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  • 1
    Electronic Resource
    Electronic Resource
    Evidence for the Formation of Amphotericin B-phospholipid Complexes in Langmuir Monolayers (1996)
    Springer
    Pharmaceutical research 13 (1996), S. 1008-1014 
    Details
    ISSN: 1573-904X
    Keywords: amphotericin B ; lecithin ; emulsion ; stability ; monolayer ; low-dimensional structures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To study the interaction of the polyene antifungal amphotericin B with phospholipid Langmuir monolayers and to correlate with stability of phospholipid-stabilized drug emulsions. Methods. Pressure—area isotherms of mixed monolayers of amphotericin B (0–20 mol%) and different phospholipid types were recorded using conventional Langmuir trough methods. Emulsion stability of amphotericin B-containing lipid emulsions was measured using dynamic light scattering. Results. Incorporation of amphotericin B into monolayers composed of saturated phospholipids (Lipoid E80-3) had a profound effect on the shape of the isotherm. This effect was directly related to the concentration of amphotericin B in the monolayer. At high drug concentrations, the shape of the isotherms became progressively similar to that of pure DPPC, thus exhibiting regions attributable to phospholipid in different phase states. This effect on isotherm shape was not observed following incorporation of the drug into monolayers composed of the equivalent unsaturated lecithin (Lipoid E80). Conclusions. These results are interpreted as indicating the formation of an amphotericin B-phospholipid complex, resulting in phase separation within the monolayer. The extent and nature of this phase separation was dependent on both the concentration of drug in the system, and the saturation state of the phospholipid component. The relevance of these observations to the stability of amphotericin B drug emulsions stabilised by saturated and unsaturated phospholipid emulsifiers is discussed. These observations may also be relevant to the toxicity of these, and other novel amphotericin B formulations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016046321726
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  • 2
    Electronic Resource
    Electronic Resource
    The Stability and Solubility of Progabide and Its Related Metabolic Derivatives (1988)
    Springer
    Pharmaceutical research 5 (1988), S. 226-231 
    Details
    ISSN: 1573-904X
    Keywords: Progabide ; metabolic derivatives ; stability ; solubility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The stability–pH profile of the γ-aminobutyric acid prodrug, Progabide, was found to be bell shaped, with maximum stability occurring at pH 6 to 7 with a t 1/2 of 126 min. Of its metabolic derivatives, the deamidated product PGA degraded in a similar fashion to Progabide, whereas the hydrolytic degradation product SL79.182 was, as expected, a stable compound. Progabide behaved as a typical weak base, with its solubility increasing with a decrease in pH. SL79.182 behaved as a typical phenolic weak acid, with its solubility increasing with an increase in pH. Both compounds displayed low intrinsic solubilities of 14.5 × 10−5 M for Progabide and 33.4 × 10−6 M for SL79.182. An increase in temperature resulted in an increase in the solubility but a decrease in the stability of Progabide. The data obtained indicate that the gastric pH and gastric emptying rate will have a profound effect on the oral bioavailability of Progabide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015941729400
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    Paper (German National Licenses)
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