Gentler risedronate forms patented by P&G

Procter & Gamble has patented a new formulation of its osteoporosis drug risedronate that overcomes the upper gastrointestinal side effects sometimes associated with the drug.

Risedronate is a member of the bisphosphonate class of osteoporosis drugs that are known to cause irritation, sometimes leading to erosion and ulceration, in the buccal cavity, pharynx, oesophagus and stomach. Patients taking these drugs are advised to follow a stringent regime to limit these side effects; for example, the recommendations are to take them with a full glass of water, on an empty stomach and to remain standing up or sitting upright for a full 30 minutes after dosing.

P&G's patent (No 6,596,710) describes a number of approaches to the production of controlled release formulations of risedronate, such as enteric-coated tablets or starch or gelatin capsules containing enteric-coated beads or particles, as well as particular excipient combinations, that deliver the active ingredient directly to the large intestine.

P&G and partner Aventis maintain that risedronate's potency at low doses makes its upper GI tolerability better than other drugs in the bisphosphonate class, such as Merck & Co's Fosamax (alendronate). However, the company notes that some patients still suffer upper GI reactions to the drug despite the low dose levels.

P&G and Aventis, in common with the manufacturers of other bisphosphonate drugs, have developed long-acting formulations of risedronate that reduce the frequency of dosing and the upper GI irritation. The companies recently secured European approval for a once-weekly oral dosage formulation of the Actonel, and researchers have also been experimenting with once yearly dosing of injectable drugs.