PROLIPOSOMES AS AN INTRANASAL DOSAGE FORM FOR THE SUSTAINED DELIVERY OF PROPRANOLOL

Free flowing proliposomes containing propranolol hydrochloride (PH) were evaluated for their potential as a nasal drug delivery system of propranolol to sustain the plasma concentration of the drug. In vitro release of PH was significantly retarded by incorporating PH in the proliposomes, when compared with PH-loaded sorbitol. The proliposomes were administered intranasally to the rats, and plasma concentrations of propranolol were compared with those after the nasal and oral administrations of aqueous solution, and the nasal administration of hydrated proliposomes and PH-loaded sorbitols. Plasma concentrations of propranolol after the oral administration of PH solution were much lower than those after the i.v. and nasal administrations. Nasal administration of the proliposomes resulted in a plasma profile of propranolol which was much lower at the initial phase and sustained at the terminal phase, when compared with that after the nasal administration of the solution, PH-loaded sorbitols and hydrated proliposomes. The bioavailability of the nasal proliposomes reached 97.5% which is comparable to those of the nasal solution (103.1%), hydrated proliposomes (97.9%) and PH-loaded sorbitol (96.2%), but much higher than that of the oral solution (14.2%). Mean hydration time (MHT) of the proliposomes, which may be defined as a difference of MRTs between the liposomes and proliposomes, was calculated to be 80.4 min implying very slow hydration of the proliposomes in the nasal cavity. The above results indicate that the proliposome system can be a potential candidate for the sustained delivery system of propranolol through nasal mucosa.