Abstract：
:Specifically tailored amino acid-based formulations were previously shown to have a high potential to avoid stress-mediated degradation of complex molecules such as monoclonal antibodies and viral vectors. By using adenovirus 5 (Ad5) as a model, we studied whether such formulations may also efficiently protect viral vectors in thermal stress experiments and during long-term liquid storage. Algorithm-based amino acid preselection using an excipient database and subsequent application of design of experiments (DoE) in combination with a 37°C challenging model enabled the prediction of long-term storage stability of Ad5. By statistical analysis of the Ad5 infectivity, amino acids with significant influence on Ad5 stability were detected after 2 and 3 weeks of liquid storage at 37°C. Ad5 formulations comprising positively selected amino acids did not reveal any loss of infectivity after 24 months in liquid storage at 5°C. By contrast, a 2 log reduction after 3 months and complete loss of infectivity after 18 months was observed with a standard viral vector formulation. By an optimization round, we designed a simple and well-balanced formulation avoiding MgCl2, previously considered essential in Ad5 formulations. This work demonstrates the efficacy of an algorithm-based development approach in the formulation development for viral vectors.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Reinauer EB,Grosso SS,Henz SR,Rabas JA,Rodenstein C,Altrichter J,Scholz M,Kemter KFdoi
10.1016/j.xphs.2019.10.063subject
Has Abstractpub_date
2020-01-01 00:00:00pages
818-829issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(19)30735-Xjournal_volume
109pub_type
杂志文章abstract：:The aim of this study was to characterize the in vitro hepatic uptake kinetics of sodium fluorescein (NaFluo) and identify the transporters involved. NaFluo exhibited saturable uptake kinetics in suspended rat and human hepatocytes as reflected by K(m) values of 22.5 and 14.1 µM, and V(max) values of 98.3 and 5.8 pmol...
journal_title：Journal of pharmaceutical sciences
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abstract：:A diffusion model for the percutaneous absorption of a solute through the skin is developed for the specific case of a constant donor concentration with a finite removal rate from the receptor due to either perfusion rate or sampling. The model has been developed to include a viable epidermal resistance and a donor-st...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js990053i
更新日期：1999-11-01 00:00:00
abstract：:The ability to successfully formulate and manufacture therapeutic protein dosage forms requires a thorough understanding of their physico-chemical properties. Proteins are inherently dynamic molecules of marginal stability. These properties present unique challenges to the pharmaceutical scientist attempting to develo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.21269
更新日期：2008-09-01 00:00:00
abstract：:There is a growing interest in developing inhibitors of the neonatal Fc-receptor, FcRn, for use in the treatment for humoral autoimmune conditions. We have developed a new physiologically based pharmacokinetic model that is capable of characterizing the pharmacokinetics and pharmacodynamics of anti-FcRn monoclonal ant...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2018.10.065
更新日期：2019-01-01 00:00:00
abstract：:A procedure is described for the analysis of urushiol content of pharmaceutical preparations containing extracts of poison ivy (Toxicodendron radicans) and poison oak (T. diversilobum) in vegetable oils. The procedure involves extraction of the urushiols from the oily solutions using 90% methanol in water followed by ...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600690530
更新日期：1980-05-01 00:00:00
abstract：:In this study, curcumin and/or docosahexaenoic acid (DHA) were encapsulated in Thai silk fibroin/gelatin (SF/G) sponges, prepared at different blending ratios, aimed to be applied as a controlled release system for localized cancer therapy. The SF/G sponges were fabricated by freeze-drying and glutaraldehyde cross-lin...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.24701
更新日期：2016-01-01 00:00:00
abstract：:The relationship between the concentration of a drug and its pharmacologic effect is of central interest in pharmacodynamics. Various compartmental and noncompartmental methods have been proposed for elucidating this relationship when the plasma drug concentration and effects are both measured. Although the relationsh...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830317
更新日期：1994-03-01 00:00:00
abstract：:When heated at temperatures in excess of 100 degrees, the stability of neomycin in aqueous ophthalmic formulations was improved by the addition of edetate disodium (0.01%). As the exposure temperature was reduced, the degree of stability enhancement diminished until the effect was reversed, and addition of edetate dis...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600700836
更新日期：1981-08-01 00:00:00
abstract：:Liposomes containing sodium ioxitalamate were prepared by sonication. Suitable amounts of purified soybean phosphatidylcholine and cholesterol were used at various molar ratios. Stearylamine or dicetylphosphate were added to this lipid composition when charged liposomes were required. After sonication and removal of u...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600731223
更新日期：1984-12-01 00:00:00
abstract：:Poor water solubility leads to low dissolution rate and consequently, it can limit bioavailability. Solid dispersions, where the drug is dispersed into an inert, hydrophilic polymer matrix can enhance drug dissolution. Solid dispersions were prepared using phenacetin and phenylbutazone as model drugs with polyethylene...
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doi：10.1002/jps.22613
更新日期：2011-10-01 00:00:00
abstract：:The purpose of this work was to investigate the self-associating behavior observed in high concentration monoclonal antibody (MAb1) solutions at pH 6.0. Zeta potential measurements over the pH range (4.0-9.0) showed lower net charges present on the molecule at pH 6.0 and 7.0. The point of zero charge or crossover from...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21898
更新日期：2010-03-01 00:00:00
abstract：:The release kinetics of a polymeric-controlled release device are determined by its geometry and dimensions. A method to calculate the required size and shape of diffusion-controlled dosage forms to achieve a particular release profile is presented. The diffusion parameters are determined for various drugs (theophylli...
journal_title：Journal of pharmaceutical sciences
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doi：10.1021/js980006a
更新日期：1998-07-01 00:00:00
abstract：:Protein aggregates are a potential risk factor for immunogenicity. The measurement, characterization, and control of protein aggregates in drug products are indispensable for the development of biopharmaceuticals, including therapeutic mAbs. In this study, Fcγ receptor (FcγR)-expressing reporter cell lines were used t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.046
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abstract：:A new extraction-spectrophotometric method for the determination of hydralazine, based on its reaction with 2-hydroxy-1-naphthaldehyde at 25 degrees C, is described. The calibration curve was linear between 0.4 and 6 mg/mL of hydralazine. The molar absorbtivity of the product at 408 nm is 40,900 L.mol-1.cm-1. The meth...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600800716
更新日期：1991-07-01 00:00:00
abstract：:Sol-to-gel systems of ciprofloxacin hydrochloride were prepared utilizing the phase transition properties of hydroxy propyl methyl cellulose K 15 M grade (HPMC) and carbopol 934. The sol-to-gel systems were sterilized by gamma radiation and/or filtration. The sol-to-gel systems were evaluated for rheological character...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.10290
更新日期：2003-02-01 00:00:00
abstract：:A novel method was established for the preparation of Eudragit S, Eudragit L, and Eudispert high-viscosity (hv) hydrogel and xerogel preparations containing a medicinal component such as pentoxifylline (an agent that improves cerebral microcirculation). A significant correlation was found between the in vitro mean dis...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810613
更新日期：1992-06-01 00:00:00
abstract：:The objectives of this study were (i) to characterize the plasmid DNA encoding the chloramphenicol acetyltransferase reporter gene (pCAT) complexed with cationic liposomes (Lipofectin and LipofectACE) in terms of particle size and zeta potential, (ii) to compare pharmacokinetic characteristics, and (iii) to study the ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600841102
更新日期：1995-11-01 00:00:00
abstract：:A GLC method is presented for the quantitative determination of menthol, phenol, benzocaine, and pyrilamine maleate. The propellent was exhausted from a pressurized can, and an aliquot of the alcoholic base was weighed. After the addition of the internal standard diluted with chloroform, 1 microliter of the mixture wa...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600701015
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abstract：:A physiological flow model was developed for the distribution of sulfathiazole residues in various tissues in swine. The approach was compartmental, in which the compartments and equilibrium constants had physiological meaning. Differential equations were developed, and appropriate parameter values and initial conditi...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600731107
更新日期：1984-11-01 00:00:00
abstract：:Cellulose derivatives are commonly used as gelling agents in topical and ophthalmic drug formulations. During the course of manufacturing, cellulose derivatives are believed to generate free radicals. These free radicals may degrade the gelling agent, leading to lower viscosity. Free radicals also may react with the a...
journal_title：Journal of pharmaceutical sciences
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更新日期：2009-07-01 00:00:00
abstract：:Alginate-based polyelectrolyte complexes (PECs) and hydrogel were engineered as platforms for local bevacizumab (BVZ) therapy. This study provides deep comprehension on the microstructures of such systems, and their correlation with drug-release patterns. PECs and hydrogel were characterized using Fourier transform in...
journal_title：Journal of pharmaceutical sciences
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doi：10.1016/j.xphs.2018.11.038
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abstract：:A method of depicting dimensional illustrations of molecules in vacuo that are sensitive to small electronic perturbations was attempted. This method would be useful in determining the effects of either perturbing groups from other molecules or changes produced by the addition or modification of an existing atom or ch...
journal_title：Journal of pharmaceutical sciences
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更新日期：1978-01-01 00:00:00
abstract：:The effect of side-chain length of desmethylretinoic acid on granuloma formation induced by implantation of cotton pellets was studied. As in the homologous series of retinoic acid studies, compounds with side chains shorter than retinoic acid were not active while compounds with side chains as long or longer than ret...
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doi：10.1002/jps.2600650425
更新日期：1976-04-01 00:00:00
abstract：:The degradation kinetics of gonadorelin were investigated systematically with reversed-phase high-performance liquid chromatography. The stability-indicating properties of this system were checked with photodiode array detection and by comparison with capillary zone electrophoretic analysis. Influences of gonadorelin ...
journal_title：Journal of pharmaceutical sciences
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更新日期：1996-10-01 00:00:00
abstract：:The inhibitory effect of dioctyl sodium sulfosuccinate of hog pepsin activity was investigated over the pH 1.5-3.0 range. The inhibitory effect was studied using a natural substrate, hemoglobin, and a synthetic substrate, N-acetyl-L-phenylalanyl-L-diiodotyrosine. The mechanistic studies revealed that a substrate-inhib...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600650914
更新日期：1976-09-01 00:00:00
abstract：:SPRYCEL® (Dasatinib) is a Biopharmaceutical Classification System II weakly basic drug that exhibits strong pH-dependent solubility. Dasatinib is currently presented in 2 drug product formulations as an adult immediate release tablet and a pediatric powder for oral suspension. A bioequivalence study comparing the form...
journal_title：Journal of pharmaceutical sciences
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更新日期：2019-01-01 00:00:00
abstract：:Optical crystallographic data were determined on a variety of newer USP drugs for which data had not been previously obtained. The ingredients in an unknown sample can be identified by polarized light microscopy by mounting small amounts of the material in successive specific refractive index liquids and determining r...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600821218
更新日期：1993-12-01 00:00:00
abstract：:Although PEGylation of biologics is currently the gold standard for half-life extension, the technology has a number of limitations, most importantly the non-biodegradability of PEG and the extremely high viscosity at high concentrations. HESylation is a promising alternative based on coupling to the biodegradable pol...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.24253
更新日期：2015-02-01 00:00:00
abstract：:Griseofulvin/cyclodextrin interactions were investigated in aqueous environment and in solid state. Two cyclodextrin derivatives (beta-cyclodextrin and 2-hydroxypropyl beta-cyclodextrin) were used to prepare different physical mixtures and kneaded systems, and the drug/cyclodextrin ratios were 1:1 and 1:2 mol/mol. Sca...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970233x
更新日期：1998-07-01 00:00:00
abstract：:A stability-indicating reversed-phase high-performance liquid chromatographic method using a refractive index detector is described for the determination of propylene carbonate in pharmaceutical formulations. Good precision and accuracy of the method was demonstrated using an aqueous formulation. This method is also a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740626
更新日期：1985-06-01 00:00:00
