Multicomponent crystalline solid forms of aripiprazole produced via hot melt extrusion techniques: An exploratory...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Poorly soluble drugs often exhibit limited bioavailability due to low dissolution rates.
• Multicomponent crystalline solid forms, including salts, cocrystals, and eutectics, offer a strategy to enhance drug solubility and dissolution.
• Aripiprazole (ARP) is an antipsychotic drug with poor aqueous solubility, necessitating formulation strategies to improve its dissolution profile.

Purpose of the Study:

• To develop novel multicomponent solid forms of aripiprazole (ARP) using succinic acid (SA) and nicotinamide (NA) as coformers.
• To investigate the efficacy of the hot melt extrusion (HME) technique in preparing these solid forms.
• To characterize the physicochemical properties and evaluate the in vitro dissolution behavior of the developed ARP-based multicomponent systems.

Main Methods:

• Hot melt extrusion (HME) was employed to prepare aripiprazole-succinic acid (ARP-SA) and aripiprazole-nicotinamide (ARP-NA) solid forms.
• Physicochemical characterization involved differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM).
• In vitro dissolution studies and microenvironment pH measurements were conducted to assess the performance of the developed solid forms.

Main Results:

• HME successfully produced multicomponent solid forms of ARP with SA and NA.
• DSC and HSM indicated the formation of new crystalline phases with distinct melting points for ARP-SA.
• ARP-SA exhibited significantly enhanced in vitro dissolution rates compared to individual components, potentially due to an acidic microenvironment.
• SEM revealed morphological differences, while FTIR and PXRD confirmed new solid form generation for ARP-SA, with less pronounced changes for ARP-NA.

Conclusions:

• The hot melt extrusion (HME) technique is applicable for developing multicomponent solid forms of aripiprazole.
• The aripiprazole-succinic acid (ARP-SA) solid form demonstrated improved dissolution characteristics, highlighting its potential for enhancing the bioavailability of poorly soluble aripiprazole.
• Further investigation into ARP-NA solid forms may be warranted, though initial results suggest less significant crystalline changes.