Nateglinide controlled release tablet containing compressionable enteric coated granules.

Area of Science:

• Pharmaceutical Sciences
• Pharmacology
• Drug Delivery Systems

Background:

• Diabetes mellitus requires effective glucose-lowering strategies.
• Short-acting oral glucose regulators need optimized delivery for sustained efficacy.
• Controlling both fasting and postprandial hyperglycemia is crucial for diabetes management.

Purpose of the Study:

• To develop and evaluate a single-unit controlled-release tablet of nateglinide.
• To assess the tablet's ability to reduce postprandial blood glucose level (PBG) and fasting blood glucose level (FBG).
• To determine the in vivo pharmacokinetic profile and bioavailability of the novel formulation.

Main Methods:

• Formulation of a single-unit tablet with immediate and controlled-release nateglinide portions.
• Preparation of compressionable enteric-coated granules using Eudragit for controlled release.
• In vivo oral administration studies in normal male beagle dogs.
• Dissolution testing and relative bioavailability assessment compared to immediate-release nateglinide tablets.

Main Results:

• The controlled-release nateglinide tablets successfully decreased both PBG and FBG in beagle dogs.
• Enteric-coated granules maintained their dissolution behavior post-tableting.
• Relative bioavailability was approximately 57.2% and 60.8% for formulations with dissolution pH 6.0 and 6.8, respectively.
• Repeated administration demonstrated continuous PBG and FBG reduction.

Conclusions:

• A single-unit controlled-release nateglinide tablet formulation is effective in managing both PBG and FBG.
• This approach holds potential for treating moderate to severe diabetes.
• The controlled-release technology can be applied to other short-acting meglitinides.