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

Abstract

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.

Development and Optimization of a Novel Lozenge Containing a Metronidazole-Peppermint Oil-Tranexamic Acid Self-Nanoemulsified Delivery System to Be Used after Dental Extraction: In Vitro Evaluation and In Vivo Appraisal

“…The in vitro disintegration was higher than 25% within 3 min, 37% within 5 min, and 61% within 15 min, and complete disintegration occurred within 30 min. All the data indicated that the manufactured lozenges could be effectively used in drug delivery, and similar outcomes were reported in the literature [67].…”

Microfluidic-on-a-chip for designing celecoxib-based amorphous solid dispersions: when the process shapes the product

“…A zero-order profile was not possible to be traced for this formulation. Focusing on the Korsmeyer-Peppas model, frequently used for determining the release kinetics of polymeric dosage forms, the value of the parameter c2 holds particular relevance in characterizing the drug transport mechanism (Gomaa et al, 2022). Accordingly, c2 values close to 0.5 are indicative of a Fickian diffusion process, whereas values ranging from 0.5 to 1.0 suggest an anomalous (non-Fickian) transport.…”