Unit:
Κατεύθυνση Βιομηχανική ΦαρμακευτικήLibrary of the School of Science
Author:
Xiroudaki Styliani
Supervisors info:
Δημήτριος Μ. Ρέκκας, Αναπληρωτής Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Μίγματα συστημάτων χορήγησης δραστικών ουσιών ως πιθανή στρατηγική για τη βελτίωση της αεροδυναμικής συμπεριφοράς ξηρών κόνεων προς εισπνοή.
Translated title:
Multiple drug delivery mixtures as a potential strategy to improve the aerodynamic performance of dry powders for inhalation
Summary:
Quality of inhalation powders is restricted by the poor solid-state properties of active ingredients. This issue requires the use of proper carriers which, although they improve rheological characteristics, have a dilution effect on the drug thus demanding higher amounts of powder to be inhaled. This affects significantly therapies limited by high dosages, such as antibiotic therapy. Furthermore, the scarcity of approved excipients for pulmonary administration poses additional problems in inhaled product development. Therefore, we propose the use of multi-drug delivery system blends as a strategy to prevent drug dilution effect and simultaneously grant the required aerodynamic properties.
Slow release and fast/immediate release microparticles were prepared using a polylactide polymer and L-leucine. These systems were combined to achieve fast systemic absorption and sufficient local retention. A capreomycin/DCA antibiotic complex and an anti-inflammatory drug were co-encapsulated using a two-fluid nozzle and piezoelectric spray-drying technologies. The obtained powders were blended using a cochlea mixer at room temperature for variable times. A 2-level factorial design was built to model the aerodynamic behavior of the blends. Content uniformity, emitted dose (Aerolizer® DPI) and fine particle fraction were assessed by HPLC and a twin-stage impinger. In vitro release was investigated on the best powder blend.
Leucine particles successfully improved the fine particle fraction of the blends, although the emitted dose was always > 95%. Mixing time and amount of PLA powder were both influential factors. The best blending combination resulted the 30/70 PLA/leucine, when mixed for 15 minutes, either in terms of content homogeneity (%RSD = 2.8) or fine particle fraction (>50%).
Suitable process conditions for obtaining inhalable multi-drug delivery blends were determined. Suitable blends showed the expected dual release pattern and excellent aerodynamic behavior, which could be extremely advantageous especially in inhaled antibiotic therapy.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
dry powders for inhalation, antibiotic therapy, aerodynamic performance
