Could spray-dried microbeads with chitosan glutamate be considered as promising vaginal microbicide carriers? The effect of process variables on the in vitro functional and physicochemical characteristics

• Published in: International journal of pharmaceutics 2019-09, Vol.568, p.118558-118558, Article 118558
• Main Authors: Szymanska, Emilia, Czarnomysy, Robert, Jacyna, Julia, Basa, Anna, Wilczewska, Agnieszka Zofia, Markuszewski, Michal, Winnicka, Katarzyna
• Format: Article
• Language: English
• Subjects: Administration, Intravaginal; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - chemistry; Cell Line; Cell Survival - drug effects; Chitosan - administration & dosage; Chitosan - chemistry; Chitosan glutamate; Desiccation; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Liberation; Female; Glutamates - administration & dosage; Glutamates - chemistry; Humans; Microspheres; Multiunit drug carrier; Spray-drying; Statistical design of experiments; Vagina; Vaginal microbicide; Zidovudine; Zidovudine - administration & dosage; Zidovudine - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.118558

[Display omitted] In order to improve efficacy and accessibility of vaginal microbicides, development of smart polymer-based delivery carriers appears essential. In scope of this study, the potential of chitosan glutamate in technology of microbicide multiunit formulations containing zidovudine-loaded microbeads was investigated. Spray-drying optimization was supported by statistical design of experiments. As polymer properties may alter upon processing, particularly important was to examine the influence of product composition and process variables on final microbeads characteristic. Data from ATR-FTIR, Raman, and DSC analysis confirmed drug compatibility with chitosan glutamate after spray-drying. Formulations with polymer:drug ratio 5:1 (w/w) prepared from azeotropic ethanol-water mixture were found to spread easily upon dilution with simulant vaginal fluid, forming viscous, shear-thinning barrier, which could impede direct contact of virus with mucus cells. Furthermore, the presence of ethanol was found crucial to overcome stickiness phenomenon by interrupting hydrogen bonding between drug and polymer. In vitro dissolution studies displayed an initial burst effect followed with prolonged (up to 4 h) drug release stage. By modifying spray-drying temperature, alterations in microbeads’ swelling capacity and drug release were observed. Cytotoxicity studies using human vaginal cell line VK2/E6E7 revealed that drug-free formulations exerted no significant impact on mucosal cells, suggesting they are safe for vaginal delivery.