Hydrophilic nanoparticles packed in oral tablets can improve the plasma profile of short half-life hydrophobic drugs

Abstract

Water insoluble drugs with a short plasma half-life face the pharmacokinetic (PK) barriers of low oral absorption from the gastrointestinal route of drug administration and rapid clearance from systemic circulation. We report the synthesis and pharmaceutical profiling of a hybrid dosage form consisting of hydrophilic polymer encapsulated nanoparticles (NPs) of a hydrophobic drug, compressed inside tablets and optimized for efficient PK oral delivery. Four different polymers, i.e. hydroxypropylmethyl cellulose, Na-alginate, pectin and polyvinylpyrrolidone were used separately to nano-encapsulate (700 nm to 1 μm diameter) lornoxicam, a model hydrophobic drug with a short PK half-life, by a solvent emulsification method. The prepared NPs were compressed directly into tablets. The PK study in rats revealed improved oral bioavailability and better PK parameters of the drug after the oral administration of NPs carrying (NC) tablets for each polymer. The same was observed for the pharmacological activity in terms of carrageenan-induced inflammation in rat paw. In the in vitro drug release study, the NC tablets provided additional control over drug release by an interaction of the surface polymer of NPs with the tablet's matrix polymer. NPs showed better rheological properties as compared to crystalline drug, enabling efficient flow and processing of NPs in the tableting machine. The NC tablets appeared advantageous compared to conventional crystalline lornoxicam carrying (CL) tablets, conventional market tablets or even nanoparticles alone in terms of the ease of administration, improved drug stability, tunable drug release and enhanced oral bioavailability.