Combined hydroxypropyl-β-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir

• Published in: International journal of pharmaceutics 2001-05, Vol.218 (1), p.113-124
• Main Authors: Boudad, H, Legrand, P, Lebas, G, Cheron, M, Duchêne, D, Ponchel, G
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; beta-Cyclodextrins; Biological and medical sciences; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Circular Dichroism; Cyanoacrylates - chemistry; Cyclodextrins - administration & dosage; Cyclodextrins - chemistry; General pharmacology; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - chemistry; Hydroxypropyl-β-cyclodextrin; Inclusion complex; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Structure; Nanoparticles; Oral administration; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymers - chemistry; Saquinavir; Saquinavir - administration & dosage; Saquinavir - chemistry; Solubility; X-Ray Diffraction
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(01)00622-6

The aim of this study was to prepare and characterize an hydroxypropyl-β-cyclodextrin–saquinavir inclusion complex with the purpose of incorporating this complex into poly(alkylcyanoacrylate) nanoparticles in order to increase the drug loading. Hydroxypropyl-β-cyclodextrin–saquinavir complex was characterized by thermal (differential scanning calorimetry), crystallographic (X-ray diffractography) and spectroscopic methods (circular dichroism, H 1-NMR). Nanoparticles were prepared by polymerization of alkylcyanoacrylate monomers (isobutyl- and isohexylcyanoacrylate) in a water solution of the complex and further characterized. The apparent solubility of saquinavir was increased 400-fold at pH 7.0 in presence of hydroxypropyl-β-cyclodextrin owing to the formation of a drug–cyclodextrin complex as demonstrated mainly by 1H NMR and confirmed by other techniques. Saquinavir-loaded nanoparticles could be easily prepared in the presence of a drug–cyclodextrin complex. It was found that large amounts of cyclodextrins remained associated with the particles, resulting in a 20-fold increase in saquinavir loading compared to nanoparticles prepared in the absence of cyclodextrins. This study has shown that the loading in saquinavir of poly(alkylcyanoacrylate) nanospheres could be dramatically improved by simultaneously increasing the apparent solubility of the drug in the preparation medium and the amount of cyclodextrin associated with the particles, making these nanospheres a promising system for oral application.