Formulation, Characterization and Physiochemical Evaluation of Rapidly Disintegrating Oral Tablets of Midazolam for Pediatric Preanesthesia Administration

Purpose. To formulate fast-disintegrating tablets of midazolam using oral disintegrating technologies combined with an effervescent system for enhanced disintegration speed. Background: Midazolam is routinely given to children in the preoperative environment to help minimize anxiety and promote the smooth induction of anesthesia. However, oral commercially available forms of midazolam that are convenient, palatable, rapidly functioning, and child-friendly do not exist. Therefore, clinicians commonly mix midazolam injections into fruit juice or soda to mask its extremely bitter taste. Nevertheless, significant challenges remain during administration including quick expectoration and large volumes to be swallowed. This study investigated the effect of incorporating midazolam into a rapidly disintegrating tablet enhanced for disintegrating speeds using an effervescent system. Methods: Different tablets were made by incorporating an effervescent system of organic acids and an alkali into our lab’s previously developed flavored and optimized oral disintegrating formulation. Tablets were drug loaded with 2.5 mg or 5 mg of midazolam and evaluated for friability (F) and hardness (H) according to USP standards. Due to the lack of an accurate USP test which discriminates small differences between fast disintegrating oral tablets, disintegration time (DT), wetting time (WT) and water uptake (WU) were tested using modified procedures that were validated to detect small differences between tablets. Results:Incorporation of the effervescent system and midazolam into the oral disintegrating tablet formulations resulted in favorable disintegration and tablet physical properties. An inverse relationship was observed between the amount of drug and disintegration rates. As the amount of midazolam increased from 2.5 mg to 5.0 mg, the disintegration speed decreased from 14.33 secs to 13.33 secs, respectively. WU also decreased at increased midazolam concentrations. Regardless of drug load, all tablets maintained consistent hardness at an average of 1.23 kgf and had acceptable friability results of Conclusion: Small oral tablet formulations containing an effervescent system and up to 5 mg of midazolam were shown to have enhanced disintegrating speeds (sec) favorable for pediatric administration. These rapidly disintegrating tablet may show success in efficiently delivering preanesthetic sedatives without liquids and avoiding quick expectoration. Grant: This study was funded by NSU HPD Grant #334867.