Novel oral LAAM immediate-release capsules for treating opioid use disorder.

Levo-alpha-acetylmethadol (LAAM) has a long duration of action offering numerous behavioral and clinical advantages for treating opioid use disorders. In this study, we aim to develop a novel oral immediate-release capsule of LAAM, as an alternative to methadone, the major medication that requires daily visits. LAAM solid dispersion-coated pellets were developed with VIVAPUR® MCC Spheres 700 as the core, and LAAM-carrier coating solution was sprayed onto the core pellets using a fluid bed coater. The coating solution formulation was optimized for reduced coating time and improved drug loading efficiency. Design of Experiments (DoE) studies were conducted, revealing the impact of critical process parameters-nozzle air pressure and airflow-on the critical quality attributes of the LAAM-coated pellets. Capsules with different dosage strengths were prepared. Capsule weight variation, content uniformity, and in vitro release tests were conducted based on USP guidelines for quality assessment. The LAAM capsules showed the immediate release profile. The storage stability of the LAAM capsules was evaluated under accelerated condition and room temperature for 6 months. The weight gain, drug content, and dissolution profile were evaluated. The results showed that drug contents and immediate-release properties remained after 6 months of storage. Pharmacokinetic (PK) study in rabbits showed that capsules have longer tmax as well as higher Cmax of LAAM compared with oral solution. These capsules have a similar AUC of LAAM and its metabolites to the oral solution. It has been demonstrated that the developed LAAM capsules have the desired properties for subsequent clinical studies.