Increasing Dissolution Rate

Sometimes, chemists and laboratory technicians attempt to dissolve a solid in water only to hnd out that it apparently will not dissolve even if solubility data show that it will. Such a situation is more of a problem with the rate of dissolving than with solubility. If the solute were allowed the time needed, it would dissolve. However, there are several methods for increasing the rate of dissolving. 

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In some cases, a small amount of nitric acid, HN03, or hydrogen peroxide, H202, is added to the solution in order to accelerate the dissolution of the metal. Heating the solution increases dissolution rates as well. Taking into... 

These mixing motions will tend to improve drug absorption for two reasons. Any factor that increases rate of dissolution will increase the rate (and possibly the extent) of absorption, especially for poorly water-soluble drugs (BCS Classes II and IV). Since rate of dissolution depends on agitation intensity, mixing movements will tend to increase dissolution rate and thereby influence absorption. As rate of absorption depends directly on membrane surface area, and since mixing increases the contact area between drug and... 

A. Goldberg, Methods of increasing dissolution rates, in Dissolution Technology (I. J. Leeson and J. T. Car-stensen, eds.), Academy of Pharmaceutical Sciences, American Pharmaceutical Association, Washington, DC, 1974, pp. 147-162. 

This aromatic alcohol has been an effective preservative and still is used in several ophthalmic products. Over the years it has proved to be a relatively safe preservative for ophthalmic products [138] and has produced minimal effects in various tests [99,136,139]. In addition to its relatively slower rate of activity, it imposes a number of limitations on the formulation and packaging. It possesses adequate stability when stored at room temperature in an acidic solution, usually about pH 5 or below. If autoclaved for 20-30 minutes at a pH of 5, it will decompose about 30%. The hydrolytic decomposition of chlorobutanol produces hydrochloric acid (HC1), resulting in a decreasing pH as a function of time. As a result, the hydrolysis rate also decreases. Chlorobutanol is generally used at a concentration of 0.5%. Its maximum water solubility is only about 0.7% at room temperature, which may be lowered by active or excipients, and is slow to dissolve. Heat can be used to increase dissolution rate but will also cause some decomposition and loss from sublimation. Concentrations as low as 0.125% have shown antimicrobial activity under the proper conditions. 

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... 

Some of the current methods of increasing dissolution rates of drugs are particle size reduction, salt formation, and development of the optimized delivery systems, such as solid dispersion, soft gelatin encapsulation, etc. 

A DDS such as a solid dispersion increases dissolution rate by dispersing the drug either molecularly or in an amorphous state in a water-soluble carrier.9 When given as a solution in a pharmaceutically acceptable organic- or lipid-based solvent that is either... 

Simulated intestinal fluid is associated more with dissolution rate determination than solubility measurements. Sometimes when a compound has particularly low solubility the dissolution is studied in simulated fluids. The intent is to try and produce an increased dissolution rate. If there is an increased rate it would be due to an interaction between the compound and the dissolution fluid. Sometimes this... 

Chiou, W.I. and Riegelman, S. (1971). Increased dissolution rates of water insoluble cardiac glycosides and steroids via solid dispersions in polyethylene glycol 6000. J. Pharm. Sci., 60(10), 1569-1571. 

Mayersohn M, Gibaldi M. New method of solid-state dispersion for increasing dissolution rates. J Pharm Sci 1966 55 1323-1324. 

An autocatalytic process is thus established in which the rate of dissolution is found to increase with time. Litter et al. [131] examined this autocatalytic process in more detail using maghemite (y-Fe203)-EDTA systems and developed a kinetic model of the process which satisfactorily described the results obtained. Consistent with the proposed process, addition of soluble ferric iron increased dissolution rates. 

Film Stress Units of (MPa) or (psi). Compressive film stress leads to increased dissolution rates, while tensile stress leads to decreased dissolution rates. Consequently, stress gradients across the wafer afiect polish rate uniformity, while pattern-dependent stress gradients can affect planarization. 

Increasing Dissolution Rate with Oxidizing Agents... 

Irradiation of gelatine capsules may not only result in photodegradation of the drug but may also affect the bioavailability of the drug. Irradiated gelatine films showed a decrease of their water vapor transmission. Even though this effect did not occur with indomethacin capsules, long-term irradiation resulted in increased dissolution rates (42). 

Goldberg, A.H. Gibaldi, M. Kanig, J.L. Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures. II. Experimental evaluation of a eutectic mixture urea-acetaminophen system. J. Pharm. Sci. 1966, 55, 482-487. 

Particle size reduction is typically used to enhance dissolution rate and/or bioavailability of APIs with limited in vivo solubility. Because the rate of dissolution of a particle is not only directly proportional to solubility, but also directly proportional to particle surface area (Pick s first law, Noyes-Whitney equation), increasing the surface area by reducing the average particle size increases dissolution rate. 

Lovrecich, M.E. Supported Drugs with Increased Dissolution Rate, and a Process for Their Preparation. US Patent 5,449,521, Sep 12, 1995 Vectorpharma N.A., Inc. Trieste, Italy. 

By virtue of having a higher apparent solubility, a metastable crystal will have an increased dissolution rate over the more stable form. The change in mass, M, as a function of time, t, for a solute is directly proportional to its apparent solubility, app, and is given by... 

McGinity JW, Harris MR. Increasing dissolution rates of poorly-soluble drugs by adsorption to montmorillonite. Drug Dev Ind Pharm 1980 6 35 8. 

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