Factors affecting the dissolution rate

The surface area of the powder (drug) can be controlled by controlling the drug s particle size. The equilibrium solubility of a drug can be controlled 

Some of the more important factors that affect the dissolution rate, especially, of slowly dissolving or poorly soluble substances, are  

Of all possible manipulations of the physicochemical properties of drugs to yield better 

1 Examples of drugs where bioavailability has been increased as a result of particle size reduction 

S Niazi, Textbook of Biopharmaceutics and Clinical Pharmacokinetics, 1979. Reproduced by permission of Pearson Education, Inc. 

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ATK Lu, ME Frisella, KC Johnson. Dissolution modeling Factors affecting the dissolution rates of polydisperse powders. Pharm Res 10 1308-1314, 1993. 

A summary of how physiological factors affect the dissolution rate is given in Table 21.2. The effective surface area will be affected by the wetting properties of the bile acids and other surface-active agents in the gastrointestinal tract. The dif-fusivity of a drug molecule in the intestinal juice will be altered by changes in viscosity that are induced, for instance, by meal components. An increased dissolution rate could be obtained at more intense intestinal motility patterns or increased... 

J. Spitael, R. Kinget, Factors affecting the dissolution rate of enteric coatings, Pharm Ind 39 502 (1977). 

Equations (2.4), (2.6), and (2.7) are also applicable to the degradation of drug substances in the solid state. However, the factors affecting the reaction rates become more complex because reactions often proceed in heterogeneous physical states. For example, apparent reaction rates depend on solubility and dissolution rates of drug substances when degradation proceeds in water layers adsorbed on the surface of solid drugs. Therefore, these and other additional factors need to be considered. 

In all cases, water and carbonic acid, the latter of which is the source of protons, are the main reactants. The net result of the reaction is the release of cations (Ca " ), Mg ", K", Na" ) and the production of alkalinity via HCO. When ferrous iron is present in the lattice, as in biotite, oxygen consumption may become an important factor affecting the weathering mechanism and the rate of dissolution. 

Orally administered dosage forms are absorbed into the systemic circulation following dissolution in the GI tract. Because substances must be in solution for the absorption from the GI lumen, the absorption rate of poorly water-soluble drugs is limited by their rate of dissolution. The dissolution rate is affected by the unique physicochemical properties of the drug and by physiological factors the pH, composition, and hydrodynamics of the GI medium. 

Solubility, dissolution rate, and intestinal permeability, are the major bio-pharmaceutic factors that affect the rate and extent of absorption of an oral drug product. Particularly for water insoluble drugs that have generally high membrane permeability (BCS Class II), dissolution, and dose are the most critical factors affecting the rate and the extent of oral absorption. 

For highly permeable, poorly soluble drugs given in lower doses, the dissolution rate rather than the saturation solubility is the limiting factor. An increase in dissolution rate due to in vivo solubilization mediated by food intake could theoretically be obtained, but this situation is not always found in vivo. For example, food does not affect the rate and extent of bioavailability for candesartan cilexitil, a very poorly soluble compound [78], An in vitro dissolution and solubility study of this compound in simulated intestinal media provided a potential explanation it was revealed that the solubility was increased as a function of bile concentration as expected, whereas the dissolution rate was not increased by the higher bile concentrations being representative for the fed state (see Fig. 21.14). Thus, although... 

The main input parameter used to define the highest possible drug concentration in the intestine and to calculate the dissolution rate in the GI tract is the solubility of the dmg in the GI fluids. As described earlier (Sect. 21.2) there are several, both physiological and physicochemical, factors that can affect the solubility in the GI tract and it is therefore important to consider the relevance of the solubility data generated in the early drug discovery phase. A common approach is to use in silico models to predict the solubility of drugs (e.g., [5]). The advantage of this approach is that only the chemical... 

The physicochemical factors affecting the absorption are lipid solubility, dissolution rate, salt from complexation, viscosity and drug stability in the GIT. 

All the drugs in any solid dosage form or suspension when administered will first change into drug solution in body fluids. So, dissolution rate is important factor affecting the rate of absorption. 

Most of the factors affecting the rate of corrosion can be understood from a graphical superposition of the current-potential curves for the metal-dissolution and electronation reactions. The principle of the graphical superposition method is straightforward. 

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. 

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