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US 8,506,998 B2Granted
Pharmaceutical formulation
AssigneeEuro-Celtique S.A.
InventorsRonald Brown Miller, Stewart Thomas Leslie, Sandra Therese Antoinette Malkowska, Derek Allan Prater, Trevor John Knott, Hassan Mohammad
Life of this patent
Estimating the term…
Abstract
A solid, oral controlled release pharmaceutical dosage form has a water-soluble active ingredient dispersed in a matrix and releases the active ingredient at such a rate upon administration that the median tmax is 2.5 to 6 hours and the ratio of mean Cmax to mean plasma level of the active ingredient at 24 hours is in the range of 1.5 to 3.5.
Claims34
A solid, oral, controlled release pharmaceutical dosage form, comprising
- one pharmaceutically active ingredient consisting of a pharmaceutically acceptable salt, of morphine, diamorphone, tramadol and dihydrocodeine, the pharmaceutically active ingredient having a solubility in water of greater than 1 gm in 250 ml water at 25° C., dispersed in a matrix of a controlled release material consisting of a hydrophobic fusible material having a melting point of greater than 40° C., and a hydrophilic, organic, polymeric fusible wicking agent,
- wherein the weight ratio of the hydrophobic fusible material to the hydrophilic, organic polymeric wicking agent in said matrix is in the range from 8:1 to 16:1, and
- the dosage form provides, as tested by the Ph. Eur. Basket method at 100 rpm 900 ml aqueous buffer (pH 6.5) containing 0.05% w/w Polysorbate 80 at 37° C., an essentially zero order rate of release of the pharmaceutically active ingredient over a period of 8 hours, an amount of pharmaceutically active ingredient released over eight hours in the range of 15% to 45%, and, when tested in a group of at least five healthy humans, a median tmax, based on blood sampling at half hourly intervals, in the range of from 2.5 to 6 hours,
- a ratio of mean Cmax to the mean plasma level at 24 hours in the range of 1.5 to 3.5, and a W50 in the range from 15 to 35 hours, and
- said pharmaceutically active ingredient is the only pharmaceutically active ingredient in the dosage form.
2 more elements
A solid, oral, controlled release pharmaceutical dosage form which comprises
- one pharmaceutically active ingredient consisting of a pharmaceutically acceptable salt, of morphine, diamorphone, tramadol and dihydrocodeine,
- the pharmaceutically active ingredient having a solubility in water of greater than 1 gm in 250 ml water at 25° C., dispersed in a matrix of a controlled release material consisting of a hydrophobic fusible material having a melting point of greater than 40° C., and a hydrophilic, organic polymeric fusible wicking agent,
- wherein the weight ratio of the hydrophobic fusible material to the hydrophilic, organic polymeric wicking agent in said matrix is in the range from 8:1 to 16:1,
- said one pharmaceutically active ingredient is the only pharmaceutically active ingredient in the dosage form,
- the dosage form provides a dissolution rate in-vitro when measured by the Ph. Eur. Basket method at 100 rpm 900 ml aqueous buffer (pH 6.5) containing 0.05% w/w Polysorbate 80 at 37° C. such that an amount of the pharmaceutically active ingredient released from the dosage over eight hours is in the range of 15% to 45% (by weight), and is being obtainable by a process comprising:
- (a) mechanically working in a high shear mixer a mixture of a hydrophobic fusible binder and an amount of an organic, fusible, polymeric material which in the finished dosage form is capable of functioning as a wicking agent at a speed and temperature at which the binder melts or softens and the mixture forms agglomerates;
- (b) extruding the agglomerates whereby the extrudate is obtained as extruded pieces or an elongate extrudate is formed into pieces;
- (c) continuing mechanically working the pieces in a high shear mixer;
- and
- (d) continuing mechanically working with additional binder material at a temperature and speed at which the additional binder melts or softens.
7 more elements
Dependencies are inferred from the claim text.