Pimozide and Adipic Acid: A New Multicomponent Crystalline Entity for Improved Pharmaceutical Behavior.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery

Background:

• Pimozide, an antipsychotic, suffers from poor solubility and bioavailability, limiting its therapeutic efficacy.
• Developing novel formulations is crucial to overcome the limitations of poorly soluble drugs like pimozide.

Purpose of the Study:

• To enhance the pharmaceutical properties of pimozide by co-crystallization with adipic acid.
• To characterize the new crystalline entity and evaluate its potential in drug formulation.

Main Methods:

• Liquid-assisted grinding was employed to prepare pimozide-adipic acid co-crystals.
• Thermal analysis, X-ray diffraction (XRD), solubility, and wettability studies were conducted.
• Tablet formulations were prepared and their dissolution profiles were compared to a commercial product.

Main Results:

• A new crystalline entity, identified as a pimozide:adipic acid salt ([PMZH]2[adipate]) in a 0.66:0.33 molar ratio, was successfully synthesized.
• The new crystalline form exhibited significantly improved solubility and wettability compared to pure pimozide.
• Tablets formulated with the new crystalline form demonstrated rapid dissolution, achieving drug availability within minutes.

Conclusions:

• The pimozide-adipic acid salt represents a promising approach to enhance the bioavailability of poorly soluble pimozide.
• This novel crystalline form has the potential to improve treatment outcomes for patients with schizophrenia and related disorders.
• The improved dissolution characteristics ensure rapid drug absorption, minimizing variability due to gastric conditions.