Citric acid monohydrate as a release-modifying agent in melt extruded matrix tablets

Area of Science:

• Pharmaceutical Technology
• Materials Science

Background:

• Controlled release matrix systems often suffer from incomplete drug release and particle size-dependent dissolution.
• Ensuring consistent drug delivery and performance is crucial for therapeutic efficacy.

Purpose of the Study:

• To evaluate citric acid monohydrate (CA MH) as an excipient to enhance diltiazem hydrochloride release from melt-extruded Eudragit RS PO tablets.
• To investigate the ability of CA MH to mitigate drug particle size effects on dissolution.

Main Methods:

• Melt extrusion was used to manufacture tablets with varying CA MH concentrations, drug particle sizes, and drug-to-polymer ratios.
• Characterization involved dissolution testing, powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM).

Main Results:

• CA MH improved thermal processability and matrix integrity through polymer plasticization.
• Drug release was significantly increased with CA MH addition, attributed to enhanced pore formation and increased polymer permeability.
• Particle size effects on dissolution were eliminated at higher CA MH concentrations due to the loss of drug crystallinity.
• CA MH-containing tablets exhibited faster and more complete drug release than those with alternative pore formers.

Conclusions:

• CA MH effectively promotes miscibility between diltiazem hydrochloride and Eudragit RS PO during hot-melt extrusion.
• The addition of CA MH results in an amorphous system with significantly improved dissolution characteristics and eliminates particle size dependency.