| Abstract | Uslijed porasta broja oboljelih od Alzheimerove bolesti (AB) te nedostataka oralne primjene donepezila
kao glavnog lijeka u liječenju simptoma AB-a, javlja se potreba za razvojem inovativnih farmaceutskih oblika
donepezila za druge putove primjene. Nazalna primjena lijeka smanjuje rizik od nuspojava te omogućuje
zaobilazak krvno-moždane barijere i izravnu dostavu lijeka u mozak. In situ gelirajući sustavi inovativni su
farmaceutski oblici za nazalnu primjenu lijekova, s potencijalom povećane bioraspoloživosti, smanjene doze
i olakšane primjene u odnosu na oralnu primjenu, koja može biti otežana u Alzheimerovoj bolesti zbog
problema s gutanjem.
Cilj ovog rada bio je pripraviti i karakterizirati in situ gelirajuće sustave za nazalnu primjenu donepezila,
temeljene na kitozanu kao gelirajućem polimeru. U okviru istraživanja uspješno su pripravljene in situ
gelirajuće otopine donepezila (0,4 – 0,5 mg mL-1, m/V), s kitozanom (6,15 i 9,23 mg mL-1, m/V) i β-GP-om
(188,46 mg mL-1, m/V) kao pomoćnim tvarima. Pripravljene in situ gelirajuće otopine prikladnog su pH za
nazalnu primjenu (pH u rasponu od 7,36 do 7,46). Variranjem formulacijskih parametara postignuto je
prikladno vrijeme geliranja u odnosu na očekivani mukocilijarni klirens (formulacije s trenutnim geliranjem
te geliranjem u vremenskom intervalu od 4,2 ± 0,0 do 4,9 ± 0,1 min). Temperatura geliranja in situ gelirajućih
otopina donepezila bila je u rasponu od 33,0 ± 0,6 do 36,5 ± 0,1 °C. Pripravljene otopine bile su
pseudoplastičnog karaktera. Viskoznost u mirovanju otopina bila je u rasponu od 22,3 ± 0,4 do 113,6 ± 0,8
mPa s te je rasla s povećanjem koncentracije kitozana. Provedena ispitivanja pokazala su potencijal in situ
gelirajuće otopine donepezila, kitozana i β-GP-a kao prikladne tehnološke platforme za nazalnu primjenu
donepezila. |
| Abstract (english) | Due to the increasing incidence of Alzheimer's disease (AD) and the lack of oral administration of
donepezil as first-line treatment of AD symptoms, there is a need to develop innovative donepezil
pharmaceutical forms for other routes of administration. Nasal drug delivery decreases a side effect risk,
enables a bypass of the blood-brain barrier and a direct transport of the drug to the brain. In situ gelling
systems are innovative pharmaceutical forms for nasal drug delivery with the potential to enhance
bioavailability, decrease the dose, and simplify administration compared to oral delivery, which can be
difficult for Alzheimer's disease patients due to swallowing problems.
The aim of this study was to prepare and characterize in situ gelling systems for nasal administration of
donepezil, based on chitosan as a gelling polymer. Within this study, in situ gelling donepezil solutions (0.4
– 0.5 mg mL-1, w/v) were successfully prepared with chitosan (6.15 – 9.23 mg mL-1, w/v) and β-GP (188.46
mg mL-1, w/v) used as excipients. Prepared in situ gelling solutions were characterised by adequate pH value
for nasal administration (pH interval 7.36 – 7.46). Appropriate gelation time considering mucocilliary
clearance was obtained by varying formulation parameters (formulations with instant gelation and gelation
within the interval of 4.2 ± 0.0 to 4.9 ± 0.1 min). Gelation temperature of in situ gelling donepezil solutions
was in the range of 33.0 ± 0.6 to 36.5 ± 0.1 °C. Prepared solutions showed pseudoplastic behavior. The zeroshear
viscosity of solutions was in the range of 22.3 ± 0.4 to 113.6 ± 0.8 mPa s, and it increased with the
increase in chitosan concentration. This study has shown the potential of in situ gelling solution of donepezil,
chitosan, and β-GP as an appropriate technological platform for nasal delivery of donepezil. |
