A pilot randomised open-label taste-testing study to evaluate the acceptability of chocolate-based midazolam in children

To achieve the benefits of a medicine, the patient must be willing to take it in the correct amount at the appropriate time. Most medicines are not formulated for use in children. For those that are, few are considered sufficiently palatable. Lack of palatability can be attributed to poor taste and, for children below 6 years, the inability to swallow solid medicines, such as tablets. Midazolam is a highly effective oral sedative and pre-procedural medicine for children and adolescents. The lack of an oral commercial product in Australia has led the local hospitals to administer midazolam injection solution which has a foul taste and is often rejected by the children. Inadequate sedation presents difficulties in children who are very anxious or uncooperative in the preoperative setting (e.g. children with autism). Uncooperative children have then to be held down and restrained for the induction of anaesthesia, which is traumatizing for the child and the family. In adolescents, this can also pose significant safety risks for the attending staff. We believe that chocolate-based mini tablets can effectively provide palatable formulations for bitter drugs such as midazolam to assist clinicians achieve the desired therapeutic outcomes in paediatric patients. The aims of this project are: 1. To evaluate the rate of acceptance of the chocolate-based midazolam tablets in children (age 3-16) required pre-procedural midazolam 2. To evaluate the pharmacokinetic prarameters of the chocolate-based midazolam tablets in children We have developed prototype chocolate tablets measuring 0.5 x 1 x 0.5 cm that can mask the taste of the highly bitter drug. The aims of this project are to perform further clinical evaluations on these formulations to fully realise the potential of midazolam for preprocedural sedation and anxiolysis of sick children in WA. This study will pave the way for the scaled up manufacture of chocolate-based midazolam tablets for use in WA paediatric hospital wards, and the adaptation of the chocolate base for the formulation of other bitter drugs (e.g. antibiotics). Pharmaceutically, the chocolate tablets, which are prepared without water, will provide more stable products for labile drugs than liquid mixtures. They are also more convenient and cheaper to store and transport than bulky liquid formulations.