Meal-Induced Acceleration of Tablet Transit Through the Human Small Intestine

Fadda, Hala M.; McConnell, Emma; Short, Michael D.; Basit, Abdul W.

doi:10.1007/s11095-008-9749-2

Cited by 85 publications

(51 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With these types of dosage forms, dissolution media and pH selection will be critical when developing an IVIVR/ IVIVC and these factors need to be considered early in the predictive dissolution testing design stage. [87][88][89] A comparison of the amount of dissolution media used in these studies is given in Figure 2a. Fiftytwo percent of the studies used 900 mL and 32% used 500 mL; these are typical volumes for many dissolution studies.…”

Section: In Vitro Factorsmentioning

confidence: 99%

“…In contrast to the majority of the dissolution medium volumes (500-900 mL) used in the papers being reviewed, Table 4 reveals that the fasted GI tract fluid volumes are approximately 100 mL or lower. 98,87 The mean regional fluid volumes in the stomach and along the small and large intestines under the fasted state have been determined to be approximately 45, 105, and 13 mL, respectively. In the fed state, the mean regional free fluid volumes in the stomach (meal and fluid combined), the small and large intestines were observed to be approximately 686, 54, and 11 mL, respectively, which are significantly different than the fasted state.…”

Section: In Vivo Factorsmentioning

confidence: 99%

See 1 more Smart Citation

Assessing the performance of amorphous solid dispersions

Newman¹,

Knipp

Zografi

2012

Journal of Pharmaceutical Sciences

337

235

View full text Add to dashboard Cite

Section: In Vitro Factorsmentioning

confidence: 99%

Section: In Vivo Factorsmentioning

confidence: 99%

Assessing the performance of amorphous solid dispersions

Newman¹,

Knipp

Zografi

2012

Journal of Pharmaceutical Sciences

337

235

View full text Add to dashboard Cite

“…Correspondingly, 52 subject groups were included within the analysis. The analysis included 11 investigations (Davis et al, 1984a(Davis et al, ,b, 1986a(Davis et al, , 1987Khosla et al, 1989;Madsen and Jensen, 1989;Coupe et al, 1991;Madsen, 1992;Billa et al, 2000;Bouras et al, 2004;Fadda et al, 2009), where estimates of intestinal transit were pooled between test conditions (e.g., fasted versus fed). For each of these investigations, mean intestinal transit times were not found to be significantly different between treatment arms as either denoted by the authors' results or independently confirmed using a paired Student's t test (P .…”

Section: Resultsmentioning

confidence: 99%

Examining Small Intestinal Transit Time as a Function of Age: Is There Evidence to Support Age-Dependent Differences among Children?

Maharaj

Edginton

2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

The small intestine represents the region where the majority of drug and nutrient absorption transpires. Among adults, small intestinal transit kinetics is well delineated; however, the applicability of these values toward children remains unclear. This article serves to examine the relationship between age and mean small intestinal transit time (SITT) based on the available literature. In addition, the influence of alterations in intestinal transit time was explored among children using a model-based approach. Primary literature sources depicting SITT from children to adults were ascertained via the PubMed database. Data were limited to subjects without pathologies that could influence intestinal motility. Random-effect meta-regression models with between-study variability were employed to assess the influence of age on SITT. Three separate models with age as a linear or higher-order (i.e., second-and third-order polynomial) regressor were implemented to assess for the potential of both linear and curvilinear relationships. Examination of the influence of altered intestinal transit kinetics on the absorption of a sustained release theophylline preparation was explored among children between 8 and 14 years using physiologically based pharmacokinetic (PBPK) modeling. Age was not found to be a significant modulator of small intestinal transit within either the linear or higher-order polynomial meta-regression models. PBPK simulations indicated a lack of influence of variations in SITT on the absorption of theophylline from the examined sustained release formulation in older children. Based on the current literature, there is no evidence to suggest that mean SITT differs between children and adults.

show abstract

“…8, 9a, 9b, 12a, and 12b for three drug constructs in a patient described by average physiological parameters. The value for small intestinal fluid volume (V l ) is 70 mL and the transit time (T l r) is 180 min, which represent median values from the literature (22,37,(44)(45)(46). The plateau concentration (C g p) was set to 10 μg/mL to reflect the low solubility values for many BCS II compounds, particularly those for which dissolution enhancement strategies, such as amorphization, are sought.…”

Section: Methodsmentioning

confidence: 99%

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Kleppe

Forney-Stevens

Haskell

et al. 2015

AAPS J

View full text Add to dashboard Cite

Abstract. Poorly soluble drugs are increasingly formulated into supersaturating drug delivery systems which may precipitate during oral delivery. The link between in vitro drug concentration profiles and oral bioavailability is under intense investigation. The objective of the present work was to develop closedform analytical solutions that relate in vitro concentration profiles to the amount of drug absorbed using several alternate assumptions and only six parameters. Three parameters define the key features of the in vitro drug concentration-time profile. An additional three parameters focus on physiological parameters. Absorption models were developed based on alternate assumptions; the drug concentration in the intestinal fluid: (1) peaks at the same time and concentration as in vitro, (2) peaks at the same time as in vitro, or (3) reaches the same peak concentration as in vitro. The three assumptions provide very different calculated values of bioavailability. Using Case 2 assumptions, bioavailability enhancement was found to be less than proportional to in silico examples of dissolution enhancement. Case 3 assumptions lead to bioavailability enhancements that are more than proportional to dissolution enhancements. Using Case 1 predicts drug absorption amounts that fall in between Case 2 and 3. The equations developed based on the alternate assumptions can be used to quickly evaluate the potential improvement in bioavailability due to intentional alteration of the in vitro drug concentration vs. time curve by reformulation. These equations may be useful in making decisions as to whether reformulation is expected to provide sufficient bioavailability enhancement to justify the effort.

show abstract

Meal-Induced Acceleration of Tablet Transit Through the Human Small Intestine

Abstract: The timing of food ingestion has a clear effect on small intestinal transit of single-unit formulations and this has implications for drug bioavailability.

Cited by 85 publications

References 32 publications

Assessing the performance of amorphous solid dispersions

Assessing the performance of amorphous solid dispersions

Examining Small Intestinal Transit Time as a Function of Age: Is There Evidence to Support Age-Dependent Differences among Children?

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

Contact Info

Product

Resources

About