Abstract：
PURPOSE:The purpose of the study is to characterize glycine crystallization during freezing of aqueous solutions as a function of the glycine salt form (i.e., neutral glycine, glycine hydrochloride, and sodium glycinate), pH, and ionic strength. METHODS:Crystallization was studied by thermal analysis, microscopy, x-ray diffraction, and pulsed Fourier transform nmr spectroscopy. RESULTS:A solution of neutral glycine with no additives undergoes rapid secondary crystallization during freezing, forming the beta polymorph, with a eutectic melting temperature of -3.4 degrees C. Glycine hydrochloride solutions undergo secondary crystallization relatively slowly, and the eutectic melting temperature is -28 degrees C. Sodium glycinate crystallizes from frozen solution at an intermediate rate, forming a eutectic mixture with a melting temperature of -17.8 degrees C. Where secondary crystallization does not occur rapidly, a complex glass transition is observed in the -70 degrees to -85 degrees C temperature range in the DSC thermograms of all systems studied. Rates of secondary crystallization and the type of crystal formed are influenced by solution pH relative the the pKs of glycine, and also by the change in ionic strength caused by adjustment of pH. Increased ionic strength significantly slows the crystallization of neutral glycine and promotes formation of the gamma polymorph. Thermal treatment or extended holding times during the freezing process may be necessary in order to promote secondary crystallization and prevent collapse during freeze drying. CONCLUSIONS:The results underscore the importance of recognizing that seemingly minor changes in formulation conditions can have profound effects on the physical chemistry of freezing and freeze drying.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Akers MJ,Milton N,Byrn SR,Nail SLdoi
10.1023/a:1016223101872subject
Has Abstractpub_date
1995-10-01 00:00:00pages
1457-61issue
10eissn
0724-8741issn
1573-904Xjournal_volume
12pub_type
杂志文章abstract：PURPOSE:The aim of this study was to investigate whether biodegradable nanocapsules could be obtained by the emulsification-diffusion technique. METHODS:This technique consists of emulsifying an organic solution containing an oil, a polymer, and a drug in an aqueous solution of a stabilizing agent. The subsequent addi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011934328471
更新日期：1998-07-01 00:00:00
abstract：PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016028707130
更新日期：1996-08-01 00:00:00
abstract：PURPOSE:To develop a semi-mechanistic population pharmacokinetic model based on gastric emptying function for acetaminophen plasma concentration in critically ill patients tolerant and intolerant to enteral nutrition before and after prokinetic therapy. METHODS:Acetaminophen plasma concentrations were available from a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0290-8
更新日期：2011-02-01 00:00:00
abstract：PURPOSE:In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated. METHODS:The mor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1568-z
更新日期：2015-05-01 00:00:00
abstract：:Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using no...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015880218535
更新日期：1991-07-01 00:00:00
abstract：PURPOSE:The Caco-2 association of lectin-grafted PLGA-nanospheres was investigated compared to plain and BSA-coated spheres. METHODS:Nanospheres made from fluorescent-labeled PLGA were coated with wheat germ agglutinin (WGA) or BSA and incubated with Caco-2 monolayers varying the concentration of nanospheres, the time...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000045247.09724.26
更新日期：2004-10-01 00:00:00
abstract：PURPOSE:To study the pulmonary absorption and tolerability of various formulations of the decapeptide cetrorelix acetate in rats by a new aerosol delivery system (ASTA-ADS) for intratracheal application. METHODS:Using the ASTA-ADS, cetrorelix liquid formulations (aqueous solutions for ultrasonic nebulization) were fir...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011028227155
更新日期：2001-06-01 00:00:00
abstract：PURPOSE:We recently developed prostaglandin E(1) (PGE(1))-encapsulated nanoparticles, prepared with a poly(lactide) homopolymer (PLA, Mw = 17,500) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA) (NP-L20). In this study, we tested whether the accelerated blood clearance (ABC) phenomenon is observed wi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9943-x
更新日期：2009-10-01 00:00:00
abstract：PURPOSE:To develop an isolated perfused rat liver (IPRL) model with low baseline levels of tumor necrosis factor (TNF)-alpha in the outlet perfusate to study the effects of immunostimulants and immunosuppressants on the release of TNF-alpha from this organ. METHODS:Isolated rat livers were perfused with a buffer conta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013603331899
更新日期：2002-01-01 00:00:00
abstract：PURPOSE:4-Phenylbutyrate (4-PBA) is expected to be a potential therapeutic for several neurodegenerative diseases. These activities require 4-PBA transport into the brain across the blood-brain barrier (BBB). The objective of the present study was to characterize the brain transport mechanism of 4-PBA through the BBB. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1912-6
更新日期：2016-07-01 00:00:00
abstract：PURPOSE:Our previous studies showed that the mRNA level of human organic anion transporter (hOAT) 3 in the kidney was correlated with the rate of elimination of an anionic antibiotic cefazolin. However, the correlation coefficient was not so high. In the present study, therefore, we enrolled more patients to examine wh...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8383-5
更新日期：2005-12-01 00:00:00
abstract：PURPOSE:The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co-administration of the two ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1988-z
更新日期：2016-11-01 00:00:00
abstract：:Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite no...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016401405119
更新日期：1987-08-01 00:00:00
abstract：PURPOSE:The stability of lipid emulsions (LE) containing various cosurfactants (oleic acid, cholesterol, Tween 80, or HCO-60) was evaluated using the maximum total interaction energy, Vtmax and the energy barrier for coalescence, W. METHODS:The Vtmax and W were calculated from the zeta potential and the rate of increa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016205203264
更新日期：1995-09-01 00:00:00
abstract：PURPOSE:Development of a human mitochondrial gene delivery vector is a critical step in the ability to treat diseases arising from mutations in mitochondrial DNA. Although we have previously cloned the mouse mitochondrial genome in its entirety and developed it as a mitochondrial gene therapy vector, the human mitochon...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0527-1
更新日期：2011-11-01 00:00:00
abstract：PURPOSE:To determine the effect of Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) on the permeation of cromolyn across Caco-2 cell monolayers and explore the molecular basis for the enhanced absorption. METHODS:Transport studies of cromolyn across Caco-2 cell monolayers were conducted in the presence of various ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-7671-9
更新日期：2004-12-01 00:00:00
abstract：PURPOSE:The specific interactions between three lectin-latex conjugates and different structures of rat intestinal mucosa have been studied ex vivo. METHODS:These systems were prepared by covalent coupling of different ligands, i.e., tomato lectin (TL), asparagus pea lectin (AL), mycoplasma gallisepticum lectin (ML), ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016405126656
更新日期：1996-11-01 00:00:00
abstract：:Although much effort has been devoted to opioid research since the identification of enkephalins, understanding of the physiological importance and mechanisms of action of endogenous opioids lags behind understanding of opiate alkaloids such as morphine. In recent years, several novel approaches have been refined with...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1015809702296
更新日期：1991-01-01 00:00:00
abstract：PURPOSE:The passage of molecules across cell membranes is a crucial step in many physiological processes. We therefore seek physical models of this process, in order to predict permeation for new molecules, and to better understand the important interactions which determine the rate of permeation. METHODS:Several sets...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007543708522
更新日期：2000-08-01 00:00:00
abstract：:Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized by a number of microorganisms. Large-scale fermentation with Aspergillus niger (ATCC 10549) and Nocardia corallina (ATCC 19070) have resulted in the isolation of four microbial metabolites which have been chara...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015845306124
更新日期：1990-02-01 00:00:00
abstract：PURPOSE:Carboxylesterases are important in the detoxification of drugs, pesticides and other xenobiotics. This study was to evaluate a series of substrates and inhibitors for characterizing these enzymes. METHODS:A series of novel aliphatic esters and thioesters were used in spectral assays to monitor human, murine an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016071311190
更新日期：1996-10-01 00:00:00
abstract：:A new technique has been developed to calculate rapidly the solid-state room-temperature degradation rate of drugs and drug candidates. The technique utilizes measurements of the initial rate of heat output at several elevated temperatures by isothermal calorimetry and the degradation rate of the compound determined a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015865319250
更新日期：1992-07-01 00:00:00
abstract：PURPOSE:The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges. METHODS:In vivo activity was investigated using six volunteers by determining the reduction in colony form...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
doi：10.1023/a:1016002322692
更新日期：1996-04-01 00:00:00
abstract：PURPOSE:For the assessment of bioequivalence it is assumed that drug clearance in each subject on each of the study days is the same and any observed differences in AUC and/or Cmax between a brand and generic formulation are due to differences in bioavailability. We hypothesized that this assumption was invalid for hig...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章
doi：10.1023/a:1016040825844
更新日期：1996-06-01 00:00:00
abstract：PURPOSE:Three types of acyl tetragastrin (TG), acetyl-TG (C2-TG), butyryl-TG (C4-TG) and caproyl-TG (C6-TG) were synthesized and their in vitro intestinal permeability characteristics were examined using Caco-2 monolayers. METHODS:The disappearance of acyl-TGs from the apical side of Caco-2 monolayers was estimated by...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011997404306
更新日期：1998-09-01 00:00:00
abstract：PURPOSE:To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to produce fine powders of recombinant human deoxyribonuclease (rhDNase), lysozyme-lactose and rhDNase-lactose powders from aqueous based solutions. METHODS:The ASES technique using high pressure carbon dioxide modified with e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000008053.69903.c1
更新日期：2003-12-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate the effect of cyclodextrins (beta-CD, HP-beta-CD and (SBE)7m-beta-CD), and co-administration of a water-soluble polymer (HPMC) and cyclodextrins, on the oral bioavailability of glibenclamide in dogs. METHODS:Effects of cyclodextrins on the aqueous solubility of glibencl...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011900527021
更新日期：1998-11-01 00:00:00
abstract：PURPOSE:Long-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1308-4
更新日期：2014-08-01 00:00:00
abstract：PURPOSE:Although flomoxef (FMOX) has attracted substantial attention as an antibiotic against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-producing E. coli), the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of FMOX against ESBL-producing E. coli is unclear. The aim of this study was t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02977-8
更新日期：2021-01-06 00:00:00
abstract：PURPOSE:We recently showed that the perfusion of isolated rat livers with perfusates containing bovine serum albumin (BSA) would significantly stimulate the release of tumor necrosis factor (TNF)-alpha. Here, we hypothesize that BSA-induced increase in the release of TNF-alpha, and possibly other cytokines, would affec...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022202926073
更新日期：2003-01-01 00:00:00
