Pharmaceutical composition for controlled release of weak acid drugs and uses thereof
AssigneePharmosa Biopharm Inc.
InventorsPei Kan, Yi Fong Lin, Ko Chieh Chen
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Abstract
Provided herein are pharmaceutical compositions containing at least one liposome, said liposome comprise an external lipid bilayer including at least one vesicle-forming phospholipid and less than 15 mole % of sterol; and an internal aqueous medium including a weak acid drug and weak acid salt. The pharmaceutical compositions reduce the burst release of the weak acid drug. Also provided is the use of the pharmaceutical composition disclosed herein to treat respiratory diseases and reduce the side effect of the weak acid drug.
Claims16
A pharmaceutical composition, comprising:
- one or more liposomes suspended in an external medium, said liposome comprises:
- (a) an external lipid bilayer, comprising
- (i) 75-99 mole % of a phosphatidylcholine,
- (ii) 0.1-25 mole % of a phosphatidylglycerol, a phosphoethanolamine, a phosphatidic acid, stearylamine or DDAB and
- (iii) less than 15 mole % of a sterol;
- and
- (b) an internal aqueous medium, comprising a weak acid drug and a weak acid salt that is a carboxylic acid salt or bicarbonate salt,
- wherein the pharmaceutical composition is incubated with a simulated lung fluid and less than 65% of the weak acid drug is released into the simulated lung fluid within 1 hour of the incubation.
A pharmaceutical composition, comprising:
- one or more liposomes suspended in an external medium, said liposomes comprising:
- (a) an external lipid bilayer, comprising a mixture of
- (i) 75-99 mole % of a phosphatidylcholine,
- (ii) 0.1-25 mole % a phosphatidylglycerol, a phosphoethanolamine, a phosphatidic acid, stearylamine or DDAB, and
- (iii) less than 13 mole % of a sterol and
- (b) an internal aqueous medium, comprising a weak acid drug and a weak acid salt,
- wherein the pharmaceutical composition has an in vitro release profile obtained by incubating the pharmaceutical composition with a simulated lung fluid, and less than 65% of the weak acid drug is released into the simulated lung fluid within one hour,
- wherein the sterol is cholesterol, cholesteryl hemisuccinate, ergosterol, lanosterol, or a combination thereof;
- wherein the weak acid salt is carboxylic acid salt or bicarbonate salt;
- wherein the carboxylic acid salt is formate, acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, benzoate or any combination thereof;
- and
- wherein the bicarbonate salt is potassium bicarbonate, sodium bicarbonate, calcium bicarbonate, magnesium bicarbonate, cesium bicarbonate, lithium bicarbonate, nickel bicarbonate, ferrous iron bicarbonate or any combination thereof,
- wherein the pH of the external medium is above the pKa of the weak acid drug, and wherein the weak acid drug is a prostaglandin or an endothelin receptor antagonist.
Dependencies are inferred from the claim text.