Partition coefficient polymer/drug

An analysis of partition coefficient data and drug solubilities in PCL and silicone rubber has been used to show how the relative permeabilities in PCL vary with the lipophilicity of the drug (58,59). The permeabilities of copolymers of e-caprolactone and dl-lactic acid have also been measured and found to be relatively invariant for compositions up to 50% lactic acid (67). The permeability then decreases rapidly to that of the homopolymer of dl-lactic acid, which is 10 times smaller than the value of PCL. These results have been discussed in terms of the polymer morphologies. 

Although the partition coefficient is expected to remain constant, its magnitude is important. Since this coefficient represents the concentration of drug in the membrane relative to that in the core, an excessively high partition coefficient will allow quick depletion of the core and an ineffective delivery system. For effective diffusional systems, the partition coefficient should be less than unity. If the value of this coefficient is greater than 1, the surrounding polymer does not represent a barrier, and drug release becomes first-order. 

The parameters that determine the release rate of a drug from a delivery device include polymer solubility, polymer diffusivity, thickness of the polymer diffiisional path, and the aqueous solubility, partition coefficient, and aqueous diffusivity of the drug. Finally, the thickness of the hydrodynamic diffusion layer, the amount of drug loaded into the matrix, and the smface area of the device all affect the release rate. 

It is not necessary to know or derive the water solubility of the drug in order to make use of the partition coefficient data. For example, it follows from equation 23 that, for any drug, the vertical displacement of the two correlation lines in Figure 10 is a measure of the ratio of the drug solubility in the two polymers. 

The various approaches to estimating diffusion coefficients and solubilities of drugs in polymers have been reviewed. The polymers typically used for drug delivery have diffusion coefficients that are characteristic of the polymer and relatively constant for drugs of a similar molecular size. Drug solubilities in a polymer can be estimated from the solubility parameters and melting points (steroids), from the melting point alone, or from the correlation of partition coefficients. 

The absorption was correlated to the octanol-water partition coefficients of the drugs, suggesting that prediction of absorption from partition data is possible [30, 31]. Polymers such as Nylon-6 (polycaprolactam) are known to adsorb drug substances such as benzocaine [32],... 

The lipophilicity of PSA polymers, which is markedly affected by chemical composition, may influence drug solubility (Table 5). In general, acrylic copolymers have medium lipophilicity compared with other PSA polymers, and have the most excellent drug solubility. A suitable lipophilicity of copolymers can be obtained by changing the compositional content of comonomers. The lipophilicity of acrylic copolymers can be roughly estimated by the theoretical calculation of the hydrophobic parameters of copolymers according to the hydrophobic fragments of each comonomer, or the calculation of the octanol-water partition coefficients (log PC). ... 

When the volume of the environmental fluid is finite, diffusion of a minor chemical species will proceed until equilibrium is attained. At equilibrium the diffusing species will partition itself between the polymer and environmental fluid phases defined by a partition coefficient K. The estimation of K is an importnat consideration in drug release from polymeric delivery devices (1 ) and in applications of polymers as food packaging materials (2 ). 

K is the octanol/water partition coefficient, k is the rate of elimination due to permeation through capillaries, D, is the diffusion coefficient of the drug in the brain. The following values are assumed, consistent with results from polymer delivery to rats and rabbits radius of spherical implant, ft = 1.5 mm mass of implant, M = lOmg drug loading in implant = 10%. 

In the SSI technique the main limitation is connected to the solubility of the additive drug. It is obvious that the solubility of most drugs in supercritical fluids is relatively low however this limitation is not so strict due to the goierally high values of partition coefficients that is possible to obtain when the supercritical solution is m contact with the polymer [60]. The polymers used can be thermoplastic or cross-linked provided that supercritical fluid can swell and in some extent plasticize the polymer. 

Although being Q normalised, L remains a function of the drug s partition coefficient between the solvent and the polymer phase and therefore is a function of drug, polymer and solvent properties. 

Like many other amphiphilic surfactants, the Pluronic copolymers used in SP1049C formulation spontaneously form micelles at concentrations equal to or exceeding the critical micellar concentration (CMC). At polymer concentration above CMC, the dmg added to the system is partitioned between the water phase and the micellar microphase. The equilibrium between the micelle-incorporated dmg and the dmg present in the water phase is described by the partitioning coefficient (P), which is equal to the ratio between the local concentration of the drug in the micellar microphase and its concentration in the water phase. 

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