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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of chemical & engineering data 21 (1976), S. 262-264 
    ISSN: 1520-5134
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 199 (1963), S. 999-1000 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1. Effect of sodium decyl sulphate on photoreduction of riboflavin by visible light in 0.05 M phosphate buffer, pH. 6.8, 26 C Fig. 2. Influence of micellar sodium decyl sulphate on rate of photo fading 9f acetyl riboflavin in 0.05 M phosphate buffer, pH 6.8, 26 C. Acetylriboflavin in: A, 0.07 ...
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  • 3
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 67 (1963), S. 1395-1396 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-904X
    Keywords: calcitonin ; polyethylene glycol ; PEGylation ; peptide ; tryptic digestion ; stability ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To separate and characterize the different positional isomers of mono-PEGylated salmon calcitonins (mono-PEG-sCTs) and to evaluate the effects of the PEGylation site on the stability of different mono-PEG-sCTs in rat kidney homogenate. Methods. Mono-PEG-sCTs were prepared using succinimidyl carbonate monomethoxy polyethylene glycol (5,000 Da) and separated by gel-filtration HPLC followed by reversed-phase HPLC. To characterize PEGylated sCTs, matrix-assisted laser desorption ionization time of flight mass spectrometry (M ALDI-TOF MS) and reversed-phase HPLC of the trypsin digested samples were performed. Mono-PEG-sCTs and sCT in rat kidney homogenates were measured by column-switching reversed-phase HPLC with on-line detection of the radioiodinated samples using a flow-through radioisotope detector. Results. Three different mono-PEGylated sCTs were separated by reversed-phase gradient HPLC. From the MALDI-TOF MS analysis, the average molecular weight of mono-PEG-sCTs was confirmed as around 8650 Da. The presence of PEG moiety in the mono-PEG-sCTs was also manifested by the fact that the distance between two adjacent mass spectum lines was 44 Da which corresponds to PEG monomer unit. Tryptic digestion analysis demonstrated that these mono-PEG-sCTs are 3 positional isomers of N-terminus, Lys18- and Lys11-residue modified mono-PEGylated sCTs. The degradation half-life of these 3 positional isomers in rat kidney homogenates significantly increased in order of the N-terminus (125.5 min), Lys11- (157.3 min), and Lysl8-residue modified mono-PEGylated sCT (281.5 min) over the native sCT (4.8 min). Conclusions. Three positional isomers of mono-PEGylated sCTs were purified and characterized. Of these, the resistance to proteolytic degradation was highest for the Lysl8-residue modified mono-PEG-sCT. These studies demonstrate that the in vivo stability of PEGylated sCTs is highly dependent on the site of PEG molecule attachment.
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  • 5
    ISSN: 1573-904X
    Keywords: bronchodilation ; prolonged action ; isoproterenol ; poly(glycolide-co-lactide) microspheres ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract An animal study was carried out to evaluate the in vivo bronchodilator action of isoproterenol (Iso) from poly(glycolide-co-lactide) (PGL) microspheres. Microspheres with a mean diameter of 4.5 µm and a drug load of 7% were administered intratracheally to Long-Evans rats. The microspheres released about 70% of the incorporated drug in the instillation medium before administration, which provided immediate action, and the remaining 30% was available for sustained release. A total of 120 animals was anesthetized, paralyzed, artificially ventilated, and divided into 15 groups (n = 8): 3 groups each for saline, blank microspheres, free Iso, blank microspheres with free Iso, and microencapsulated Iso. All instillations were made in a volume of 1 ml/kg and the dose of all Iso preparations was 0.1 mg/kg. At 3, 6, or 12 hr after the intratracheal instillation, a serotonin challenge (40 µg/rat) was administered intravenously to constrict the airways. Airway function tests were performed at each time interval on one group of animals by a maximal expiratory flow-volume maneuver. The heart rate in animals receiving Iso formulations was similar to that in the saline control group, indicating minimal systemic effect of the dose administered. The systemic serum levels were below 2 ng/ml in all the groups. Animals receiving encapsulated Iso resisted the serotonin challenge for at least 12 hr after intratracheal instillation, indicating that the drug was still present over this period of time. On the other hand, the serotonin-induced airway constriction observed in the animals receiving blank microspheres, free Iso, or free Iso with blank microspheres was similar to that in saline controls at all time points. The results clearly show that only a small fraction of the free dose is required in sustained-release form for a prolonged pharmacological effect, resulting in a 50- to 100-fold reduction in the total dose administered.
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  • 6
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-904X
    Keywords: controlled release ; microspheres ; DNA ; DNA/poly(L-lysine) complex ; poly(lactide-co-glycolide)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To produce and characterize controlled release formulations of plasmid DNA (pDNA) loaded in poly (D,L-lactide-co-glycolide) (PLGA) microspheres both in free form and as a complex with poly (L-lysine). Methods. Poly (L-lysine) (PLL) was used to form pDNA/PLL complexes with complexation ratio of 1:0.125 and 1:0.333 w/w to enhance the stability of pDNA during microsphere preparation and protect pDNA from nuclease attack. pDNA structure, particle size, zeta potential, drug loading, in vitro release properties, and protection from DNase I were studied. Results. The microspheres were found to be spherical with average particle size of 3.1-3.5 μm. Drug loading of 0.6% was targeted. Incorporation efficiencies of 35.1% and 29.4-30.6% were obtained for pDNA and pDNA/PLL loaded microspheres respectively. Overall, pDNA release kinetics following the initial burst did not correlate with blank microsphere polymer degradation profile suggesting that pDNA release is convective diffusion controlled. The percentage of supercoiled pDNA in the pDNA and pDNA/PLL loaded microspheres was 16.6 % and 76.7-85.6% respectively. Unencapsulated pDNA and pDNA/PLL degraded completely within 30 minutes upon the addition of DNase I. Encapsulation of DNA/PLL in PLGA microspheres protected pDNA from enzymatic degradation. Conclusions. The results show that using a novel process, pDNA can be stabilized and encapsulated in PLGA microspheres to protect pDNA from enzymatic degradation.
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  • 8
    ISSN: 1573-904X
    Keywords: poly(D,L-lactide-co-glycolide) ; polyester degradation ; gamma irradiation ; polymer mass loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The objective of the reported work was to quantitatively establish γ-irradiation dose effects on initial molecular weight distributions and in vitro degradation rates of a candidate credible biopolymeric delivery system. Methods. Poly(D,L-lactide-co-glycolide) (PLGA) porous microparticles were prepared by a phase-separation technique using a 50:50 copolymer with 30,000 nominal molecular weight. The microparticles were subjected to 0, 1.5, 2.5, 3.5, 4.5, and 5.5 Mrad doses of γ-irradiation and examined by size exclusion chromatography (SEC) to determine molecular weight distributions. The samples were subsequently incubated in vitro at 37°C in pH 7.4 PBS and removed at timed intervals for gravimetric determinations of mass loss and SEC determinations of molecular weight reduction. Results. Irradiation reduced initial molecular weight distributions as follows (Mn values shown parenthetically for irradiation doses): 0 Mrad (Mn = 25200 Da), 1.5 Mrad (18700 Da), 2.5 Mrad (17800 Da), 3.5 Mrad (13800 Da), 4.5 Mrad (12900 Da), 5.5 Mrad (11300 Da). In vitro degradation showed a lag period prior to zero-order loss of polymer mass. Onset times for mass loss decreased with increasing irradiation dose: 0 Mrad (onset = 3.4 weeks), 1.5 Mrad (2.0 w), 2.5 Mrad (1.5 w), 3.5 Mrad (1.3 w), 4.5 Mrad (1.0 w), 5.5 Mrad (0.8 w). The zero-order mass loss rate was 12%/week, independent of irradiation dose. Onset of erosion corresponded to Mn = 5200 Da, the point where the copolymer becomes appreciably soluble. Conclusions. The data demonstrated a substantial effect of γ-irradiation on initial molecular weight distribution and onset of mass loss for PLGA, but no effect on rate of mass loss.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 12 (1995), S. 484-490 
    ISSN: 1573-904X
    Keywords: lyophilization ; tertiary butyl alcohol ; freeze-drying microscope ; phase diagram ; crystal habit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Utilizing differential scanning calorimetry (DSC) for tertiary butyl alcohol (TBA) solutions a phase diagram was constructed for the TBA-water system. By utilizing thermal treatment during the DSC measurements the metastable states were eliminated. The phase diagram fit that for a congruently melting compound in which compound formation occurred with a maximum at 70% TBA representing pure TBA hydrate. Two eutectics occurred at 20% (Eutectic A) and 90% (Eutectic B). A freeze-drying microscope revealed that TBA altered the crystal habit of ice. A concentration of 3% TBA was required before large needle-shaped ice crystals became evident. The addition of 10% TBA to the system resulted in even finer needle-shaped ice crystals. At the eutectic compositions (20% and 90% TBA), the frozen eutectic mixture could not be resolved with the microscope because eutectic crystals are very small. The 70% TBA solution, which corresponds to the melting of pure TBA hydrate, formed very large hydrate crystals. The rate of sublimation of the TBA and water molecules was found to be concentration dependent. At concentrations below 20% TBA (water rich portion of the phase diagram) water molecules sublimed faster while at concentrations above 20% TBA (TBA rich portion of the phase diagram) TBA molecules sublimed faster. At the eutectic A composition, both TBA and water molecules sublimed at the same rate. This may be because all of the TBA molecules are strongly associated with each other in the form of a clathrate hydrate.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 12 (1995), S. 491-495 
    ISSN: 1573-904X
    Keywords: lyophilization ; tertiary butyl alcohol ; collapse temperature ; primary drying ; freeze-drying microbalance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The addition of low concentrations of tertiary butyl alcohol (TBA) (3–10% w/v) was shown to influence the crystal habit of ice by causing the formation of needle-shaped ice crystals. The sublimation of these needle-shaped ice crystals resulted in a dry product layer with little resistance. Using a microbalance technique it was shown that the primary drying stage for 5% w/v sucrose solution was considerably shorter when 5% w/v TBA was added due to a lower resistance of the dried cake above the frozen solution. In the absence of TBA the frozen solution had an initially high resistance of approximately 60 cm2 torr hr/gm due to the formation of a skin; once the skin cracked the resistance reached a constant value of 10 cm2 torr hr/gm. The solution containing TBA had a dried product resistance in the range of 0.5–3 cm2 torr hr/gm. The total time required to dry the product in the absence of TBA in the microbalance was 100 hours as compared to 10 hours for the solution containing 5% w/v TBA. The specific surface area of the freeze-dried cake produced from a 5% w/v sucrose solution containing 5% w/v TBA was 8.57 m2/gm as compared to 0.67 m2/gm for solutions not containing TBA. The addition of TBA to the sucrose solution did not change the collapse temperature, but the rapid rate of sublimation prevented the product from ever reaching the collapse temperature.
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