Particle Size of Drugs and Its Relationship to Absorption and Activity

Fincher, Julian H.

doi:10.1002/jps.2600571102

Cited by 107 publications

(29 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was also found to be in good agreement with previously reported values. 24 Effect of Bile Salts and Lecithin on Solubility and DissolutionsSIBLM increased the solubility of phenytoin and its prodrugs moderately for some (1)(2)(3)(4)(5) and dramatically for others (6-10) ( Table 3). To study the effect of the lecithin, a component of SIBLM, phenytoin solubility was measured in a simulated intestinal bile salts mixture (SIBM) and compared to that in SIBLM.…”

Section: Resultsmentioning

confidence: 97%

See 1 more Smart Citation

Some Relationships Between the Physical Properties of Various 3-Acyloxymethyl Prodrugs of Phenytoin to Structure: Potential in Vivo Performance Implications

Stella

Martodihardjo²,

Terada³

et al. 1998

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Physicochemical properties of neutral N-acyloxyalkyl derivatives of phenytoin in aqueous, organic solvents and simulated intestinal fluid were evaluated. Based on the hypothesis that these low melting prodrugs may have improved physical properties such as solubility and dissolution rate in gastrointestinal fluid, an enhanced bioavailability of these prodrugs may be observed relative to phenytoin. Melting points, aqueous solubilities, and octanol-water (Poct) and cylcohexane-water (Pcyc) partition coefficients of phenytoin and its prodrugs were determined. A simulated intestinal bile salts-lecithin mixture (SIBLM) was also prepared to possibly mimic the intestinal fluid content. Solubility and dissolution rates of phenytoin and its prodrugs were conducted in aqueous buffer and SIBLM. Apparent micelle-water partition coefficients (Kapp) were calculated by using the aqueous and SIBLM equilibrium solubility data. These properties were qualitatively or quantitatively correlated to the alkyl chain length of the prodrugs. The melting points and aqueous solubilities of all the prodrugs were lower than that of the parent compound, phenytoin. The apparent micelle-water partition coefficient increased with an increase in chain length but unlike the octanol-water and cyclohexane-water partition coefficients the relationship was complex. There was a disproportionate increase in the interaction between the micelle and the prodrug with the prodrugs with alkyl groups larger than four carbons. In SIBLM, the solubilities and dissolution rates were increased to a greater extent for the prodrugs than that for phenytoin. The implications are that the bioavailability of phenytoin from these prodrugs may be comparable to or higher than that of phenytoin despite having lower aqueous solubilities, especially after a meal inducing bile flow.

show abstract

Section: Resultsmentioning

confidence: 97%

“…Examples of these types of compounds include allopurinol, 1 5-flourouracil, 2 griseofulvin, 3 nitrofurantoin, 4 and phenytoin. 5,6 The bioavailability of many of these drugs is often limited by their low dissolution rates.…”

Section: Introductionmentioning

confidence: 99%

Some Relationships Between the Physical Properties of Various 3-Acyloxymethyl Prodrugs of Phenytoin to Structure: Potential in Vivo Performance Implications

Stella

Martodihardjo²,

Terada³

et al. 1998

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…Among these, poorly water-soluble drugs that exhibit low (e.g., incomplete) oral absorption, the absorption rate is often limited by dissolution. That is, the dissolution rate is less than the diffusion rate to the site of absorption and the absorption rate itself [Fincher, 1968]. In this context, ''a drug may be defined as poorly-soluble when its dissolution rate is so slow that dissolution takes longer than the transit time past its absorptive sites, resulting in incomplete bioavailability'' [Hö rter .…”

Section: Introductionmentioning

confidence: 99%

A quantitative approach to probe the dependence and correlation of food-effect with aqueous solubility, dose/solubility ratio, and partition coefficient (LogP) for orally active drugs administered as immediate-release formulations

Singh

2005

Drug Dev. Res.

View full text Add to dashboard Cite

The purpose of the present review was to systematically evaluate if aqueous solubility, dose/solubility ratio, and partition coefficient (Log P ) could be used as useful parameters to quantitatively probe the dependence and correlation of in vivo food effects with these physicochemical properties of orally active drugs administered as immediate-release (IR) formulations. Mean AUC data obtained under fasted and fed states of over 100 structurally diverse orally active drugs with different physicochemical properties were obtained from the primary literature. Correlations of AUC ratio (Fed/Fasted) with aqueous solubility, dose/solubility ratio, and Log P were derived and statistically evaluated by Pearson's correlation test (two-tailed). A negative correlation was obtained between the logarithm of the aqueous solubility and the AUC ratio (r 5 À0.5982, N 5 93), whereas a positive correlation existed between AUC ratio and Log P (r 5 0.5147, N 5 110) and between AUC ratio and dose/solubility ratio (r 5 0.5511, N 5 87). All these correlations were significant (Po0.0001). Based on this study, the estimated range within which a drug is not expected to be significantly affected by food falls between 0.148-89.39 mg/ml for aqueous solubility and between 0.23-624 ml for the dose:solubility ratio. The corresponding range of Log P for expecting a lack of food-effect lies between À1.13 and 2.98. Quantitatively, the effect of food was most pronounced for lipophilic, poorly water-soluble drugs (with only a few exceptions), irrespective of whether the drug is acidic, basic, or neutral. It is concluded that aqueous solubility, dose/solubility ratio, and partition coefficient can be used as useful parameters to probe the dependence and correlation of food-effect with these physicochemical parameters for immediate-release formulations. Drug Dev. Res. 65:55-75, 2005.

show abstract

“…The oral bioavailability of lipophilic drugs is known to be limited by in vivo dissolution rate, which in turn is related to drug particle size [4,5]. Taking lipophilic drugs with a high-fat meal is also known to increase their rate of dissolution [6].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Food on the Absorption of Abiraterone Acetate from a Fine Particle Dosage Form: A Randomized Crossover Trial in Healthy Volunteers

et al. 2017

View full text Add to dashboard Cite

Particle Size of Drugs and Its Relationship to Absorption and Activity

Cited by 107 publications

References 63 publications

Some Relationships Between the Physical Properties of Various 3-Acyloxymethyl Prodrugs of Phenytoin to Structure: Potential in Vivo Performance Implications

Some Relationships Between the Physical Properties of Various 3-Acyloxymethyl Prodrugs of Phenytoin to Structure: Potential in Vivo Performance Implications

A quantitative approach to probe the dependence and correlation of food-effect with aqueous solubility, dose/solubility ratio, and partition coefficient (LogP) for orally active drugs administered as immediate-release formulations

The Effect of Food on the Absorption of Abiraterone Acetate from a Fine Particle Dosage Form: A Randomized Crossover Trial in Healthy Volunteers

Contact Info

Product

Resources

About