Dissolution factors affecting rate

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

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. 

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. 

There are in addition several other factors that accelerate corrosion and must betaken into account these include crevices, galvanic coupling, tensile stress, aeration, presence of impurities, surface finish, etc. If these were also taken into consideration then several million experiments would have to be performed to compile such data. There are many instances where two or more chemicals exert a marked synergistic action such that low dissolution rates obtained in either environment become much greater in the presence of both. Further, the corrosiveness of a chemical will be affected by the presence of certain impurities, which may act as either accelerators or inhibitors. To take all these factors into account would add to an already impossible task and as Evans has remarked, There are not enough trained investigators in the world to obtain the empirical information to cover all combinations of conditions likely to arise . Unfortunately corrosion science has not yet reached the stage where prediction, based on a few well established laws, allows selection of materials to be made without recourse to a vast amount of data. 

Drugs in Class II have low aqueous solubility (but high membrane permeability), and any factor affecting dissolution rate would be expected to have an impact on the absorption of such compounds. Factors that are noted in Fig. 11, such as fluid pH, volume and viscosity, and bile secretion (especially in response to fatty foods), might be expected to play a role in dissolution rate and thereby affect absorption. Compounds that fall into this class include carbamazepine, cyclosporin, digoxin, griseofulvin, and spironolactone. Food would be expected to exert a potentially significant affect on... 

The bioavailability of drugs from tablets can be markedly influenced by the rate and efficiency of the initial disintegration and dissolution process. Unfortunately, one is faced with a compromise situation — a structure that has both a durable structure prior to administration and the ability to readily break down when placed in the in vivo environment. One of the major factors affecting both these properties is the structure of the tablet, in particular its density (or porosity) and the pore structure. Study of the significance of such measurements and interpretation of the results is a relatively recent field of interest. 

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. 

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... 

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. 

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

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. 

As is clear from the above discussion, reduction of surface-located Fe(III) (which may or may not lead to oxide dissolution) is associated in most instances with oxidation of the electron donor at the particle surface and many of the same factors that influence the rate of reductive dissolution will also affect the rate of donor oxidation. Leland and Bard [138] found that the rate constants of photooxidation of oxalate and sulfite varied by about two orders of magnitude with different Fe(III) oxides and concluded that this appears to be due to differences in crystal and surface structure rather than to differences in surface area, hydrodynamic diameter or band gap . 

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