Seham A Elkheshen1, Rania M Hathout2, Engy A Abdel Azim3, Marwa A Fouly4, Nada M El Hoffy3. 1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. 2. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. 3. Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University in Egypt, New Cairo, Cairo, 11835, Egypt. 4. Research Institute of Ophthalmology, Giza, Cairo, 12557, Egypt.
Abstract
Background: The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized core liposomes (GCLs) were fabricated to increase the drug entrapment, corneal penetration, and physical stability of the investigated molecule. Research Design and Methods: GCLs encapsulating BRT were prepared and optimized utilizing D-optimal design (DOD). The effect of plasticizer incorporation on the physicochemical characteristics and on the in vivo performance was studied. The optimized formulations were investigated for pH, rheological properties, morphological characteristics, in vitro release profiles, biological performance, safety profile. The effects of storage and gamma sterilization were also investigated. Results: The results revealed the great success of the prepared formulations to achieve high entrapment efficiency reaching 98% after a maturation period of 10 days. The addition of glycerol as plasticizer significantly minimized the particle size and shortened the maturation period to 7 days. The selected formulations were stable for 3 months after gamma sterilization. The formulations showed significant lowering of intra-ocular pressure (IOP) in glaucomatous rabbits with sustainment of the pharmacological effect for 24 hours compared to drug solution. Conclusions: Enhanced in vitro and in vivo profiles of brimonidine tartrate loaded gelatinized-core-liposomes were obtained.
Background: The low entrapment efficiency of the hydrophilic drugs such as brimonidine tartrate (BRT) in liposomes represents a challenge that requires interventions. Gelatinized core liposomes (GCLs) were fabricated to increase the drug entrapment, corneal penetration, and physical stability of the investigated molecule. Research Design and Methods: GCLs encapsulating BRT were prepared and optimized utilizing D-optimal design (DOD). The effect of plasticizer incorporation on the physicochemical characteristics and on the in vivo performance was studied. The optimized formulations were investigated for pH, rheological properties, morphological characteristics, in vitro release profiles, biological performance, safety profile. The effects of storage and gamma sterilization were also investigated. Results: The results revealed the great success of the prepared formulations to achieve high entrapment efficiency reaching 98% after a maturation period of 10 days. The addition of glycerol as plasticizer significantly minimized the particle size and shortened the maturation period to 7 days. The selected formulations were stable for 3 months after gamma sterilization. The formulations showed significant lowering of intra-ocular pressure (IOP) in glaucomatous rabbits with sustainment of the pharmacological effect for 24 hours compared to drug solution. Conclusions: Enhanced in vitro and in vivo profiles of brimonidine tartrate loaded gelatinized-core-liposomes were obtained.