|Title:|| Compressible sustained release solid dosage forms|
|Abstract:||A free-flowing directly compressible granulation useful as a slow release pharmaceutical excipient is disclosed. The excipient includes a hydrodrophilic matrix which includes heteropolysaccharide and a polysaccharide material capable of cross-linking the heteropolysaccharide, and an inert diluent.|
|Inventor(s):|| Baichwal; Anand R. (Poughkeepsie, NY), Staniforth; John N. (Bath, GB2) |
|Assignee:|| Edward Mendell Co., Inc. (Carmel, NY) |
|Filing Date:||Jan 16, 1991|
|Claims:||1. A method for providing a univeral tableting granulated excipient which is free-flowing and directly compressible for a controlled release of a relatively soluble or insoluble therapeutically active medicament comprising |
determining the solubility of a therapeutically active medicament which is to be tableted;
mixing an effective amount of said therapeutically active medicament to render a desired therapeutic effect with a premanufactured granulated slow release excipient comprising from about 30 to about 50 percent by weight of a hydrophilic material comprising from about 90 to about 10 percent by weight of a heteropolysaccharide and from about 10 to about 90 percent by weight of a cross-linking agent capable of cross-linking said heteropolysaccharide in the presence of gastric fluid and from about 50 to about 70 percent by weight of an inert pharmaceutical filler,
providing a final mixed product having a ratio of said therapeutically active medicament to said hydrophilic material of about 1:3-7 and a sufficient amount of said hydrophilic material such that a gel matrix is created when said tablet is exposed to gastric fluid and such that at least 3.5 hours are required for 50 percent of said therapeutically active medicament to be released following exposure to gastric fluid, and
thereafter directly compressing the resulting blend to form a tablet.
2. The method according to claim 1, wherein said heteropolysaccharide is xanthan gum and said cross-linking agent is locust bean gum in a 1:1 ratio.
3. The method according to claim 2, further comprising providing a tablet wherein said hydrophilic material constitutes at least 20 percent by weight of said tablet.
4. A method of using a hydrophilic gum matrix to obtain a controlled-release oral solid dosage form comprising
preparing a hydrophilic gum matrix comprising a xanthan gum and a galactomannan gum capable of cross-linking said xanthan gum when exposed to gastric fluid, the ratio of said xanthan gum to said galactomannan gum being from about 1:3 to about 3:1;
mixing said hydrophilic gum matrix with an inert diluent selected from the group consisting of a monosaccharide, a disaccharide, a polyhydric alcohol, and mixtures thereof, in a ratio of said inert diluent to said hydrophilic gum matrix from about 4:1 to about 0.67:1;
combining the mixture of hydrophilic gum matrix and inert diluent with an effective amount of a medicament to render a desired therapeutic effect via dry granulation, wet granulation or a combination of dry and wet granulation such that the ratio of said medicament to said hydrophilic gum matrix is from about 1:3 to about 1:7, and
compressing the resultant mixture to form solid tablets.
5. A method for preparing a controlled release solid dosage form, comprising
mixing a sufficient amount of a therapeutically active medicament to render a desired therapeutic effect with a granulated slow release excipient comprising from about 30 to about 50 percent by weight a heteropolysaccharide comprising from about 90 to about 10 percent by weight xanthan gum and from about 10 to about 90 percent by weight locust bean gum, with from about 50 to about 70 percent by weight of an inert pharmaceutical filler, and
preparing a final mixed solid product which, when exposed to gastric fluid, requires at least 3.5 hours to release about 50 percent of said therapeutically active medicament.
6. The method of claim 5, wherein the ratio of xanthan gum to locust bean gum in from about 1:3 to about 3:1.
7. The method of claim 5, further comprising compressing the final mixed solid product to form solid tablets.