Химия и химические технологии / 4. Химико-фармацевтическое производство

C.pharm.sci. Borschevskiy G. I.¹, c.phys-math.sci. Yanchuk I. B.¹,

d.pharm.sci. Yarnykh T. G.²

¹ JSC “Farmak”, Kiev

² National University of Pharmacy

Investigation of the chemical and structural properties of the liposome medicines obtained from various lipids

Obtaining and experimental study of liposomes is one of the priority areas of nanobiotechnology. It is known that liposomal membranes from phospholipids are prone to hydrolysis due to the ester bond.

When creating liposomal drugs are used substances LIPOID S 100 and LIPOID E 80. The main difference of these substances is a quantitative content of phosphatidylcholine (~ 93 % in S100, and ~ 85 % in E80).

The difference in the quantitative composition of the obtained liposomal medicines determines the ability to penetrate cell membranes and, accordingly, alters pharmacokinetics of the medicine [2, p. 7-12; 3, p. 22-31; 4, p. 18-29].

We investigated the chemical stability (phospholipids composition and the peroxide value), the structure and size of the liposomes obtained from lipoids of different nature.

Liposomes were prepared by high pressure via a high pressure homogenizer. The study of phospholipids composition of the liposomes was carried out by TLC.

Determination of peroxide value was carried out by the method of State Pharmacopoeia of Ukraine [1, p. 226-231].

Liposomes size was determined by the method of dynamic light scattering (DLS) and transmission electron microscopy (TEM).

Obtained data confirmed that substances which were used are highly purified and minimally oxidized for double bonds in fatty acids.

By TLC was determined phospholipids composition of medicines [5, p. 15-23; 7, p. 5-7].

The results showed that in the composition of the liposomes there are phosphatidylcholine, diphosphatidylglycerol, phosphatidylethanolamine, sphingomyelin. The amount of lysophosphatidylcholine in different samples varied from 1.33 % to 1.61 % (the content of phosphatidylcholine), which indicates the stability of phosphatidylcholine in the process of obtaining liposomes.

The results of determination of the peroxide number showed that the peroxide number in prototypes (value 0) does not exceed the value given in the certificates. The index of lipid liposome oxidization during the technological process did not change comparing with baseline lipid mixture.

The structure and size of the received medicines were confirmed by TEM and DLS spectrum. Liposomes have a shape close to spherical, average size is 42-44 nm. Liposome sizes, determined by DLS are slightly greater (5-7 %) of liposome sizes determined by TEM.

This discrepancy is typical and due to the fact that when using the DLS measured hydrodynamic radius of the particles which is always greater than the real. The size of liposomes produced from various raw materials is virtually identical.

Thus, analytical methods that are specific for the study of physical and chemical properties of the liposomes are determined. These methods include thin-layer chromatography, dynamic light scattering, electron microscopy, determination of the index of lipid peroxidation and the peroxide number [6, p. 5-11].

These methods allow identifying and evaluating the critical parameters of technology of liposomal medicines.

TLC, determination of the index of lipid peroxidation and the peroxide number allows quantifying the content of impurities in the production process and storage of medicines.

DLS and TEM techniques allow visualizing the process of obtaining liposomal medicines and judge the physical processes occurring in the formation of liposomes.

References:

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