Dissolution rate particle size

Exploring the influence of fines removal and dissolution on particle size anhancemant is the next topic of interest. Using the kinetic parameters gens rated from the laboratory tests (t was obtained) and the pilot... 

Sufficient kinetic information should be collected to proceed the process design for a specific reaction system. The factors affecting the performance of SLPTC includes agitation rate, particle size of solid salt, reaction temperature, the amount of solid reactant, the kinds and amount of PT catalyst, the solubility and the dissolution rate of solid reactant in the organic solvent, extra addition of other metal salts, the polarity, surface tension, and... 

Relation Between Rate of Dissolution and Particle Size... 

The dissolution of soluble sihcates is of considerable commercial importance. Its rate depends on the glass ratio, sohds concentration, temperature, pressure, and glass particle size. Commercially, glasses are dissolved in either batch atmospheric or pressure dissolvers or continuous atmospheric processes. Dissolution of sodium sihcate glass proceeds through a two-step mechanism that involves ion exchange (qv) and network breakdown (18). 

Additional purification of the product and improvement of particle size and shape can be achieved by re-ciystallization. The process consists of sequential dissolutions of potassium heptafluorotantalate in appropriate solutions at increased temperatures, filtration of the solution to separate possible insoluble parts of the product and cooling of the filtrated solution at a certain rate. The precipitated crystals are filtrated, washed and dried to obtain the final product. Re-crystallization can be performed both after filtration of the preliminary precipitated salt or after drying if the quality of the product is not sufficient. HF solutions of low concentrations are usually used for re-ciystallization. In general, even water can be used as a solvent if the process is performed fast enough. Nevertheless, practical experience suggested the use of a 30—40% HF solution within the temperature interval of 80-25°C, and a cooling rate of about 8-10°C per hour. The above conditions enable to achieve an acceptable process yield and good performance of the product. 

Figure 13 compares the dissolution rate of pure phenacetin particles with the granulated particles of the same size and with tablets prepared from these granules. These comparisons were made by using... 

In addition to these in vitro demonstrations of the importance of the effective surface area of drug particles on dissolution rate, many in vivo studies are available. Phenacetin plasma levels versus time are plotted for three different particle sizes of phenacetin in Fig. 14. Healthy adult volunteers received 1.5-g doses of phenacetin as an aqueous suspension on an empty stomach. The results show that both the rate and... 

The effect of particle size reduction on the bioavailability of nitrofurantoin was shown in Fig. 4. The microcrystalline form (< 10 pm) is more rapidly and completely absorbed from the tablet dosage form than is the macrocrystalline form (74-177 pm) from the capsule dosage form. This is not a completely satisfactory illustration of the effect of particle size on the rate and extent of availability, since other manufacturing variables have not been held constant. Nevertheless, it does suggest some correlation between particle size, dissolution rate, and rate of availability. 

In summary, it is the effective surface area of a drug particle that determines its dissolution rate. The effective surface area may be increased by physically reducing the particle size, by adding hydrophilic diluents to the final dosage form, or by adding surface-active agents to the dissolution medium or to the dosage form. 

Although it is possible to control the dissolution rate of a drug by controlling its particle size and solubility, the pharmaceutical manufacturer has very little, if any, control over the D/h term in the Nernst-Brunner equation, Eq. (1). In deriving the equation it was assumed that h, the thickness of the stationary diffusion layer, was independent of particle size. In fact, this is not necessarily true. The diffusion layer probably increases as particle size increases. Furthermore, h decreases as the stirring rate increases. In vivo, as GI motility increases or decreases, h would be expected to decrease or increase. In deriving the Nernst-Brunner equation, it was also assumed that all the particles were... 

M Bisrat, C Nystrom. Physicochemical aspects of drug release. VIII. The relation between particle size and surface specific dissolution rate in agitated suspensions. Int J Pharm 47 223-231, 1988. 

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. 

Where the instructions for use of the product involve admixture or dilution with drinks or other materials, appropriate compatibility data will be required. Factors to consider include ease and rate of dissolution, homogeneity, chemical and physical stability over the period of use, particle size, etc. 

As decreases in particle size produce increases in surface area, S, it becomes evident that particle size reduction provides an increase in the rate of dissolution... 

RB Hintz, KC Johnson. The effect of particle size on dissolution rate and oral absorption. Int J Pharm 51 9-17, 1989. 

WI Higuchi, EN Heistand. Dissolution rates of finely divided drug powders I. Effect of a distribution of particle sizes in a diffusion-controlled process. J Pharm Sci 52 67-71, 1963. 

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