Particle size oral bioavailability

Adult subjects who ingested soil (particle size less than 250 im) from the Bunker Hill NPL site absorbed 26% of the resulting 250 pg/70 kg body weight lead dose when the soil was ingested in the fasted state and 2.5% when the same soil lead dose was ingested with a meal (Maddaloni et al. 1998). There are no reported measurements of the absorption of soil-bome lead in infants or children. Additional evidence for a lower absorption of soil-bome lead compared to dissolved lead is provided from studies in laboratory animal models. In immature swine that received oral doses of soil from one of four NPL sites (75 or 225 ig Pb/kg body weight), bioavailability of soil-bome lead ranged from 50% to 82% of that of a similar... 

Fig. 15 Effect of phenytoin (PHT) particle size on (a) dissolution in simulated gastric fluid, pH 1.2, 37°C and (b) bioavailability in human volunteers after oral administration of 300 mg PHT. Dark circles lot with particle size range 74-350 /u.m open circles lot with particle size range 177-350 /am. (From Ref. 64.)...

Other possibilities for insoluble materials are to mix the desired amount of material with a small amount of the animal s diet or to use capsules. The difficulty with the diet approach is the likelihood that the animal will not consume all of the treated diet or that it may selectively not consume chunks of test material. Use of capsules, meanwhile, is labor intensive. In rare cases, if all of these approaches fail, it may not be possible to test a material by oral administration. In capsules, particle size is generally inversely related to solubility and bioavailability. However, milling of solids may adversely affect their chemical nature and/or pose issues of safety. 

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. 

Oral dmg product formulation and manufacturing process development can use a hierarchical approach to meeting three conditions based on, in order of importance, bioavailability, stability, and manufacturability. The bioavailability of a drug product is the most critical condition and must meet established criteria or the product is not viable. Dmg substance properties such as salt form, solubility, and particle size can significantly affect pharmacokinetic and pharmacodynamic performance of a product. The dosage form platform, formulation design, and manufacturing process can also affect the PK/PD profile of a product. Therefore, all selections must maintain the required pharmacokinetic/pharmacodynamic outcome and work within these confines to achieve a stable and robust product/process. 

Bioaccessibility, and therefore oral bioavailability of soil contaminants, depends on soil type and contaminant (Davis et al., 1997 Gr0n and Anderson, 2003 Hamel et al, 1998 Ruby et al., 1999). PTMs occur in soil as a complex mixture of solid-phase chemical compounds of varying particle size and morphology, characterised by variable metal bioavailability. Mineral phases that form under acidic conditions (e.g. lead sulphate, iron-lead sulphate) will tend to be more stable in the acidic conditions of the stomach and hence less bioaccessible. By contrary, mineral phases... 

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

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