Unit:
Κατεύθυνση Βιομηχανική ΦαρμακευτικήLibrary of the School of Science
Author:
Karadima Konstantina-Evangelia
Supervisors info:
Βαλσαμή Γεωργία, αναπληρώτρια καθηγήτρια τμήματος Φαρμακευτικής του Εθνικού & Καποδιστριακού Πανεπιστημίου Αθηνών
Ρέκκας Δημήτριος, αναπληρωτής καθηγητής του τμήματος Φαρμακευτικής του Εθνικού & Καποδιστριακού Πανεπιστημίου Αθηνών
Δάλλας Παρασκευάς, επίκουρος καθηγητής του τμήματος Φαρμακευτικής του Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών
Original Title:
Development of ASA nasal formulations and in-vitro/ex vivo evaluation of permeation across nasal mucosa
Translated title:
Development of ASA nasal formulations and in-vitro/ex vivo evaluation of permeation across nasal mucosa
Summary:
Aspirin or ASA is a well-known anti-inflammatory, analgesic, antipyretic and antiplatelet drug. There is evidence that ASA can be useful in the prevention of Alzheimer’s disease (AD) or delaying its appearance. This is based on the aspect that AD may be caused by a neuroinflammation. The common problem of all the relevant studies was the increased bleeding rates. Thus, the investigation of the potential use of intranasally administrated ASA for the prevention and/or delay of AD is challenging.
The purpose of this study was the formulation of ASA nasal powder and solution and in addition the estimation of nasal permeation using artificial membrane and rabbit nasal mucosa as barrier in Franz-type diffusion cells.
Stability studies were carried out in 3 pH values (3, 4.5 and 7.4). ASA pure powder was milled in a mortar. Excipients microparticles of mannitol and lecithin (92:8 w/w) were prepared by spray-drying. ASA microparticles with L-leucine were provided from the University of Perugia. Nasal solutions of ASA in PBS were also prepared. ASA microparticles were further mixed with spray-dried excipients in mass ratios of 25(ASA microparticles with L-leucine):75(excipients), 50(ASA microparticles with L-leucine):50(excipients), 75(ASA microparticles with L-leucine):25(excipients) and were further formulated as agglomerates by tumbling and vibration technique. The content of ASA in all formulations was quantified with HPLC-UV analysis. Then, the nasal permeation was estimated using Franz-type diffusion cells and as barriers both regenerated cellulose membrane and rabbit nasal mucosa. The process yield of spray drying procedure and agglomeration process was also estimated as well as the particle size by laser light diffraction.
According to stability study, it was proven that PBS is appropriate for use in ASA permeation study. The transport of ASA across both regenerated cellulose membrane and rabbit nasal mucosa was high enough for nasal administration and followed linear increase with time in most cases. In all cases the degradation of ASA to SA was estimated. The permeability was higher in the case of 75(ASA microparticles with L-leucine):25(excipients) blend (80-85% compared to the loading amount), thanks to the beneficial properties of excipients. The agglomeration procedure was applied with all blends but proper agglomerates were only obtained from 25(ASA microparticles with L-leucine):75(excipients) The permeation of agglomerates seems to be higher and faster achieved than the 25(ASA microparticles with L-leucine):75(excipients) blend and all the other formulations , but further experiments are need in order to confirm this estimation.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
ASA, aspirin, Franz cells, spray drying, agglomerates, lecithin, mannitol, L-leucine, blends, nasal powder, nasal administartion, permeation studies, blends
File:
File access is restricted.
Master Thesis.pdf
5 MB
File access is restricted.
