Development of nanoparticle-based orodispersible palatable pediatric formulations

Despite a collaborative effort towards developing suitable oral drug products for pediatrics over the past decade, appropriate pediatric dosage forms have remained lacking due to special considerations in dose flexibility, swallowability, palatability, and safety of excipients for pediatrics. The present research aims to develop a nanoparticle-based orodispersible pediatric drug delivery platform to improve oral bioavailability and taste of poorly water-soluble and unpalatable therapeutics. Two Biopharmaceutics Classification System II/IV compounds lopinavir (LPV) and ritonavir (RTV) with unpleasant taste were chosen as the model compounds. LPV and RTV Eudragit® E PO nanoparticles (NP) were prepared using a nanoprecipitation method and their key quality attributes and taste-masking effect were evaluated. Moreover, in vitro dissolution testing was conducted at simulated gastrointestinal pH conditions. The in vivo bioavailability of the developed NP formulations was assessed using a rat model. Following the formulation optimization, over 98% encapsulation efficiency was obtained for both LPV and RTV NP and both drugs remained amorphous in its respective NP. LPV/RTV NP combination (4/1, w/w) showed comparable in vitro dissolution to that of the commercial LPV/RTV tablet (Kaletra®). In addition, the taste-masking effect of the developed NP formulations was confirmed by an E-tongue study. The lyophilized LPV and RTV NP were completely dispersible in water within 7 sec and remained stable at 4 ± 2 °C over three months. Lastly, the pharmacokinetic study demonstrated that the LPV/RTV NP combination (4/1, w/w) had improved oral bioavailability compared to Kaletra® and their corresponding raw drug powders. The results demonstrated a novel nanoparticle-based orodispersible platform that is capable of improving oral bioavailability and taste of poorly water-soluble and unpalatable therapeutics for pediatric use.