Naslov
Development of a cyclodextrin based nasal delivery system for lorazepam

Autori
Jug, Mario ; Bećirević-Laćan, Mira

Izvornik
Drug Development and Industrial Pharmacy (0363-9045) 34 (2008), 8; 817-826

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Lorazepam; Hydroxypropyl-ß-cyclodextrin; Mucoadhesion; Nasal delivery

Sažetak
A new drug delivery system containing hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and a mucoadhesive polymer was developed with the aim to overcome the limitations connected with the nasal application of drugs with low water solubility. Lorazepam, free or as cyclodextrin inclusion complex, was loaded into mucoadhesive microparticles by spray drying, using hydroxypropylmethylcellulose (HPMC), carbomer and HPMC/carbomer interpolymer complex (IPC) as mucoadhesive components. DSC analysis indicated the presence of drug crystalline areas in microparticles loaded with free lorazepam, while in those loaded with HP-ß-CD inclusion complex, the drug was amorphous. Zeta potential measurement revealed that the polymer was the main component on the surface of the microparticles. The swelling rate and mucoadhesive properties of the microparticles were determined by the polymer type used in formulation. IPC and carbomer based microparticles shoved superior swelling rate and mucoadhesion compared to the HPMC based microparticles (P<0.05). Drug loading into the polymer matrix decreased the swelling rate as well as the mucoadhesive properties of microparticles (P<0.05), while the presence of HP-ß-CD in the matrix did not induce any additional reduction of those parameters (P>0.05). The in vitro dissolution studies demonstrated that the microparticles containing the lorazepam inclusion complex displayed 1.8 - 2.5 times faster drug release compared to those containing free lorazepam. The change in the drug release rate could be connected with improved drug solubility inside the polymer matrix due to inclusion complex formation, as well as to the reduction in crystallinity following complexation, as confirmed by DSC studies.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA