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EP-3078368-B1 - STEROIDAL COMPOSITIONS

EP3078368B1EP 3078368 B1EP3078368 B1EP 3078368B1EP-3078368-B1

Inventors

  • GILIYAR, CHANDRASHEKAR
  • CHIDAMBARAM, NACHIAPPAN
  • PATEL, MAHESH V.
  • VENKATESHWARAN, SRINIVASAN

Dates

Publication Date
20260506
Application Date
20100108

Claims (11)

  1. A pharmaceutical composition formulated for oral administration which releases 80% or less of testosterone C 2 -C 13 alkyl ester after 30 minutes in an aqueous medium and which comprises: (i) a therapeutically effective amount of one or more testosterone C 2 -C 13 alkyl ester; and (ii) a pharmaceutically acceptable carrier which comprises a hydrophilic carrier, a lipophilic carrier and a solidifying agent, wherein the solidifying agent is a polyethylene glycol.
  2. The pharmaceutical composition of claim 1, wherein the testosterone C 2 -C 13 alkyl ester is testosterone undecanoate.
  3. The pharmaceutical composition of claim 1 or 2, wherein the solidifying agent is high molecular weight polyethylene glycol, preferably PEG 8000.
  4. The pharmaceutical composition of any one of claims 1 to 3, wherein the hydrophilic carrier is a hydrogenated and polyoxylated castor oil.
  5. The pharmaceutical composition of any one of claims 1 to 4, wherein the lipophilic carrier is a monoglyceride, a diglyceride, a Vitamin E compound, or a combination thereof, wherein the lipophilic carrier is preferably a monoglyceride.
  6. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises 10 mg to 1000 mg of testosterone C 2 -C 13 alkyl ester.
  7. The pharmaceutical composition of claim 1, releasing 50% or less of the testosterone alkyl ester after 6 hours in an aqueous medium.
  8. The pharmaceutical composition of claim 1, wherein the composition is formulated to provide a solid, a semi-solid, a gel, a jelly or a paste.
  9. The pharmaceutical composition of claim 1 for use in the treatment of androgen deficiency in an individual in need thereof.
  10. The pharmaceutical composition for use of claim 9, wherein the pharmaceutical composition is for administration with a meal.
  11. The pharmaceutical composition for use of claim 9, wherein the medicament is for administration b.i.d. or q.d.

Description

BACKGROUND OF THE INVENTION Testosterone is an androgenic compound crucial for human health. Certain embodiments of the invention and reference embodiments described herein generally relate to compositions for the administration of testosterone, testosterone analogs, other steroids and related compounds. SUMMARY OF THE INVENTION The present invention relates to a pharmaceutical composition formulated for oral administration which releases 80% or less of testosterone C2-C13 alkyl ester after 30 minutes in an aqueous medium and which comprises: (i) a therapeutically effective amount of one or more testosterone C2-C13 alkyl ester; and(ii) a pharmaceutically acceptable carrier which comprises a hydrophilic carrier, a lipophilic carrier and a solidifying agent, wherein the solidifying agent is a polyethylene glycol. The invention further relates to said pharmaceutical composition, wherein the testosterone C2-C13 alkyl ester is testosterone undecanoate. The invention further relates to said pharmaceutical composition, wherein the solidifying agent is high molecular weight polyethylene glycol, preferably PEG 8000. The invention further relates to said pharmaceutical composition, wherein the hydrophilic carrier is a hydrogenated and polyoxylated castor oil. The invention further relates to said pharmaceutical composition, wherein the lipophilic carrier is a monoglyceride, a diglyceride, a Vitamin E compound, or a combination thereof, wherein the lipophilic carrier is preferably a monoglyceride. The invention further relates to said pharmaceutical composition, wherein the pharmaceutical composition comprises 10 mg to 1000 mg of testosterone C2-C13 alkyl ester. The invention further relates to said pharmaceutical composition, releasing 50% or less of the testosterone alkyl ester after 6 hours in an aqueous medium. The invention further relates to said pharmaceutical composition, wherein the composition is formulated to provide a solid, a semi-solid, a gel, a jelly or a paste. The invention further relates to said pharmaceutical composition for use in the treatment of androgen deficiency in an individual in need thereof. The invention further relates to said pharmaceutical composition for use, wherein the pharmaceutical composition is for administration with a meal. The invention further relates to said pharmaceutical composition for use, wherein the medicament is for administration b.i.d. or q.d. The present invention as well as reference embodiments disclosed herein will be described in more detail in the following. Disclosed in certain embodiments herein is a delayed release oral dosage form comprising a therapeutically effective amount of one or more testosterone alkyl ester and at least one pharmaceutically acceptable carrier, wherein a single dose of the delayed release oral dosage form provides a mean plasma Cmax of testosterone that is at least 5%, at least 10% or at least 15% lower than the mean plasma Cmax of testosterone that is provided by a single dose of an immediate release oral dosage form having an identical amount of the testosterone alkyl ester. In some embodiments, disclosed herein is a delayed release oral dosage form, wherein a single dose of the delayed release oral dosage form provides a mean plasma Cmax of testosterone alkyl ester that is at least 5%, at least 10% or at least 15% lower than the mean plasma Cmax of testosterone alkyl ester that is provided by a single dose of an immediate release oral dosage form having an identical amount of the testosterone alkyl ester. In certain embodiments, a single dose of the delayed release oral dosage form described herein provides a mean plasma Cmax of that is at least 5% lower than the mean plasma Cmax of dihydrotestosterone provided by a single dose of an immediate release oral dosage form having an identical amount of the testosterone alkyl ester. In some embodiments, a delayed release oral dosage form described herein provides a mean plasma Cmax at steady state of testosterone alkyl ester that is at least 5%, at least 10% or at least 15% lower than the mean plasma Cmax of testosterone alkyl ester at steady state provided by an immediate release oral dosage form having an identical amount of the testosterone alkyl ester. In certain embodiments, a delayed release oral dosage form described herein provides a fluctuation index of testosterone at steady state that is at least 5%, or at least 10% lower than a fluctuation index of testosterone at steady state of an immediate release oral dosage form having an identical amount of the testosterone alkyl ester. In some embodiments, a delayed release oral dosage form described herein provides a fluctuation index of testosterone alkyl ester at steady state that is at least 5%, or at least 10% lower than a fluctuation index of testosterone alkyl ester at steady state of an immediate release oral dosage form having an identical amount of the testosterone alkyl ester. In some embodiments, a single dose of the de