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US-20260124221-A1 - INJECTABLE PHARMACEUTICAL COMPOSITION FOR TREATMENT OF BREAST CANCER

US20260124221A1US 20260124221 A1US20260124221 A1US 20260124221A1US-20260124221-A1

Abstract

The invention relates to an injectable composition comprising compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the injectable composition provides sustained release of compound I and thereby maintains blood plasma fulvestrant concentration. Also, the present invention used for method of treatment of breast cancer comprising compound of formula I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient.

Inventors

  • Parva Yogeshchandra Purohit
  • Ganesh Vishwanath SANGLE
  • Sandip Pareshbhai Mehta
  • Vishal Bharatbhai UNADKAT
  • Heta Nishil PANDYA
  • Sagar Laxmanbhai Vekariya

Assignees

  • KASHIV BIOSCIENCES, LLC

Dates

Publication Date
20260507
Application Date
20221029
Priority Date
20211029

Claims (20)

  1. 1 . An intramuscular composition comprising compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the composition administered to a subject in need thereof has concentration of compound I, pharmaceutically acceptable salts or solvates thereof from about 10 mg/ml to about 300 mg/ml.
  2. 2 . The composition according to claim 1 , wherein the concentration of compound I, pharmaceutically acceptable salts or solvates thereof; is selected from group consisting of about 20 mg/ml to about 300 mg/ml, about 30 mg/ml to about 300 mg/ml, about 40 mg/ml to about 300 mg/ml, about 50 mg/ml to about 300 mg/ml, about 60 mg/ml to about 300 mg/ml, about 70 mg/ml to about 300 mg/ml, about 80 mg/ml to about 300 mg/ml, about 90 mg/ml to about 300 mg/ml, about 100 mg/ml to about 300 mg/ml, about 110 mg/ml to about 300 mg/ml, about 120 mg/ml to about 300 mg/ml, about 130 mg/ml to about 300 mg/ml, about 140 mg/ml to about 300 mg/ml, about 150 mg/ml to about 300 mg/ml, about 160 mg/ml to about 300 mg/ml, about 170 mg/ml to about 300 mg/ml, about 180 mg/ml to about 300 mg/ml, about 190 mg/ml to about 300 mg/ml, about 200 mg/ml to about 300 mg/ml, about 210 mg/ml to about 300 mg/ml, about 220 mg/ml to about 300 mg/ml, about 230 mg/ml to about 300 mg/ml, about 240 mg/ml to about 300 mg/ml, about 250 mg/ml to about 300 mg/ml, about 260 mg/ml to about 300 mg/ml, about 270 mg/ml to about 300 mg/ml, about 280 mg/ml to about 300 mg/ml, or about 290 mg/ml to about 300 mg/ml.
  3. 3 . The composition according to claim 1 , wherein the concentration of compound I or pharmaceutically acceptable salts and solvates thereof; is selected from about 20 mg/ml, about 30 mg/ml, about 40 mg/ml, about 50 mg/ml, about 60 mg/ml, about 70, mg/ml, about 80 mg/ml, about 90 mg/ml, about 100 mg/ml, about 110 mg/ml, about 120 mg/ml, about 130 mg/ml, about 140 mg/ml, about 150 mg/ml, about 160 mg/ml, about 170 mg/ml, about 180 mg/ml, about 190 mg/ml, about 200 mg/ml, about 210 mg/ml, about 220 mg/ml, about 230 mg/ml, about 240 mg/ml, about 250 mg/ml, about 260 mg/ml, about 270 mg/ml, about 280 mg/ml, about 290 mg/ml, or about 300 mg/mi.
  4. 4 . An intramuscular composition comprising compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration for a desired period of time after injecting the composition comprising compound I, pharmaceutically acceptable salts or solvates thereof.
  5. 5 . The composition according to claim 4 , wherein the desired period of time to maintain blood plasma fulvestrant concentration is selected from at least one week, at least two weeks, at least three weeks, at least four weeks, at least one month, at least two months or at least three months.
  6. 6 . The composition according to claim 4 , wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration of at least 1 ng/ml for a desired period of time after injecting the composition comprising compound I, pharmaceutically acceptable salts or solvates thereof.
  7. 7 . The composition according to claim 6 , wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration selected from group consisting of at least 2 ng/ml, at least 3 ng/ml, at least 4 ng/ml, at least 5 ng/ml, at least 6 ng/ml, at least 7 ng/ml, at least 8 ng/ml, at least 9 ng/ml, at least 10 ng/ml, at least 11 ng/ml, at least 12 ng/ml, at least 13 ng/ml, at least 14 ng/ml, at least 15 ng/ml, at least 16 ng/ml, at least 17 ng/ml, at least 18 ng/ml, at least 19 ng/ml, at least 20 ng/ml, at least 21 ng/ml, at least 22 ng/ml, at least 23 ng/ml, at least 24 ng/ml, at least 25 ng/ml, at least 26 ng/ml, at least 27 ng/ml, at least 28 ng/ml, at least 29 ng/ml, at least 30 ng/ml, at least 31 ng/ml, at least 32 ng/ml, at least 33 ng/ml, at least 34 ng/ml, at least 35 ng/ml, at least 36 ng/ml, at least 37 ng/ml, at least 38 ng/ml, at least 39 ng/ml, at least 40 ng/ml, at least 41 ng/ml, at least 42 ng/ml, at least 43 ng/ml, at least 44 ng/ml, at least 45 ng/ml, at least 46 ng/ml, at least 47 ng/ml, at least 48 ng/ml, at least 49 ng/ml, at least 50 ng/ml, at least 51 ng/ml, at least 52 ng/ml, at least 53 ng/ml, at least 54 ng/ml, at least 55 ng/ml, at least 56 ng/ml, at least 57 ng/ml, at least 58 ng/ml, at least 59 ng/ml, at least 60 ng/ml, at least 61 ng/ml, at least 62 ng/ml, at least 63 ng/ml, at least 64 ng/ml, at least 65 ng/ml, at least 66 ng/ml, at least 67 ng/ml, at least 68 ng/ml, at least 69 ng/ml, at least 70 ng/ml, at least 71 ng/ml, at least 72 ng/ml, at least 73 ng/ml, at least 74 ng/ml, at least 75 ng/ml, at least 76 ng/ml, at least 77 ng/ml, at least 78 ng/ml, at least 79 ng/ml or at least 80 ng/ml, at least 81 ng/ml, at least 82 ng/ml, at least 83 ng/ml, at least 84 ng/ml, at least 85 ng/ml, at least 86 ng/ml, at least 87 ng/ml, at least 88 ng/ml, at least 89 ng/ml, at least 90 ng/ml, at least 91 ng/ml, at least 92 ng/ml, at least 93 ng/ml, at least 94 ng/ml, at least 95 ng/ml, at least 96 ng/ml, at least 97 ng/ml, at least 98, at least 99 ng/ml or at least 100 ng/ml.
  8. 8 . The composition according to claim 4 , wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration of about 1 ng/ml to about 500 ng/ml for a desired period of time after injecting the composition comprising compound I, pharmaceutically acceptable salts or solvates thereof.
  9. 9 . The composition according to claim 8 , wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration selected from group consisting of about 1 ng/ml to about 490 ng/ml, about 1 ng/ml to about 480 ng/ml, about 1 ng/ml to about 470 ng/ml, about 1 ng/ml to about 460 ng/ml, about 1 ng/ml to about 450 ng/ml, about 1 ng/ml to about 440 ng/ml, about 1 ng/ml to about 430 ng/ml, about 1 ng/ml to about 420 ng/ml, about 1 ng/ml to about 410 ng/ml, about 1 ng/ml to about 400 ng/ml, about 1 ng/ml to about 390 ng/ml, about 1 ng/ml to about 380 ng/ml, about 1 ng/ml to about 370 ng/ml, about 1 ng/ml to about 360 ng/ml, about 1 ng/ml to about 350 ng/ml, about 1 ng/ml to about 340 ng/ml, about 1 ng/ml to about 330 ng/ml, about 1 ng/ml to about 320 ng/ml, 1 ng/ml to about 310 ng/ml, about 1 ng/ml to about 300 ng/ml, about 1 ng/ml to about 290 ng/ml, about 1 ng/ml to about 280 ng/ml, about 1 ng/ml to about 270 ng/ml, about 1 ng/ml to about 260 ng/ml, about 1 ng/ml to about 250 ng/ml, about 1 ng/ml to about 240 ng/ml, about 1 ng/ml to about 230 ng/ml, about 1 ng/ml to about 220 ng/ml, about 1 ng/ml to about 210 ng/ml, about 1 ng/ml to about 200 ng/ml, about 1 ng/ml to about 190 ng/ml, about 1 ng/ml to about 180 ng/ml, about 1 ng/ml to about 170 ng/ml, about 1 ng/ml to about 160 ng/ml, about 1 ng/ml to about 150 ng/ml, about 1 ng/ml to about 140 ng/ml, about 1 ng/ml to about 130 ng/ml, about 1 ng/ml to about 120 ng/ml, about 1 ng/ml to about 110 ng/ml, or about 1 ng/ml to about 100 ng/ml.
  10. 10 . The composition according to claim 9 , wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration selected from group consisting of about 2 ng/ml to about 100 ng/ml, about 4 ng/ml to about 100 ng/ml, about 6 ng/ml to about 100 ng/ml, about 8 ng/ml to about 100 ng/ml, about 10 ng/ml to about 100 ng/ml, about 12 ng/ml to about 100 ng/ml, about 14 ng/ml to about 100 ng/ml, about 16 ng/ml to about 100 ng/ml, about 18 ng/ml to about 100 ng/ml, about 20 ng/ml to about 100 ng/ml, about 22 ng/ml to about 100 ng/ml, about 24 ng/ml to about 100 ng/ml, about 26 ng/ml to about 100 ng/ml, about 28 ng/ml to about 100 ng/ml or about 30 ng/ml to about 100 ng/ml.
  11. 11 . An intramuscular composition comprising compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the composition administered to a subject in need thereof has concentration of compound I, pharmaceutically acceptable salts or solvates thereof; from about 10 mg/ml to about 300 mg/ml and maintains blood plasma fulvestrant concentration of at least 1 ng/ml for desired period of time after injecting the composition comprising compound I, pharmaceutically acceptable salts or solvates thereof.
  12. 12 . The composition according to claim 11 , wherein the desired period of time is selected from group consisting of at least one week, at least two weeks, at least three weeks, at least four weeks, at least one month, at least two months or at least three months.
  13. 13 . An intramuscular composition comprising compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the composition administered to a subject in need thereof has concentration of compound I, pharmaceutically acceptable salts or solvates thereof; from about 10 mg/ml to about 300 mg/ml and maintains blood plasma fulvestrant concentration of about 1 ng/ml to about 500 ng/ml for desired period of time after injecting the composition comprising compound I, pharmaceutically acceptable salts or solvates thereof.
  14. 14 . The composition according to claim 13 , wherein the desired period of time is selected from group consisting of at least one week, at least two weeks, at least three weeks, at least four weeks, at least one month, at least two months or at least three months.
  15. 15 . The composition according to claim 1 , wherein at least one excipient is selected from oil, solvent, surfactant, antioxidant, polymer, or mixture thereof.
  16. 16 . A method for treating a hormonal dependent benign or malignant disease of the breast or reproductive tract, comprising administering intramuscularly to a subject in need of such treatment the composition having compound I pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the composition administered to a subject in need thereof has concentration of compound I, pharmaceutically acceptable salts or solvates thereof from about 10 mg/ml to about 300 mg/ml.
  17. 17 . The method of treatment according to claim 16 , wherein the concentration of compound I, pharmaceutically acceptable salts or solvates thereof; is selected from group consisting of about 20 mg/ml to about 300 mg/ml, about 30 mg/ml to about 300 mg/ml, about 40 mg/ml to about 300 mg/ml, about 50 mg/ml to about 300 mg/ml, about 60 mg/ml to about 300 mg/ml, about 70 mg/ml to about 300 mg/ml, about 80 mg/ml to about 300 mg/ml, about 90 mg/ml to about 300 mg/ml, about 100 mg/ml to about 300 mg/ml, about 110 mg/ml to about 300 mg/ml, about 120 mg/ml to about 300 mg/ml, about 130 mg/ml to about 300 mg/ml, about 140 mg/ml to about 300 mg/ml, about 150 mg/ml to about 300 mg/ml, about 160 mg/ml to about 300 mg/ml, about 170 mg/ml to about 300 mg/ml, about 180 mg/ml to about 300 mg/ml, about 190 mg/ml to about 300 mg/ml, about 200 mg/ml to about 300 mg/ml, about 210 mg/ml to about 300 mg/ml, about 220 mg/ml to about 300 mg/ml, about 230 mg/ml to about 300 mg/ml, about 240 mg/ml to about 300 mg/ml, about 250 mg/ml to about 300 mg/ml, about 260 mg/ml to about 300 mg/ml, about 270 mg/ml to about 300 mg/ml, about 280 mg/ml to about 300 mg/ml, or about 290 mg/ml to about 300 mg/ml.
  18. 18 . The method of treatment according to claim 17 , wherein the composition administered to a subject in need thereof has concentration of compound I, pharmaceutically acceptable salts or solvates thereof selected from about 20 mg/ml, about 30 mg/ml, about 40 mg/ml, about 50 mg/ml, about 60 mg/ml, about 70, mg/ml, about 80 mg/ml, about 90 mg/ml, about 100 mg/ml, about 110 mg/ml, about 120 mg/ml, about 130 mg/ml, about 140 mg/ml, about 150 mg/ml, about 160 mg/ml, about 170 mg/ml, about 180 mg/ml, about 190 mg/ml, about 200 mg/ml, about 210 mg/ml, about 220 mg/ml, about 230 mg/ml, about 240 mg/ml, about 250 mg/ml, about 260 mg/ml, about 270 mg/ml, about 280 mg/ml, about 290 mg/ml or about 300 mg/ml.
  19. 19 . A method for treating a hormonal dependent benign or malignant disease of the breast or reproductive tract comprising administering intramuscularly to a subject in need the intramuscular composition comprising compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration for a desired period of time after injecting the composition comprising compound I, pharmaceutically acceptable salts or solvates thereof
  20. 20 . The method of treatment according to claim 19 , wherein the composition administered to a subject in need thereof maintains blood plasma fulvestrant concentration of at least 1 ng/ml for desired period of time after injecting the composition comprising compound I, pharmaceutically acceptable salts or solvates thereof.

Description

FIELD OF INVENTION The invention relates to an injectable composition comprising compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient wherein the injectable composition provides sustained release of compound I and thereby maintains blood plasma concentration of fulvestrant. The composition of the present invention is intended for intravenous or intramuscular administration by injection containing the compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient. BACKGROUND OF THE INVENTION Well known estrogen receptor antagonist Fulvestrant is used for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. Fulvestrant has clinical therapeutic effect in a subjects failed in treatment with tamoxifen which has initiated a new way of treating hormone-sensitive breast cancer. Oestrogen deprivation is fundamental to the treatment of many benign and malignant diseases of the breast and reproductive tract. In premenopausal women, this is achieved by the ablation of ovarian function through surgical, radiotherapeutic, or medical means, and, in postmenopausal women, by the use of aromatase inhibitors. Fulvestrant shows, along with other steroidal based compounds, certain physical properties which make composition of these compound difficult. Fulvestrant is highly lipophilic molecule, even when compared with other steroidal compounds, and its aqueous solubility is extremely low. To maintains blood plasma Fulvestrant concentration, the release rate the amount of fulvestrant needed would require the composition volume to be large, at least 10 ml. This requires the doctor to inject an excessively large volume of fulvestrant composition significantly high for human therapy. A drug with poor solubility will often exhibit poor bioavailability and require administration of high dosages to attain therapeutically effective blood levels of the drug. Due to the poor solubility and oral bioavailability of fulvestrant, the drug is currently administered via intramuscular injection of an oil based Fulvestrant composition. The Faslodex™ product is approved for administration by intramuscular injection on days 1, 15, 29, and once monthly thereafter. This injection contains castor oil which can be viscous and can be painful at the time of injection. SUMMARY OF THE INVENTION The invention relates to an injectable composition comprising the compound I pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the injectable composition provides sustained release of compound I and thereby maintains blood plasma concentration of fulvestrant for a desired period of time. In one embodiment, the present invention provides an injectable composition containing the compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein an injectable sustained release composition is intended for intravenous or intramuscular administration. In one embodiment, the invention relates to an intramuscular composition comprising the compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient, wherein the injectable composition provides sustained release of compound I and thereby maintains blood plasma concentration of fulvestrant from about 1 ng/ml to about 100 ng/ml for a desired period of time. In one embodiment, the present invention provides a method for treating a hormonal dependent benign or malignant disease of the breast or reproductive tract comprising administering intramuscularly to a subject in need of such treatment the compound I, pharmaceutically acceptable salts or solvates thereof; and at least one pharmaceutically acceptable excipient. In one embodiment, wherein the hormonal dependent benign or malignant disease of the breast or reproductive tract is breast cancer. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1.—Mean±SD plasma concentration—time profile of fulvestrant following a single intramuscular administration of composition having compound I to female Sprague Dawley (SD) Rats. FIG. 2.—Mean±SD plasma concentration—time profile of Compound I following a single intramuscular administration to female Sprague Dawley (SD) Rats. FIG. 3.—Mean±SD plasma concentration—time profile of fulvestrant following a single intramuscular administration of composition having compound I to Female Beagle dogs. FIG. 4.—Mean±SD plasma concentration—time profile of Compound I following a single intramuscular administration to Female Beagle dogs. FIG. 5.—Mean±SD plasma concentration—time profile of Fulvestrant following a single intramuscular administration of composition having compound I to Female Beagle dogs. FIG. 6.—Mean±SD plasma concentration—time profile of