Formulation development and evaluation of hydroxyurea dry syrup in sickle cell disease management in pediatrics

Abstract

Background. Sickle cell disease (SCD) is a genetic disease which affects global population with annual birth of 300,000 SCD infants whom 75% are born in Africa. Tanzania has the highest prevalence (13%) of SCD in the world. Pediatric population is the most affected age group. Currently, hydroxyurea (HU) is the drug of choice for management of SCD but available dosage form exists as capsule with strength of 500mg which fail to match with pediatric dose of 20mg/kg. Current practice of compounding is prone to dose errors and contamination. Also, shortage of compounding laboratories in health facilities in the developing countries the major issue. Aim. The aim of this study was to develop and evaluate the HU dry syrup formulation for the management of SCD in pediatrics. Methodology. Preformulation and formulation phases involved use of high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FITR) rotational rheometers, USP type II dissolution apparatus, digital pH meters. Evaluation of dry syrup involved measurement of angle of repose, compressibility index, Hausner’s ratio, assay, dissolution and moisture content. The reconstituted syrup was then subjected to in use stability testing as part of evaluation. In that case the reconstituted syrup was evaluated for duration of 14 days for its pH, viscosity and assay. Results. All the formulations showed promising physicochemical features which were in agreement with pharmacopeia range, excellent in flowability, assay, dissolution, pseudoplastic flow property and good pH. Conclusion. The HU dry syrup formulation was successfully developed, optimized and evaluated. It has a potential to address the dose challenges in pediatric population. Further studies on important issues such as stability studies and formulation up-scaling are recommended.