Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof
First Claim
Patent Images
1. A pharmaceutical solution comprising:
- (i) β
-cyclodextrin sulfobutyl ether, hydroxypropyl β
-cyclodextrin, or a combination thereof;
(ii) about 0.2% to about 1.0% of polyvinylpyrrolidone; and
(iii) about 30 mg/mL to about 60 mg/mL of an ophthalmic therapeutic agent having a solubility of less than 1 mg/mL in water;
wherein the weight ratio of (i) to (iii) is from about 2;
1 to about 8;
1.
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Abstract
The present disclosure relates to stable formulations of receptor tyrosine kinase inhibitors (TKI), e.g., pazopanib; methods of preparation thereof; and use of the disclosed formulations in sustained delivery of the active agent to a target site. The disclosure further relates to methods of converting one polymorphic Form of a TKI to another polymorphic Form and/or an amorphous form.
463 Citations
20 Claims
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1. A pharmaceutical solution comprising:
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(i) β
-cyclodextrin sulfobutyl ether, hydroxypropyl β
-cyclodextrin, or a combination thereof;(ii) about 0.2% to about 1.0% of polyvinylpyrrolidone; and (iii) about 30 mg/mL to about 60 mg/mL of an ophthalmic therapeutic agent having a solubility of less than 1 mg/mL in water; wherein the weight ratio of (i) to (iii) is from about 2;
1 to about 8;
1.- View Dependent Claims (2, 3, 4, 5)
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6. A pharmaceutical solution comprising:
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(i) hydroxypropyl-β
-cyclodextrin, methyl-β
-cyclodextrin, randomly methylated-β
-cyclodextrin, ethylated-β
-cyclodextrin, triacetyl-β
-cyclodextrin, peracetylated-β
-cyclodextrin, carboxymethyl-β
-cyclodextrin, hydroxyethyl-β
-cyclodextrin, 2-hydroxy-3-(trimethylammonio)propyl-β
-cyclodextrin, glucosyl-β
-cyclodextrin, maltosyl-β
-cyclodextrin, sulfobutyl ether-β
-cyclodextrin, branched-β
-cyclodextrin, hydroxypropyl-γ
-cyclodextrin, randomly methylated-γ
-cyclodextrin, trimethyl-γ
-cyclodextrin, or a combination of two or more thereof,(ii) about 0.1% to about 5.0% of trehalose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, sodium hyaluronate, sodium alginate, polyethylene glycol, glycerin, propylene glycol, triacetin, N,N-dimethylacetamide, polyvinylpyrrolidone, pyrrolidone, or a combination of two or more thereof; and (iii) about 30 mg/mL to about 70 mg/mL of an ophthalmic therapeutic agent having a solubility of less than 1 mg/mL in water. - View Dependent Claims (7, 8, 9, 10, 11)
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- 12. A pharmaceutical solution comprising (i) a cyclodextrin, and (ii) about 30 mg/mL to about 90 mg/mL of an ophthalmic therapeutic agent having a solubility of less than 1 mg/mL in water.
Specification