Drug solubilities in polymers

K., The correlation of polymer-water and octanol-water coefficients Estimation of drug solubilities in polymers, Int. J. Pharm., 45, 1-11, 1988. 

Since most other modeling techniques for polymers are extremely demanding, the limited capabilities of COSMO-RS for efficient prediction of solubilities in polymers can be of great help in practical applications when suitable polymers with certain solubility requirements are desired. One application may be the selection of appropriate membrane polymers for certain separation processes. Predictions of drug solubility in polymers are sometimes of interest for pharmaceutical applications. Furthermore, it is most likely that COSMO-RS can also be used to investigate the mutual compatibility of polymers for blends. This aspect, and many other aspects of the potential of COSMO-RS for polymer modeling, still awaits systematic investigation. 

Haddadin R, Qian F, Desikan S, Hussain M, Smith RL (2009) Estimation of drug solubility in polymers via differential scanning calorimetry and utilization of the fox equation. Pharm Dev Technol 14(1) 18-26... 

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. 

If the solubility (C ) of a drug in a low molecular weight solvent is known, it follows from equation 14 that the drug solubility in a polymer can be derived from the distribution of the drug between the... 

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. 

To examine the effect of time-dependent diffusion coefficient on the release behavior from a swellable polymer system containing dissolved or dispersed drug, we consider a polymer sheet with half thickness i, an initial drug loading A, a drug solubility in the polymer matrix C, and a time-dependent drug diffusion coefficient of the following form ... 

The dissolution profiles for LBZ B110-l-2 and PPL B110-l-2 tablets were also compared using similarity factor f2. A value obtained for f2 that is below 50 (37.48) indicates the influence of drug solubility in the dissolution profile. Furthermore, other parameters, such as dextran-drug ratio, particle size of polymer and drug, and influence of pH, have to be studied to obtain an optimum and robust formulation. 

For the biomedical applications and development of drug delivery systans, polymers that have already received regulatory approval are mostly used, apart from polymer physicochonical properties such as bulk hydrophilidty, morphology, and structure, solute solubility in polymer and degradation rate of both the polymer and the device are to be kept in mind for the selection of proper polymers. 

The interfacial partitioning of the drug is related to its solubility in polymer and in solution as defined by... 

In order to overcome some of these restrictions in the development of the impregnation processes Perman [56] suggests using a liquid solvent (preferentially water) to solubilize the drug. This solvent is insoluble in the supo critical fluid. The system is then pressurized with die supercritical fluid in order to swell the polymer and to allow rapid difi isional transport of the solute into the polymeric substrate. At the end, pressure is released and the liquid diffuses out of the matrix. The process proposed seems in some extent similar to the recrystallization processes since the impregnation of the solutes is partially enhanced by the decrease of the drug solubility in the liquid solvent. The most important parameters are ... 

Yang M, Gogos CG, Wang P (2001) A new systematic methodology to determine drug s solubility in polymer, pp 1354-1359... 

In a method analogous to the determination of drug solubility in a polymer, the heats of fusion may be used to further characterise a system. Again the heats of fusion of the eutectic and excess components can be plotted as a function of composition. There are straight line relationships between the heats of fusion attributable to the excess components which decrease with addition of the second component [107]. Each should intersect zero enthalpy at the eutectic composition. Concomitantly, the heats of fusion of the eutectic components increase directly from zero at the pure components to intersect at the eutectic composition. Such a technique was used to evaluate the sulphamethoxazole-mannitol system. [107], The technique can be further extended when complexation occurs, as for example with the dapsone-dilauryldapsone system [108],... 

Poly[(4-carboxylatophenoxy)(methoxyethoxyethoxy)phosphazene] copolymers of variable compositions were synthesized by Allcock [645] in 1996. These polymers were found to be soluble in alkaline solutions. When crosslinked (by y-rays or by addition of CaCl2 to the polymer solution) the resulting hydrogels were found able to contract or expand as a function of the pH of the solution and their utilization as pH-responsive materials for drug delivery systems could be envisaged. 

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