Polymorphs of sodium 4-[(4-chloro-2-hydroxybenzoyl) amino]butanoate
View Patent ↗The present invention relates to amorphous and polymorphic forms of sodium 4-[(4-chloro-2-hydroxybenzoyl)amino]butanoate and their use for facilitating the delivery of active agents, such as insulin, to a target.
1. Sodium 4-[(4-chloro-2-hydroxybenzoyl)amino]-butanoate pentahydrate exhibiting an X-ray powder diffraction pattern having peaks in degrees 2θ±0.2° 2θ at 5.47, 10.2, 16.3, 19.8, 21.7, 23.5, 27.3, 28.9, 30.6, and 33.3.
2. The sodium 4-[(4-chloro-2-hydroxybenzoyl)amino]-butanoate pentahydrate of claim 1 , wherein the pentahydrate has a melting point onset as determined by differential scanning calorimetry at about 213.05° C.
3. A pharmaceutical composition comprising:
(a) the sodium 4-[(4-chloro-2-hydroxybenzoyl)amino]-butanoate according to claim 1 ; and
(b) a biologically active agent.
4. The pharmaceutical composition of claim 3 , wherein the biologically active agent insulin.
5. The pharmaceutical composition of claim 3 , wherein the biologically active agent is insulin.
6. A dosage unit form comprising:
(A) the pharmaceutical composition of claim 3 ; and
(B)
(a) an excipient
(b) a diluent,
(c) a disintegrant,
(d) a lubricant,
(e) a plasticizer,
(f) a colorant,
(g) a dosing vehicle, or
(h) any combination thereof.
7. A method of administering insulin to an animal, the method comprising the step of administering the pharmaceutical composition of claim 3 to the animal.
8. The method of claim 7 , wherein the animal is a human.
9. The method of claim 7 , wherein the animal is suffering from diabetes.
10. A method of preparing Form IV of sodium 4-[(4-chloro-2-hydroxybenzoyl) amino]butanoate as recited in claim 1 the step of exposing Form I, II, or III of sodium 4- [(4-chloro-2-hydroxybenzoyl) amino]butanoate or a mixture thereof to a relative humidity of at least about 75% for a time sufficient to yield Form IV of sodium 4-[(4-chloro-2-hydroxybenzoyl) amino]butanoate.
11. A method of preparing Form IV of sodium 4-[(4-chloro-2-hydroxybenzoyl) amino]butanoate as recited in claim 1 the step of heating Form III of sodium 4-[(4-chloro-2-hydroxybenzoyl) amino]butanoate to a temperature between about 160° C and the melting point of anhydrous sodium 4-[(4-chloro-2-hydroxybenzoyl)amino]butanoate in an environment free of air and water.