Hydroxyurea granules for the management of sickle cell disease in children

Background: Many studies have demonstrated the effectiveness of hydroxyurea in the management of sickle cell disease. The drug, which is an antimetabolite initially developed for the treatment of myeloproliferative disorders has been repurposed, even though its use for the initial indication has been retained. Currently, in most developing countries the only available dosage form is the 500 mg capsule. Pediatric hydroxyurea formulations are yet to appear on many markets, thus, patients have to rely on compounding facilities to have their medications extemporaneously prepared for them from the adult solid dosage form. Interestingly, pharmacies that provide compounding services are limited, additionally; most extemporaneously compounded products have very short shelf lives. The aim of this study was to formulate and optimize dry powder granules of hydroxyurea to be reconstituted into an oral suspension in order to prolong the shelf life of the product. Method: Two different batches of Hydroxyurea granules were formulated using the wet granulation method. Granules were characterized by appearance, pH and drug content. Microbial contamination test was conducted using the pour plate method. Results: Granules prepared were easy to reconstitute. pH of the suspensions were between 7 and 8. Drug content in formulated granules were 95 and 92% of expected values. No E. coli was found in the suspensions and the total microbial count was less than the USP limits. Granules remained stable over the study period of 60 days. Conclusion: Dry granules of hydroxyurea can be produced in bulk and packaged into bottles for reconstitution into suspensions by patients. These formulations have better stability than extemporaneously compounded suspensions. Making hydroxyurea granules available for children with sickle cell disease will be a convenient, time and cost effective way of meeting their medical needs.