Tailoring lipid nanoconstructs for the oral delivery of paliperidone: Formulation, optimization and in vitro evaluation

• Published in: Chemistry and physics of lipids 2021-01, Vol.234, p.105005-105005, Article 105005
• Main Authors: Rehman, Saleha, Nabi, Bushra, Baboota, Sanjula, Ali, Javed
• Format: Article
• Language: English
• Subjects: Box-behnken design; Confocal microscopy; Lipid nanoconstructs; Paliperidone; Quality by design approach; Schizophrenia
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2020.105005

[Display omitted] •Lipid nanoconstructs (LNC) bears potential for augmenting the solubility and bioavailability of the poorly soluble drugs.•Paliperidone (PPD), a second-generation antipsychotic presents poor aqueous solubility and low oral bioavailability.•PPD-loaded LNC were prepared and optimized using Quality by design approach.•Enhanced solubility and improved permeation were achieved through PPD-LNC.•In vitro lipolysis studies advocated greater absorption in vivo. The present research work involves Quality by Design (QbD)-based fabrication of lipid nanoconstructs (LNC) of paliperidone (PPD) bearing superior biopharmaceutical attributes. LNC of paliperidone was prepared by melt emulsification-probe sonication and high-pressure homogenization method followed by optimization using QbD approach. Preparing LNC by both these methods will give the benefit of identifying the best optimized formulation which will be further evaluated for in vitro studies. The best optimized formulation was obtained using melt emulsification-probe sonication technique with small particle size (86.35 nm), high entrapment efficiency (90.07 %), and high loading capacity (8.49 %). The drug release from LNC was found to be 5, 8, and 9-folds greater than drug suspension in pH 1.2, 6.8, and 7.4 respectively (p < 0.001). Stability studies of LNC in simulated gastric fluid pH 1.2 and fasted state simulated intestinal fluid depicted no alteration in particle size and polydispersity index of LNC but were found to increase in fed state simulated intestinal fluid. The drug permeability through rat intestine for LNC was found to be approximately 6-folds (p < 0.05) greater as compared to the drug suspension which was further confirmed by confocal microscopy. The in vitro lipolysis study presented significantly highest solubilization (p < 0.001) in the aqueous phase thereby anticipating higher in vivo absorption. Thus, it was concluded that LNC bears the knack of improving the solubilization and permeation potential of an otherwise hydrophobic drug, paliperidone.”