BCS-based biowaivers: Extension to paediatrics

Martir, Joana; Flanagan, Talia; Mann, James; Fotaki, Nikoletta

doi:10.1016/j.ejps.2020.105549

Cited by 5 publications

(7 citation statements)

References 36 publications

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“…Pediatric D 0 was also calculated and interpretated as adult D 0 using Equation (3); however, it was necessary to adjust the V 0 according to the age group, using Equation (4):

{V}_{0}=\frac{\mathrm{weight}\hspace*{.5em}(\mathrm{kg})\times 0.56\hspace*{.5em}(\mathrm{mL}/\mathrm{kg})}{37.1\hspace*{.5em}(\mathrm{mL})}\hspace*{.5em}\times \,250\,\mathrm{mL}

where 0.56 mL/kg and 37.1 mL are estimates of fasted gastric fluids volumes in pediatrics (Crawford et al., 1990; Martir et al., 2020).…”

Section: Methodsmentioning

confidence: 99%

“…where 0.56 mL/kg and 37.1 mL are estimates of fasted gastric fluids volumes in pediatrics (Crawford et al, 1990;Martir et al, 2020).…”

Section: Pediatric Dose Numbermentioning

confidence: 99%

“…Some authors have warned about problems related to extrapolation of biopharmaceutical properties from adults to children. Martir et al (2020) worked with the classic concept of BCS using water as the medium for solubility and warned that the use of BCS-based biowaivers for pediatric products needs to be undertaken with caution due to differences in the drug D 0 between adults and pediatrics.…”

Section: Pediatricsmentioning

confidence: 99%

“…According to the BCS, drugs are considered highly soluble if the highest single dose is soluble in at least 250 mL of aqueous liquid at a relevant physiological pH range of 1.2–6.8, and these aspects concern adult physiology (Kaye, 2011; The International Council for Harmonisation, 2019). So, in vivo drug solubility is dependent on the physiological conditions, such as the initial gastric volume and the characteristics of GI fluids (Kaye, 2011; Martir et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Considering all this information, some authors have discussed the impacts of extrapolating the biopharmaceutical property of a drug in adults to pediatrics (delMoral‐Sanchez et al., 2019; Gandhi et al., 2014; Martir et al., 2020). Despite this, in most of these studies the solubility considered is in water and at 25°C, which does not correspond to the physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

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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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“…Pediatric D 0 was also calculated and interpretated as adult D 0 using Equation (3); however, it was necessary to adjust the V 0 according to the age group, using Equation (4):

{V}_{0}=\frac{\mathrm{weight}\hspace*{.5em}(\mathrm{kg})\times 0.56\hspace*{.5em}(\mathrm{mL}/\mathrm{kg})}{37.1\hspace*{.5em}(\mathrm{mL})}\hspace*{.5em}\times \,250\,\mathrm{mL}

where 0.56 mL/kg and 37.1 mL are estimates of fasted gastric fluids volumes in pediatrics (Crawford et al., 1990; Martir et al., 2020).…”

Section: Methodsmentioning

confidence: 99%

“…where 0.56 mL/kg and 37.1 mL are estimates of fasted gastric fluids volumes in pediatrics (Crawford et al, 1990;Martir et al, 2020).…”

Section: Pediatric Dose Numbermentioning

confidence: 99%

Section: Pediatricsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

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Solubility of lamotrigine in age-specific biorelevant media that simulated the fasted- and fed-conditions of the gastric and intestinal environments in pediatrics and adults: implications for traditional, re-formulated, modified, and new oral formulations

Shawahna,

Saba’aneh,

Daraghmeh

et al. 2023

BMC Biotechnol

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Background Lamotrigine is an effective antiseizure medication that can be used in the management of focal and generalized epilepsies in pediatric patients. This study was conducted to quantify and compare the solubility of lamotrigine in age-specific biorelevant media that simulated the fasted and fed conditions of the gastric and intestinal environments in pediatrics and adults. Another aim was to predict how traditional, re-formulated, modified, and new oral formulations would behave in the gastric and intestinal environments across different age groups. Methods Solubility studies of lamotrigine were conducted in 16 different age-specific biorelevant media over the pH range and temperature specified by the current biopharmaceutical classification system-based criteria. The age-specific biorelevant media simulated the environments in the stomach and proximal gastrointestinal tract in both fasted and fed conditions of adults and pediatric sub-populations. The solubility of lamotrigine was determined using a pre-validated HPLC-UV method. Results Lamotrigine showed low solubility in the 16 age-specific biorelevant media as indicated by a dose number of > 1. There were significant age-specific variabilities in the solubility of lamotrigine in the different age-specific biorelevant media. Pediatric/adult solubility ratios of lamotrigine fell outside the 80-125% range in 6 (50.0%) and were borderline in 3 (25.0%) out of the 12 compared media. These ratios indicated that the solubility of lamotrigine showed considerable differences in 9 out of the 12 (75.0%) of the compared media. Conclusion Future studies are still needed to generate more pediatric biopharmaceutical data to help understand the performances of oral dosage forms in pediatric sub-populations.

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Evaluating Solubility of Celecoxib in Age-Appropriate Fasted- and Fed-State Gastric and Intestinal Biorelevant Media Representative of Adult and Pediatric Patients: Implications on Future Pediatric Biopharmaceutical Classification System

et al. 2021

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BCS-based biowaivers: Extension to paediatrics

Cited by 5 publications

References 36 publications

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

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

Solubility of lamotrigine in age-specific biorelevant media that simulated the fasted- and fed-conditions of the gastric and intestinal environments in pediatrics and adults: implications for traditional, re-formulated, modified, and new oral formulations

Evaluating Solubility of Celecoxib in Age-Appropriate Fasted- and Fed-State Gastric and Intestinal Biorelevant Media Representative of Adult and Pediatric Patients: Implications on Future Pediatric Biopharmaceutical Classification System

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