Journal of pharmaceutical sciences 2017 05 09() pii 10.1016/j.xphs.2017.05.004
Current presentations of the anti-HIV drugs lopinavir and ritonavir make appropriate dosing for children difficult. We conducted a feasibility study to develop a formulation for these drugs with child-safe excipients in a flexible dosage form for children across the pediatric age spectrum. The freeze-drying-in-blister approach was used to produce fast-dissolving tablets (FDTs), as these can be dispersed in fluids for easy administration, even to infants, and appropriate portions of the dispersion can be given for different ages/weights. We combined various ratios of polymers, surfactants, and bulking agents to incorporate the two highly hydrophobic drugs while maintaining drug stability, rapid disintegration, and good handling properties. The final FDT was robust and disintegrated in 0.5 mL of fluid in 10 seconds, with up to four tablets dissolving in 2 mL to achieve varying doses accommodated in a common teaspoon. Drug recovery after dissolution in small volumes of liquid or fluid foods was 90% to 105%. The final candidate FDT was stable at 40°C, 75% relative humidity for up to three months. FDTs are a promising flexible dosage form for antiretroviral treatment for pediatric patients, especially in low-resource settings.