Physical and chemical evaluation of liposomes, containing artesunate

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 31; no. 4; pp. 655 - 667
• Main Authors: Gabriels, M, Plaizier-Vercammen, J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 26.03.2003; Elsevier Science
• Subjects: Analysis; Artemisinins - analysis; Artemisinins - chemistry; Artesunate; Biological and medical sciences; Drug Evaluation, Preclinical - methods; General pharmacology; Liposomes; Liposomes - analysis; Liposomes - chemistry; Malaria; Medical sciences; Pharmacology. Drug treatments; Sesquiterpenes - analysis; Sesquiterpenes - chemistry; Sterile production; Liposomes; Sterile production; Malaria; Artesunate; Human; Protozoal disease; Chemical stability; Elimination; Liposome; Parasitosis; Chemical degradation; In vitro; Cholesterol; Parenteral administration; Infection
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(02)00678-7

As artesunate has a rapid onset of therapeutic effect and quick elimination, frequent administration is required, especially in the treatment of malaria. Such treatment courses led to bad patients' compliance, leading to high recrudescence rate. Therefore, slow release preparations seemed to be a logical approach in artesunate monotherapies, as can be developed with liposomal suspensions, especially for parenteral administration. Thus, the aim of this study was to develop sterile liposomes. The suspension was evaluated on its chemical/physical stability, including chemical degradation and crystallization of artesunate, and release capacities, by use of the dialysis technique. The maximal encapsulation degree of artesunate without crystals was 1.5 mg in 300 mg lipids per ml suspension, containing egg-phosphatidylcholine/cholesterol in a molar ratio of 4:3. The highest stability was obtained with a phosphate buffer of pH 5, which could be expected, as artesunate is almost totally encapsulated. But by reason of instability in water, the suspension containing artesunate 1 mg/ml was preferred, as the encapsulation efficiency is 100%. The in vitro release test proves that artesunate is reversibly encapsulated in liposomes. A method for sterile production of liposomes at lab-scale level is also presented.