Orally administered controlled drug delivery system providing temporal and spatial control

• US 6,261,601 B1
• Filed: 09/14/1998
• Issued: 07/17/2001
• Est. Priority Date: 09/19/1997
• Status: Expired due to Fees

• Current Assignee: Ranbaxy Laboratories Limited (Sun Pharmaceutical Industries Limited)
• Original Assignee: Ranbaxy Laboratories Limited (Sun Pharmaceutical Industries Limited)
• Inventors: Sen, Himadri, Talwar, Naresh, Staniforth, John N.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Ware, Todd
• Application Number:
  US09/152,932
• Time in Patent Office: 1,037 Days
• Field of Search: 424/466, 424/43, 424/44, 424/452, 424/465, 424/484, 424/485, 424/486, 424/488, 424/468, 424/469
• US Class Current: 424/469
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus

Abstract

A pharmaceutical composition in the form of tablets or capsules provides a combination of temporal and spatial control of drug delivery to a patient for effective therapeutic results. The pharmaceutical composition comprises a drug, a gas generating component, a swelling agent, a viscolyzing agent, and optionally a gel forming polymer. The swelling agent belongs to a class of compounds known as superdisintegrants (e.g., cross-linked polyvinylpyrrolidone or sodium carboxymethylcellulose). The viscolyzing agent initially and the gel forming polymer thereafter form a hydrated gel matrix which entraps the gas, causing the tablet or capsule to be retained in the stomach or upper part of the small intestine (spatial control). At the same time, the hydrated gel matrix creates a tortuous diffusion path for the drug, resulting in sustained release of the drug (temporal control). A preferred once daily ciprofloxacin formulation comprises 69.9% ciprofloxacin base, 0.34% sodium alginate, 1.03% xanthan gum, 13.7% sodium bicarbonate, 12.1% cross-linked polyvinylpyrrolidone, and optionally other pharmaceutical excipients, the formulation being in the form of a coated or uncoated tablet or capsule.

Claims

1. A once daily tablet formulation for oral administration in humans for the controlled release of ciprofloxacin comprising a pharmaceutically effective amount of ciprofloxacin, about 0.2% to about 0.5% sodium alginate, about 0.5 to about 2.0% xanthan gum, about 10.0% to about 25% sodium bicarbonate, and about 5.0% to about 20% cross-linked polyvinylpyrrolidone, said percentages being w/w of the composition, wherein the weight ratio of sodium alginate to xanthan gum is between about 1:

1 to about 1;

10.

2. The formulation of claim 1 comprising 69.9% ciprofloxacin base, 0.34% sodium alginate, 1.03% xanthan gum, 13.7% sodium bicarbonate, 12.1% cross-linked polyvinylpyrrolidone, and optionally other pharmaceutical excipients.

3. The formulation of claim 1 in the form of a tablet.

4. A once daily homogenous, single layer tablet formulation for oral administration in humans for the controlled release of ciprofloxacin in the stomach or upper part of the small intestine comprising a pharmaceutically effective amount of ciprofloxacin, about 0.2% to about 0.5% sodium alginate, about 0.5 to about 2.0% xanthan gum, about 10.0% to about 25% sodium bicarbonate, and about 5.0% to about 20% cross-linked polyvinylpyrrolidone, said percentages being w/w of the composition, wherein the weight ratio of sodium alginate to xanthan gum is between about 1:

1 to about 1;

10.

5. The formulation of claim 4 comprising 69.9% ciprofloxacin base, 0.34% sodium alginate, 1.03% xanthan gum, 13.7% sodium bicarbonate, 12.1% cross-linked polyvinylpyrrolidone, and optionally other pharmaceutical excipients.

6. A once daily tablet formulation for oral administration in humans for the controlled release of ciprofloxacin in the stomach or upper part of the small intestine comprising a pharmaceutically effective amount of ciprofloxacin, about 0.2% to about 0.5% sodium alginate, about 0.5 to about 2.0% xanthan gum, about 10.0% to about 25% sodium bicarbonate, and about 5.0% to about 20% cross-linked polyvinylpyrrolidone, said percentages being w/w of the composition, wherein the weight ratio of sodium alginate to xanthan gum is between about 1:

1 to about 1;

10, said ingredients present in said relative proportions in a single layer.

7. The formulation of claim 6 comprising 69.9% ciprofloxacin base, 0.34% sodium alginate, 1.03% xanthan gum, 13.7% sodium bicarbonate, 12.1% cross-linked polyvinylpyrrolidone, and optionally other pharmaceutical excipients.

8. The formulation of claim 6 in the form of a tablet.

9. A once daily tablet formulation for oral administration in humans for the controlled release of ciprofloxacin in the stomach or upper part of the small intestine comprising a pharmaceutically effective amount of ciprofloxacin, about 0.2% to about 0.5% sodium alginate, about 0.5 to about 2.0% xanthan gum, about 10.0% to about 25% sodium bicarbonate, and about 5.0% to about 20% cross-linked polyvinylpyrrolidone, said percentages being w/w of the composition, wherein the weight ratio of sodium alginate to xanthan gum is between about 1:

1 to about 1;

10.

10. The formulation of claim 9 comprising 69.9% ciprofloxacin base, 0.34% sodium alginate, 1.03% xanthan gum, 13.7% sodium bicarbonate, 12.1% cross-linked polyvinylpyrrolidone, and optionally other pharmaceutical excipients.

11. The formulation of claim 9 in the form of a tablet.