Studies on lactulose formulations for colon-specific drug delivery

Area of Science:

• Pharmacology
• Gastroenterology
• Drug Delivery Systems

Background:

• Lactulose is a non-absorbable disaccharide degraded by colonic bacteria into organic acids.
• This property can be leveraged for colon-specific drug release.
• A colon-targeted delivery system (CODES) was designed utilizing lactulose.

Purpose of the Study:

• To investigate a novel colon-targeted delivery system (CODES) based on lactulose.
• To evaluate the drug release mechanism and pharmacokinetic profile of CODES.
• To assess the potential of lactulose as a colon-specific release trigger.

Main Methods:

• CODES formulation: lactulose core, acid-soluble inner layer, enterosoluble outer layer.
• In vivo study in rats: direct cecal instillation of pigment-loaded CODES.
• Pharmacokinetic study in dogs: oral administration of 5-aminosalicylic acid (5-ASA)-loaded CODES in fasting and fed states.

Main Results:

• Pigment release observed 1 hour after direct cecal introduction in rats.
• 5-ASA detected in plasma 3 hours post-dose in fasting dogs, correlating with colon arrival.
• Delayed Tmax in fed dogs (9 hours) but similar Cmax and AUC compared to fasting dogs, indicating gastric emptying influences release timing.

Conclusions:

• Lactulose effectively triggers drug release in the colon through bacterial degradation.
• CODES demonstrates potential for targeted delivery of drugs to the colon.
• Lactulose-based systems offer a viable strategy for colon-specific pharmacotherapy.