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
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
  • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
• • 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
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
• • 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
  • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels

Definitions

• the present invention relates to a stable transdermal gel composition
• a stable transdermal gel composition comprising Testosterone, a penetration enhancer, a gelling agent with pharmaceutically acceptable excipients. Further, the invention relates to the method of administering the said transdermal gel and its uses thereof.
• Testosterone is the primary endogenous male steroid hormone, produced primarily by the Leydig's cells in the testes in varying amounts throughout a person's lifespan.
• Testosterone's pharmacological uses include hormone replacement therapy in males with a congenital or acquired deficiency or absence of endogenous testosterone (resulting in e.g. hypogonadism, erectile dysfunction), and treatment of AIDS wasting syndrome in HIV infected men.
• Testosterone is not effective when taken oral ly or by injection, because it is susceptible to relatively rapid breakdown by the liver. Systemic administration of testosterone should therefore preferably be effected transdermally.
• transdermal delivery system in which testosterone is mentioned as one of a number of active agents includes U.S. Pat. No. 5,505,958, U.S. Pat. No. 5,744, 162; U.S. Pat. No. 5,891 ,463, U.S. Pat. No. 5,902,603.
• U. S. Pat. No. 4,804,541 teaches use of benzyl alcohol; WO 95/05 137 teaches a permeation enhancer composition, which includes benzyl alcohol, propylene glycol monolaurate and a C2-C6 alkanediol; U.S. Pat. No. 5,760,096 teaches use of a glycol and an alcohol : U.S. Pat. No. 5.885,565 reaches use of a sterol ; U.S. Pat. No. 6,3 19,91 3 teaches oleic acid; U .S. Pat. No. 6,562,369 and US 2003/01 29220 which teach use of an inorganic base as penetration enhancer; and US 2003/091620, which teaches a quaternary ammonium salt penetration enhancer.
• hydroalcohol ic gels for the transdermal del i very o f hormones such as testosterone or dihydrotestosterone.
• hydroalcoholic gels provide delivery rates which are generally not sufficiently high; therefore a large amount of gel must be applied to a relatively large skin surface area.
• Another drawback of the hydroalcohol ic gels is the sticky feel ing caused by the gelling agents remaining on the skin after the evaporation o f the alcohol .
• the commercial products Androgel.RTM. and Testim.TM. contain isopropyl myristate and pentadecalactone respectively, as penetration enhancers.
• the primary object of the invention is to provide a stable transdermal gel composition comprising testosterone, a penetration enhancer, a gelling agent with pharmaceutically acceptable excipients.
• the invention relates to a stable transdermal gel composition
• a stable transdermal gel composition comprising testosterone, a penetration enhancer, a gelling agent with pharmaceutically acceptable excipients.
• the invention relates to a stable transdermal gel composition
• a stable transdermal gel composition comprising testosterone with at least one gelling agent, at least one penetration enhancer, at least one pH adjusting agent, and at least one solvent.
• the invention relates to a stable transdermal testosterone gel, wherein the pH of the transdermal gel is greater than 4.5.
• the present invention relates to a stable transdermal gel composition
• a stable transdermal gel composition comprising testosterone with at least one gelling agent, at least one penetration enhancer, at least one pH adjusting agent, and at least one solvent.
• the "stable transdermal geT of the present invention refers to the testosterone gel with a trace amount of testosterone-related impurities (i.e. Impurities A, B, C, D, E, F, G, H, I, J) specified under the British Pharmacopoeia; Testosterone Monograph.
• the testosterone-related impurities of the stable transdermal gel are control led such that the total impurity is not more than 2%.
• the total impurity of the stable transdermal gel is not more than 1 %.
• the "gelling agent" of the present invention includes Carbopol, hydroxypropyl cellulose, hydroxy ethylcellulose, or other cellulosic ethers, other polymeric gelling agents such as xanthan gum, guar gum, and the l ike, fatty alcohols, fatty acids and their alkali salts and mixtures thereof, as well as inorganic gelling agents.
• the gelling agent of the present invention is Carbopol 980.
• the amount of gelling agent is not particularly critical, and can be selected to provide the desired product consistency or viscosity to al low for easy appl ication to the skin.
• amounts of gelling agent of up to about 5 weight percentages, preferably from about 0.1 weight percentages to about 2 weight percentages, of the Composition will provide the desired effect.
• the "penetration enhancer" of the present invention includes, non-limiting examples, such as isopropyl myristate, alkanolamine salts of fatty acids, alkyl benzene sulphonates, alkyl ether sulphates, alkyl sulphates, anionic surface-active agents, benzyl benzoate, benzyl salicylate, butyl benzoate, butyl laurate, butyl myrisite, butyl stearate, cationic surface-active agents, decyl methyl sul foxide, decyl oleate, dibutyl azelate, dibutyl phthalate, dibenzyl sebacate, dibutyl sebacate, dibutyl suberate, dibutyl succinate, dicapryl adipate, didecyl phthalate, diethylene glycol, diethyl sebacate, diethyl-m-toluamide, N,N-dimethyl
• the penetration enhancer of the present invention is isopropyl myristate.
• the "pH adjusting agent" of the present invention includes, non-limiting examples, such as triethanolamine, ammonium hydrox ide, calci um hydrox ide, trolamine, di- isopropanolamine, and tri-isopropanolamine.
• the pH adj usting agent of the present invention is triethanolamine.
• the "solvent" of the present invention includes, non-limiting examples, such as dehydrated alcohol (ethanol ), monohydric and polyhydric alcohols, water, isopropanol .
• the solvents of the present invention include dehydrated alcohol and water.
• the composition of the present i nvention may be formulated into any form normal ly employed for topical appl ication.
• the composition of the present invention can be, for example, in a form of a cream, an ointment, a paste, a gel, a lotion, a suspension, an aerosol, a spray, a foam, a scrum, a swab, a -pledget, a pad and a patch.
• the final form of a topical composition plays an important role in its efficacy and its usage convenience.
• gels, and particularly hydroalcoholic gels are highly advantageous for transdermal administration of testosterone drug.
• Example 1 Stable transdermal testosterone gel.
• the transdermal gel of the present invention is prepared by following steps as described below. Manufacturing Process:
• step (iii) Add triethanolamine to adjust pH of the viscous solution of step (ii) until a stable gel consistency is obtained.
• Example 2 Stable transdermal testosterone gel.
• Triethanolamine solution in puri fied water has to be used in batch manufacturing.
• the Example 2 is manufactured by the process as described in the Example 1.
• Example 3A Stability study of transdermal testosterone gel.
• Example 3B Stability study of transdermal testosterone gel.
• Example 3C Stability study of transdermal testosterone gel.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Epidemiology (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Dermatology (AREA)
• Inorganic Chemistry (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Publications (2)

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• 2015
  • 2015-02-23 WO PCT/IN2015/000101 patent/WO2015128876A2/en not_active Ceased
  • 2015-02-23 IN IN667MU2014 patent/IN2014MU00667A/en unknown
  • 2015-02-23 US US15/121,269 patent/US20160361321A1/en not_active Abandoned

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