TY - JOUR
T1 - Partial molal volumes and solubilities of physostigmine in isopropanol:isopropyl myristate solvents in relation to skin penetrability
AU - Pardo, Asher
AU - Shiri, Yoseph
AU - Cohen, Sasson
N1 - Funding Information:
This work was financially supported by The Committee For Research & Prevention in Occupational Safety & Health, State of Israel, and was presented a~ part of the Ph.D. thesis of A. P., Tel Aviv University.
PY - 1991/6
Y1 - 1991/6
N2 - Partial molal volumes (V i∞) of physostigmine, ranging from 232.9 to 239.8 cm3 · mol−1, and its mole fraction solubilities (Xi), ranging from 0.051 to 0.009, were determined at 25 °C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between V i∞ and Xi. At solubility →; O, V i∞ → 240.6 (by extrapolation). The experimentally derived liquid molal volume in the standard state, V i∞ (231.1), of physostigmine was lower than its lowest Vi (value 232.9) in the series tested. Virtual cohesion parameters (Λ) and excess free energies (ΔEGi) of physostigmine in the various solutions were estimated from the partial molal volumes, assuming regular solution behavior. For each solution, the free energy (‐RT In Xi) of the drug was estimated from its solubility. An increase in the virtual cohesion parameter and a decrease in the excess free energy and the free energy was found with an increase in volume fraction of IPA in the mixed solvent. The increase in Λi over the invariant cohesion parameter, δi (10.2), reflects a compensation effect needed to maintain the geometric mean assumption of Regular Solution Theory. Deviation from the theoretically expected linearity between ‐RT In Xi and ΔEGi of physostigmine is ascribed to the existence of solvated molecules distinct from unsolvated molecules of physostigmine. The highest permeability coefficient of the delivery of physostigmine through excised human skin from IPA:IPM mixtures was seen from the mixture exhibiting the highest solvation effect, giving additional evidence that physostigmine penetrates through the skin, possibly in combination with IPA.
AB - Partial molal volumes (V i∞) of physostigmine, ranging from 232.9 to 239.8 cm3 · mol−1, and its mole fraction solubilities (Xi), ranging from 0.051 to 0.009, were determined at 25 °C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between V i∞ and Xi. At solubility →; O, V i∞ → 240.6 (by extrapolation). The experimentally derived liquid molal volume in the standard state, V i∞ (231.1), of physostigmine was lower than its lowest Vi (value 232.9) in the series tested. Virtual cohesion parameters (Λ) and excess free energies (ΔEGi) of physostigmine in the various solutions were estimated from the partial molal volumes, assuming regular solution behavior. For each solution, the free energy (‐RT In Xi) of the drug was estimated from its solubility. An increase in the virtual cohesion parameter and a decrease in the excess free energy and the free energy was found with an increase in volume fraction of IPA in the mixed solvent. The increase in Λi over the invariant cohesion parameter, δi (10.2), reflects a compensation effect needed to maintain the geometric mean assumption of Regular Solution Theory. Deviation from the theoretically expected linearity between ‐RT In Xi and ΔEGi of physostigmine is ascribed to the existence of solvated molecules distinct from unsolvated molecules of physostigmine. The highest permeability coefficient of the delivery of physostigmine through excised human skin from IPA:IPM mixtures was seen from the mixture exhibiting the highest solvation effect, giving additional evidence that physostigmine penetrates through the skin, possibly in combination with IPA.
UR - http://www.scopus.com/inward/record.url?scp=0025868957&partnerID=8YFLogxK
U2 - 10.1002/jps.2600800615
DO - 10.1002/jps.2600800615
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:0025868957
SN - 0022-3549
VL - 80
SP - 567
EP - 572
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 6
ER -