Although liposome has may advantages as a pharmaceutical dosage form, its application in the industrial field has been limited because of some problems suchs as preparation method. Reproducibility, scale-up, stability and sterilization etc.
Liposomes
prepared by microemulsification method had define size, narrow size distribution, reproducibility and high entrapment efficiency For enhancing the stability, the dry form of liposome was recommended. These types of liposome are proliposome and
freeze-dried liposome. The liposome must have some properties for preparing of freeze-dried liposome, small size (50~200mm), narrow size distribution and cryoprotectant. In this experiment, the liposomes containing 5-Fluorouracil(5-FU) and its
prodrug
(pentyl-5-FU-1-acetate: PFA, hexyl-5-FU-1-acetate: HFA) were made with soybean phosphatidylcholine, cholesterol, stearylamine(SA)and dicetyl phosphate(DCP) employing hydration method or microemulsification method using Microfluidizer . Both of
liposome
types were MLV and MEL. After preparation. Freeze drying and rehydration were performed. In the process of freezing, trehalose(Tr) was added as a cryoprotectant. Their evaluation methods were as follows: entrapment efficiency, mean particle size
and
size distribution, dissolution test, retain of entrapment efficiency and turbidity after freeze-drying. The results are summarized as belows. The entrapment efficiency of 5-FU was dependent on total lipid concentration and cholesterol content
butthat of
PFA and HFA was decreased when cholesterol was added. When DCP and SA were added, entrapment efficiency was decreased. As the partition coefficient of drug was increased. Entrapment efficiency was increased, Under the same condition entrapment
efficiency of MEL is simillar to that of MLV. The mean particle size and size and size distribution of MEL were smaller than those of MLV. Dissolution rates of drug from both liposome types were comparatively similar. Dissolution rates of drugs
with
serum and liver homogenate faster than without these materials. After preparation of liposome. Free drug was removed effectively by Dowex50W-X4, When liposome was freeze-dried and then rehydrated in the presence of Tr. Characteristics of liposome
were
maintained well in MEL than MLV. Tr was used successfully as a cryoprotectant in the process of freeze drying and the optimal ratio of Tr: Lipid was 4:1(g/g).
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