in vitro. Cytocompatibility of the hydrogels with the human myelomonocytic cell line (MUTZ-3) was investigated, as well as their influence on cellular phenotype changes. Elastic Young’s moduli in compression of the hydrogels were measured by a texture analyser and compared to ex vivo human samples. MUTZ-3 cells were differentiated into dendr...
Source: International Journal of Pharmaceutics - April 27, 2018 Category: Drugs & Pharmacology Source Type: research

Redox-responsive microbeads containing thiolated pectin-doxorubicin conjugate inhibit tumor growth and metastasis: An in vitro and in vivo study
The objective of this study was to investigate the in vitro cytotoxicity and in vivo anticancer efficacy of redox-responsive microbeads containing thiolated pectin–doxorubicin (DOX) conjugate. Oral microbeads were coated with an enteric polymer to protect the drug from release in the upper gastrointestinal (GI) tract and allow redox-triggered drug release in the colon. Morphology, particle size, drug content, and in vitro drug release behavior of the microbeads were characterized; in vitro cytotoxicity was tested on mouse colon carcinoma, human colorectal adenocarcinoma, and human bone osteosarcoma cell lines. In viv...
Source: International Journal of Pharmaceutics - April 27, 2018 Category: Drugs & Pharmacology Source Type: research

Investigating elastic relaxation effects on the optical properties of functionalised calcium carbonate compacts using optics-based Heckel analysis
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Prince Bawuah, Anssi-Pekka Karttunen, Daniel Markl, Cathy Ridgway, Ossi Korhonen, Patrick Gane, J. Axel Zeitler, Jarkko Ketolainen, Kai-Erik Peiponen Heckel analysis is a widely used method for the characterisation of the compression behaviour of pharmaceutical samples during the preparation of solid dosage formulations. The present study introduces an optical version of the Heckel equation that is based on a combination of the conventional Heckel equation together with the linear relationship defined between the e...
Source: International Journal of Pharmaceutics - April 26, 2018 Category: Drugs & Pharmacology Source Type: research

Enhanced brain delivery with lower hepatic exposure of lazaroid loaded nanostructured lipid carriers developed using a design of experiment approach
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): P. Gadgil, J. Shah, D.S.-L. Chow The current study was designed to develop and optimize lazaroid loaded nano-structured lipid carriers (LAZ-NLCs) using design of experiment approach for enhancing lazaroid brain exposure. Response surface plots were used to determine the effects of independent variables (amount of PEGylating agent and liquid lipid) on dependent variables (particle size, zeta potential and encapsulation efficiency), while numerical optimization was used for optimizing LAZ-NLCs composition. The optima...
Source: International Journal of Pharmaceutics - April 26, 2018 Category: Drugs & Pharmacology Source Type: research

Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Hossam Kadry, Taslim A. Al-Hilal, Ali Keshavarz, Farzana Alam, Changxue Xu, Abraham Joy, Fakhrul Ahsan Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loa...
Source: International Journal of Pharmaceutics - April 26, 2018 Category: Drugs & Pharmacology Source Type: research

Formulation characteristics and in vitro release testing of cyclosporine ophthalmic ointments
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Yixuan Dong, Haiou Qu, Naresh Pavurala, Jiang Wang, Vasanthakumar Sekar, Marilyn N. Martinez, Raafat Fahmy, Muhammad Ashraf, Celia N. Cruz, Xiaoming Xu The aim of the present study was to investigate the relationship between formulation/process variables versus the critical quality attributes (CQAs) of cyclosporine ophthalmic ointments and to explore the feasibility of using an in vitro approach to assess product sameness. A definitive screening design (DSD) was used to evaluate the impact of formulation and proces...
Source: International Journal of Pharmaceutics - April 26, 2018 Category: Drugs & Pharmacology Source Type: research

Limitations of high dose carrier based formulations
Conclusion As the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Influence of excipients on physical and aerosolization stability of spray dried high-dose powder formulations for inhalation
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Nivedita Shetty, Heejun Park, Dmitry Zemlyanov, Sharad Mangal, Sonal Bhujbal, Qi (Tony) Zhou The aim of this study is to investigate the influence of excipients on physical and aerosolization stability of spray dried Ciprofloxacin dry powder inhaler formulations. The model drug, Ciprofloxacin hydrochloride, was co-spray dried with excipients such as disaccharides (sucrose, lactose, trehalose), mannitol and l-leucine. The spray dried samples were stored at two different relative humidity (RH) conditions of: (1) 20% ...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Hollow mesoporous hydroxyapatite nanostructures; smart nanocarriers with high drug loading and controlled releasing features
We report the development of effective drug loaded nanocarriers to combat multidrug resistant infection especially in case of osteomyelitis. The hollow mesoporous hydroxyapatite nanoparticles (hmHANPs) and solid/non-hollow hydroxyapatite nanoparticles (sHANPs) were synthesized by core–shell and co-precipitation techniques respectively. High encapsulation of the drug (ciprofloxacin) was observed in hmHANPs as compared to sHANPs, which may be due to the hollow porous structure of hmHANPs. These nanoparticles were characterized by scanning electron microscope (FESEM), N2 adsorption/desorption, Fourier transform infrared...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Poly(propyleneimine) glycodendrimers non-covalently bind ATP in a pH- and salt-dependent manner – model studies for adenosine analogue drug delivery
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Michał Gorzkiewicz, Adam Buczkowski, Dietmar Appelhans, Brigitte Voit, Łukasz Pułaski, Bartłomiej Pałecz, Barbara Klajnert-Maculewicz Adenosine analogue drugs (such as fludarabine or cladribine) require transporter-mediated uptake into cells and subsequent phosphorylation for anticancer activity. Therefore, application of nanocarrier systems for direct delivery of active triphosphate forms has been proposed. Here, we applied isothermal titration calorimetry and zeta potential titration to determine the stoichi...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Solubility determination of raloxifene hydrochloride in ten pure solvents at various temperatures: Thermodynamics-based analysis and solute –solvent interactions
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Abdul Ahad, Faiyaz Shakeel, Omar Ali Alfaifi, Mohammad Raish, Ajaz Ahmad, Fahad I. Al-Jenoobi, Abdullah M. Al-Mohizea The purpose of the present study was to determine the solubility of raloxifene hydrochloride (RHCl) in ten solvents: water, ethanol, isopropyl alcohol (IPA), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), Transcutol, 1-butanol, dimethyl sulfoxide (DMSO), and ethyl acetate (EA) at temperatures of 298.2–323.2 K and a pressure of 0.1 MPa. The solubility data o...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Pseudomonas aeruginosa pyocyanin production reduced by quorum-sensing inhibiting nanocarriers
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Hoang D. Lu, Elizabeth Pearson, Kurt D. Ristroph, Gregg A. Duncan, Laura M. Ensign, Jung Soo Suk, Justin Hanes, Robert K. Prud'homme Pseudomonas aeruginosa is an opportunistic gram-negative pathogen that causes a wide range of infections; it is becoming increasingly difficult to treat due to antibiotic resistance. Quorum-sensing (QS) based therapeutics, which function by disabling pathogen virulence without killing pathogens, are a promising class of drugs that may be used to treat bacterial infections without elic...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Sustained ophthalmic delivery of highly soluble drug using pH-triggered inner layer-embedded contact lens
In conclusion, cellulose acetate/Eudragit S100 inner layer-embedded contact lenses are quite promising as controlled-release carrier of highly water soluble drug for ophthalmic delivery. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Ville Vartiainen, Janne Raula, Luis M. Bimbo, Jenni Viinamäki, Janne T. Backman, Nurcin Ugur, Esko Kauppinen, Eva Sutinen, Emmi Joensuu, Katri Koli, Marjukka Myllärniemi The aim of this work was to study the antifibrotic effect of pulmonary administration of tilorone to lung fibrosis. L-leucine coated tilorone particles were prepared and their aerosolization properties were analyzed using two dry powder inhalers (Easyhaler and Twister). In addition, the biological activity and cell monolayer permeation wa...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmaceutical 3D printing: Design and qualification of a single step print and fill capsule
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Derrick M. Smith, Yash Kapoor, Gerard R. Klinzing, Adam T. Procopio Fused deposition modeling (FDM) 3D printing (3DP) has a potential to change how we envision manufacturing in the pharmaceutical industry. A more common utilization for FDM 3DP is to build upon existing hot melt extrusion (HME) technology where the drug is dispersed in the polymer matrix. However, reliable manufacturing of drug-containing filaments remains a challenge along with the limitation of active ingredients which can sustain the processing r...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): A rapid test for enteric coating thickness and integrity of controlled release pellet formulations
In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic soluti...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Enhanced oral absorption of sorafenib via the layer-by-layer deposition of a pH-sensitive polymer and glycol chitosan on the liposome
This study aimed to design the effective formulation of sorafenib (SF) to enhance the oral drug absorption. Three liposomal formulations of SF were prepared including uncoated liposome (SF-Lip), glycol chitosan-coated liposome (GC-SF-Lip), and Eudragit S100-glycol-chitosan coated liposome (SGC-SF-Lip). All formulations showed a narrow size distribution with a high encapsulation efficiency. Both GC-SF-Lip and SGC-SF-Lip exhibited good stability at acidic and neutral pHs without any significant drug leakage, while SF-Lip appeared to be unstable at pH 1.2. In the case of double coated SGC-SF-Lip, its size changed significantl...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in situ gel: Fabrication, in vitro optimization and in vivo evaluation
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Mona Basha, Mona M. AbouSamra, Ghada A. Awad, Soheir S. Mansy Wound healing following skin injury is a natural phenomenon that usually lacks quality, rapidity, and aesthetics. Thus, the purpose of this study was to fabricate a new easily applied in situ gel of cefadroxil (CDX) loaded chitosan nanoparticles (CDX-CSNPs) that could promote wound healing, capable of inhibiting the possible accompanying bacterial infection. The nanoparticles were prepared by double emulsion technique and the influence of formulation par...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Structural properties for selective and efficient l-type amino acid transporter 1 (LAT1) mediated cellular uptake
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Jussi Kärkkäinen, Mikko Gynther, Tarja Kokkola, Aleksanteri Petsalo, Seppo Auriola, Maija Lahtela-Kakkonen, Krista Laine, Jarkko Rautio, Kristiina M. Huttunen l-Type amino acid transporter 1 (LAT1) is a sodium-independent exchanger transporting large neural amino acids and several amino-acid mimicking drugs across the cell membranes. LAT1 is highly expressed at the blood brain barrier (BBB) and in numerous cancer cells and is therefore a potential drug target. However, structural features affecting the ab...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Downstream processing of a ternary amorphous solid dispersion: The impacts of spray drying and hot melt extrusion on powder flow, compression and dissolution
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Mark T. Davis, Catherine B. Potter, Gavin M. Walker Downstream processing aspects of a stable form of amorphous itraconazole exhibiting enhanced dissolution properties were studied. Preparation of this ternary amorphous solid dispersion by either spray drying or hot melt extrusion led to significantly different powder processing properties. Particle size and morphology was analysed using scanning electron microscopy. Flow, compression, blending and dissolution were studied using rheometry, compaction simulation and...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

PAMAM dendrimers as a carbamazepine delivery system for neurodegenerative diseases: A biophysical and nanotoxicological characterization
In conclusion, a stable and biocompatible drug delivery system based on the DG4.5 capable of complex the CBZ has been developed. This achievement highlights the advantages of using negatively charged dendrimers for nanomedicine. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Impact of functionalized particle structure on roll compaction/dry granulation and tableting of calcium carbonate
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Simon Grote, Peter Kleinebudde The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO3) was investigated. Therefore, a milled grade of CaCO3 was compared to different binary mixtures of milled and functionalized CaCO3. Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the p...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

A fast and reliable DSC-based method to determine the monomolecular loading capacity of drugs with good glass-forming ability in mesoporous silica
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Nele-Johanna Hempel, Katharina Brede, Niels Erik Olesen, Natalja Genina, Matthias Manne Knopp, Korbinian Löbmann The aim of this study was to introduce a fast and reliable differential scanning calorimetry (DSC)-based method to determine the monomolecular loading capacity of drugs with good glass-forming ability in mesoporous silica (MS). The proposed method is based on a solvent-free melting/fusion of drug into the MS during a heat-cool-heat cycle in the DSC. Overloaded drug-MS systems were analyzed in the DS...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Thermodynamic compatibility between cyclodextrin supramolecular complexes and surfactant
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Larissa H.R. Meira, Guilherme A.B. Soares, Homero I.M. Bonomini, Juliana Fedoce Lopes, Frederico B. De Sousa Supramolecular structures based on cyclodextrins have been extensively used for drug delivery systems over decades. However, combining host and guest molecules in a pharmaceutical formulation is not a trivial process, being one of the majors concern the inclusion complex compatibility with other excipients presented in the final formulation. Herein, experimental and theoretical calculations were used to inve...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Solubility and bioavailability improvement of pazopanib hydrochloride
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Maikel Herbrink, Stefanie L. Groenland, Alwin D.R. Huitema, Jan H.M. Schellens, Jos H. Beijnen, Neeltje Steeghs, Bastiaan Nuijen The anti-cancer drug pazopanib hydrochloride (PZH) has a very low aqueous solubility and a variable oral bioavailability. A new pharmaceutical formulation with an improved solubility may enhance the bioavailability and reduce the variability. A broad selection of polymer excipients was tested for their compatibility and solubilizing properties by conventional microscopic, thermal and spec...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Microparticle preparation by a propylene carbonate emulsification-extraction method
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Daris Grizić, Alf Lamprecht The use of various harmful organic solvents for microparticle formulations is still widespread. Here, an alternative low toxicity solvent (propylene carbonate; PC) is proposed for the preparation of poly(lactic-co-glycolic-acid) (PLGA) microparticles. Based on the classical emulsification-solvent extraction methodology, the use of PC offers the unique advantage of an additional solvent extraction step using hydrolytic solvent cleavage during microparticle preparation. Spherical, rough-s...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Qualitative and quantitative analysis of lateral diffusion of drugs in human skin
This study aimed to qualitatively and quantitatively analyze lateral diffusion of drugs in dermatomed human skin. Lateral diffusion of calcein and methylene blue dyes in skin was investigated using confocal laser microscopy, calcein imaging, and histology studies. In in vitro permeation studies, two linear microdialysis probes were inserted into the dermis of untreated, poly lacto-glycolic acid microneedle-treated, and ablative laser-treated skin such that one was in the center of the diffusion area and the other was parallel, at 8 mm from the central probe. Skin was mounted on Franz cells, sandwiched between donor conta...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

The effect of mesoporous silica impregnation on tribo-electrification characteristics of flurbiprofen
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Mohammad Suhail Afzal, Faiza Zanin, Muhammad Usman Ghori, Marta Granollers, Enes Šupuk Tribo-electrification is a common occurrence within the pharmaceutical industry where solid dosage forms constitute majority of pharmaceutical formulations. Tribo-electrification of powders leads to a range of complications such as adhesion of particulate material to the processing equipment resulting in segregation, affecting the content uniformity. Flurbiprofen, a highly charging material, was used as a model drug to inv...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Comparison of pH and motility of the small intestine of healthy subjects and patients with symptomatic constipation using the wireless motility capsule
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): A. Aburub, M. Fischer, M. Camilleri, J.R. Semler, H.M. Fadda Gastrointestinal luminal pH shows a rise from the duodenum to the terminal ileum in healthy individuals. Our objectives were to compare the pH in the proximal small intestine (SI) (first 60 min of small intestinal transit) lumen of human volunteers and patients with symptomatic constipation; to quantify contractile pressure profiles of the proximal SI, and to assess the relationship between luminally-recorded contractile pressure and small intestinal tr...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Undesired co-amorphisation of indomethacin and arginine during combined storage at high humidity conditions
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Ina Petry, Korbinian Löbmann, Holger Grohganz, Thomas Rades, Claudia S. Leopold The use of co-amorphous systems for solubility enhancement of poorly water-soluble drugs has recently gained interest in the field of pharmaceutical technology. However, undesired co-amorphisation of a drug may lead to an alteration of the performance of the drug product, e.g. the previously observed co-amorphisation of indomethacin and arginine upon storage of tablets containing both components in an initially crystalline form at ...
Source: International Journal of Pharmaceutics - April 25, 2018 Category: Drugs & Pharmacology Source Type: research

Improvement of intestinal transport, absorption and anti-diabetic efficacy of berberine by using Gelucire44/14: In vitro, in situ and in vivo studies
In conclusion, Gelucire44/14 exhibited potential for enhancing the oral absorption of BBR, thereby improving the antidiabetic efficacy of BBR. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - April 17, 2018 Category: Drugs & Pharmacology Source Type: research

Electrostatically assembled dendrimer complex with a high-affinity protein binder for targeted gene delivery
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Jong-won Kim, Joong-jae Lee, Joon Sig Choi, Hak-Sung Kim Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-r...
Source: International Journal of Pharmaceutics - April 15, 2018 Category: Drugs & Pharmacology Source Type: research

Mass Median Plume Angle: A novel approach to characterize plume geometry in solution based pMDIs
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Daniel Moraga-Espinoza, Eli Eshaghian, Hugh D.C. Smyth High-speed laser imaging (HSLI) is the preferred technique to characterize the geometry of the plume in pressurized metered dose inhalers (pMDIs). However, current methods do not allow for simulation of inhalation airflow and do not use drug mass quantification to determine plume angles. To address these limitations, a Plume Induction Port Evaluator (PIPE) was designed to characterize the plume geometry based on mass deposition patterns. The method is e...
Source: International Journal of Pharmaceutics - April 13, 2018 Category: Drugs & Pharmacology Source Type: research

Long chain fatty acid conjugation remarkably decreases the aggregation induced toxicity of Amphotericin B
Publication date: 10 June 2018 Source:International Journal of Pharmaceutics, Volume 544, Issue 1 Author(s): Kaushik Thanki, Rameshwar Prajapati, Abhay T. Sangamwar, Sanyog Jain Amphotericin B is an antimicrobial membrane-acting drug used in the treatment of systemic fungal infections. However, the clinical utility of AmB is often low as a result of (i) dose-limiting toxicity which is closely associated with its aggregation wherein the selectivity for its target i.e. ergosterol in fungal membranes is diminished and (ii) limited oral bioavailablity. The latter is attributed to the unfavorable physicochemical properties of ...
Source: International Journal of Pharmaceutics - April 13, 2018 Category: Drugs & Pharmacology Source Type: research

Defined drug release from 3D-printed composite tablets consisting of drug-loaded polyvinylalcohol and a water-soluble or water-insoluble polymer filler
In this study, we fabricated composite tablets consisting of two components, a drug and a filler, by using a fused deposition modeling-type 3D printer. Polyvinylalcohol (PVA) polymer containing calcein (a model drug) was used as the drug component and PVA or polylactic acid (PLA) polymer without drug was used as the water-soluble or water-insoluble filler, respectively. Various kinds of drug-PVA/PVA and drug-PVA/PLA composite tablets were designed, and the 3D-printed tablets exhibited good formability. The surface area of the exposed drug component is highly correlated with the initial drug release rate. Composite tablets ...
Source: International Journal of Pharmaceutics - April 11, 2018 Category: Drugs & Pharmacology Source Type: research

Polysorbate 20 alters the oral bioavailability of etoposide in wild type and mdr1a deficient Sprague-Dawley rats
In conclusion, PS20 increases oral bioavailability of etoposide through inhibition of P-glycoprotein. However, the use of the excipient may be challenged by etoposide retention at higher concentrations. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - April 11, 2018 Category: Drugs & Pharmacology Source Type: research

Preparation of sustained release capsules by electrostatic dry powder coating, using traditional dip coating as reference
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Yan Yang, Lian Shen, Feng Yuan, Hui Fu, Weiguang Shan Lately, a great deal of attention is being paid to capsule coating, since the coat protects active pharmaceutical ingredients (APIs) from damage, as is in the case of tablet and pellet. However, moisture and heat sensitivity of gelatin shells make it challenging to coat capsules using the conventional aqueous coating techniques. In an effort to overcome this challenge, the present study aims to coat capsules using two different coating techniques: electr...
Source: International Journal of Pharmaceutics - April 11, 2018 Category: Drugs & Pharmacology Source Type: research

Current regulatory requirements and practical approaches for stability analysis of pharmaceutical products: A comprehensive review
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Pinaki Sengupta, Bappaditya Chatterjee, Rakesh Kumar Tekade Different regulatory guidelines recommend establishing stability profile of pharmaceuticals at the time of drug development. The expiry date, retesting period and storage conditions of active drugs or products are established through stability analysis. Several regulatory guidelines exist for stability testing of pharmaceuticals. Mostly, ICH stability guidelines are followed in practice. This guideline recommends to validate stability indicating me...
Source: International Journal of Pharmaceutics - April 11, 2018 Category: Drugs & Pharmacology Source Type: research

Manipulation of spray-drying conditions to develop dry powder particles with surfaces enriched in hydrophobic material to achieve high aerosolization of a hygroscopic drug
This study aimed to develop dry powder particles with surfaces enriched in hydrophobic material by manipulation of spray-drying conditions and to investigate the effect of hydrophobic surface enrichment on aerosolization of hygroscopic drug. The composite dry powder formulations of kanamycin (hygroscopic drug) and rifampicin (hydrophobic drug) were produced by systematically (23 full factorial design) varying the drug ratio, co-solvent composition and inlet temperature using Buchi B-290 Mini Spray-Dryer. All the composite powder particles were inhalable in size (3.1–3.9 µm), wrinkled, flake-shaped and amorpho...
Source: International Journal of Pharmaceutics - April 10, 2018 Category: Drugs & Pharmacology Source Type: research

Hybrid nanoparticles as a new technological approach to enhance the delivery of cholesterol into the brain
This article aims to investigate the production of hybrid nanoparticles composed by Chol and PLGA (MIX-NPs) modified with g7 ligand for BBB crossing. We described the impact of ratio between components (Chol and PLGA) and formulation process (nanoprecipitation or single emulsion process) on physico-chemical and structural characteristics, we tested MIX-NPs in vitro using primary hippocampal cell cultures evaluating possible toxicity, uptake, and the ability to influence excitatory synaptic receptors. Our results elucidated that both formulation processes produce MIX-NPs with a Chol content higher that 40%, meaning that Cho...
Source: International Journal of Pharmaceutics - April 7, 2018 Category: Drugs & Pharmacology Source Type: research

Improved properties of fine active pharmaceutical ingredient powder blends and tablets at high drug loading via dry particle coating
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Kuriakose Kunnath, Zhonghui Huang, Liang Chen, Kai Zheng, Rajesh Davé It has been shown that dry coating cohesive active pharmaceutical ingredients (APIs) with nano-silica can improve packing and flow of their blends, facilitating high speed direct compression tableting. This paper examines the broader scope and generality of previous work by examining three fine APIs; micronized Acetaminophen (mAPAP), coarse Acetaminophen (cAPAP) and micronized Ibuprofen (mIBU), and considers dry coating with both h...
Source: International Journal of Pharmaceutics - April 7, 2018 Category: Drugs & Pharmacology Source Type: research

Effects of cationic liposomes with stearylamine against virus infection
In this study, we demonstrated that cationic liposomes with incorporated stearylamine (SA) inhibit viral infectivity without preloaded active pharmaceutical ingredients. Specifically, we correlated physiochemical properties of liposomes, such as zeta potentials and particle sizes, with virus infectivity using the BacMam™ reagent, which is based on recombinant baculovirus (BV). Compared with neutral or negatively-charged liposomes, SA liposomes suppressed BV infectivity in several mammalian cell lines, including A549 cells. SA liposomes inhibited BV infection over 80% by optimizing the liposomal concentration and expo...
Source: International Journal of Pharmaceutics - April 7, 2018 Category: Drugs & Pharmacology Source Type: research

Modeling the effects of material properties on tablet compaction: A building block for controlling both batch and continuous pharmaceutical manufacturing processes
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): M.S. Escotet-Espinoza, S. Vadodaria, F.J. Muzzio, M.G. Ierapetritou As the pharmaceutical industry modernizes its manufacturing practices and incorporates more efficient processing approaches, it is important to reevaluate which process design elements affect product quality and the means to study these systems. The purpose of this work is to provide insight on a methodology to correlate the effect of raw material properties to equipment and process performance using both data-driven and semi-empirical mode...
Source: International Journal of Pharmaceutics - April 6, 2018 Category: Drugs & Pharmacology Source Type: research

On the dilemma of fractal or fractional kinetics in drug release studies: A comparison between Weibull and Mittag-Leffler functions
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Kosmas Kosmidis, Panos Macheras We compare two of the most successful models for the description and analysis of drug release data. The fractal kinetics approach leading to release profiles described by a Weibull function and the fractional kinetics approach leading to release profiles described by a Mittag-Leffler function. We used Monte Carlo simulations to generate artificial release data from euclidean and fractal substrates. We have also used real release data from the literature and found that both mo...
Source: International Journal of Pharmaceutics - April 6, 2018 Category: Drugs & Pharmacology Source Type: research

The application of STEP-technology ® for particle and protein dispersion detection studies in biopharmaceutical research
In conclusion, we could demonstrate some applications as well as limitations of this technique for biopharmaceutical samples. In comparison to orthogonal methods this technique is a great complementary approach if particle data e.g. density or refractive index can be determined. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - April 5, 2018 Category: Drugs & Pharmacology Source Type: research

Pegylated nanoparticles for the oral delivery of nimodipine: Pharmacokinetics and effect on the anxiety and cognition in mice
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Lina Clara Gayoso e Almendra Ibiapina Moreno, Maite Solas, María Cristina Martínez-Ohárriz, Egoitz Muñoz, Nereide Stela Santos-Magalhães, Maria J. Ramirez, Juan M. Irache Nimodipine may be of interest to treat behavioral alterations and memory deficits. However, its oral administration is hampered by a low bioavailability. The aim of this work was to develop pegylated nanoparticles as oral carriers of nimodipine and test their capability to both reverse the anxiety and pro...
Source: International Journal of Pharmaceutics - April 5, 2018 Category: Drugs & Pharmacology Source Type: research

A mechanistic study on tablet ejection force and its sensitivity to lubrication for pharmaceutical powders
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Bekuechukwu Uzondu, Lap Yin Leung, Chen Mao, Chia-Yi Yang Pharmaceutical powders can exhibit markedly different tablet ejection forces. The purpose of this study is to understand the factors leading to the variability of the tablet ejection force and its sensitivity to lubrication. The study showed that the tablet ejection force is mainly governed by 1) tablet diameter and thickness, 2) compact-die wall friction coefficient, and 3) residual die wall stress upon ejection; the latter was further controlled by...
Source: International Journal of Pharmaceutics - April 4, 2018 Category: Drugs & Pharmacology Source Type: research

Star-shaped poly(oligoethylene glycol) copolymer-based gels: Thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
Publication date: 30 May 2018 Source:International Journal of Pharmaceutics, Volume 543, Issues 1–2 Author(s): Mahmoud E. Soliman, Enas Elmowafy, Luca Casettari, Cameron Alexander The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glyco...
Source: International Journal of Pharmaceutics - April 4, 2018 Category: Drugs & Pharmacology Source Type: research

Kaempferol-loaded mucoadhesive nanoemulsion for intranasal administration reduces glioma growth in vitro
This study aimed to prepare nanoemulsions containing KPF with and without chitosan to investigate their potential for brain delivery following intranasal administration, and to evaluate their antitumor activity against glioma cells. KPF-loaded nanoemulsion (KPF-NE) and KPF-loaded mucoadhesive nanoemulsion (KPF-MNE) were prepared by high-pressure homogenization technique and were characterized for their globule size, zeta potential, drug content, pH, viscosity, mucoadhesive strength and morphology. KPF from KPF-MNE showed significantly higher permeation across the mucosa in ex vivo diffusion studies. Histopathological exami...
Source: International Journal of Pharmaceutics - April 4, 2018 Category: Drugs & Pharmacology Source Type: research