Description

This unique combination of Diclofenac Sodium and Misoprostol is a fixed-dose oral medication with a specialized, multi-layered tablet structure. The tablet is engineered with a gastro-resistant core containing Diclofenac Sodium and an immediate-release outer mantle containing Misoprostol. This innovative formulation is designed to provide the therapeutic benefits of a potent nonsteroidal anti-inflammatory drug (NSAID) while simultaneously and immediately protecting the gastrointestinal lining from its damaging effects.

Indications

This combination drug is specifically indicated for patients who require long-term NSAID therapy for conditions like osteoarthritis and rheumatoid arthritis but are at a high risk for developing gastric or duodenal ulcers. This risk is typically seen in patients with a history of gastrointestinal bleeding or ulcers, the elderly, or those on concomitant therapies that increase the risk of GI complications.

The unique formulation ensures that the gastroprotective agent (misoprostol) is released first, offering immediate protection, while the diclofenac is released later in the small intestine, bypassing the stomach and further reducing gastric irritation.

Mechanism of Action

The therapeutic effect of this combination is based on the distinct yet complementary mechanisms of its two components and the strategic timing of their release.

1. Misoprostol (Immediate-Release Outer Mantle):
   • Mechanism: Misoprostol is a synthetic analog of prostaglandin E1​.
   • Role: The immediate-release outer mantle of misoprostol dissolves quickly in the stomach. Its main actions are to:
     • Inhibit Gastric Acid Secretion: It directly inhibits the secretion of stomach acid, which is a key factor in ulcer formation.
     • Enhance Mucosal Protection: It stimulates the production of mucus and bicarbonate, which form a protective barrier over the stomach lining.
   • Timing: The immediate release of misoprostol ensures that the stomach is protected from the very beginning of the digestive process, anticipating the arrival of the diclofenac.
2. Diclofenac Sodium (Gastro-Resistant Core):
   • Mechanism: Diclofenac works by inhibiting the cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2.
   • Role: The gastro-resistant core prevents the diclofenac from dissolving in the acidic environment of the stomach. It remains intact until it reaches the more alkaline environment of the small intestine. This delayed release minimizes local irritation to the stomach lining, which can be a direct cause of gastritis. Once released, it inhibits prostaglandin synthesis, providing the analgesic and anti-inflammatory effects necessary for managing arthritis.

Synergistic Effect:

This formulation’s design provides a synchronized and synergistic effect. Misoprostol provides immediate gastroprotection, mitigating the ulcerogenic effects of NSAIDs, while the delayed release of diclofenac provides effective pain and inflammation relief. This multi-layered approach offers a safer long-term NSAID therapy for at-risk patients.