文獻(xiàn)名： Novel β-cyclodextrin nanosponges by chain growth condensation for solubility enhancement of dexibuprofen: Characterization and acute oral toxicity studies

 

 

作者： Qandeel Khalid^a，Mahmood Ahmad^b，Muhammad Usman Minhas^c，Fakhra Batool^d，Nadia Shamshad Malik^e，Mubashar Rehman^f

^a School of Pharmacy, The University of Faisalabad, Faisalabad, 38000, Pakistan

^b Faculty of Pharmacy, University of Central Punjab, Lahore, 54000, Pakistan

^c College of Pharmacy, University of Sargodha, Sargodha, 40100, Pakistan

^d Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, 63100, Punjab, Pakistan

^e Department of Pharmacy, Capital University of Science and Technology, Islamabad, 44000, Pakistan

^f Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320, Pakistan

 

 

 

摘要：This study was designed to enhance solubility of dexibuprofen, an NSAID drug used to treat moderate to severe pain, by fabricating first generation, carbonate type nanosponges of β-CD. Novel chain-growth polycondensation method was used for the first time for preparation of the β-CD nanosponges. The results exhibited 6.3-fold enhancement of dexibuprofen solubilization which is higher than previously reported β-CD formulations. The particle size of nanosponges was 275.1 ± 28.5 nm and suitable negative zeta potential indicated formation of stable nanosponges. The formation of a new polymeric network in nanosponges and interaction of dexibuprofen with nanosponges were confirmed by FTIR and DSC/TGA studies. PXRD analysis also revealed the decline in crystallinity of dexibuprofen due to its complexation with nanosponges which is desirable for complete solubilization of drugs. At pH 6.8, β-CD nanosponges exhibited swelling index of 3 whereas solubility was enhanced more than 3 times as compared to pure drug and 2 times as compared to dexibuprofen loaded β-CD complexes. In-vitro release studies exhibited 89% drug release within 30 min at pH 6.8 with β-CD nanosponges. Dexibuprofen release at pH 1.2 was remarkably slower yet β-CD nanosponges showed superior dissolution as compared to β-CD or pure drug. Acute oral toxicity studies in rats exhibited no sign of illness, mortality, adverse clinical signs and toxicologically relevant changes in hematology, clinical biochemistry and histological findings. Thus, β-CD nanosponges prepared by optimized condensation method may be superior to other nano-formulation of β-CD to improve oral administration of lipophilic drugs such as dexibuprofen.

 

關(guān)鍵詞：Nanoparticles，Nanosponges，pH sensitive，Solubility enhancement，Histopathology，NSAIDs