Injectable triamcinolone formulations

Patent metadata

Field	Value
Publication number	US-12419833-B2
Application number	US-202017603816-A
Country	US
Kind code	B2
Filing date	Apr 16, 2020
Priority date	Apr 16, 2019
Publication date	Sep 23, 2025
Grant date	Sep 23, 2025

Abstract

The present disclosure relates to pharmaceutical suspensions of triamcinolone acetonide, methods of producing such suspensions and methods of using of such suspensions. The pharmaceutical suspensions of the present disclosure are stable and suitable for administration by suprachoroidal injection through a 30-gauge microneedle.

First claim

What is claimed is:

1. A pharmaceutical suspension comprising:
(a) about 40 mg/mL of triamcinolone acetonide; and
(b) a wetting agent;
wherein the suspension is essentially particulate-free and aggregate-free,
wherein the triamcinolone acetonide particles have a D 50 of less than about 3.0 μm; and
wherein the viscosity of the suspension is about 5 cPs to about 20 cPs.

2. The suspension of claim 1 , wherein the triamcinolone acetonide particles have a D 10 of less than about 2.0 μm.

3. The suspension of claim 1 , wherein the triamcinolone acetonide particles have a D 90 of less than about 7.0 μm.

4. The suspension of claim 1 , wherein the suspension is essentially particulate-free as determined by the visual inspection methods described in USP <790>.

5. The suspension of claim 1 , wherein the suspension is essentially particulate-free as determined by destructive sample preparation and the visual inspection methods described in USP <1790>.

6. The suspension of claim 1 , wherein the suspension is essentially aggregate-free as determined by a Syringeability Force Test.

7. The suspension of claim 1 , wherein the Syringeability Force Distribution (D f 90) of the suspension is not more than about 760 g f .

8. The suspension of claim 1 , wherein the suspension comprises about 0.02% w/v of the wetting agent.

9. The suspension of claim 1 , wherein the wetting agent is polysorbate 80.

10. The suspension of claim 1 , further comprising one or more isotonicity agents and one or more viscosity agents.

11. The suspension of claim 10 , wherein the one or more isotonicity agents comprise sodium chloride, potassium chloride, calcium chloride, and magnesium chloride.

12. The suspension of claim 10 , wherein the viscosity agent is carboxymethylcellulose sodium.

13. The suspension of claim 1 , wherein after 10 seconds of vigorous agitation, microscopic analysis of the agitated suspension indicates a homogenous suspension that is visually dispersed and is essentially free of aggregates.

14. The suspension of claim 1 , wherein the viscosity of the suspension is about 10 cPs.

15. The suspension of claim 1 , wherein less than about 70% of the particles are settled after about 8 h as determined by the Settling Test.

16. The suspension of claim 1 , wherein the suspension comprises 40 mg/mL of triamcinolone acetonide, 0.55% w/v of sodium chloride, 0.5% w/v of carboxy methylcellulose sodium, 0.02% w/v of polysorbate 80, 0.075% w/v of potassium chloride, 0.048% w/v of calcium chloride dihydrate, 0.03% w/v of magnesium chloride hexahydrate, 0.39% w/v of sodium acetate trihydrate, and 0.17% w/v of sodium citrate dihydrate.

17. A method of treating macular edema in a patient in need thereof comprising administering a therapeutically effective amount of the suspension of claim 1 to the posterior region of the patient's eye, wherein the suspension is administered by suprachoroidal injection.

18. A process for preparing a pharmaceutical suspension comprising:
(a) providing an essentially particulate-free first solution comprising one or more viscosity agents, one or more one tonicity agents, and one or more pH buffer agents in an aqueous solvent;
(b) providing an essentially particulate-free second solution comprising one or more wetting agents in an aqueous solvent;
(c) adding triamcinolone acetonide particles having a D 70 of less than about 5 μm to the solution of Step (b) to provide a suspension;
(d) adding the suspension of Step (c) to the solution of Step (a); and
(e) sonicating the suspension of Step (d),
wherein the suspension comprises about 40 mg/mL of triamcinolone acetonide.

19. A process for preparing a pharmaceutical suspension comprising:
(a) heating a mixture of one or more wetting agents, one or more tonicity agents, one or more pH buffer agents and triamcinolone acetonide having a D 50 of less than about 3 μm in an aqueous solvent to provide a suspension;
(b) cooling the suspension of Step (a);
(c) adding an aqueous solution of one or more viscosity agents to the suspension of Step (b);
(d) stirring the suspension of Step (c) at a low-shear stirring rate; and
(e) sonicating the suspension of Step (d),
wherein the suspension comprises about 40 mg/mL of triamcinolone acetonide.

20. A pharmaceutical suspension prepared by the process of claim 18 .

21. The process of claim 18 , wherein a filtering step provides the essentially particulate-free first solution and the essentially particulate-free second solution.

22. The process of claim 21 , wherein the filter has a pore size of 0.1 μm to 0.5 μm.

23. The suspension of claim 1 , wherein the triamcinolone acetonide particles have a D 50 of about 2.0 μm to about 2.5 μm.

24. A pharmaceutical suspension comprising:
(a) about 40 mg/mL of triamcinolone acetonide; and
(b) a wetting agent;
wherein the suspension is essentially particulate-free and aggregate-free;
wherein the viscosity of the suspension is about 5 cPs to about 20 cPs; and wherein the triamcinolone acetonide particles have a D 10 of less than about 2.0 μm, a D 50 of less than about 3.0 μm, and a D 90 of less than about 7.0 μm.

25. The pharmaceutical suspension of claim 24 , wherein the viscosity of the suspension is about 6 cPs to about 12 cPs.

26. The pharmaceutical suspension of claim 25 , wherein the viscosity of the suspension is about 10 cPs.

Assignees

• Clearside Biomedical Inc

Inventors

• Nguyen Thai Q
• Burke Brian
• Lee Edward
• Andino Rafael Victor

Classifications

• A61M5/32

  Needles; Details of needles pertaining to their connection with syringe or hub (infusion needles A61M5/158); Accessories for bringing the needle into, or holding the needle on, the body {(A61M5/42, A61M5/46 take precedence; guide needles for catheters A61M25/065)}; Devices for protection of needles {(apparatus specially adapted for cleaning or sterilising needles A61M5/001)} · CPC title

• A61K47/38

  Cellulose; Derivatives thereof · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K47/02

  Inorganic compounds · CPC title

• A61K31/58

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title