Pharmaceutical Chemistry

Marilena Vlachou is a Professor at the National and Kapodistrian University of Athens (NKUA), Greece. She obtained her Pharmacy and Ph.D. (Pharmaceutical Technology) degrees from the NKUA. Just prior to obtaining her Ph.D. she moved to the University of Rhode Island, United States, as a Visiting Research Scientist to conduct state-of-the art research on Pharmaceutical Technology techniques. Her research interests include: the formulation and in vitro release of bioactive substances from topical formulations; the efficacy and safety of formulations in skin disease therapies; the modified release of novel synthetic derivatives, with diverse activity; the investigation of the physicochemical properties of new excipients, including those of marine origin (Ulvans), and nanomaterials, with respect to their interaction with active pharmaceutical ingredients (APIs); 3D/4D printlets; pediatric delivery systems.

Hydrocortisone (HCT) is widely used for glucocorticoid replacement and anti-inflammatory therapy and is the preferred treatment for adrenal insufficiency due to its similarity to endogenous cortisol. In paediatric patients, accurate dose administration is essential, as insufficient exposure may lead to adrenal crisis and poor disease control, whereas excessive exposure may impair growth. Conventional immediate-release formulations are limited by hydrocortisone’s short half-life, rapid clearance, multiple daily dosing, and difficulties in dose adjustment for children (1-5). This study aimed at developing a paediatric bilayer matrix tablet containing 5 mg HCT, with a 2 mg immediate-release (IR) layer and a 3 mg sustained-release (SR) layer, to provide rapid initial availability followed by prolonged drug release. HCT and excipients were accurately weighed (Table 1), blended, lubricated with magnesium stearate, and directly compressed into 10 mm diameter tablets. Drug release was evaluated using a USP II paddle apparatus at 50 rpm and 37 ± 0.5 °C. Excipient composition markedly affected HCT release. Formulations F2 and F4, containing lower levels of Compritol® 888 ATO and Celny VH in the SR layer and higher drug loading in the IR layer, showed faster and higher release, reaching approximately 75% and 93%, respectively. F1 and F3, with higher lipid and polymer contents, exhibited slower release, consistent with formation of a stronger diffusion barrier. The F4 formulation showed the greatest initial burst, whilst preserving sustained-release behaviour.