Primjena ciklodekstrina u razvoju oftalmika za topikalnu primjenu

master's thesis

• Title (english): Use of cyclodextrins in the development of ophthalmics for topical administration
• Author: Lana Hasnaš
• Mentor: Mario Jug (mentor)
• Committee member: Mario Jug (predsjednik povjerenstva)
• Committee member: Anita Hafner (član povjerenstva)
• Committee member: Karmela Barišić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2022-11-03, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Bolesti oka, posebice bolesti stražnjeg segmenta oka kao što su dijabetička retinopatija, senilna makularna degeneracija, katarakt i glaukom pogađaju velik broj ljudi. Kao vodeći uzrok sljepoće u razvijenim zemljama nepovoljno utječu na kvalitetu života bolesnika. Obzirom da je oko organ kompleksne i robusne građe, a indicirani lijekovi nepovoljne okularne farmakokinetike, konvencionalna se terapija svodi na topikalne oblike niske bioraspoloživosti i invazivne intravitealne injekcije. Ciklodekstrini su derivati oligosaharida građeni od nekoliko α,D- glukopiranoznih jedinica koje su međusobno povezane α-1,4-glikozidnim vezama. U prostoru formiraju strukturu nalik krnjem stošcu s hidrofilnom vanjštinom i lipofilnom šupljinom, a njihovo se djelovanje temelji na stvaranju inkluzijskih kompleksa. U ovom radu razmatran je potencijal primjene ciklodekstrina u topikalnim oblicima lijekova koji se koriste u liječenju bolesti oka s visokim rizikom od gubitka vida. Utvrđeno je da primjena ciklodekstrina u formulacijeama dorzolamida, deksametazona i latanoprosta osiguravaju uklapanje terapijski relevantne doze u volumenu prikladnom za oftalmičku primjenu, a njihova primjena rezultira povećanom koncentracijom lijekova u suznom filmu i stražnjem segmentu oka. Kod formulacije s diklofenaknatrijem primjena ciklodekstrina omogućuje otapanje terapijske doze lijeka izbjegavajući potrebu za tenzidima te omogućuje konzerviranje primjenom fiziološki podnošljivijeg konzervansa. Također, zahvaljujući mukoadhezivnim svojstvima agregata ciklodekstrina omogućeno je kontrolirano oslobađanje i produljeno zadržavanje lijeka u suznom filmu uz manje iritacija, nelagode i peckanja pri topikalnoj primjeni. Solubilizacijska i stabilizacijska svojstva ciklodekstrina mogu se dodatno unaprijediti formiranjem ternarnih i kvarternih kompleksa pri čemu najveći potencijal pokazuje hipromeloza.

Abstract (english)

Eye diseases, especially those affecting the posterior segment of the eye, such as diabetic retinopathy, senile macular degeneration, cataract and glaucoma, are recognized as the leading cause of blindness in developed countries, adversely affecting the patient's quality of life. Complex and robust eye anatomy and unfavorable ocular pharmacokinetics of the indicated drugs reduce conventional therapy to topical dosage forms of low bioavailability and invasive intravital injections. Cyclodextrins are cyclic oligosaccharides consisting of several α, D-glucopyranose units interconnected by α-1,4-glycosidic bonds. They appear as a truncated cone with a hydrophilic exterior and a lipophilic central cavity, enabling the formation of inclusion complexes. In this thesis, the potential of cyclodextrins in the development of topical dosage forms of drugs used in the therapy of ophthalmic diseases with a high risk of vision loss was discussed. It was found that the use of cyclodextrin in the formulations of dorzolamide, dexamethasone and latanoprost ensures the entrapment of a therapeutically relevant dose in a volume suitable for ophthalmic use, and their use results in an increased concentration of drugs in the tear film and the posterior segment of the eye. In the eye drop formulation with diclofenac sodium, the use of cyclodextrin enables the dissolution of the therapeutic dose of the drug, avoiding the need for surfactants, and enabling preservation by using a more physiologically tolerable preservative. Also, owing to the mucoadhesive properties of cyclodextrin aggregates, controlled release and prolonged retention of the drug in the tear film is obtained with less irritation, discomfort and burning sensation after topical administration. The solubilizing and stabilizing properties of cyclodextrin can be further improved by forming ternary and quaternary complexes, where hypromellose showed the highest potential.

• Keywords: oči; ciklodekstrini; topikalna primjena lijeka; okularna bioraspoloživost lijeka
• Keywords (english): eyes; cyclodextrins; topical drug delivery; ophtalmic drug bioavailability
• Language: croatian
• URN:NBN: urn:nbn:hr:163:477457
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-11-03
• Created on: 2022-11-07 11:47:54