Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility

Maharaj, Anil; Edginton, Andrea N.; Fotaki, Nikoletta

doi:10.1007/s11095-015-1762-7

Cited by 50 publications

(72 citation statements)

References 106 publications

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“…The gastric release was again variable and low in both experiments, as a result of a variable capsule rupture time. Also, the bile salt content, an important constituent to nifedipine solubility, is much lower in (paediatric) FaSSGF compared to FaSSIF‐V2 …”

Section: Resultsmentioning

confidence: 99%

“…Compared to FaSSGF, solubility in FaSSIF was increased. Paediatric investigations examining luminal fluids within the fasted‐state proximal intestine are thus far limited, therefore the different FaSSIF media were developed to explore the impact of variations in bile salt concentrations . The nifedipine solubility values that were found in FaSSIF‐V2 (12.9 μg/mL), FaSSIF‐50% (9.3 μg/mL) and FaSSIF‐150% (15.1 μg/mL) reflected these variations.…”

Section: Resultsmentioning

confidence: 99%

“…Simulated gastric fluid without pepsin (SGF sp ) pH 1.2 and simulated intestinal fluid without pancreatin (SIF sp ) pH 6.8 were used in dissolution studies . Freshly prepared adult and age‐specific (neonate and infant) biorelevant media were used in solubility and dissolution studies (Table ) …”

Section: Methodsmentioning

confidence: 99%

“…To study the influence of age‐related changes in GI fluid composition on compound solubility, nifedipine solubility studies were performed according to methods described by Maharaj et al . In summary, for aqueous based media, an excess amount of nifedipine was added to 2 mL of medium, dwelled for 24 hours at a shaking water bath at 37°C, filtered through an 0.45‐μm RC filter and diluted with fresh medium prior to HPLC analysis.…”

Section: Methodsmentioning

confidence: 99%

“…In recent years, advances towards the availability of suitable paediatric biorelevant dissolution tests have been made with the development of paediatric media . These media were based on the available literature on the composition of paediatric luminal fluids and the established adult media .…”

Section: Introductionmentioning

confidence: 99%

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Potential prediction of formulation performance in paediatric patients using biopharmaceutical tools and simulation of clinically relevant administration scenarios of nifedipine and lorazepam

Vossen

Hanff

Vulto

et al. 2019

Brit J Clinical Pharma

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Aims: This study explores the impact of paediatric patient related factors and choice of formulation on the dissolution characteristics of nifedipine and lorazepam, 2 drug substances regularly applied in very young patients and in compounded formulations.Methods: Dissolution experiments were designed to reflect clinical practice in a paediatric hospital, with respect to dosage forms, feeding regimens and methods of administration. Solubility studies addressed the influence of age and prandial state.Drug solubility and dissolution experiments were conducted in biorelevant media and adapted age-specific (neonate and infant) media. Dissolution studies were performed with the mini-paddle apparatus and the flow-through cell apparatus.Results: Dissolution of nifedipine formulations was not affected by age-related changes of the fasted state simulated gastrointestinal fluids, and by disintegration of the formulation before administration. However, a significant difference in nifedipine's dissolution rate from commercial tablets and compounded capsules was observed. The dissolution of lorazepam tablets was affected by fasted-vs fed-state media, but it was deemed less likely to be clinically relevant. The significant effect of fed-state media on nifedipine's solubility was considered to have possible clinical relevance since very young patients are almost continuously in a fed state. Conclusion:The in vitro results obtained from these studies reveal the potential of biorelevant solubility and dissolution studies reflecting clinical practice to predict drug performance in paediatric patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Potential prediction of formulation performance in paediatric patients using biopharmaceutical tools and simulation of clinically relevant administration scenarios of nifedipine and lorazepam

Vossen

Hanff

Vulto

et al. 2019

Brit J Clinical Pharma

Self Cite

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Exploring in vitro solubility of lamotrigine in physiologically mimetic conditions to prospect the in vivo dissolution in pediatric population

Caleffi-Marchesini

Borghi-Pangoni

Macente

et al. 2023

Biopharm & Drug Disp

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Pediatric drugs knowledge still leaves several gaps to be filled, all the while many biopharmaceutic properties applied to adults do not work in pediatrics. The solubility in many cases is extrapolated to pediatrics; however, sometimes it may not represent the real scenario. In this context, the aim of this study was to assess the possibility of the extrapolation of the solubility data assumed for adults to children aged 2-12 years using lamotrigine (LTG) as a model. LTG showed that its solubility is dependent on the pH of the medium, no precipitate formation was seen, and biomimetic media showed a greater capacity to solubilize it. Based on the dose number (D 0 ) in adults, the LTG was soluble in acidic pH media and poorly soluble in neutral to basic. Similar behavior was found in conditions which mimic children aged 10-12 years at a dose of 5 and 15 mg/kg. The D 0 for 5-year-old children at a dose of 15 mg/kg showed different behaviors between biorelevant and pharmacopeial buffers media. For children aged 2-3 years, LTG appeared to be poorly soluble under both gastric and intestinal conditions. Solubility was dependent on the volume of fluid calculated for each age group, and this may impact the development of better pharmaceutical formulations for this population, better pharmacokinetic predictions in tools as PBPK, and physiologically-based biopharmaceutics modeling, greater accuracy in the justifications for biowaiver, and many other possibilities.

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Predictive Performance of Physiology‐Based Pharmacokinetic Dose Estimates for Pediatric Trials: Evaluation With 10 Bayer Small‐Molecule Compounds in Children

Ince

Dallmann

Frechen

et al. 2021

The Journal of Clinical Pharma

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Development and guidance of dosing schemes in children have been supported by physiology‐based pharmacokinetic (PBPK) modeling for many years. PBPK models are built on a generic basis, where compound‐ and system‐specific parameters are separated and can be exchanged, allowing the translation of these models from adults to children by accounting for physiological differences. Owing to these features, PBPK modeling is a valuable approach to support clinical decision making for dosing in children. In this analysis, we evaluate pediatric PBPK models for 10 small‐molecule compounds that were applied to support clinical decision processes at Bayer for their predictive power in different age groups. Ratios of PBPK‐predicted to observed PK parameters for the evaluated drugs in different pediatric age groups were estimated. Predictive performance was analyzed on the basis of a 2‐fold error range and the bioequivalence range (ie, 0.8 ≤ predicted/observed ≤ 1.25). For all 10 compounds, all predicted‐to‐observed PK ratios were within a 2‐fold error range (n = 27), with two‐thirds of the ratios within the bioequivalence range (n = 18). The findings demonstrate that the pharmacokinetics of these compounds was successfully and adequately predicted in different pediatric age groups. This illustrates the applicability of PBPK for guiding dosing schemes in the pediatric population.

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Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility

Abstract: Developmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.

Cited by 50 publications

References 106 publications

Potential prediction of formulation performance in paediatric patients using biopharmaceutical tools and simulation of clinically relevant administration scenarios of nifedipine and lorazepam

Potential prediction of formulation performance in paediatric patients using biopharmaceutical tools and simulation of clinically relevant administration scenarios of nifedipine and lorazepam

Exploring in vitro solubility of lamotrigine in physiologically mimetic conditions to prospect the in vivo dissolution in pediatric population

Predictive Performance of Physiology‐Based Pharmacokinetic Dose Estimates for Pediatric Trials: Evaluation With 10 Bayer Small‐Molecule Compounds in Children

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