Metformin Hydrochloride and Sitagliptin Phosphate Fixed-Dose Combination Product Prepared Using Melt Granulation...

Area of Science:

• Pharmaceutical Technology
• Drug Delivery Systems
• Materials Science

Background:

• Developing high-dose oral solid dosage forms requires minimizing excipients to reduce tablet size for patient acceptability.
• Traditional manufacturing often involves multi-step batch processes, which can be inefficient.
• There is a need for advanced manufacturing techniques to produce smaller, patient-friendly high-dose medications.

Purpose of the Study:

• To develop and produce a high-dose immediate-release fixed-dose combination (FDC) of metformin hydrochloride (MET) and sitagliptin phosphate (SIT) using twin-screw melt granulation.
• To evaluate the feasibility of melt granulation for creating direct-compressible caplets with reduced weight compared to existing products.
• To optimize processing conditions for melt granulation of MET and SIT.

Main Methods:

• Twin-screw melt granulation was employed to process mixtures of MET (80% w/w) and SIT (6% w/w) with selected binders.
• Melt granulation temperatures were maintained below the melting points of MET and SIT but above the glass transition or melting temperature of the binders.
• The resulting granules were characterized for flow properties and particle size before direct compression into caplets.

Main Results:

• Successfully produced direct-compressed immediate-release caplets with desired product profiles.
• The final caplet weight for an 850/63 mg MET/SIT dose was approximately 1063 mg, which is lighter than the marketed Janumet® product (1143 mg).
• Melt granules exhibited good flow properties, larger particle size, and excellent compressibility.

Conclusions:

• Twin-screw melt granulation is a suitable technology for developing direct-compressible, high-dose, immediate-release FDC products.
• This method allows for the incorporation of high drug loads while maintaining acceptable tablet size and manufacturability.
• The developed process offers a potential improvement over conventional methods for producing complex oral solid dosage forms.