Bioavailability particle size distribution

The particle size distribution of an ultraLne material may increase spontaneously if measures are not taken to stabilize the particles. Particle size growth can occur via agglomeration or crystal growth. This particle size increase will result in a decrease of the available surface area, and hence a decrease of the dissolution rate, potentially lowering drug bioavailability. 

The physical characteristics of final dosage forms such as texture (porosity and surface area) and particle size distribution can affect the dissolution rate, and therefore the bioavailability of the product. It is common to see an increase in particle size when scaling up, therefore to anticipate the in vitro release profiles for a Spray Dried Drug Product (SDDP) manufactured at a larger scale, we have evaluated the influence of particle size and texture on dissolution in the case of a laboratory scale SDDP. 

Particle size For some herbal substances intended for use in herbal teas or solid herbal medicinal products, particle size can have a significant effect on dissolution rates, bioavailability, and/or stability. In such instances, testing for particle size distribution should be carried out using an appropriate procedure, and acceptance criteria should be provided. Particle size can also affect the disintegration time of solid dosage forms. 

The particle size distribution of the API can affect the dissolution rate of the drug product and thus the bioavailability of the product. Once particle size requirements have been defined from formulation studies, the process must be capable of routinely meeting these requirements. One of the ways that particle size distribution can be controlled is by the conditions under which the product is... 

Early work by Pouton demonstrated that a good SEDDS formulation could significantly enhance the dissolution and bioavailability of poorly soluble compounds (113). Pouton proposed two criteria to describe the efficiency of SEDDS formulation (l)the rate of emulsification and (2) the particle size distribution of the resultant emulsion. An efficient SEDDS should produce fine dispersions (<1 gm) rapidly at a reproducible rate. Efficient SEDDS or SMEDDS have demonstrated their potential in delivering hydrophobic compounds. The most notable case is a SMEDDS formulation of cyclosporin A (Neoral), in which the formulation has significantly increased the bioavailability as well as decreased patient variability (114,115). 

One of the main requirements of pharmaceutical suspension is the lack of Ost-wald ripening (crystal growth), i.e. the growth of particles on storage that results in shift of particle size distribution to larger values. This may affect bioavailability and results in physical instability. 

Hydrophobic drug substances are often presented as simple acjueous suspensions for use in pre-clinical studies. The resulting suspensions must have a stable particle size distribution to ensure consistent drug dissolution and subsequent bioavailability. 

The physical characteristics should be considered (in combination as appropriate) in relation to the proposed dosage form and route of administration. Factors to be considered extend to solubility characteristics, crystal form and properties, moisture or solvent content, particle size and size distribution (which may affect bioavailability, content uniformity, suspension properties, stability, and preclinical or clinical acceptability), polymorphism, etc. 

Bioavailability from Environmental Media. The absorption and distribution of nickel as a result of inhalation, ingestion, and dermal exposure are discussed in Sections 2.3.1 and 2.3.2. Quantitative data relating the physical/chemical properties of nickel (e.g., particle size, chemical forms of nickel) with its bioavailability are available for inhaled nickel. In aqueous media, nickel is in the form of the hexahydrate ion, which is poorly absorbed by most living organisms (Sunderman and Oskarsson 1991). Additional studies which examine the absorption of nickel from soil would be useful. 

Polybrominated Diphenyl Ethers. The absorption and distribution of PBDEs as a result of inhalation, ingestion, and dermal exposure are discussed in Sections 3.3.1, 3.3.2, and 3.3.3. Studies that describe the bioavailability of PBDEs from ambient air, surface water, and groundwater, or soil do not exist. Studies determining the effect of particle size and organic matter content on the bioavailability of PBDEs from soil and the role of microparticle-sorbed PBDEs on the bioavailability of PBDEs from drinking water are needed. Such studies would be useful in assessing the health effects of PBDEs on people living near hazardous waste sites. 

---