Info

Phosphatidylethanolamine

A mixture of l^-diacyl-sra-glycero-S-

phosphoethanolamines with the composition varying with the source.

Avanti Polar Lipids

Zwitterion

Dioleoylphosphatidylethanolamine

l,2-Dioleoyl-sra-glycero-3-phosphoethanolamine (DOPE)

Avanti Polar Lipids

Zwitterion

Distearoylphosphatidylethanolamine

l,2-Distearoyl-sra-glycero-3-phosphoethanolamine (DSPE)

Avanti Polar Lipids

Zwitterion

Phosphatidylglycerol

A mixture of l^-diacyl-sra-glycero-S-lphospho-rac-

(1-glycerol)]s with the composition varying with the source.

Avanti Polar Lipids

Negative

Dimyristoylphosphatidylglycerol

l,2-Dimyristoyl-j'ra-glycero-3-[phospho-rac-(1-glycerol)] (DMPG)

Avanti Polar Lipids

Negative

Dioleoylphosphatidylglycerol

l,2-Dioleoyl-î«-glycero-3-[phospho-rac-(1-glycerol)] (DOPG)

Avanti Polar Lipids

Negative

Dipalmitoylphosphatidylglycerol

l,2-Dipalmitoyl-î«-glycero-3-[phospho-rac-(1-glycerol)] (DPPG)

Avanti Polar Lipids

Negative

Distearoylphosphatidylglycerol

l,2-Distearoyl-î«-glycero-3-[phospho-rac-(1-glycerol)] (DSPG)

Avanti Polar Lipids

Negative

Table 11 Cholesterol and Phospholipids (Continued)

Excipient

Chemical name or composition

Trade name/supplier

Charge

Palmitoyl-

oleoylphosphatidylglycerol Phosphatidylinositol

Phosphatidylserine

Dioleoylphosphatidylserine

Palmitoyl-oleoylphosphatidylserine

Sphingomyelin

Proprietary vehicle

Proprietary vehicle Proprietary vehicle Proprietary vehicle

Proprietary vehicle Proprietary vehicle l-Pahnitoyl-2-oleoyl-j,ra-glycero-3-[phospho-rac-

(1-glycerol)] (POPG) A mixture of l^-diacyl-sra-glycero-S-phosphoinositols with the composition varying with the source. A mixture of l^-diacyl-sra-glycero-S-phospho-L-serines with the composition varying with the source.

l^-Dioleoyl-sra-glycero-S-phospho-L-serine (DOPS) l-Pahnitoyl-2-oleoyl-j,ra-glycero-3-phospho-L-serine (POPS) (2S,3R,4E)-2-Acylaminooctadec-4-ene-3-hydroxy-

1-phosphocholine. Also called ceramide-l-phosphocholine. Empty liposomes for addition of drugs containing: NLT 20% phospholipids from soybeans (primarily phosphatidylcholine), 14—18% ethanol, water to 100% NLT 34% phosphatidylcholine and other phospholipids in sunflower oil NLT 50% phosphatidylcholine NMT 6%

lysophosphatidylcholine 33.8- 41.2% propylene glycol NLT 50% phosphatidylcholine NMT 6%

lysophosphatidylcholine in safflower oil, glycerin, caprylic/capric triglycerides, alcohol, glyceryl stearate, and ascorbyl palmitate NLT 53% phosphatidylcholine, NMT 6% lysophosphatidylcholine, 3-6% ethanol in caprylic/capric triglycerides, glyceryl stearate, oleic acid, and ascorbyl palmitate 72-78% Phosphatidylcholine, NMT 6% lysophosphatidylcholine in alcohol, safflower oil, glyceryl stearate, coconut oil, and ascorbyl palmitate

Avanti Polar Lipids Negative

Avanti Polar Lipids Negative

Avanti Polar Lipids Zwitterion Alcolec PS 90P/

American Lecithin

Avanti Polar Lipids Zwitterion

Avanti Polar Lipids Zwitterion

Avanti Polar Lipids Zwitterion

Natipide II/American Lecithin

Phosal 35 SB/American

Lecithin Phosal 50 PG/American

Lecithin Phosal 50 SA+/American Lecithin

Phosal 53 MCT/American Lecithin

Phosal 75 SA/American Lecithin

However, the fatty acid ester bonds are the most labile (30). Studies of soybean phosphatidylcholine, hydrogenated phosphatidylcholine, partially saturated egg phosphatidylcholine, and phosphatidylglycerol have shown the rate of hydrolysis to be pseudo first order and to depend strongly on pH and temperature. For each of these phospholipids, the rate of hydrolysis reached a nadir at pH 6.5 and accelerated as pH either decreased or increased around this value (30,31). Also, some buffer species showed relatively smaller increases in the rate of hydrolysis related to catalytic effects (30,31). Hydrolytic cleavage of one of the two fatty acids associated with a phospholipid molecule results in the production of one molecule of the corresponding lyso-phospholipid and one molecule of the free fatty acid. Studies have shown that the permeability of liposomes to leakage of calcein was minimal until about 10% of the phosphatidylcholine had hydrolyzed to lysophosphatidylcholine and free fatty acid, after which additional hydrolysis resulted in an increase in the permeability and rate of leakage (30).

To minimize instability due to oxidation, formulators can choose phospho-lipids comprised only of saturated fatty acids or may consider the addition of antioxidants to formulations containing phospholipids comprised of oxidation-prone unsaturated fatty acids. In addition, maintaining an approximate pH of 6.5 during processing and in the final formulation, as well as avoidance of exposure to excessive heat, will help to minimize oxidation and hydrolysis.

It should also be noted that the use of charged phospholipids, such as the phosphatidylglycerols or phosphatidic acids, may prevent liposome aggregation and fusion. Incorporation of cholesterol into the formulation tends to decrease the fluidity and permeability of the liposomal bilayer membrane and promotes formation of smaller, more stable and more uniformly sized vesicles (31,32).

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