Drug particles size, reduction

Liversidge, G G. and Conzentino, P. (1995) Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rite, J. Pharm., 125(2) 309-313. 

An increased rate of dissolution resulting from particle size reduction has also been observed for several excipients. For example, griseofulvin systems containing ethylcellulose of size fraction 710-850 /im released the drug almost 25% faster than the same systems containing ethylcellulose of size fraction 1000-2000 fim. The authors interpret these results in terms of more excipient particles being available to interact with the drug in the fraction of lower size [69],... 

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. 

Lee RW, Shaw JM, McShane J, Wood RW. Particle size reduction. In Liu R, ed. Water-Insoluble Drug Formulation. Interpharm, 2000 478. 

The shape of the micronized particles was irregular and, according to SEM pictures, it was assumed that the particles were porous. With particle-size reduction and, therefore, increased specific surface area (external and internal) the dissolution rate increased to some extent, but the anticipated effective surface area was probably reduced by the drug s hydrophobicity and agglomeration of the particles during and after micronization. 

In many cases in drug development, the solubility of some leads is extremely low. Fast dissolution rate of many drug delivery systems, for example, particle size reduction, may not be translated into good Gl absorption. The oral absorption of these molecules is usually limited by solubility (VWIImann et al., 2004). In the case of solubility limited absorption, creating supersaturation in the Gl Luids for this type of insoluble drugs is very critical as supersaturation may provide great improvement of oral absorption (Tanno et al., 2004 Shanker, 2005). The techniques to create the so-called supersaturation in the Gl Luids may include microemulsions, emulsions, liposomes, complexations, polymeric micelles, and conventional micelles, which can be found in some chapters in the book. 

Liversidge, G. G and K. C. Cundy (1995). Particle size reduction for improvement of oral bioavailability of hydrophobic drugs I. Absolute bioavailability of nanocrystalline danazol in beagle takbgii.Pharm., 125 91-97. 

In the case of formulations intended for intravenous administration, size reduction of APIs to nanometer-sized particles render a sterile, aqueous dispersion of such particles infusible. Indeed, particle size reduction methodologies have advanced to the point where nanometer-sized crystalline API particles can be realized. This size reduction approach provides a valuable formulation alternative to the traditional formulation approach of ensuring that a drug is solubilized before intravenous administration. It alleviates the potential issues associated with utilizing high concentrations of aqueous compatible cosolvents and surfactants to solubilize the drug. 

There are a number of physicochemical properties of an API that are impacted upon size reduction, which need to be considered while resolving pharmaceutical problems related to solubility limitations. Clearly, dissolution rate and its dependence upon particle size reduction is one of those critical properties (Ross and Morrison, 1988 Rabinow, 2004 Kocbek et al., 2006). For example, in the case of oral administration of a poorly water-soluble API, the increase in dissolution rate attendant with size reduction provides for more drug in solution, and available for absorption, during its gastrointestinal transit (Chaumeil, 1998 Merisko-Liversidge et al., 2003 Patravale et al., 2004 Pouton, 2006). 

The dependence of dissolution rate to speciLc surface area is the basis for pursuing particle size reduction as a method of increasing the bioavailability of poorly water-soluble drugs. 

The drug particle size is also an important parameter [19]. Scholz et al. [20] studied the influence of drug particle size on felodipine absorption in dogs. Micronized (8 pm) or coarse (125 pm) suspensions of felodipine were orally administered to dogs, and absorption parameters were studied. The reduction in particle size led to a 22-fold increase in Cmax and to a... 

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