Partial molal volumes and solubilities of physostigmine in isopropanol:isopropyl myristate solvents in relation to skin penetrability.
Partial molal volumes (Vi infinity) 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 degrees C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between Vi infinity and Xi. At solubility----0, Vi infinity----240.6 (by extrapolation). The experimentally derived liquid molal volume in the standard state, Vi degrees (231.1), of physostigmine was lower than its lowest Vi infinity (value 232.9) in the series tested. Virtual cohesion parameters (lambda i) and excess free energies (delta EGi) 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 lambda i over the invariant cohesion parameter, delta i (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 delta EGi 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.
Department of Physiology and Pharmacology, Tel Aviv University, Sackler School of Medicine, Israel.
A
A
Pardo
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Shiri
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Cohen
D000433:1-Propanol / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D009226:Myristates / Q000737:chemistry*; D009994:Osmolar Concentration; D010830:Physostigmine / Q000737:chemistry / Q000493:pharmacokinetics*; D012869:Skin Absorption; D012995:Solubility; D013816:Thermodynamics
D009226:Myristates; C008205:isopropyl myristate; D000433:1-Propanol; D010830:Physostigmine