Abstract：
:This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for developing continuous processes compared with batch. In addition to the specific sequence of operations required to deliver the necessary chemical and physical transformations for continuous drug substance manufacture, consideration is also given to how adoption of continuous technologies may impact different manufacturing stages in development from discovery, process development, through scale-up and into full scale production. The impact of continuous manufacture on drug substance quality and the associated challenges for control and for process safety are also emphasized. In addition to the technology and operational considerations necessary for the adoption of continuous manufacturing (CM), this whitepaper also addresses the cultural, as well as skills and training, challenges that will need to be met by support from organizations in order to accommodate the new work flows. Specific action items for industry leaders are.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Baxendale IR,Braatz RD,Hodnett BK,Jensen KF,Johnson MD,Sharratt P,Sherlock JP,Florence AJdoi
10.1002/jps.24252subject
Has Abstractpub_date
2015-03-01 00:00:00pages
781-791issue
3eissn
0022-3549issn
1520-6017pii
S0022-3549(16)30005-3journal_volume
104pub_type
杂志文章abstract：:The objectives of this work are to explore the pi-pi complexation of amitriptyline with pi electron-deficient aromatic rings and demonstrate the feasibility of pi-pi complexation for overdosed drug detoxification. Water-soluble oligochitosan was chemically modified with dinitrobenzenesulfonyl groups to induce selectiv...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20256
更新日期：2005-02-01 00:00:00
abstract：:Robust higher order structure (HOS) characterization capability and strategy are critical throughout biopharmaceutical development from initial candidate selection and formulation screening to process optimization and manufacturing. This case study describes the utility of several orthogonal HOS methods as investigati...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24293
更新日期：2015-04-01 00:00:00
abstract：:The binding of nine diazepines to human serum albumin (HSA) and to alpha 1-acid glycoprotein (AGP) was investigated by means of fluorescence and circular dichroism (CD) spectroscopies. The binding parameters of diazepam obtained from fluorescence agreed with those obtained from CD measurements. Diazepines have one tig...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810104
更新日期：1992-01-01 00:00:00
abstract：:This article discusses the evaluation of drug candidates as hepatic transporter substrates. Recently, research on the applications of hepatic transporters in the pharmaceutical industry has improved to meet the requirements of the regulatory guidelines for the evaluation of drug interactions. To identify the risk of t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2017.05.009
更新日期：2017-09-01 00:00:00
abstract：:The poor aqueous solubility of carbamazepine was dramatically increased via complexation with various chemically modified beta-cyclodextrins and gamma-cyclodextrins. A preparation of carbamazepine and 2-hydroxypropyl-beta-cyclodextrin was found to be stable to steam sterilization and to storage under a variety of cond...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600800420
更新日期：1991-04-01 00:00:00
abstract：:Methods for monitoring mechanical events occurring within particulate solids systems in a dynamic state are described. The electrical conductance and capacitance characteristics of such systems, as they relate to the degree of bed dilation or expansion, extent of interparticulate contact, and intensity of particle mot...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670825
更新日期：1978-08-01 00:00:00
abstract：:The overall apparent first-order rate constants (Kab) of small intestinal absorption of sulfadiazine were determined in rats in situ at various pHs (4.01-7.42) of the recirculation fluids at 32 degrees. The purpose of the study was to verify our hypothesis that the rate-determining step for the absorption of sulfonami...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830208
更新日期：1994-02-01 00:00:00
abstract：:A rapid and simple high-performance liquid chromatographic (HPLC) method for the analysis of dichlorophen in raw material and in dichlorophen-toluene soft gelatin capsules for veterinary use was developed using a reverse-phase technique. This HPLC system was shown to isolate dichlorophen from its major impurity (the t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730629
更新日期：1984-06-01 00:00:00
abstract：:Upon exposure to shaking stress, an IgG1 mAb formulation in both the liquid and lyophilized state formed subvisible particles. Because freeze-drying was expected to minimize protein physical instability under these conditions, the extent and nature of aggregate formation in the lyophilized preparation were examined us...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24242
更新日期：2015-02-01 00:00:00
abstract：:beta-Cyclodextrin was ethylated at the 2- and 6-hydroxyl positions. Diethyl sulfate was employed as an alkylating reagent. NMR spectra data indicate that heptakis(2,6-di-O-ethyl)-beta-cyclodextrin (DCD) is the principal component of the product obtained. In addition, the FAB mass spectra obtained in nitrobenzyl alcoho...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840819
更新日期：1995-08-01 00:00:00
abstract：:Glycerol stabilizes cyanocob(III)alamin (vitamin B12) against anaerobic photolysis by a high-intensity UV light source or a low-intensity fluorescent light source. The likely mechanism for stabilization by viscosigens is a decrease in diffusion and an enhancement of radical-pair recombination. Glycerol (25% or greater...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820619
更新日期：1993-06-01 00:00:00
abstract：:Judicious choice of the salt form of a drug can greatly affect the aqueous solubility and formulation of the compound. The objective of this work was to demonstrate the effect of various counteranions on the aqueous solubility of the antimalarial agent alpha-(2-piperidyl)-3, 6-bis(trifluoromethyl)-9-phenanthrenemethan...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650533
更新日期：1976-05-01 00:00:00
abstract：:Previous studies from this laboratory suggested that a solution model (Flory-Huggins equation) modified by a free volume model (Vrentas equation) could satisfactorily describe water absorption into an amorphous solid composed of a sugar or a polymer. This paper has extended the studies of single solutes to binary mixt...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1090
更新日期：2001-09-01 00:00:00
abstract：:Benzydamine hydrochloride (Tantum, 1) is a photoallergic and phototoxic anti-inflammatory and analgesic agent. This drug is photolabile under aerobic and anaerobic conditions. Irradiation of a methanol solution of benzydamine under oxygen or argon at 300 nm affords 5-hydroxybenzydamine (2) and 2-beta-dimethylaminoprop...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820407
更新日期：1993-04-01 00:00:00
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
更新日期：2004-05-01 00:00:00
abstract：:A rapid, sensitive, and accurate reversed-phase HPLC method has been developed for the analysis and quantification of pharmaceutical formulations containing tyrothricin (1), an antibiotic used in antiseptic buccal compressed tablets for local application. The assay has been carried out under isocratic conditions, usin...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830815
更新日期：1994-08-01 00:00:00
abstract：:The crystal structures of the analgesic compounds anhydrous naloxone and naltrexone hydrochloride were determined ab initio from high resolution laboratory X-ray powder diffraction data. Both compounds crystallize in the orthorhombic space group P2(1)2(1)2(1) with lattice parameters of a = 14.6588(10) A, b = 17.4363(9...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20972
更新日期：2007-12-01 00:00:00
abstract：:Lipids were extracted from human stratum corneum and the remaining corneocytes were reaggregated with different lyotropic liquid crystals. Water transport through the reaggregated stratum corneum was determined using a diffusion chamber according to Smith and Blank. The permeability constant for the reaggregated strat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600800506
更新日期：1991-05-01 00:00:00
abstract：:Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in rela...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.06.028
更新日期：2017-01-01 00:00:00
abstract：:Dabrafenib is a small-molecule inhibitor of BRAF kinase activity that is currently being developed for the treatment of BRAF V600 mutation-positive melanoma. This clinical, open-label, two-cohort (n = 14 per cohort), randomized study was designed to evaluate the effect of drug substance particle size, and food on the ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,随机对照试验
doi：10.1002/jps.23519
更新日期：2013-09-01 00:00:00
abstract：:A novel in-line technique utilising pulsed terahertz radiation for direct measurement of the film coating thickness of individual tablets during the coating process was previously developed and demonstrated on a production-scale coater. Here, we use this technique to monitor the evolution of tablet film coating thickn...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24503
更新日期：2015-08-01 00:00:00
abstract：:The use of various synthetic lipids and polymers to deliver DNA for gene therapy applications has been the subject of intense examination for the last 15 years. Our understanding of the processes involved in the delivery of DNA, although still limited, can be described in terms of specific physical and chemical barrie...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.10286
更新日期：2003-02-01 00:00:00
abstract：:A simple, sensitive GLC assay was developed for fusaric acid, the active metabolite of bupicomide, to follow the disposition of this investigational antihypertensive agent in patients undergoing therapy. Fusaric acid is efficiently extracted from biological samples, derivatized by on-column methylation, and chromatogr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650430
更新日期：1976-04-01 00:00:00
abstract：:A mathematical model based on convective diffusion was developed to describe the rate of dissolution form the surface of a compressed compact. Experimental studies were carried out to test the model. The basic experimental apparatus consisted of a modified rotating-filter-stationary basket dissolution test apparatus. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640407
更新日期：1975-04-01 00:00:00
abstract：:Spray freeze-drying is an evolving technology that combines the benefits of spray-drying and conventional lyophilization techniques to produce drug substance and drug product as free-flowing powders. The high surface-to-volume ratio associated to the submillimeter spray-frozen particles contributes to shorter drying a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.01.011
更新日期：2019-06-01 00:00:00
abstract：:The purpose of this study was to evaluate the cardiovascular effects of two potential beta-hydroxylase inhibitors, a dithiocarbamate and a thiourea derivative of d-amphetamine, 1 and 2, respectively. These compounds when given intravenously elicited a significant dose-dependent depressor effect in normotensive rats an...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740621
更新日期：1985-06-01 00:00:00
abstract：:The aims of the present study were to formulate stable onion phases of the biodegradable surfactant PEG-8 Distearate (PEG8DS) and evaluate application of the onion phases in encapsulating sumatriptan succinate, a BCS class III potent antimigraine drug. Drug loaded and placebo onion phases were prepared by shearing lyo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20863
更新日期：2007-09-01 00:00:00
abstract：:Methods are presented for the separation of tetracycline, tetracycline analogs, and their potential impurities by reversed-phase ion-pair chromatography. The mobile phase consisted of a phosphate buffer with tripropylamine or N,N-dimethyloctylamine as counterions and acetonitrile as the organic modifier. The chromatog...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710221
更新日期：1982-02-01 00:00:00
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
更新日期：1988-09-01 00:00:00
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
