Bimodal Release Two-In-One Clonazepam Matrix Lozenge Tablets for Managing Anxiety-Related Disorders: Formulation, Optimization and In Vivo Evaluation

• Published in: Scientia pharmaceutica 2022-07, Vol.90 (3), p.43
• Main Authors: Gomaa, Eman, El Deeb, Sami, Ibrahim, Adel Ehab, Faisal, Mennatullah M.
• Format: Article
• Language: English
• Subjects: Anxiety; bimodal behavior; buccal lozenge tablets; Cellulose; Clonazepam; Diffusion models; Drug dosages; Lactose; Optimization; Pharmaceutical industry; pharmacokinetic; Polymers
• ISSN: 2218-0532; 0036-8709; 2218-0532
• DOI: 10.3390/scipharm90030043

Clonazepam (CLZ), an antipsychotic drug reported for its efficiency in managing anxiety-related disorders, is being marketed only as conventional tablets. Some patients have abstention to swallow the conventional tablets; therefore, the proposed study was aimed at developing a buccal lozenge tablet by direct compression of two types of optimized granules. Conazepam’s water solubility was first enhanced by a solid dispersion technique for a fast and better dissolution of type 1 granules, while the impact of gelling polymers was investigated on controlled-release type 2 granules. The optimized formulae met the acceptable pharmacopeial limits for tablets’ evaluation. A differential scanning calorimetry study revealed the compatibility between the drug and used excipients. All formulae gave a burst release of CLZ in the first hour of investigation, followed by a sustained release over 24 h. The formula that showed the highest prolonged in vitro release (99.0 + 0.1%), following the Higuchi diffusion model (R2 = 0.99), was then selected for further study. The formula succeeded in controlling the induced stress in a rat model with a significant impact on the behavioral tests throughout the experiment. The results were further confirmed by a pharmacokinetic study that showed a significant increase in Cmax, Tmax, and AUC (1.5, 2, and 3.9 folds), respectively, compared to oral suspension. The newly proposed delivery system has proven a better efficacy with a reduced dosing frequency.