assessed the possible harms associated with expanding the BCS-based biowaiver standards for fluconazole to subgroups of children. Previous studies have classified the drugs listed by the WHO as essential drugs for adults and children into provisional BCS classes. Recently, there has been a growing interest in studying how the permeability and solubility of APIs can change using age-specific criteria for the volume and constituents of the gastrointestinal fluids. The permeability and solubility of APIs can vary by age, developmental status, and maturation. Therefore, pediatrics can be divided into subpopulations that include: neonates, infants, children, and adolescents.

Moreover, the volume and composition of the gastrointestinal fluids vary by age, development, and maturation.

Additionally, there are recognizable variabilities in the quantities and qualities of the gastrointestinal fluids between adult and pediatric populations. It is important to note that the principles guiding IVBESs in pediatrics were not developed. Therefore, biowaiver decisions can reduce the costs of developing IRSODFs, accelerate regulatory processing and approval, and reduce the regulatory burden. These biowaiver decisions allow pharmaceutical scientists to surrogate IVBESs by in vitro dissolution tests. Drug regulatory agencies like the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and the World Health Organization (WHO) use the BCS to allow waiving in vivo bioequivalence studies (IVBESs) (biowaiver) for IRSODFs that contain highly soluble active pharmaceutical ingredients (APIs). The biopharmaceutical classification system (BCS) has been used to support and hasten the development of traditional, new, and/or modified immediate-release solid oral dosage forms (IRSODFs). Conclusionįuture studies are still needed to generate more pediatric biopharmaceutical data to help understand the performances of oral dosage forms in pediatric sub-populations. These ratios indicated that the solubility of lamotrigine showed considerable differences in 9 out of the 12 (75.0%) of the compared 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. There were significant age-specific variabilities in the solubility of lamotrigine in the different age-specific biorelevant media. Lamotrigine showed low solubility in the 16 age-specific biorelevant media as indicated by a dose number of > 1.

The solubility of lamotrigine was determined using a pre-validated HPLC-UV method. 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. 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. 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. 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. Lamotrigine is an effective antiseizure medication that can be used in the management of focal and generalized epilepsies in pediatric patients.

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