Manipulating hydrate formation during high shear wet granulation using polymeric excipients

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Active pharmaceutical ingredients (API) can undergo polymorphic transformations during wet granulation, potentially affecting drug product quality.
• Previous research suggests polymeric excipients may inhibit these API phase transformations.

Purpose of the Study:

• To investigate the ability of various polymeric excipients to inhibit anhydrate to hydrate transformations of model APIs during high shear wet granulation.
• To evaluate the impact of these polymers on the physical properties of the granulated product.

Main Methods:

• Three model APIs (caffeine, carbamazepine, sulfaguanidine) were subjected to high shear wet granulation.
• In-line Raman spectroscopy was used to monitor API phase transformations.
• Granulation was performed with and without different polymeric excipients.

Main Results:

• Cross-linked poly(acrylic) acid completely inhibited caffeine transformation; hydroxypropyl methylcellulose and cross-linked poly(acrylic) acid inhibited carbamazepine transformation.
• Sulfaguanidine transformation was rapid and unaffected by the tested polymers.
• Inhibitory polymers did not significantly alter the compaction or flow properties of the final granulation.

Conclusions:

• Specific polymeric excipients can effectively inhibit API hydrate transformations during wet granulation, preserving desired crystalline forms.
• Inhibitory mechanisms likely involve specific API-polymer interactions or significant water absorption by the polymer.
• The use of inhibitory polymers is a viable strategy to control API solid-state properties without compromising manufacturability.