Title of Invention

FORMULATION COMPRISING TESTOSTERON UNDECANOATE AND CASTOR OIL

Abstract

ABSTRACT IN/PCT/2001 /Ol 345/CHE Formulation comprising testosteron undecanoate and castor oil The present invention relates to 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, characterized in that the liquid carrier comprises at least 50 % by weight of castor oil.

Full Text

The invention is in the field of androgen formutation for oral adnimistration. Such formulations have acquired new attertion in view of the development of preparations for male contraception and male HRT (hnrmnne replacement therapy), m 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 undesrred effects of the (partiaQ androgeo-deficiency which may result of age. Androgens can also be used in me female, e.g. as androgen replacement therapy in postmenopausal women. Oral preparations of androgens are rare, the only oral natural testosteiuije 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, eg. Andriol* or Restandol®, is a sonVgelatme capsule fhrnrnlatina containing 40 mg of TU dissolved in oleic acid. To achieve and miniun acceptable testosterone levels in the blood, 3-4 such capsules should be administered dairy. A leghneniirvDlvingsiKhalargeiiumbef of seosnite aili nil ligations is not very suitable for the practical use of TU as an acceptable HRT product, let alone mat it would be accepted mis way in contraception. The invention seeks to solve the problem of providing an orally active androgen immolation which is well absorbed in the human body. Particularly, the mvennon seeks to provide a fbmuilatiott 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 adnmnstrauon coanprismg testosterone undecanoate as an active ingredient dissolved in a pharmaceuticaOy acceptable liquid carrier, wherein the liquid carrier is castor ofl. Although, in one embodiment, castor oO can be the sole liquid carrier, it is also possible to combine castor ml 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 man 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 admmisterable solution of testosterone in any form. The invention, in one aspect, therefore includes a pharmaceutical fonnulation in the form of a capsule for oral admmistratiori 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 mat Exp.Clin.EndocrinolJHabetis 105 Suppl.1,21,1997 and Eur. J. Endocrinol.l23:514-9 (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 fonnulation, and, moreover, an injection directly into the muscle cannot be used as a model for administration via the oral route, hi 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 mat 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 me 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 adrninistration of testosterone undecanoate to a human male or d-a-tocopheroL BHA, BHT; co-solvents such as ethanol and Ttanscutol (diethylene glycol inonoethylether), 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 file formulations can be made by known techniques. Gelatine softgels, as with Andriol®, are preferred, but flu wall of the capsule may be made from any phannaceuticalry acceptable softshell or hardshell material Methods of softgel encapsulation are disclosed in Theory and Practice of Industrial Pharmacy - Lacfrman & Leibennann, 2"d 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 die Example. EXAMPLE The following ingredients are added to a suitable mixer (Unhnix) and heated to 40°C; Castor oil BP 53 parts by weight Laurogtycol FCC 35 parts by weight Testosteron undecanoate 12 parts by weight Aner complete dissolution the resulting solution is filled info soft gelatine capsules of 330 ml using standard equipment A stable formulation is obtained, from which TU is absorbed well orally. WE CLAIM: 1. A pharmaceutical formulation in the form of a capsule for oral administration comprising testosterone undecanote as an active ingredient dissolved in a pharmaceutically acceptable liquid carrier, characterized in that the liquid carrier comprises at least 50% by weight of castor oil and optionally from 30% to 50% by weight of lipophillic surfactant. 2. The pharmaceutical formulation as claimed in claim 1, wherein the sole liquid carrier is castor oil. 3. The pharmaceutical formulation as claimed in claim 3, wherein the lipophillic surfactant is lauroglycol. 4. The pharmaceutical formulation as claimed in any one of the preceeding claims, wherein tosterone undecanoate is dissolved in a concentration of 200-250 mg/ml.

Documents:

in-pct-2001-1345-che abstract.pdf

in-pct-2001-1345-che abstrcat-duplicate.pdf

in-pct-2001-1345-che assignment.pdf

in-pct-2001-1345-che claims-duplicate.pdf

in-pct-2001-1345-che claims.pdf

in-pct-2001-1345-che correspondence-others.pdf

in-pct-2001-1345-che correspondence-po.pdf

in-pct-2001-1345-che description(complete)-duplicate.pdf

in-pct-2001-1345-che description(complete).pdf

in-pct-2001-1345-che form-1.pdf

in-pct-2001-1345-che form-19.pdf

in-pct-2001-1345-che form-26.pdf

in-pct-2001-1345-che form-3.pdf

in-pct-2001-1345-che form-5.pdf

in-pct-2001-1345-che pct.pdf