Partition CoefLcients

The next step in developing the solubility equation by partition theory is the estimation of the activity coefLcient of solute in watersolution. If an aqueous solution is equilibrated with octanol, then it can be shown th i can be related to the octanol-water partition coefLcient by... 

When the cohesive energy of the solute is similar to that of octanol, the activity coefLcient in octanol can be approximated as unity. As a result, the activity coefLcient in water can be approximated using the octanol-water partition coefLcient ... 

The mole fraction partition coefLcientgiven by Equation 3.24 can be replaced by the conventional concentration-based partitioning coefLcient, PC, deLned by... 

Solution. The octanol-water partition coefLcient of methyl paraben is estimated using a fragmental method as described by the following equation (Rekker, 1977) ... 

Caution should be exercised when considering temperature effects on solubilization by micelles, since the aqueous solubility of the solute and thus its micelle/water partition coefLcient can also change in response to temperature changes. For example, it has been reported that although tt solubility of benzoic acid in a series of polyoxyethylene nonionic surfactants increases with temperature, the micelle/water partition coefLci rt, shows a minimum at 2C, presumably due to the increase in the aqueous solubility of benzoic acid (Humphreys and Rhodes, 1968). The increasr in Km with increasing temperature was attributed to an increase in micellar size, as the cloud point temperature of the surfactant is approached (Humphreys and Rhodes, 1968). 

Solubilization oftropicamide, a poorly water-soluble mydriatic/cycloplegicdrug, by poloxamers or Pluronics was studied (Saettone et al., 1988). The polymers evaluated as solubilizers for the drug included L-64, P-65, F-68, P-75, F-77, P-84, P-85, F-87, F-88, and F-127. The authors measured a range of physicochemical properties, such as solubility oftropicamide in polymer solutions, partition coefLcient of the drug between isopropyl myristate and copolymer solutions, critical micelle concentration of the copolymers, and viscosity of the copolymeric solutions containing tropicamide. 

The solubility and release of naproxen from Pluronic PF-127 micelles were studied as a function of temperature and pH by Suh and Jun (1996). The solubility of the drug at pH 2 was signiLcantly increased as a linear function of PF-127 concentrations for three temperatures. Naproxen was highly entrapped by the micelles as indicated by large partition coefLcient. The micellar solubilization was a spontaneous (AG 0) and exothermic (AH< 0) process that resulted in a less ordered state (AS > 0). In the presence of PF-127, the release of naproxen was sustained at pH 2 and inversely proportional to the surfactant concentration. In contrast, at pH 7, PF-127 had little effect on the membrane transport of naproxen. The release of naproxen from the PF-127 gel into isopropanol myristate was also found to be dependent on the medium pH with the highest release observed at pH 6.3. 

Physicochemical properties of the drug, such as ionization consult, Aqueous solubility, partition coefLcient (log P), and chemical stability signiLcantly inLuence the dosage form design. Since... 

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