Effect of formulation design and freeze-drying on properties of fluconazole multilamellar liposomes

Abstract

Fluconazole-entrapped multilamellar liposomes were prepared using the thin-film hydration method. The effects of cholesterol molar ratio, charge-inducing agents, and α-tocopherol acetate on encapsulation efficiency values and in vitro drug release of multilamellar liposomes were studied. Freeze-dried liposomal products were prepared with or without cryoprotectants. Results showed that incorporation of stearylamine resulted in an increased entrapment of fluconazole, whereas incorporation of dicetyl phosphate decreased the drug entrapment efficiency. The incorporation of α-tocopherol acetate into fluconazole multilamellar liposomes resulted in the increase of entrapment efficiency of fluconazole liposomes. In vitro release studies revealed that incorporation of cholesterol into multilamellar liposomal formulations decreased drug permeability from formulations. Positively charged fluconazole multilamellar liposomes gave rise to a slow release rate compared to neutral liposomes whereas negatively charged fluconazole liposomes showed a rapid release rate. Physical stability studies showed that lyophilized cake of liposomes without cryoprotectants was compact and difficult to reconstitute compared to fluffy easily reconstituted cakes upon using cryoprotectants. Fluconazole retained in freeze-dried liposomes without cryoprotectants was 63.452% compared to 91.877% using three grams of trehalose as a cryoprotectant per gram lipid in positively charged multilamellar liposomes. Physical stability studies showed superior potentials of the lyophilized product after reconstitution in comparison with those of a solution product.

Glycosylated Sertraline-Loaded Liposomes for Brain Targeting: QbD Study of Formulation Variabilities and Brain Transport

“…Accordingly, larger cumulative internal aqueous phase within the unilamellar vesicles was available for the entrapment process (20). The effect of cholesterol to augment SerHCl EE could be explained by its influence to increase the lamellar rigidity, hence greater bilayers' stability with reduced leakage to enhance the entrapment capacity would resulted in (21). Despite being nonsignificant to drug EE, dicetyl phosphate exhibited a positive effect due to its charge-charge interaction with the ionized form sertraline base (22).…”

“…In particular, it might not only reduce the density of the phospholipid head groups at the interfacial region of the liposomal lamellae but also increase the packing intensity of the phospholipid hydrophobic alkyl chains in the middle region of lamellae to retard drug leakage (35). The negative effect of dicetyl phosphate on both leakage responses could be attributed to its ionic interaction with the ionized drug molecules at liposomal surface (21). NAG showed also a negative effect on both Q2h and Q24h due to the electrostatic repulsion between the positively charged NAG ammonium salt and drug molecules at liposomal surface.…”

Comparison of the Characteristics of Transfersomes and Protransfersomes Containing Azelaic Acid

“…The increased of entrapment efficiency was due to the aggregation of particel so that the size becomes large and the more active substances were entrapped. 20 Moreover, the rigidity of lipid membrant increases, so the permeability from the lipid membrant decreases, and the leak of the drug from the transfersome membrant can be prevented. In room temperature, the particel size of transfersome was stable.…”

Clinical development of liposome based drugs: formulation, characterization, and therapeutic efficacy

“…In general, freeze-drying increases the shelf-life of liposomal formulations and preserves them in dried form as lyophilized cakes to be reconstituted with water for injection prior to administration. 66 Furthermore, cryoprotectants need to be added to maintain particle size distribution of liposomes after the freeze-drying-rehydration cycle. Various types and concentrations of sugars have been investigated for their ability to protect liposomes against fusion and leakage during lyophilization processes.…”

“…Various types and concentrations of sugars have been investigated for their ability to protect liposomes against fusion and leakage during lyophilization processes. 66 In commercial liposome lyophilized products, lactose has been used as a cryoprotectant in the formulations of Amphotec, Myocet, and Visudyne, and sucrose was added in the formulations of AmBisome and LEP-ETU to increase liposome stability during lyophilization. Interestingly, these commercial lyophilized products showed similar shelf-life in comparison with other liposome products (eg, suspension and emulsions) and hence lyophilization may not have the expected effect on liposome stability.…”