Intravaginal drug delivery devices for the administration of 17.beta.-oestradiol precursors
AssigneeGalen (Chemicals) Limited
InventorAllen McClay
Life of this patent
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Abstract
The invention relates to an intravaginal drug delivery device for administration to a female mammal of certain 17.beta.-oestradiol precursors at a substantially constant rate for a period of at least three weeks. The 17.beta.-oestradiol precursor is a 17.beta.-oestradiol moiety in which the, or each, hydroxyl group of the 17.beta.-oestradiol moiety is blocked by a blocking group, which blocking group is readily removed from the 17.beta.-oestradiol in vivo. The 17.beta.-oestradiol precursor must have either a solubility in liquid silicone of not less than 0.1 mg/100 ml or a standard k value of not less than 0.1 .mu.g/day/mm. The 17.beta.-oestradiol precursor must also have a solubility in distilled water of not less than 1 .mu.g/100 ml.
Claims24
A cylindrical intravaginal drug delivery device suitable for administration to a female mammal, the device comprising a 17.beta.-oestradiol precursor in a biocompatible hydrophobic elastomeric polymer matrix, the device releasing the 17.beta.-oestradiol precursor in a substantially zero order pattern for at least three weeks, the precursor being a 17.beta.-oestradiol moiety in which the, or each, hydroxyl group of the 17.beta.-oestradiol moiety is blocked by a blocking group, the precursor having sufficient lipophilicity as determined either by a solubility in liquid silicone of not less than 0.1 mg/100 ml or by a standard k value, in which k=2C.sub.S D.pi., of not less than 0.1 .mu.g/day/mm, the precursor having sufficient hydrophilicity as determined by a solubility in distilled water of not less than 1 .mu.g/100 ml, the, or each, blocking group being so linked to the 17.beta.-oestradiol moiety as to be readily removed from the 17.beta.-oestradiol moiety in vivo, and the, or each, blocking group being so chosen as to yield a substance which is non-toxic to the female mammal when removed from the 17.beta.-oestradiol moiety in vivo wherein C.sub.S corresponds to the precursor's saturation solubility in the polymer matrix and D corresponds to the precursor's diffusion coefficient in the polymer matrix.
A process for the preparation of a cylindrical intravaginal drug delivery device for release in a substantially zero order pattern for at least three weeks and suitable for administration to a female mammal, the process comprising the steps of:
- combining a 17.beta.-oestradiol precursor, the precursor being a 17.beta.-oestradiol moiety in which the, or each, hydroxyl group of the 17.beta.-oestradiol moiety is blocked by a blocking group;
- the precursor having sufficient lipophilicity as determined either by a solubility in liquid silicone of not less than 0.1 mg/100 ml or by standard k value as defined hereinabove of not less than 0.1 .mu.g/day/mm, the precursor having sufficient hydrophilicity as determined by a solubility in distilled water of not less than 1 .mu.g/100 ml, the, or each, blocking group being so linked to the 17.beta.-oestradiol moiety as to be readily removed from the 17.beta.-oestradiol moiety in vivo;
- and the, or each, blocking group being so chosen as to yield a substance which is non-toxic to the female mammal, when removed from the 17.beta.-oestradiol moiety in vivo, with a biocompatible hydrophobic elastomeric polymer, a suitable cross-linking agent and a curing catalyst to form a mix;
- and
- curing the mix to form a polymer matrix.
A method of using a 17.beta.-oestradiol precursor in a cylindrical intravaginal drug delivery device for release in a substantially zero order pattern for at least three weeks, which method comprises the step of incorporating in the drug delivery device the 17.beta.-oestradiol precursor, wherein the 17.beta.-oestradiol precursor is a 17.beta.-oestradiol moiety in which the, or each, hydroxyl group of the 17.beta.-oestradiol moiety is blocked by a blocking group, the precursor has sufficient lipophilicity as determined either by a solubility in liquid silicone of not less than 0.1 mg/100 ml or by a standard k value as defined hereinabove of not less than 0.1 .mu.g/day/mm, the precursor has sufficient hydrophilicity as determined by a solubility in distilled water of not less than 1 .mu.g/100 ml, the, or each, blocking group is so linked to the 17.beta.-oestradiol moiety as to be readily removed from the 17.beta.-oestradiol moiety in vivo, and the, or each, blocking group is so chosen as to yield a substance which is non-toxic to the female mammal when removed from the 17.beta.-oestradiol moiety in vivo.
A method of releasing a 17.beta.-oestradiol precursor in a substantially zero order pattern for a least three weeks, which method comprises the steps of:
- incorporating the 17.beta.-oestradiol precursor in a cylindrical intravaginal drug delivery device, the 17.beta.-oestradiol precursor being a 17.beta.-oestradiol moiety in which the, or each, hydroxyl group of the 17.beta.-oestradiol moiety is blocked by a blocking group, the precursor having sufficient lipophilicity as determined either by a solubility in liquid silicone of not less than 0.1 mg/100 ml or by a standard k value as defined hereinabove of not less than 0.1 .mu.g/100 ml, the precursor having sufficient hydrophilicity, as determined by a solubility in distilled water or not less than 1 .mu.g/100 ml, the, or each, blocking group being so linked to the 17.beta.-oestradiol moiety as to be readily removed from the 17.beta.-oestradiol moiety in vivo, the, or each, blocking group being so chosen as to yield a substance which is non-toxic to the female mammal when removed from the 17.beta.-oestradiol moiety in vivo;
- and
- inserting the drug delivery device into a vagina of a female mammal for the at least three weeks.
Dependencies are inferred from the claim text.