Abstract:
:Polydimethylsiloxane (PDMS)-based levonorgestrel intrauterine systems (LNG-IUSs) contain a large amount of potent LNG, and therefore it is important to understand the impact of product design parameters on the in vitro and in vivo performance to ensure safety and efficacy, as well as to avoid serious side effects resulting from dose dumping. LNG-IUS is a complex drug-device combination product, and its formulation design, requires consideration of additional factors such as device configuration and dimensions, in addition to formulation and processing parameters. In this study, ten qualitatively (Q1) and quantitatively (Q2) equivalent LNG-IUSs were manufactured with differences in source (supplier) and dimensions (i.e., thickness) of the outer membrane, drug particle size, dimensions of the drug reservoir (i.e., inner diameter), as well as configuration of the entire IUS. A real-time in vitro release testing method was developed for the LNG-IUSs. In addition, an accelerated release testing method was developed using hydro-alcoholic media in order to reduce the time associated with formulation design. Source variations and thickness of their outer membranes had a great impact on the in vitro drug release from the LNG-IUSs. It was demonstrated that the thicker the outer membrane, the slower the drug release rate. The physicochemical properties of the outer membranes obtained from different sources were characterized to understand their impact on the in vitro drug release of the LNG-IUSs. The composition and mechanical strength may play a role in differences in drug release. The LNG-IUS formulation prepared with the larger drug particle size showed a slightly slower daily release rate. The drug release rates from the compositionally equivalent LNG-IUSs linearly correlated to the surface area of the corresponding drug reservoirs. Another factor that affected the drug release rate was the configuration of the entire IUS. It was shown that the placement of the outer membrane was significant, i.e. whether the ends of the drug reservoir were covered or not. It is important to note that real-time release showed zero-order release kinetics over the test period of approximately 900 days. The current study provides a comprehensive understanding of the impact of product design parameters on the in vitro drug release of LNG-IUSs. In addition, the developed real-time and accelerated release testing methods showed good discriminatory ability for compositionally equivalent LNG-IUSs prepared using different product design parameters.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Bao Q,Zou Y,Wang Y,Choi S,Burgess DJdoi
10.1016/j.ijpharm.2020.119135subject
Has Abstractpub_date
2020-03-30 00:00:00pages
119135eissn
0378-5173issn
1873-3476pii
S0378-5173(20)30119-8journal_volume
578pub_type
杂志文章abstract::Hesperetin, an aglycone of the flavanone hesperidin, is a potential candidate for the treatment of diabetic retinopathy and macular edema. The purpose of this investigation was to determine solubility, stability and in vitro permeability characteristics of hesperetin across excised rabbit corneas. Aqueous and pH depen...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2010.04.036
更新日期:2010-07-15 00:00:00
abstract::Cell replacement therapy is a widely discussed novel concept of medical treatment. The increased knowledge in the stem cell field, particularly pluripotent stem cells, potentially provides powerful tools for this therapeutic concept. A large number of disease characterized by the loss of functional cells are potential...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2009.03.003
更新日期:2009-11-03 00:00:00
abstract::To optimize the in vivo ocular transfection efficiency of plasmid DNA (pDNA)/cationic liposome complexes, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/dioleoylphosphatidylethanolamine (DOPE) (1:1 molar ratio) liposomes and DOTMA/cholesterol (Chol) (1:1 molar ratio) liposomes were prepared with...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2004.03.013
更新日期:2004-07-08 00:00:00
abstract::Cancer cells increase their metabolism to produce the energy and biomolecules necessary for growth and proliferation. Thus, energy metabolism pathways may serve as targets for anti-cancer therapy. NCL-240 is a second generation anti-cancer drug belonging to the PITenins class of PI3K-Akt inhibitors. Our analysis sugge...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.08.095
更新日期:2017-10-30 00:00:00
abstract::A new targeted intravenous conjugate of nystatin with pentaerythritol poly(ethylene glycol)ether has been prepared and characterised (NY(4)-sPEG, M=25 160). The conjugate contains a beta-d-glucopyranoside molecular switch sensitive to beta-glucosidases (E.C.3.2.1.21), which are specifically present in the enzyme outfi...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2009.10.034
更新日期:2010-02-15 00:00:00
abstract::In a previous study we demonstrated the dependency of cyclosporine (CyA) pharmacokinetics on the age and gender of Wistar rats given 10 mg/kg intravenously. The present study has been conducted under the same experimental conditions (10 mg/kg as a single intravenous dose) to identify the mechanisms behind such differe...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(99)00461-5
更新日期:2000-03-20 00:00:00
abstract::The purpose of the present study was to design an optimal ketoprofen gel with appropriate penetration rate, shortened lag time and acceptable skin irritation. The combination of different mechanism enhancers including nonivamide, menthol and ethanol were used as multi-enhancers for producing a synergistic enhancement ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2007.02.020
更新日期:2007-07-18 00:00:00
abstract::Distribution of PLGA-microparticles in porcine skin, after its topical application, was studied in vitro using microparticles containing rhodamine as a fluorescent probe. PLGA-microparticles loaded with rhodamine were prepared using a solvent evaporation technique. Skin distribution of fluorescent microparticles was p...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(01)00811-0
更新日期:2001-09-11 00:00:00
abstract::A novel drug delivery system (DDS) with sustained release properties was developed to allow ocular protein delivery. The DDS developed is aimed at overcoming stability issues during preparation such as denaturation of proteins caused by shear forces applied or due to elevated temperatures and air entrapment potentiall...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.01.042
更新日期:2015-03-15 00:00:00
abstract::Multilayered coated liposomes were prepared using the layer-by-layer (LbL) technique in an effort to improve their stability in biological media. The formulation strategy was based on the alternate deposition of two biocompatible and biodegradable polyelectrolytes - poly(L-lysine) (PLL) and poly(L-glutamic acid) (PGA)...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119568
更新日期:2020-08-30 00:00:00
abstract::Chitosan (CS) is a biodegradable and biocompatible polysaccharide which displays immune-stimulatory effects and anti-bacterial properties to facilitate wound closure. Over the years, different CS-based dressings have been developed; however, most of them are not fully biodegradable due to the involvement of synthetic ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2019.05.045
更新日期:2019-07-20 00:00:00
abstract::Bisphenol A (BPA) is an endocrine disruptor found in food containers and plastic beverages and also in medical devices such as dialyzers. The aim of this study is while taking into account the BPA originating in medical devices and the water used in dialysate production, to provide the first published investigation of...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.03.003
更新日期:2016-05-30 00:00:00
abstract::The characterization of a pharmaceutical microemulsion system with glycerol monolaurate as oil, ethanol as cosurfactant, Tween 40 as surfactant, sodium diacetate and water, and the antimicrobial activities against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Aspergillus niger and Penic...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2010.05.022
更新日期:2010-08-16 00:00:00
abstract::Effects of pH and co-solvents on the bio-mimetic artificial membrane permeation assay were investigated to determine the optimal conditions for the prediction of oral absorption. The permeability (P(am)) of 33 structurally diverse drugs to the PC/PE/PS/PI/CHO/1,7-octadiene membrane system (bio-mimetic lipid (BML) memb...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(01)00845-6
更新日期:2001-10-09 00:00:00
abstract::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 ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.04.052
更新日期:2018-07-10 00:00:00
abstract:PURPOSE:Evaluate ex vivo the bacterial metabolism induced degradation rates of mesalamine (negative control), metronidazole and olsalazine in distal ileum and in cecum. METHODS:The contents of distal ileum and cecum were collected during colonoscopy under anaerobic conditions from twelve healthy adults in the fasted a...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.10.015
更新日期:2017-12-20 00:00:00
abstract::A simple and readily manoeuverable method for preparing immuno-magnetic liposomes that indigenously contain binding sites for attaching other molecules like antibodies on their exterior surface is described. In this method magnetic unilamellar vesicles are prepared from a mixture of phosphatidylcholine, cholesterol, s...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00667-0
更新日期:2001-03-14 00:00:00
abstract::Continuously increasing application of silver nanoparticles (AgNPs) requires information on their safety and performance under biological conditions. Assessment of AgNPs in biological systems is also related to availability of robust toxicological methods for evaluation of toxic potential of AgNPs and information on t...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.05.026
更新日期:2017-07-15 00:00:00
abstract::Selective relaxation rate measurements effectively proved the affinity of dexamethasone 21-phosphate disodium salt for quaternary ammonium-chitosan conjugates, their thiolated derivatives and the corresponding nanostructured aggregates. Affinity was also probed by dynamic dialysis. The release profile of dexamethasone...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2013.12.018
更新日期:2014-01-30 00:00:00
abstract::Inhalation drug delivery has seen a swift rise in the use of dry powder inhalers (DPIs) to treat chronic respiratory conditions. However, universal adoption of DPIs has been restrained due to their low efficiencies and significant drug losses in the mouth-throat region. Aerosol efficiency of DPIs is closely related to...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119966
更新日期:2021-01-05 00:00:00
abstract::The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly water-soluble drugs c...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2012.04.066
更新日期:2013-08-30 00:00:00
abstract::Conventional lipid microspheres (LM) were prepared using soybean oil and lipid at a 5.5:1 weight ratio with lipid phase consisting of PC (phosphatidyl choline):CH (cholesterol) (1:0.5) by molar ratio. The average diameter of the particles was 150 nm. Long-circulating microspheres (S-LM) were also prepared similarly bu...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2004.11.017
更新日期:2005-02-16 00:00:00
abstract::Mixing of raw materials (drug+polymer) in the investigated mini pharma melt extruder is achieved by using co-rotating conical twin screws and an internal recirculation channel. In-line Raman spectroscopy was implemented in the barrels, allowing monitoring of the melt during processing. The aim of this study was twofol...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.11.065
更新日期:2017-01-30 00:00:00
abstract::A method for predicting dissolution profiles of directly compressed tablets for a fixed sustained release formulation manufactured in a continuous direct compaction (CDC) system is presented. The methodology enables real-time release testing (RTRt). Tablets were made at a target drug concentration of 9% Acetaminophen,...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.08.033
更新日期:2016-10-15 00:00:00
abstract::Docetaxel (DTX) is one of the important antitumor drugs, being used in several common chemotherapies to control leading cancer types. Severe toxicities of the DTX are prominent due to sudden parenteral exposure of desired loading dose to maintain the therapeutic concentration. Field of nanotechnology is leading to res...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2017.07.018
更新日期:2017-08-30 00:00:00
abstract::Symprove, a multi-strain probiotic, has been shown to exert a mild anti-inflammatory effect in patients with ulcerative colitis (UC). We examined stool samples from 3 patients with UC in order to create microbiotas in an in-vitro gut model. The effects of Symprove on bacterial diversity and metabolic activity in the m...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119648
更新日期:2020-09-25 00:00:00
abstract::Hot-melt coating (HMC) as a solvent-free technology grants faster and more economic coating processes with reduced risk of dissolving the drug during the process. Moreover, traditional coating equipment can be modified to enable the HMC process. Despite the indubitable advantages and feasibility of the process, HMC is...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2017.08.086
更新日期:2017-11-30 00:00:00
abstract::The purpose of this work was to investigate the in vitro transdermal delivery of low molecular weight heparin (LMWH). Hairless rat skin was mounted on Franz diffusion cells and treated with various enhancement strategies. Passive flux was essentially zero and remained low even after iontophoresis (0.065 U cm(-2) h(-1)...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2008.08.028
更新日期:2009-01-05 00:00:00
abstract::For use in chronic oral chemotherapeutic regimens, the potent anticancer drug docetaxel needs a solid oral dosage form. Because docetaxel has a very low permeability and a very low aqueous solubility (biopharmaceutical classification system class IV), a pharmacokinetic booster was combined with a newly developed solid...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ijpharm.2011.08.041
更新日期:2011-11-28 00:00:00
abstract::For many years, researchers have worked with supramolecular structures involving inclusion complexes with cyclodextrins. These studies have resulted in new commercially available drugs which have been of great benefit. More recently, studies using nanoparticles, including nanosystems containing cyclodextrins, have bec...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2019.01.041
更新日期:2019-03-25 00:00:00