WO2000059512A1 - Formulation comprising testosteron undecanoate and castor oil - Google Patents

Formulation comprising testosteron undecanoate and castor oil Download PDF

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Publication number
WO2000059512A1
WO2000059512A1 PCT/EP2000/002677 EP0002677W WO0059512A1 WO 2000059512 A1 WO2000059512 A1 WO 2000059512A1 EP 0002677 W EP0002677 W EP 0002677W WO 0059512 A1 WO0059512 A1 WO 0059512A1
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WO
WIPO (PCT)
Prior art keywords
castor oil
liquid carrier
testosterone undecanoate
pharmaceutical formulation
weight
Prior art date
Application number
PCT/EP2000/002677
Other languages
French (fr)
Inventor
Henrik Nijs De
Susan Chandler
Elizabeth Anne Perry
Josephine Joan Christine Ferdinando
Original Assignee
Akzo Nobel N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to EP00920588A priority Critical patent/EP1189620B1/en
Priority to MXPA01009919A priority patent/MXPA01009919A/en
Application filed by Akzo Nobel N.V. filed Critical Akzo Nobel N.V.
Priority to NZ514290A priority patent/NZ514290A/en
Priority to IL14552400A priority patent/IL145524A0/en
Priority to JP2000609075A priority patent/JP2002541111A/en
Priority to AU41111/00A priority patent/AU768537B2/en
Priority to PL00351259A priority patent/PL195163B1/en
Priority to BR0009465-0A priority patent/BR0009465A/en
Priority to SK1372-2001A priority patent/SK286071B6/en
Priority to PT00920588T priority patent/PT1189620E/en
Priority to DE60011771T priority patent/DE60011771T2/en
Priority to CA002366856A priority patent/CA2366856C/en
Priority to HU0200453A priority patent/HU229455B1/en
Priority to AT00920588T priority patent/ATE269708T1/en
Publication of WO2000059512A1 publication Critical patent/WO2000059512A1/en
Priority to IL145524A priority patent/IL145524A/en
Priority to NO20014718A priority patent/NO329420B1/en
Priority to HK02105288A priority patent/HK1043544A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/16—Masculine contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
    • A61P5/26—Androgens

Definitions

  • the invention is in the field of androgen formulations for oral administration.
  • Such formulations have acquired new attention in view of the development of preparations for male contraception and male HRT (hormone replacement therapy).
  • the androgen may particularly be used as a replacement for endogenic testosterone.
  • androgen is administered in order to relieve the undesired effects of the (partial) androgen-deficiency which may result of age.
  • Androgens can also be used in the female, e.g. as androgen replacement therapy in postmenopausal women.
  • Oral preparations of androgens are rare, the only oral natural testosterone product available on the market being a solution of testosterone undecanoate (TU) in oleic acid.
  • TU testosterone undecanoate
  • This product which is known in various countries under various tradenames, e.g. Andriol® or Restandol®, is a soft-gelatine capsule formulation containing 40 mg of TU dissolved in oleic acid.
  • 3-4 should be administered daily.
  • a regimen involving such a large number of separate administrations is not very suitable for the practical use of TU as an acceptable HRT product, let alone that it would be accepted this way in contraception.
  • the invention seeks to solve the problem of providing an orally active androgen formulation which is well absorbed in the human body. Particularly, the invention seeks to provide a formulation of TU which has a higher strength than the known TU formulation referred to above.
  • the invention provides a pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate as an active ingredient dissolved in a pharmaceutically acceptable liquid carrier, wherein the liquid carrier is castor oil.
  • the liquid carrier is castor oil.
  • castor oil can be the sole liquid carrier, it is also possible to combine castor oil with other liquid carriers. It is desired, however, that castor oil is the main component of the liquid carrier, i.e. it makes up more than 50% by weight of said carrier.
  • the invention in one aspect, therefore includes a pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate as the active ingredient dissolved in a pharmaceutically acceptable liquid carrier in a concentration of 200-250 mg/ml.
  • the invention also includes the use of testosterone undecanoate for the manufacture of a medicine in the form of an oral solution, wherein testosterone undecanoate is dissolved in a pharmaceutically acceptable liquid carrier, characterised in that the liquid carrier comprises at least 50% by weight of castor oil.
  • the invention is a method of treatment comprising the administration of testosterone undecanoate to a human male or female in need of androgen supplementation, characterised in that the testosterone undecanoate is administered orally in the form of a solution in a carrier, the latter comprising at least 50% by weight of castor oil.
  • the capsules should be taken preferably during or just after a meal.
  • the capsules include additives such as disclosed in WO 97/40823 and WO 95/24893. It is most preferred to base the formulation on a particular combination of castor oil and a lipophilic surfactant, as such a combination provides a liquid vehicle for dissolving TU resulting in the most stable formulations which best promote lymphatic absorption.
  • the preferred formulation is one in which TU is dissolved in a liquid vehicle which comprises of from 50 to 70% by weight of castor oil, and from 30 to 50% by weight of a lipophilic surfactant having an HLB ⁇ 10, and, optionally, from 0 to 20% by weight of a hydrophilic surfactant, wherein the liquid vehicle is substantially free from the free fatty acid and contains less than 10% by weight of ethanol.
  • a liquid vehicle which comprises of from 50 to 70% by weight of castor oil, and from 30 to 50% by weight of a lipophilic surfactant having an HLB ⁇ 10, and, optionally, from 0 to 20% by weight of a hydrophilic surfactant, wherein the liquid vehicle is substantially free from the free fatty acid and contains less than 10% by weight of ethanol.
  • Suitable lipophilic surfactants having an HLB ⁇ 10 are known to the person skilled in the art.
  • mono- and/or diglycerides of fatty acids as well as mono-
  • the lipophilic surfactant is preferably used in an amount in the range of from 35 to 45% by weight of the liquid vehicle.
  • a preferred lipophilic surfactant is lauroglycol (propylene glycol monolaurate).
  • the optional hydrophilic surfactants are also known to the person skilled in the art. Any pharmaceutically acceptable hydrophilic surfactant (i.e., having an HLB value greater than 10) may be used in the present invention.
  • the formulations may contain minor amounts of other additives, e.g., anti-oxidants, such as d- ⁇ -tocopherol, BHA, BHT; co-solvents such as ethanol and Transcutol (diethylene glycol monoethylether), plasticisers, such as propylene glycol, etc.
  • anti-oxidants such as d- ⁇ -tocopherol, BHA, BHT
  • co-solvents such as ethanol and Transcutol (diethylene glycol monoethylether), plasticisers, such as propylene glycol, etc.
  • the formulations of the invention may readily be prepared by known methods, e.g. as described in WO 95/24893.
  • the capsules encapsulating the formulations can be made by known techniques. Gelatine softgels, as with Andriol®, are preferred, but the wall of the capsule may be made from any pharmaceutically acceptable softshell or hardshell material.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Diabetes (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Fats And Perfumes (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

Disclosed is a pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate as an active ingredient dissolved in a pharmaceutically acceptable liquid carrier, characterised in that the liquid carrier comprises at least 50 % by weight of castor oil. The choice of castor oil as the liquid carrier, in conjunction with the choice of testosterone undecanoate as the androgen, makes for a solution which can comprise about 200-250 mg/ml of TU. This is a novel achievement for any orally administerable solution of testosterone. The solution may also contain a lipophilic surfactant such as lauroglycol.

Description

FORMULATION COMPRISING TESTOSTERON UNDECANOATE AND CASTOR OIL
The invention is in the field of androgen formulations for oral administration. Such formulations have acquired new attention in view of the development of preparations for male contraception and male HRT (hormone replacement therapy). In both cases the androgen may particularly be used as a replacement for endogenic testosterone. Thus, e.g., in male HRT, androgen is administered in order to relieve the undesired effects of the (partial) androgen-deficiency which may result of age. Androgens can also be used in the female, e.g. as androgen replacement therapy in postmenopausal women.
Oral preparations of androgens are rare, the only oral natural testosterone product available on the market being a solution of testosterone undecanoate (TU) in oleic acid. This product, which is known in various countries under various tradenames, e.g. Andriol® or Restandol®, is a soft-gelatine capsule formulation containing 40 mg of TU dissolved in oleic acid. To achieve and maintain acceptable testosterone levels in the blood, 3-4 such capsules should be administered daily. A regimen involving such a large number of separate administrations is not very suitable for the practical use of TU as an acceptable HRT product, let alone that it would be accepted this way in contraception.
The invention seeks to solve the problem of providing an orally active androgen formulation which is well absorbed in the human body. Particularly, the invention seeks to provide a formulation of TU which has a higher strength than the known TU formulation referred to above.
To meet these and other objectives, the invention provides a pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate as an active ingredient dissolved in a pharmaceutically acceptable liquid carrier, wherein the liquid carrier is castor oil. Although, in one embodiment, castor oil can be the sole liquid carrier, it is also possible to combine castor oil with other liquid carriers. It is desired, however, that castor oil is the main component of the liquid carrier, i.e. it makes up more than 50% by weight of said carrier.
The choice of castor oil as the liquid carrier, in conjunction with the choice of testosterone undecanoate as the androgen, makes for a solution which can comprise about 200-250 mg of TU per ml. This amounts to approximately 127 to 137 mg of testosterone per ml. This is a novel achievement for any orally administerable solution of testosterone in any form. The invention, in one aspect, therefore includes a pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate as the active ingredient dissolved in a pharmaceutically acceptable liquid carrier in a concentration of 200-250 mg/ml.
It is noted that Exp.Clin.Endocrinol.Diabetis 105 Suppl.1,21,1997 and Eur. J. Endocrinol.123:514-9 (195) make mention of an injectable solution of 250 mg/ml of TU in castor oil. This, however, does not at all lead the way to the possibility of achieving oral administration of a similar level of TU. These are separate fields of pharmaceutical formulation, and, moreover, an injection directly into the muscle cannot be used as a model for administration via the oral route. In addition, it is all the more surprising that notably castor oil is a suitable carrier for this type of administration, since its normal capacity is that of a laxative. This, of course, is a use completely opposite to that underlying the present invention, wherein the goal is to make something (in this case TU) enter and be absorbed into the human body rather than make it leave the body by inducing excretion. Hence it is fully unexpected that castor oil turns out to be a highly suitable carrier for the oral administration of TU, which is absorbed well.
The invention also includes the use of testosterone undecanoate for the manufacture of a medicine in the form of an oral solution, wherein testosterone undecanoate is dissolved in a pharmaceutically acceptable liquid carrier, characterised in that the liquid carrier comprises at least 50% by weight of castor oil. In yet another aspect, the invention is a method of treatment comprising the administration of testosterone undecanoate to a human male or female in need of androgen supplementation, characterised in that the testosterone undecanoate is administered orally in the form of a solution in a carrier, the latter comprising at least 50% by weight of castor oil. In order to achieve optimal administration of TU, the capsules should be taken preferably during or just after a meal.
In all of the above aspects, it is preferred that, in addition to the TU and the castor oil, the capsules include additives such as disclosed in WO 97/40823 and WO 95/24893. It is most preferred to base the formulation on a particular combination of castor oil and a lipophilic surfactant, as such a combination provides a liquid vehicle for dissolving TU resulting in the most stable formulations which best promote lymphatic absorption. Thus the preferred formulation is one in which TU is dissolved in a liquid vehicle which comprises of from 50 to 70% by weight of castor oil, and from 30 to 50% by weight of a lipophilic surfactant having an HLB <10, and, optionally, from 0 to 20% by weight of a hydrophilic surfactant, wherein the liquid vehicle is substantially free from the free fatty acid and contains less than 10% by weight of ethanol. Suitable lipophilic surfactants having an HLB <10 are known to the person skilled in the art. These include mono- and/or diglycerides of fatty acids as well as mono- and or diglycerides of fatty acids in which the remaining free OH groups of glycerol can be esterified, such as the acetic, succinic, lactic, citric and or tartaric esters thereof; propylene glycol mono- and or di-esters of fatty acids; ethoxylates of castor oil or of hydrogenated castor oil (low ethoxylate content, HLB < 10); acid and ester ethoxylates formed by reacting ethylene oxide with fatty acids or glycerol esters of fatty acids; sorbitan esters of fatty acids; unsaturated polyglycolised glycerides (if HLB < 10); alcohol ethoxylates (if HLB <10); polyoxyethylene-polyoxypropylene co-polymers and block copolymers (if HLB < 10). The lipophilic surfactant is preferably used in an amount in the range of from 35 to 45% by weight of the liquid vehicle. A preferred lipophilic surfactant is lauroglycol (propylene glycol monolaurate). The optional hydrophilic surfactants are also known to the person skilled in the art. Any pharmaceutically acceptable hydrophilic surfactant (i.e., having an HLB value greater than 10) may be used in the present invention.
The formulations may contain minor amounts of other additives, e.g., anti-oxidants, such as d-α-tocopherol, BHA, BHT; co-solvents such as ethanol and Transcutol (diethylene glycol monoethylether), plasticisers, such as propylene glycol, etc.
The formulations of the invention may readily be prepared by known methods, e.g. as described in WO 95/24893. The capsules encapsulating the formulations can be made by known techniques. Gelatine softgels, as with Andriol®, are preferred, but the wall of the capsule may be made from any pharmaceutically acceptable softshell or hardshell material.
Methods of softgel encapsulation are disclosed in Theory and Practice of Industrial
Pharmacy - Lachman & Leibermann, 2nd Edition, published by Henry Kimpton Publishers, London. Methods of liquid-fill hardshell encapsulation are disclosed in Hardcapsules -
Development and Technology - Edited by K. Ridgeway, published by Pharmaceutical Press
1987.
The invention will be further illustrated hereinafter with reference to the Example.
EXAMPLE
The following ingredients are added to a suitable mixer (Unimix) and heated to 40°C: Castor oil BP 53 parts by weight
Lauroglycol FCC 35 parts by weight
Testosteron undecanoate 12 parts by weight
After complete dissolution the resulting solution is filled into soft gelatine capsules of 330 ml using standard equipment. A stable formulation is obtained, from which TU is absorbed well orally.

Claims

Claims:
1. A pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate as an active ingredient dissolved in a pharmaceutically acceptable liquid carrier, characterised in that the liquid carrier comprises at least 50% by weight of castor oil.
2. A pharmaceutical formulation according to claim 1, characterised in that the sole liquid carrier is castor oil.
3. A pharmaceutical formulation according to claim 1, characterised in that the liquid carrier further comprises from 30 to50% by weight of a lipophilic surfactant having an HLB value below 10.
4. A pharmaceutical formulation according to claim 3, characterised in that the lipophilic surfactant is lauroglycol.
5. A pharmaceutical formulation according to any one of the preceding claims, characterised in that testosterone undecanoate is dissolved in a concentration of 200-250 mg/ml.
6. The use of testosterone undecanoate for the manufacture of a medicine in the form of an oral solution, wherein testosterone undecanoate is dissolved in a in a pharmaceutically acceptable liquid carrier, characterised in that the liquid carrier comprises at least 50% by weight of castor oil.
7. A method of treatment comprising the administration of testosterone undecanoate to a human male in need of androgen supplementation, characterised in that the testosterone undecanoate is administered orally in the form of a solution in a carrier, the latter comprising at least 50% by weight of castor oil. A pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanoate as the active ingredient dissolved in a pharmaceutically acceptable liquid carrier in a concentration of 200-250 mg/ml.
PCT/EP2000/002677 1999-04-01 2000-03-27 Formulation comprising testosteron undecanoate and castor oil WO2000059512A1 (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
HU0200453A HU229455B1 (en) 1999-04-01 2000-03-27 Formulation comprising testosteron undecanoate and castor oil
BR0009465-0A BR0009465A (en) 1999-04-01 2000-03-27 Pharmaceutical formulation in the form of a capsule for oral administration, use of testosterone undecanoate, and, treatment method comprising the administration of testosterone undecanoate to a man in need of androgen supplementation
NZ514290A NZ514290A (en) 1999-04-01 2000-03-27 Formulation comprising testosterone undecanoate and castor oil
IL14552400A IL145524A0 (en) 1999-04-01 2000-03-27 Formulation comprising testosterone undecanoate and castor oil
JP2000609075A JP2002541111A (en) 1999-04-01 2000-03-27 Formulation containing testosterone undecanoate and castor oil
AU41111/00A AU768537B2 (en) 1999-04-01 2000-03-27 Formulation comprising testosteron undecanoate and castor oil
PL00351259A PL195163B1 (en) 1999-04-01 2000-03-27 Composition containing testosterone undexanate and castor oil
EP00920588A EP1189620B1 (en) 1999-04-01 2000-03-27 Formulation comprising testosteron undecanoate and castor oil
SK1372-2001A SK286071B6 (en) 1999-04-01 2000-03-27 Pharmaceutical composition comprising testosterone undecanoate
DE60011771T DE60011771T2 (en) 1999-04-01 2000-03-27 FORMULA CONTAINING TESTOSTEONUNDECANOAT AND RISIN OIL
PT00920588T PT1189620E (en) 1999-04-01 2000-03-27 FORMULATION THAT UNDECANOATES COMPOSITION OF TESTOSTERONE AND OIL OF RICINO
CA002366856A CA2366856C (en) 1999-04-01 2000-03-27 Formulation comprising testosteron undecanoate and castor oil
MXPA01009919A MXPA01009919A (en) 1999-04-01 2000-03-27 Formulation comprising testosteron undecanoate and castor oil.
AT00920588T ATE269708T1 (en) 1999-04-01 2000-03-27 FORMULATION CONTAINING TESTOSTEONUNDECANOATE AND CASCIN OIL
IL145524A IL145524A (en) 1999-04-01 2001-09-20 Formulation comprising testosterone undecanoate and castor oil
NO20014718A NO329420B1 (en) 1999-04-01 2001-09-28 Formulation containing testosterone undecanoate and castor oil and their use in the manufacture of a medicament for the treatment of disease
HK02105288A HK1043544A1 (en) 1999-04-01 2002-07-17 Formulation comprising testosteron undecanoate andcastor oil.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP99302581.6 1999-04-01
EP99302581 1999-04-01

Publications (1)

Publication Number Publication Date
WO2000059512A1 true WO2000059512A1 (en) 2000-10-12

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Application Number Title Priority Date Filing Date
PCT/EP2000/002677 WO2000059512A1 (en) 1999-04-01 2000-03-27 Formulation comprising testosteron undecanoate and castor oil

Country Status (27)

Country Link
EP (1) EP1189620B1 (en)
JP (1) JP2002541111A (en)
KR (1) KR100666016B1 (en)
CN (1) CN1155385C (en)
AT (1) ATE269708T1 (en)
AU (1) AU768537B2 (en)
BR (1) BR0009465A (en)
CA (1) CA2366856C (en)
CZ (1) CZ298573B6 (en)
DE (1) DE60011771T2 (en)
DK (1) DK1189620T3 (en)
ES (1) ES2222199T3 (en)
HK (1) HK1043544A1 (en)
HU (1) HU229455B1 (en)
ID (1) ID30481A (en)
IL (2) IL145524A0 (en)
MX (1) MXPA01009919A (en)
NO (1) NO329420B1 (en)
NZ (1) NZ514290A (en)
PL (1) PL195163B1 (en)
PT (1) PT1189620E (en)
RU (1) RU2246296C2 (en)
SK (1) SK286071B6 (en)
TR (1) TR200102769T2 (en)
TW (1) TWI280124B (en)
WO (1) WO2000059512A1 (en)
ZA (1) ZA200107781B (en)

Cited By (22)

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EP1173153A1 (en) * 1999-04-01 2002-01-23 R.P. Scherer Corporation Oral pharmaceutical compositions containing long-chain triglycerides and lipophilic surfactants
US6652880B1 (en) 1999-04-01 2003-11-25 R.P. Scherer Technologies, Inc. Oral pharmaceutical compositions containing long-chain triglycerides and liphophilic surfactants
EP1457208A1 (en) * 2003-03-14 2004-09-15 Schering Aktiengesellschaft Methods and pharmaceutical compositions for reliable achievement of acceptable serum testosterone levels
EP1530965A1 (en) * 2003-11-11 2005-05-18 Mattern, Udo Controlled release delivery system of sexual hormones for nasal application
EP1871384A2 (en) * 2005-04-15 2008-01-02 Clarus Therapeutics, Inc. Pharmaceutical delivery systems for hydrophobic drugs and compositions comprising same
EP2373295A2 (en) * 2009-01-08 2011-10-12 Lipocine Inc. Steroidal compositions
US8492369B2 (en) 2010-04-12 2013-07-23 Clarus Therapeutics Inc Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
US8609043B2 (en) 2004-12-28 2013-12-17 M & P Patent Aktiengesellschaft Use of a container of an inorganic additive containing plastic material
US8784869B2 (en) 2003-11-11 2014-07-22 Mattern Pharma Ag Controlled release delivery system for nasal applications and methods of treatment
US9186320B2 (en) 2006-10-04 2015-11-17 Mattern Pharma Ag Controlled release delivery system for nasal application of neurotransmitters
US9205057B2 (en) 2010-11-30 2015-12-08 Lipocine Inc. High-strength testosterone undecanoate compositions
US9358241B2 (en) 2010-11-30 2016-06-07 Lipocine Inc. High-strength testosterone undecanoate compositions
US9498485B2 (en) 2014-08-28 2016-11-22 Lipocine Inc. Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters
US9757388B2 (en) 2011-05-13 2017-09-12 Acerus Pharmaceuticals Srl Intranasal methods of treating women for anorgasmia with 0.6% and 0.72% testosterone gels
US9925200B2 (en) 2014-06-17 2018-03-27 Merck Sharp & Dohme B.V. Stable formulations of testosterone undecanoate
US10111888B2 (en) 2011-05-13 2018-10-30 Acerus Biopharma Inc. Intranasal 0.15% and 0.24% testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder
US10561615B2 (en) 2010-12-10 2020-02-18 Lipocine Inc. Testosterone undecanoate compositions
US10668084B2 (en) 2011-05-13 2020-06-02 Acerus Biopharma Inc. Intranasal lower dosage strength testosterone gel formulations and use thereof for treating anorgasmia or hypoactive sexual desire disorder
US11090312B2 (en) 2013-03-15 2021-08-17 Acerus Biopharma Inc. Methods of treating hypogonadism with transnasal testerosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event
US11433083B2 (en) 2010-11-30 2022-09-06 Lipocine Inc. High-strength testosterone undecanoate compositions
US11559530B2 (en) 2016-11-28 2023-01-24 Lipocine Inc. Oral testosterone undecanoate therapy
US11707467B2 (en) 2014-08-28 2023-07-25 Lipocine Inc. (17-ß)-3-oxoandrost-4-en-17YL tridecanoate compositions and methods of their preparation and use

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GB0818473D0 (en) 2008-10-08 2008-11-12 Probio Nutraceuticals As Composition
ES2525520T3 (en) * 2010-04-12 2014-12-26 Clarus Therapeutics, Inc. Oral testosterone ester formulations and methods to treat testosterone deficiency with them
GB201006200D0 (en) * 2010-04-14 2010-06-02 Ayanda As Composition
HUE037660T2 (en) * 2011-01-26 2018-09-28 Allergan Inc Androgen composition for treating an ophthalmic condition
WO2015193380A2 (en) * 2014-06-19 2015-12-23 Solural Pharma ApS Solid oral dosage form of lipophilic compounds
US20160193225A1 (en) * 2014-08-29 2016-07-07 Lipocine Inc. (17-ß)-3-OXOANDROST-4-EN-17-YL UNDECANOATE COMPOSITIONS AND METHODS OF THEIR PREPARATION AND USE

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