Effect of micronization on the extent of drug absorption from suspensions in humans

Abstract

A microscopic mass balance approach has shown that the initial saturation (Is), absorption number (An), dose number (Do), and dissolution number (Dn) are four fundamental dimensionless parameters that can be used to estimate the fraction dose absorbed (~ of suspensions of poorly soluble drugs in humans. The dissolution number of a drug increases with decreasing its particle size. The effect of micronization on F for suspensions was investigated in terms of Dn. About 90% of maximal Fcan be achieved at Dn-~2. Increasing the solubility of a drug results in better oral absorption through increasing Dn and decreasing Do. The fractions dose absorbed of digoxin, griseofulvin, and benoxaprofen agree with predicted F values using estimated parameters. Drugs with low Do and low Dn can be more completely absorbed by reducing particle size, while absorption of drugs with high Do and low Dn is limited by solubility and requires higher solubility to enhance the fraction dose absorbed in addition to micronization. Solubility at the physiological pH should be used for the estimation of the fraction dose absorbed.

Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain

“…Lipidic molecules such as PEA can present challenges in terms of solubility and bioavailability when administered orally. Because increasing a drug’s surface area enhances its rate of dissolution [ 14 ] while reducing variability of absorption [ 15 ], we investigated the influence of micronization/ultramicronization on PEA action in carrageenan-induced inflammation in the rat paw. Figure 1 shows the PSD profile of micronized and ultramicronized PEA in comparison to a commercial formulation of nonmicronized PEA.…”

“…By application of this technique, microparticles are produced by reducing large drug crystals down to the micron range (<10 μm) [ 10 - 13 ]. Given that the dissolution rate of a drug is proportional to its surface area, major benefits of microcrystal formulations are enhanced rate of dissolution [ 14 ] and reduced variability of drug absorption when orally administered [ 15 ]. Carrageenan-induced inflammation in the rat paw represents a classical model of edema formation and hyperalgesia [ 16 ] that has been extensively used in the development of anti-inflammatory drugs.…”

Effect of a new formulation of micronized and ultramicronized N-palmitoylethanolamine in a tibia fracture mouse model of complex regional pain syndrome

“…Reports in the literature also highlighted the capability of other PEA formulations in the possible treatment of abnormal pain induced by several experimental models [13–17]. The micronization technique can be used to achieve microparticles <10 μm) [18, 19], with increased surface area and rate of dissolution [20], together with a reduced variability of absorption [21]. In this study, we investigated the effect of oral administration of a formulation of micronized and ultramicronized PEA (PEA-MPS) in a model of CRPS-I.…”

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

“…Because the dissolution rate of a drug is proportional to its surface area, a major benefit of microcrystallization is enhanced rate of dissolution [48]. Moreover, the rate of absorption of small drug particles is not influenced by the hydrodynamics in the gastrointestinal tract-an important factor in reducing variability of drug absorption when orally administered [49]. Using the air-jet milling technique to produce micronized and ultramicronized PEA, Impellizzeri et al [50] tested these PEA formulations in carrageenan-induced inflammation in the rat paw-a classical model of edema formation and hyperalgesia [51] extensively used in the development of anti-inflammatory drugs.…”