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  • physical aging  (4)
  • intestinal permeability  (3)
  • 1
    Electronic Resource
    Electronic Resource
    An Investigation into the Mechanical and Transport Properties of Aqueous Latex Films: A New Hypothesis for the Film-Forming Mechanism of Aqueous Dispersion System (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 405-410 
    Details
    ISSN: 1573-904X
    Keywords: latex ; physical aging ; permeability ; plasticizer ; creep compliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effects of plasticizer, physical aging, and film-forming temperature on the mechanical and transport properties of films formed from aqueous dispersions of ethylcellulose latex were investigated. The water vapor permeability of latex films was found to decrease with diethyl phthalate to a minimum value and then to increase with diethyl phthalate at higher concentrations. Because of the decrease in free volume and the further coalescence of particles of latex polymer films in the physical aging range, the creep compliance of latex films decreased with physical aging time. Within 60 to 100°C, the film-forming temperature was found to have no effect on the mechanical and transport properties of Aquacoat films. However, since many pinholes formed in the latex films when the film-forming temperature was above 100°C, the water vapor permeability of latex films was higher than that of latex films formed between 60 and 100°C. The formation of films from aqueous latex dispersions is suggested to proceed gradually from the top to the bottom of the latex dispersion in this study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018992423232
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  • 2
    Electronic Resource
    Electronic Resource
    Human Intestinal Permeability of Piroxicam, Propranolol, Phenylalanine, and PEG 400 Determined by Jejunal Perfusion (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 1127-1132 
    Details
    ISSN: 1573-904X
    Keywords: intestinal permeability ; drug absorption ; piroxicam ; propranolol ; biopharmaceutic classification scheme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the human jejunal permeabilities of compounds utilizing different transport mechanisms using a regional perfusion approach and to establish a standard procedure for determining drug permeability class to be used for the establishment of drug product bioequivalence standards. Methods. Six healthy male volunteers participated in this study. A multi-lumen perfusion tube was inserted orally and positioned in the proximal region of the jejunum. A solution containing piroxicam, phenylalanine, propranolol, PEG 400 and PEG 4000 was perfused through the intestinal segment at a rate of 3.0 ml/min. Perfusate samples were quantitatively collected every 10 minutes for two 100 minute periods with an intermediate wash out period to determine intra and intersubject variation. Results. The mean Peff (±SD) of piroxicam, phenylalanine, propranolol, and PEG 400 were 10.40 ± 5.93, 6.67 ± 3.42, 3.59 ± 1.60, 0.80 ± 0.46 × 10−4 cm/sec, respectively. The coefficient of variation for the intersubject variability, first and second perfusion periods were: piroxicam, 60.5% and 57.1%; phenylalanine, 52.8% and 57.8%: propranolol, 62.1 % and 44.6%; and PEG 400, 81.7% and 42.3%, indicating a slightly lower CV for the second perfusion period in the same subject. The intrasubject CV's between the two perfusion periods were: 19.4%, 21.3%, 23.6% and 41.0% respectively, indicating a smaller intraindividual variation for all compounds studied. Conclusions. Piroxicam, a nonpolar drug exhibited the highest permeability of the compounds studied. The intrasubject CV was lower than the intersubject CV, indicating consistent permeability estimation within subjects. The methodology is useful for permeability estimation regardless of absorption mechanism and can be used to establish a consistent data base of human permeabilities for estimation of human drug absorption and for establishing the biopharmaceutic permeability class of drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012134219095
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  • 3
    Electronic Resource
    Electronic Resource
    Use of the Peptide Carrier System to Improve the Intestinal Absorption of L-α-Methyldopa: Carrier Kinetics, Intestinal Permeabilities, and In Vitro Hydrolysis of Dipeptidyl Derivatives of L-α-Methyldopa (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 66-70 
    Details
    ISSN: 1573-904X
    Keywords: dipeptides ; intestinal permeability ; L-α-methyldopa ; L-α-methyldopa-L-phenylalanine ; uptake kinetics ; peptide carrier system ; in vitro hydrolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Intestinal permeabilities of five dipeptidyl derivatives of L-α-methyldopa (I) were studied by an in situ intestinal perfusion method. The dipeptides displayed a significant increase in their permeabilities compared to L-α-methyldopa. The increases ranged from 4 to 20 times. These results suggest that the peptide transport system is less structurally specific than the amino acid transport systems and can be used as an absorption pathway for peptide analogues. The kinetic advantage demonstrated by the dipeptide, L-α-methyldopa-L-phenylalanine, over the amino acid analogue, L-α-methyldopa, suggests that the peptide carrier would be a possible route for improving the intestinal absorption of pharmacologically active amino acid analogues. Furthermore, the preliminary results of in vitro hydrolysis studies of selected dipeptidyl derivatives indicate that the peptide carrier system could be used as a base for a prodrug strategy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015855820488
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  • 4
    Electronic Resource
    Electronic Resource
    Prediction of Physical Aging in Controlled-Release Coatings: The Application of the Relaxation Coupling Model to Glassy Cellulose Acetate (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 698-705 
    Details
    ISSN: 1573-904X
    Keywords: physical aging ; water transport ; controlled-release coating ; mechanical relaxation ; cellulose acetate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of physical aging on both the water transport properties and the mechanical properties of glassy cellulose acetate was investigated. Results indicate a reduction in the mechanical rate of relaxation as well as a reduction in the water permeability as the glass ages. A model which describes the low-frequency relaxation behavior of condensed, amorphous systems is used to quantitate the mechanical relaxation data. Systematic changes in key parameters from this model signify alterations in the microscopic or short-range structure as the glass physically ages. Predictions from this model correlate quite closely with the observed water permeability reductions and thus indicate that the transport properties of glassy polymers are dependent on the structure of the glass. This approach may provide further insight into the effects of nonequilibrium behavior on pharmaceutically important properties and may serve as a basis for predicting aging and permeability changes in controlled-release dosage forms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015837614475
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  • 5
    Electronic Resource
    Electronic Resource
    The Effect of Physical Aging on the Dissolution Rate of Anionic Polyelectrolytes (1990)
    Springer
    Pharmaceutical research 7 (1990), S. 648-653 
    Details
    ISSN: 1573-904X
    Keywords: physical aging ; dissolution ; enteric coating ; creep compliance ; hydroxypropyl methylcellulose phthalate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of physical aging on the dissolution and mechanical properties of hydroxypropyl methyl-cellulose phthalate (HPMCP) was investigated. Dissolution rate measurements were performed on films which, initially above the glass transition temperature, T g, were quenched to a sub-T g storage temperature, aged at that temperature for a period of time and then quenched again to 25°C. Within the time scale of observation, reductions in the dissolution rate to a limiting value were observed. HPMCP was also found to age in the same storage temperature range as determined by a creep compliance technique. These mechanical results indicate a change in glass structure and show that a limiting density was approached. Parallel changes were observed in the dissolution rate studies suggest that dissolution rate is governed in part by glass density. Therefore, mechanical changes of glassy films can yield pharmaceutically relevant information about the extent of physical aging and serve as an indicator of the effect of aging on dissolution rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015882631082
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  • 6
    Electronic Resource
    Electronic Resource
    Influence of Physical Aging on Mechanical Properties of Polymer Free Films: The Prediction of Long-Term Aging Effects on the Water Permeability and Dissolution Rate of Polymer Film-Coated Tablets (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 1500-1504 
    Details
    ISSN: 1573-904X
    Keywords: physical aging ; creep compliance ; permeability ; dissolution rate ; glass transition temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effects of physical aging on the water permeation of cellulose acetate and ethylcellulose, the mechanical properties of ethylcellulose, and the dissolution property of hydroxypropyl methylcellulose phthalate were investigated. The water permeabilities of cellulose acetate and ethylcellulose and the dissolution rate of hydroxypropyl methylcellulose phthalate were found to decrease with physical aging time after being quenched from above the glass transition temperatures to sub-T g temperatures. The gradual approach toward thermodynamic equilibrium during physical aging decreases the free volume of the polymers. This decrease in free volume is accompanied by a decrease in the transport mobility, with concomitant changes in those properties of the polymer that depend on it. The effects of long-term aging on the dissolution rate and water permeabilities of these polymers can be estimated from a linear double-logarithmic relationship between the mobility properties and physical aging time. The existence of the linear double-logarithmic relationship can be derived from the Williams–Landel–Ferry (1) equation, the Doolittle (2) equation, Struik's (3) model, and Fujita's (4) relationship between diffusion and free volume.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015890232106
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  • 7
    Electronic Resource
    Electronic Resource
    A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 413-420 
    Details
    ISSN: 1573-904X
    Keywords: bioavailability ; drug absorption ; mathematical modeling ; in vitro–in vivo correlation ; intestinal permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transport model and human permeability results for estimating in vivo drug absorption to illustrate the primary importance of solubility and permeability on drug absorption. The fundamental parameters which define oral drug absorption in humans resulting from this analysis are discussed and used as a basis for this classification scheme. These Biopharmaceutic Drug Classes are defined as: Case 1. High solubility-high permeability drugs, Case 2. Low solubility-high permeability drugs, Case 3. High solubility-low permeability drugs, and Case 4. Low solubility-low permeability drugs. Based on this classification scheme, suggestions are made for setting standards for in vitro drug dissolution testing methodology which will correlate with the in vivo process. This methodology must be based on the physiological and physical chemical properties controlling drug absorption. This analysis points out conditions under which no in vitro-in vivo correlation may be expected e.g. rapidly dissolving low permeability drugs. Furthermore, it is suggested for example that for very rapidly dissolving high solubility drugs, e.g. 85% dissolution in less than 15 minutes, a simple one point dissolution test, is all that may be needed to insure bioavailability. For slowly dissolving drugs a dissolution profile is required with multiple time points in systems which would include low pH, physiological pH, and surfactants and the in vitro conditions should mimic the in vivo processes. This classification scheme provides a basis for establishing in vitro-in vivo correlations and for estimating the absorption of drugs based on the fundamental dissolution and permeability properties of physiologic importance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016212804288
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