Abstract：
:High protein concentration formulations are required for low-volume administration of therapeutic antibodies targeted for subcutaneous, self-administration by patients. Ultra-high concentrations (≥150 mg/mL) can lead to dramatically increased solution viscosities, which in turn can lead to stability, manufacturing, and delivery challenges. In this study, various categories and individual types of pharmaceutical excipients and other additives (56 in total) were screened for their viscosity reducing effects on 2 different mAbs. The physicochemical stability profile, as well as viscosity ranges, of several candidate antibody formulations, identified and designed based on the results of the excipient screening, were evaluated over a 6-month time period under accelerated and real-time storage conditions. In addition to reducing the solution viscosities to acceptable levels for parenteral administration (using currently available and acceptable delivery devices), the candidate formulations did not result in notable losses of physicochemical stability of the 2 antibodies on storage for 6 months at 25°C. The experiments described here demonstrate the feasibility of a formulation development and selection approach to identify candidate high-concentration antibody formulations with viscosities within pharmaceutically acceptable ranges that do not adversely affect their physicochemical storage stability.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Whitaker N,Xiong J,Pace SE,Kumar V,Middaugh CR,Joshi SB,Volkin DBdoi
10.1016/j.xphs.2017.06.017subject
Has Abstractpub_date
2017-11-01 00:00:00pages
3230-3241issue
11eissn
0022-3549issn
1520-6017pii
S0022-3549(17)30486-0journal_volume
106pub_type
杂志文章abstract：:Quantification of protein binding of new chemical entities is an important early screening step during drug discovery and is of fundamental interest for the estimation of safety margins during drug development. In this publication, we describe the development of a new high-throughput assay for the determination of the...
journal_title：Journal of pharmaceutical sciences
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abstract：:Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to ...
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abstract：:The purpose of the present experiment was to prepare and characterize the aqueous-based pseudolatex system of cellulose acetate butyrate (CAB) for controlled drug delivery. Aqueous pseudolatex systems are advantageous over organic-based coating systems because these systems are devoid of criteria pollutants such as ca...
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abstract：:Methods for the determination of diphenoxylate hydrochloride and atropine sulfate combinations in solutions and powdered tablet composites are presented. A semiautomated assay for diphenoxylate hydrochloride in individual tablets (content uniformity) also is presented. The USP XIX assays for these products are cumbers...
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doi：10.1002/jps.2600661113
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abstract：:A method has been developed for the estimation of the distribution coefficient (D), which considers the microspecies of a compound. D is calculated from the microscopic dissociation constants (microconstants), the partition coefficients of the microspecies, and the counterion concentration. A general equation for the ...
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doi：10.1021/js960177k
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abstract：:Hyperthermia (HT)-dependent cisplatin (CDDP) release and tumor CDDP level increase after the administration of thermosensitive, large unilamellar vesicles (LUVs: LUV-1 and LUV-2) and a thermosensitive, small unilamellar vesicle (SUV: SUV-1) were examined in comparison with those following administration of a non-therm...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600800604
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doi：10.1021/js980287m
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abstract：:In this paper we describe the synthesis and characterization of magnetic microcapsules, intended for use in vivo, and which contain polyethyleneimine nucleophilic targets capable of trapping electrophilic carcinogens. The microcapsules, 15-50 microns in diameter, consist of a semipermeable cross-linked nylon membrane ...
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doi：10.1002/jps.2600750902
更新日期：1986-09-01 00:00:00
abstract：:Successful development of stable solid protein formulations usually requires the addition of one or several excipients to achieve optimal stability. In these products, there is a potential risk of an inhomogeneous distribution of the various ingredients, specifically the ratio of protein and stabilizer may vary. Such ...
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abstract：:The binding of representative chemical classes of nonsteroidal anti-inflammatory drugs (NSAIDs) to human serum albumin (HSA) was investigated by equilibrium dialysis. Warfarin enantiomers were used as specific markers in displacement studies. Data were analyzed by a computerized nonlinear least squares approach design...
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doi：10.1002/jps.2600770314
更新日期：1988-03-01 00:00:00
abstract：:A convenient and sensitive analytical method for determination of plasma morphine and its metabolites in cancer patients was established using HPLC with a column-switching technique. Sample plasma which has been deproteinized with trichloroacetic acid is injected onto a precolumn, then the compounds of interest are pr...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.2600790503
更新日期：1990-05-01 00:00:00
abstract：:High-throughput lyophilization process was designed and developed for protein formulations using a single-step drying approach at a shelf temperature (Ts) of ≥40°C. Model proteins were evaluated at different protein concentrations in amorphous-only and amorphous-crystalline formulations. Single-step drying resulted in...
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doi：10.1016/j.xphs.2018.11.021
更新日期：2019-04-01 00:00:00
abstract：:A novel method is described for the preparation of sterile and pyrogen-free submicron liposomes of narrow size distribution. The method is based on the formation of a homogeneous dispersion of lipids in water-soluble carrier materials. To obtain the lipid-containing solid dispersion, liposome-forming lipids and water-...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.20055
更新日期：2004-06-01 00:00:00
abstract：:The suppression of imipramine hydrochloride (IMP)- induced hemolysis by native cyclodextrins (alpha-, beta-, and gamma-CDs) and beta-CD derivatives is measured as a function of CD concentration and is quantitatively correlated with the surface tension of the solution determined at 37.0 degrees C. The modified beta-CDs...
journal_title：Journal of pharmaceutical sciences
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doi：10.1002/jps.1059
更新日期：2001-08-01 00:00:00
abstract：:The pharmacokinetics of erythromycin and erythromycin 2'-propanoate were studied in healthy male volunteers following single and repeated doses of erythromycin stearate tablets, erythromycin estolate capsules, and a suspension. Estolate dosages gave rise to higher plasma levels of total drug than the stearate. However...
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doi：10.1002/jps.2600680208
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abstract：:Some N,N'-bis(3-substituted benzylideneaminopropyl) piperazines were synthesized and characterized by their sharp melting points and elemental analyses. These substituted piperazines possessed anti-inflammatory activity, and the protection afforded by these compounds against carrageenan-induced edema ranged from 23 to...
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doi：10.1002/jps.2600650323
更新日期：1976-03-01 00:00:00
abstract：:The objective of this study was to identify the important factors that determine plasma concentrations of diphenhydramine (DPHM) in the mother and the fetus after maternal as well as fetal steady-state drug administration. Inter-relationships were evaluated between maternal and fetal placental and nonplacental clearan...
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更新日期：1992-04-01 00:00:00
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abstract：:A high-performance liquid chromatographic (HPLC) assay to quantitate methylparaben in urine was developed. Standard curves were linear and recovery of the paraben from urine averaged 82.6%. The urinary excretion of methylparaben in six preterm infants (less than or equal to 31 weeks gestational age), who were receivin...
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abstract：:A procedure for the simultaneous analysis of diphenylhydantoin and phenobarbital in plasma by high-pressure liquid chromatography was developed and evaluated. Separation is effected on a porous particle silicic acid column with chloroform dioxane-isopropanol-acetic acid (310:9.7:1.0:0.1 by volume) and is monitored at ...
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doi：10.1002/jps.2600640516
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