Enhanced Precision of Circular Dichroism Spectral Measurements Permits Detection of Subtle Higher Order Structural Changes in Therapeutic Proteins.

Abstract:

:Protein higher order structure (HOS) is an essential quality attribute to ensure protein stability and proper biological function. Protein HOS characterization is performed during comparability assessments for product consistency as well as during forced degradation studies for structural alteration upon stress. Circular dichroism (CD) spectroscopy is a widely used technique for measuring protein HOS, but it remains difficult to assess HOS with a high degree of accuracy and precision. Moreover, once spectral changes are detected, interpreting the differences in terms of specific structural attributes is challenging. Spectral normalization by the protein concentration remains one of the largest sources of error and reduces the ability to confidently detect differences in CD spectra. This work develops a simple method to enhance the precision of the CD spectral measurements through normalization of the CD spectra by the protein concentration determined directly from the CD measurement. This method is implemented to successfully detect small CD spectral changes in multiple forced degradation studies as well as comparability assessments during biologics drug development. Furthermore, the interpretation of CD spectral changes in terms of HOS differences are provided based on orthogonal data in conjunction with structural insights gained through in silico homology modeling of the protein structure.

journal_name

J Pharm Sci

authors

Barnett GV,Balakrishnan G,Chennamsetty N,Meengs B,Meyer J,Bongers J,Ludwig R,Tao L,Das TK,Leone A,Kar SR

doi

10.1016/j.xphs.2018.06.007

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

2559-2569

issue

10

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(18)30340-X

journal_volume

107

pub_type

杂志文章
  • Intravascular bioresorbable polymeric stents: a potential alternative to current drug eluting metal stents.

    abstract::Stent implantation following angioplasty is the standard treatment of coronary artery disease necessitating interventional procedures. The use of stents as a platform for local drug delivery is a popular strategy to achieve local pharmacological treatment to the diseased artery. Drug eluting stents (DES) are now large...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1002/jps.20957

    authors: Sharkawi T,Cornhill F,Lafont A,Sabaria P,Vert M

    更新日期:2007-11-01 00:00:00

  • Effects of Kaempferia parviflora extracts and their flavone constituents on P-glycoprotein function.

    abstract::The purpose of this study was to examine the effects of extracts and flavone derivatives from the rhizome of Kaempferia parviflora on P-glycoprotein (P-gp)-mediated transport in LLC-GA5-COL150, a transfectant cell line of a porcine kidney epithelial cell line LLC-PK1 with human MDR1 cDNA. Ethanol extract obtained from...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20769

    authors: Patanasethanont D,Nagai J,Yumoto R,Murakami T,Sutthanut K,Sripanidkulchai BO,Yenjai C,Takano M

    更新日期:2007-01-01 00:00:00

  • Thermodynamic evaluation of activated charcoal as a poison antidote by high-performance liquid chromatography. II: In vitro method for the evaluation of activated charcoal as a poison antidote.

    abstract::A previous report detailed the derivation and validation of an equation for calculating the Gibbs free energy of liquid-solid adsorption via high-performance liquid chromatography (HPLC). This study utilizes an improved form of that equation in conjunction with an in vitro model of solute adsorption to give an ordered...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600770609

    authors: Kleeman WP,Bailey LC

    更新日期:1988-06-01 00:00:00

  • A hot-melt extruded intravaginal ring for the sustained delivery of the antiretroviral microbicide UC781.

    abstract::Microbicide intravaginal rings (IVRs) are a promising woman-controlled strategy for preventing sexual transmission of human immunodeficiency virus (HIV). An IVR was prepared and developed from polyether urethane (PU) elastomers for the sustained delivery of UC781, a highly potent nonnucleoside reverse transcriptase in...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22781

    authors: Clark MR,Johnson TJ,McCabe RT,Clark JT,Tuitupou A,Elgendy H,Friend DR,Kiser PF

    更新日期:2012-02-01 00:00:00

  • Video characterization of flume patterns of inhalation aerosols.

    abstract::An in vitro technique was developed to characterize the intermittent flume patterns associated with the short bursts of metered-dose aerosols. Two orthogonal video images are utilized to describe the complex shape and direction of the flume pattern. This technique facilitates the evaluation of components manufactured ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600690628

    authors: Miszuk S,Gupta BM,Chen FC,Clawans C,Knapp JZ

    更新日期:1980-06-01 00:00:00

  • Determination of serum tulobuterol concentrations by mass fragmentography: comparison with an electron-capture gas chromatographic method.

    abstract::A simple and sensitive method is reported for the quantitative determination of the bronchodilator tulobuterol in human serum. Tulobuterol and an internal standard were extracted from alkalinized serum with ether and then back-extracted into dilute hydrochloric acid. After alkalinization and extraction of the aqueous ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600720526

    authors: Matsumura K,Kubo O,Sakashita T,Kato H,Watanabe K,Hirobe M

    更新日期:1983-05-01 00:00:00

  • Microbial transformations of natural antitumor agents XXII: Conversion of bouvardin to O-desmethylbouvardin and bouvardin catechol.

    abstract::Bouvardin is a cyclic hexapeptide antitumor agent which undergoes two major microbial transformation reactions. Screening with 220 cultures revealed 17 different strains capable of producing O-desmethylbouvardin in good yield. O-Desmethylbouvardin was isolated and characterized from preparative scale incubations with ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600721114

    authors: Petroski RJ,Bates RB,Linz GS,Rosazza JP

    更新日期:1983-11-01 00:00:00

  • Incidence of experimental fascioliasis on hepatic disposition of [3H]tetracycline and [14C]rafoxanide in rats.

    abstract::[7-3H]Tetracycline and [carbonyl-14C]rafoxanide were injected intravenously into anesthetized controls and rats in which experimental fascioliasis had been induced by 20 Fasciola hepatica metacercariae. The biliary excretion (1 and 3 h, respectively) of the radioactivity consisted of approximately 4% of the administer...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600740921

    authors: Galtier P,Larrieu G,Franc M

    更新日期:1985-09-01 00:00:00

  • GLC determination of procainamide in biological fluids.

    abstract::A GLC method for the determination of procainamide in biological fluids is presented. By using a dipropyl analog of procainamide as an internal standard, both compounds can be chromatographed directly, yielding linear calibration curves and a sensitivity that allows quantitative determination of concentrations as low ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600641213

    authors: Simons KJ,Levy RH

    更新日期:1975-12-01 00:00:00

  • A novel multivariate approach for estimating the degree of similarity in bioavailability between two pharmaceutical products.

    abstract::Statistical assessment of bioavailability and bioequivalence of drug products is generally carried out with a univariate analysis by independently comparing each relevant parameter [such as, area under the drug concentration curve (AUC) and peak drug concentration (Cmax)] of the test and reference products. The assump...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600840620

    authors: Hsu HC,Lu HL,Chan KK

    更新日期:1995-06-01 00:00:00

  • Development of a method for study of the tendency of drug products to adhere to the esophagus.

    abstract::A method to determine the adherence of drugs to the esophagus was developed using isolated swine esophagi. A number of types of tablets and capsules (e.g., of doxycycline) were tested. The results showed that the tendency of products to adhere to the esophagus can be regulated by pharmaceutical properties. It was conc...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600710904

    authors: Marvola M,Vahervuo K,Sothmann A,Marttila E,Rajaniemi M

    更新日期:1982-09-01 00:00:00

  • Perforated coated tablets for controlled release of drugs at a constant rate.

    abstract::Tablets with a central hole and a water-impermeable coating were prepared. These perforated coated tablets (PCTs) dissolve and release drug through the central hole only. In vitro release of the model drugs sodium benzoate and benzamide from PCTs occurred at a constant rate up to 80% release. The zero-order release ra...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600770408

    authors: Hansson AG,Giardino A,Cardinal JR,Curatolo W

    更新日期:1988-04-01 00:00:00

  • Progestin permeation through polymer membrane V: Progesterone release from monolithic hydrogel devices.

    abstract::Progesterone release from monolithic devices prepared from various copolymers of poly(hydroxyethyl methacrylate) and poly(methoxyethoxyethyl methacrylate) or poly(methoxyethyl methacrylate) was examined. In general, plots of the fraction of drug released versus (time)1/2 were linear during the early stages of drug rel...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600700226

    authors: Song SZ,Cardinal JR,Kim SH,Kim SW

    更新日期:1981-02-01 00:00:00

  • Physicochemical and structural characterization of quercetin-beta-cyclodextrin complexes.

    abstract::Quercetin is a bioactive flavonoid widely used as a health supplement. Being sparingly soluble and chemically unstable in aqueous intestinal fluids, quercetin is poorly absorbed orally. This study aimed to investigate the effects of three beta-cyclodextrins, namely, unsubstituted beta-cyclodextrin (beta-CD), hydroxypr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20325

    authors: Zheng Y,Haworth IS,Zuo Z,Chow MS,Chow AH

    更新日期:2005-05-01 00:00:00

  • Prediction of Losartan-Active Carboxylic Acid Metabolite Exposure Following Losartan Administration Using Static and Physiologically Based Pharmacokinetic Models.

    abstract::The aim of this study was to evaluate a strategy based on static and dynamic physiologically based pharmacokinetic (PBPK) modeling for the prediction of metabolite and parent drug area under the time-concentration curve ratio (AUCm/AUCp) and their PK profiles in humans using in vitro data when active transport process...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2017.03.032

    authors: Nguyen HQ,Lin J,Kimoto E,Callegari E,Tse S,Obach RS

    更新日期:2017-09-01 00:00:00

  • Use of parenteral dipeptides to increase serum tyrosine levels and to enhance catecholamine-mediated neurotransmission.

    abstract::The use of intravascular tyrosine (TYR) to enhance catecholamine release in hemorrhagic shock and other cardiovascular diseases, or as a constituent of nutrient mixtures used for total parenteral nutrition, is limited by the unusually poor solubility of the amino acid in water. We have thus examined the ability of var...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600790807

    authors: Maher TJ,Kiritsy PJ,Moya-Huff FA,Casacci F,De Marchi F,Wurtman RJ

    更新日期:1990-08-01 00:00:00

  • Correlation of log P with molecular connectivity in hydroxyureas: influence of conformational system on log P.

    abstract::The correlation of log P (in octanol--water) with the nonempirical, topologically dependent, calculated molecular connectivity index (1chiv) delineates substituted hydroxyureas into two families of linearly related groups of compounds. The first group, composed of the 3-substituted ethyl, n-propyl, and n-butyl analogs...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670419

    authors: Parker GR

    更新日期:1978-04-01 00:00:00

  • Determination of drug plasma protein binding by solid phase microextraction.

    abstract::The plasma protein binding of drugs has been shown to have significant effects on the quantitative relationship between clinical pharmacokinetics and pharmacodynamics. In many clinical situations, measurement of the total drug concentration does not provide the needed information concerning the unbound fraction of dru...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20558

    authors: Musteata FM,Pawliszyn J,Qian MG,Wu JT,Miwa GT

    更新日期:2006-08-01 00:00:00

  • Microstructure of calcium stearate matrix pellets: a function of the drying process.

    abstract::Drying is a common pharmaceutical process, whose potential to modify the final drug and/or dosage form properties is often underestimated. In the present study, pellets consisting of the matrix former calcium stearate (CaSt) incorporating the active pharmaceutical ingredient ibuprofen were prepared via wet extrusion a...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23707

    authors: Schrank S,Kann B,Windbergs M,Glasser BJ,Zimmer A,Khinast J,Roblegg E

    更新日期:2013-11-01 00:00:00

  • Robust calibration design in the pharmaceutical quantitative measurements with near-infrared (NIR) spectroscopy: Avoiding the chemometric pitfalls.

    abstract::Quantification analysis with near-infrared (NIR) spectroscopy typically requires utilizing chemometric techniques, such as partial least squares (PLS) method, to achieve the desired selectivity. This article points out a major limitation of these statistical-based calibration methods. The limitation is that the techni...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21482

    authors: Xiang D,Berry J,Buntz S,Gargiulo P,Cheney J,Joshi Y,Wabuyele B,Wu H,Hamed M,Hussain AS,Khan MA

    更新日期:2009-03-01 00:00:00

  • Preparation and Characterization of Ascosome Vesicles Loaded with Khellin.

    abstract::Ascorbic acid has a unique role in the prevention and treatment of a large number of chronic diseases, including skin disorders but it can hardly penetrate the skin due to its solubility in water and its high instability. This study explored the formation of phosphatidylcholine-based vesicles upon addition of ascorbyl...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2020.06.017

    authors: Risaliti L,Ambrosi M,Calamante M,Bergonzi MC,Lo Nostro P,Bilia AR

    更新日期:2020-10-01 00:00:00

  • Pharmacokinetic aspects of biotechnology products.

    abstract::In recent years, biotechnologically derived peptide and protein-based drugs have developed into mainstream therapeutic agents. Peptide and protein drugs now constitute a substantial portion of the compounds under preclinical and clinical development in the global pharmaceutical industry. Pharmacokinetic and exposure/r...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1002/jps.20125

    authors: Tang L,Persky AM,Hochhaus G,Meibohm B

    更新日期:2004-09-01 00:00:00

  • Dequaternization of curare bases with sodium thiophenoxide and ethanolamine.

    abstract::To prepare (+)-tubocurine and O,O-dimethyl-(+)-tubocurine, the commonly used dequaternization procedures with sodium theophenoxide and ethanolamine were investigated. The quaternary compounds were (+)-tubocurarine chloride and the chloride and iodide salts of O,O-dimethyl-(+)-chondocurarine. The results obtained with ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670904

    authors: Naghaway JA,Soine TO

    更新日期:1978-09-01 00:00:00

  • Effect of pH on the in vitro dissolution and in vivo absorption of controlled-release theophylline in dogs.

    abstract::Dogs were used to examine the effect of elevated gastric pH on the absorption of controlled-released theophylline dosage forms with pH-dependent dissolution. In vitro studies showed that a controlled-release theophylline tablet dissolved more rapidly if it was initially exposed to an acidic media. In contrast, a contr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600770908

    authors: Vashi VI,Meyer MC

    更新日期:1988-09-01 00:00:00

  • Characterization of site I of human serum albumin using spectroscopic analyses: locational relations between regions Ib and Ic of site I.

    abstract::Site I of human serum albumin is an important and complex region for high-affinity binding of drugs. Equilibrium dialysis showed independent binding of dansyl-L-asparagine (DNSA) and n-alkyl p-aminobenzoates (p-ABEs) to regions Ib and Ic, respectively, in the pH range 6.0-9.0. However, individual binding of DNSA incre...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20203

    authors: Yamasaki K,Maruyama T,Takadate A,Suenaga A,Kragh-Hansen U,Otagiri M

    更新日期:2004-12-01 00:00:00

  • Self-association of cromolyn sodium in aqueous solution characterized by nuclear magnetic resonance spectroscopy.

    abstract::The major objective of this study was to investigate and characterize the solution properties of cromolyn sodium (in D(2)O or D(2)O/H(2)O phosphate buffer at pH 7.5) using nuclear magnetic resonance (NMR) spectroscopy. The self-association of cromolyn molecules was examined primarily via one-dimensional (1)H and (13)C...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20034

    authors: Ding X,Stringfellow TC,Robinson JR

    更新日期:2004-05-01 00:00:00

  • 3D Printing of Solid Oral Dosage Forms: Numerous Challenges With Unique Opportunities.

    abstract::Since the FDA approval of Spritam, there has been a growing interest in the application of 3D printing in pharmaceutical science. 3D printing is a method of manufacturing involving the layer-by-layer deposition of materials to create a final product according to a digital model. There are various techniques used to ac...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.xphs.2020.08.029

    authors: Okafor-Muo OL,Hassanin H,Kayyali R,ElShaer A

    更新日期:2020-12-01 00:00:00

  • Stabilization of proteins by recombinant human gelatins.

    abstract::Porcine gelatins have been widely used as stabilizers of macromolecular based pharmaceuticals but the mechanism by which they stabilize has not been precisely established. Their variability and immunogenicity, however, make them less than ideal excipients. In this work, we take advantage of the availability of recombi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20980

    authors: Thyagarajapuram N,Olsen D,Middaugh CR

    更新日期:2007-12-01 00:00:00

  • A physiologically based pharmacokinetic model of zidovudine (AZT) in the mouse: model development and scale-up to humans.

    abstract::After having been used in treating HIV infection for a decade, zidovudine (AZT) continues to be an essential component of antiretroviral regimens. Because antiviral responses and toxicity of AZT seem to be related to cells in specific target tissues, being able to understand and predict the distribution of AZT into di...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js970243y

    authors: Chow HH

    更新日期:1997-11-01 00:00:00

  • Dissolution media for in vitro testing of water-insoluble drugs: effect of surfactant purity and electrolyte on in vitro dissolution of carbamazepine in aqueous solutions of sodium lauryl sulfate.

    abstract::The intrinsic dissolution rate and solubility of carbamazepine was measured in aqueous solutions of sodium lauryl sulfate (SLS) prepared with two different grades of purity, 95 and 99%, and 95% SLS in 0.15 M NaCl to determine the effect of surface-active impurities and electrolytes. Four significant observations resul...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js960105t

    authors: Crison JR,Weiner ND,Amidon GL

    更新日期:1997-03-01 00:00:00