Abstract:
:Drug development is a long process which requires careful evaluation of the drug substance (active pharmaceutical ingredient, API), drug product (tablet, capsule etc.) and the bioperformance (both pre-clinical and clinical) before testing the efficacy of the final dosage form. The earliest assessment of a new drug substance requires an understanding of the safety and clinical performance (Phase 1) wherein faster processes (like on-site formulation strategy) have been set in place for quick clinical read-outs. One key gap that exists in this early assessment is the ability to evaluate modified release drug products. Here, an additive manufacturing approach is used to prepare polyvinyl alcohol (PVA) capsule shells using 3D printing (3DP), where the shells can be filled with either a solid or a liquid vehicle containing the API. In this work we demonstrate how we can delay the release of the API from the printed capsules allowing us to evaluate regional absorption in pre-clinical studies. By using 3DP, a new method to provide a series of release profiles is demonstrated, where the induction time of a delayed burst release is controlled by the wall thicknesses of printed capsules. New hanging baskets were also designed and 3D printed for the dissolution tests to better understand the rupturing of these capsules in an USP 2 dissolution apparatus. By controlling the wall thickness of the capsule, the induction time of drug release can be controlled from 12 to 198 min. This wide range of induction times demonstrated with this 3DP strategy is not currently available in a commercially available oral drug product form. Varying the induction times to the drug release to interrogate different regions of the GI tract is exhibited in vivo (beagle dogs) and initial analysis suggested a good in vitro/in vivo relationship (IVIVR).
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Smith D,Kapoor Y,Hermans A,Nofsinger R,Kesisoglou F,Gustafson TP,Procopio Adoi
10.1016/j.ijpharm.2018.08.055subject
Has Abstractpub_date
2018-10-25 00:00:00pages
418-428issue
1-2eissn
0378-5173issn
1873-3476pii
S0378-5173(18)30631-8journal_volume
550pub_type
杂志文章abstract::Colloid probe atomic force microscopy (AFM) was utilised to quantify the cohesive forces of salbutamol sulphate in a model non-pressurised fluorinated liquid (mHFA), in the presence of increasing concentrations of poly(ethylene glycol) (PEG; molecular weight (MW) 200, 400 and 600). In addition, samples of PEG 400 (0.0...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2006.04.016
更新日期:2006-08-31 00:00:00
abstract::Ciprofloxacin (CPX) physicochemical properties, mainly hydrophobicity and microspeciation, appear to be related with the ability of this drug to adsorb and diffuse through lipid environments. We have combined the information from fluorescence anisotropy, quenching and epifluorescence of phospholipid monolayers, to exp...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00633-6
更新日期:2003-02-18 00:00:00
abstract::This is the first report on the efficacy of a new controlled release system developed for rasagiline mesylate (RM) in a rotenone-induced rat model of Parkinson's disease (PD). PLGA microspheres in vitro released RM at a constant rate of 62.3 μg/day for two weeks. Intraperitoneal injection of rotenone (2 mg/kg/day) to ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2011.07.029
更新日期:2011-10-31 00:00:00
abstract::Resistance to antiepileptic drugs (AEDs) is a major clinical problem. The overexpression of P-glycoprotein (Pgp), one of the main transporters limiting the entry of xenobiotics into the brain, is among the factors contributing to the AED resistance. Presently, there is no consensus on the interaction of carbamazepine ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.05.023
更新日期:2018-08-25 00:00:00
abstract::This work investigates the dispersion performance of fine lactose particles as function of processing time, and compares it to the API, using Beclomethasone Dipropionate (BDP) as model API. The total load of fine particles is kept constant in the formulations while the proportions of API and lactose fines are varied. ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.03.004
更新日期:2016-05-17 00:00:00
abstract::Matrix metalloproteinases (MMPs) overexpression plays a critical role in cancer invasion and metastasis. We utilized this key feature of tumor microenvironment to develop a disease-stimuli triggered drug delivery system. Poly(acrylic acid) hydrogels were synthesized by UV polymerization and pendant MMP-2 sensitive pep...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.03.012
更新日期:2012-06-15 00:00:00
abstract::In the current study, two series of antimicrobial dressings conjugated with silver sulfadiazine (SSD) and silver nanoparticles (AgNPs) were developed and evaluated for chronic wound healing. Highly porous polycaprolactone (PCL)/polyvinyl alcohol (PVA) nanofibers were loaded with different concentrations of SSD or AgNP...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2019.04.068
更新日期:2019-06-10 00:00:00
abstract::Three innovative components (an annular gap spray system, a booster bottom and an outlet filter) have been developed by Innojet Technologies to improve fluid bed technology and to reduce the common interference factors (clogging of nozzles and outlet filters, spray loss, spray drying and fluidized bed heterogeneity). ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2004.07.051
更新日期:2005-03-03 00:00:00
abstract::Spray-freezing into liquid (SFL) is a novel particle engineering technology where a feed solution containing an active pharmaceutical ingredient (API) and pharmaceutical excipient(s) is atomized beneath the surface of a cryogenic liquid, such as liquid nitrogen. Intense atomization results from the impingement that oc...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00154-0
更新日期:2002-08-21 00:00:00
abstract::The particle size of peptide DNA condensates were studied after freeze-drying and rehydration as a function of sugar excipient, concentration, pH, DNA concentration, and peptide condensing agent. In the absence of an excipient, freeze-dried 50 microg/ml AlkCWK(18) (iodoacetic acid alkylated Cys-Typ-Lys(18)) DNA conden...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00435-x
更新日期:2000-08-10 00:00:00
abstract::The absorption enhancing effects of polyamidoamine (PAMAM) dendrimers with various concentrations and generations on the nasal absorption of fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4400 (FD4) were initially studied in rats. PAMAM dendrimers with different generations improved the...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2010.04.021
更新日期:2010-06-30 00:00:00
abstract::The forces experienced by the particles inside a twin screw granulator (TSG) are one of the most difficult parameters to measure quantitatively. However, it is possible to perform accurately this measurement through the use of dye containing calibrated microencapsulated sensors (CAMES) whose rupture is directly depend...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.12.052
更新日期:2019-03-10 00:00:00
abstract::Isoniazid (INH) is a first-line therapy for bone tuberculosis (TB), but its clinic benefits are limited by severe side-effects after long-time administration. While nano-drug delivery systems present as promising strategies for INH delivery, the therapeutic efficacies are usually suboptimal due to ineffective drug acc...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.12.083
更新日期:2019-03-10 00:00:00
abstract::Superdisintegrants are a key excipient used in immediate release formulations to promote fast tablet disintegration, therefore understanding the impact of superdisintegrant variability on product performance is important. The current study examined the impact of superdisintegrant critical material attributes (viscosit...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2020.119080
更新日期:2020-03-15 00:00:00
abstract::In this work, the influence factors of pulsed frequency, binder spray rate and atomisation pressure of a top-spray fluidised bed granulation process were studied using the Box-Behnken experimental design method. Different mathematical models were developed to predict the mean size of granules, yield, relative width of...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2013.03.057
更新日期:2013-05-20 00:00:00
abstract::The aims of this study were to examine the phase behavior of itraconazole-phenol mixtures and assess the feasibility of topical formulations of itraconazole using eutectic mixture systems. Itraconazole-phenol eutectic mixtures were characterized using differential scanning calorimetry, Fourier transform infrared spect...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.07.054
更新日期:2012-10-15 00:00:00
abstract::The dose-dependency in the pharmacokinetics of a macromolecular prodrug of methylprednisolone (MP), dextran-methylprednisolone succinate (DMP), was investigated in rats. Single doses (MP equivalent) of 2.5, 5.0, 10, 20, and 30 mg/kg of DMP were administered intravenously to rats (n=5/group), and serial blood samples (...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(01)00854-7
更新日期:2001-10-23 00:00:00
abstract::Using salmeterol xinafoate (SX) as an active pharmaceutical ingredient, the effects of carrier lactose particle type, total lactose fines content and device resistance on dry powder inhaler performance were investigated in vitro. To mimic drug levels in commercial preparations, interactive mixtures containing 0.58% w/...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.05.028
更新日期:2015-07-25 00:00:00
abstract::The role of water activity (a(w)), relative humidity (RH) and temperature on the hydration state of theophylline has been investigated. Slurry bridging experiments at controlled water activities, using powder X-ray diffraction (PXRD) and thermogravimetric analysis (TGA) to characterise the solid phase, established tha...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(02)00277-6
更新日期:2002-10-24 00:00:00
abstract::Vesicular systems have shown their ability to increase dermal and transdermal drug delivery. Their mechanism of drug transport into and through the skin has been investigated but remains a much debated question. Several researchers have outlined that drug penetration can be influenced by modifying the surface charge o...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2011.03.049
更新日期:2011-06-15 00:00:00
abstract::Oxidative stress has been implicated in the progression of age-related macular degeneration (AMD). Treatment with antioxidants seems to delay progression of AMD. In this study, we suggested an antioxidant delivery system based on redox-sensitive liposome composed of phospholipids and a diselenide centered alkyl chain....
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.05.056
更新日期:2018-09-05 00:00:00
abstract::A unique polymer-based sustained-release implant was formulated using biodegradable hemostatic gauze as the scaffold. A piece of commercial gauze, Surgicel was coated with a poly(lactic-co-glycolic) acid (PLGA) solution in which drugs were loaded, followed by evaporating the solvent. Drug release kinetics from the PLG...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2007.12.019
更新日期:2008-05-01 00:00:00
abstract::The objective of this study was to evaluate mucoadhesive properties and gastrointestinal transit of microspheres made of oppositely charged dextran derivatives and cellulose acetate butyrate (CAB). The microspheres were prepared by emulsion solvent evaporation method. A reference microsphere was made of lactose instea...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(03)00159-5
更新日期:2003-06-04 00:00:00
abstract::There is a realisation that small quantities of amorphous material can have a significant impact on the properties of crystalline solids. Consequently there is a growing interest in quantifying the amount of amorphous material that is present in "crystalline powders". Success has been reported when using isothermal mi...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(00)00527-5
更新日期:2000-10-10 00:00:00
abstract::The high incidence of degenerative tears and prevalence of retears (20-95%) after surgical repair makes rotator cuff injuries a significant health problem. This high retear rate is attributed to the failure of the repaired tissue to regenerate the native tendon-to-bone insertion (enthesis). Biological augmentation of ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章,评审
doi:10.1016/j.ijpharm.2018.01.006
更新日期:2018-06-15 00:00:00
abstract::We have previously developed a fast screening method on the ability of twenty amino acids (AA) to form co-amorphous formulations with six drugs upon ball milling. In this work, the potential advantages in physical stability and dissolution rate of the 36 successful co-amorphous formulations, compared to the pure amorp...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2018.12.036
更新日期:2019-02-25 00:00:00
abstract::An aerosol system is described for the generation and delivery of measured doses of monodisperse therapeutic drug particles to the human lungs. The system comprises a spinning top aerosol generator (STAG), aerosol chamber and inhalation control unit. Monodisperse aerosols allow drug particle size effects to be studied...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/s0378-5173(03)00032-2
更新日期:2003-03-26 00:00:00
abstract::The objective of this study was to examine the use of transdermal iontophoresis for the delivery of ranitidine hydrochloride in children. Constant, direct current, anodal iontophoresis of ranitidine was performed in vitro across dermatomed pig skin. The effect of donor vehicle, current intensity, and drug concentratio...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2012.03.006
更新日期:2012-10-01 00:00:00
abstract::The aim of this study was to prepare spherical agglomerates of lactose and to evaluate their physicochemical properties, flow properties, particle friability and compaction properties, and to compare them to commercially available types of lactose for direct compression (spray-dried, granulated and anhydrous β-lactose...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2016.11.040
更新日期:2017-01-10 00:00:00
abstract::The aim of the present work was to develop a lymph targeted SLN formulation of antiretroviral (ARV) drug and to have an understanding of its underlying mechanism of uptake by the lymphatics. The lymphatics are the inaccessible reservoirs of HIV in human body. Efavirenz (EFV) is a BCS class II, ARV drug that undergoes ...
journal_title:International journal of pharmaceutics
pub_type: 杂志文章
doi:10.1016/j.ijpharm.2015.09.014
更新日期:2015-11-10 00:00:00