Dissolution rate surfactant effects

Apart from the above effect on dissolution rate, surfactant micelles also affect the membrane permeability of the solute [8j. Solubilization can, under certain circumstances, help the transport of an insoluble chemical across a membrane. The driving force for transporting the substance through an aqueous system is always the difference in its cdiemical potential (or to a first approximation the difference in its relative saturation) between the starting point and its destination. The principal steps involved are dissolution, diffusion or convection in bulk liquid and crossing of a membrane. As mentioned above, solubilization will enhance the diffusion rate by affecting transport away from the boundary layer adjacent to the crystal [8j. However, to enhance transport the solution should remain saturated, i.e. excess solid particles must be present since an unsaturated solution has a lower activity. 

Ong et al. [134] found that several hydrophilic anionic, non ionic, or cationic surfactants can alleviate the deleterious effect of magnesium stearate over-mixing on dissolution from capsules when added with the lubricant in a ratio as low as 1 5 (w/w). These successful surfactants were sodium A-lauroyl sarcosinate, sodium stearoyl-2-lactylate, sodium stearate, polox-amer 188, cetylpyridinium chloride, and sodium lauryl sulfate. The lipophilic surfactant glyceryl monostearate did not alleviate the magnesium stearate mixing effect. A reduction in thier particle size was shown to enhance effectiveness, particularly in the case of surfactants with low solubility and slow dissolution rate. 

E. K. Anderberg, M. Bisrat, C. Nystrom. Physicochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug. Int. I. Pharm. 1988, 47, 67-77. 

Surfactants have been explored widely for their effects on drug absorption, in particular using experimental animals (Gibaldi and Feldman, 1970 Gibaldi, 1976). Surfactants alter dissolution rates (of lipid materials), surface areas of particles and droplets, and membrane characteristics, all of which affect absorption. 

Anderberg, E.K., Bisrat, M., and Nystrom, C. (1988), Physicochemical Aspects of Drug Release. VII. The Effect of Surfactant Concentration and Drug Particle Size on Solubility and Dissolution Rate of Felodipine, a Sparingly Soluble Drug, Intemat. J. of Pharma., 47, 67-77. 

Chen, D., and R. Zhang. 1993. Effects of surfactants on the dissolution rate of aspirin from tablets in water. Shenyang Yaoxueyuan XuebfcQ 240-246, 292. 

The effects of surfactant on the solubility and dissolution rate of poorly soluble drugs are well characterized. In general, the surfactant increases both solubility and dissolution rate even if the increment in dissolution rate is less pronounced due to the low diffusivity of the drug loaded into the micelle [9-16]. 

If has been observed fhaf by adsorbing surfactants onto the crystal surfaces of poorly water-soluble drugs, dissolution rate can be enhanced. Chen et al. " showed that the dissolution rate of Cl-1041, a poorly water-soluble compound, in 0.1 N HCl may be affected by the surfactant Tween 80. The effects of surfactant are complicated, and many factors are involved. Above the CMC of Tween 80, the adsorption of the surfactant onto the crystal surface may inhibit crystal nucleation on the surface, and causes the dissolution rate to increase. By adsorbing a very small amount of poloxamer onto the hydrophobic drug particle surface. 

The combined effect of pH and surfactants on the dissolution of piroxicam has been reported. " In this system, the dissolution rate and solubility of the drug substance could be well estimated by a simple additive model for the effect of pH and surfactant, where the total dissolved concentration equaled the summation of the amoimt of dissolved non-ionized substance, the amount of dissolved ionized substance, and the amoimt of substance solubilized in the surfactant micelles. It was suggested that the model developed in this work could be useful in establishing an in vitro-in vivo correlation for piroxicam. 

Surface-active agents have been widely shown to enhance drug dissolution rates. This may be due to wetting effects, resulting in increased surface area, effects on solubility and effective diffusion coefficient or a combination of effects. Consequently surfactants have been included in tablet and capsule formulations to improve wetting and deaggregation of drug particles and thus increase the surface area of particles available for dissolution. 

Bioavailability of triamterene has been studied in healthy human subjects.59 62 65 79 The bioavailability of triamterene was found to be 52%, corresponding to absorption of 83%, in a study done in six volunteers after intravenous administration of the drug.62 Another study reported that triamterene bioavailability from capsules was poorer and more variable than that from suspension.65 Effect of various vehicles and vehicle volumes on oral bioavailability of triamterene has been investigated.80 Addition of a combination of a surfactant and carbonate or bicarbonate as diluents to a triamterene gelatin capsule is reported to result in better bioavailability of the drug.81 When both calcium carbonate and cetylpyridinium chloride were present in a triamterene capsule the dissolution rates were greatly increased over triamterene capsules containing neither diluent or either... 

---