Comparison of Different Liquid and Semisolid Vehicles Selected for Oral Administration of Pellets and Minitablets with Diazepam: In Vitro Investigation.

The acceptability and palatability of a dosage form are extremely important to improve patient compliance. Mixing oral solid dosage forms with food carriers is often necessary to ease swallowing and provide the taste-masking effect. The present research investigated how a liquid or semisolid carrier influences the disintegration time and drug dissolution rate of pellets and minitablets with diazepam. The disintegration of pellets and minitablets in liquid carriers (water, milk and apple juice) was determined using a texture analyser. Dissolution tests were performed for the dosage forms dispersed in gel vehicles (2% carmellose and 0.5% carbomer gels) or applesauce. The disintegration of minitablets in water and apple juice was fast (1 min), but it slowed to 3 and 5 min in milk and gel vehicles, respectively. The pellets disintegrated in liquid carriers within 3 min. The drug dissolution rate in 0.1 M HCl depended on the gel viscosity in this medium. The preserved high viscosity of a carmellose gel inhibited the dissolution of diazepam. On the other hand, the viscosity of the carbomer gel decreased rapidly, and in effect, the dissolution rate of diazepam from the incorporated pellets or minitablets was comparable to the dissolution from loose pellets or minitablets. Graphical abstract.

The use of novel tools for the assessment of powders and granules flow properties and for the analysis of minitablets compression process.

Objective: The purpose of this study was to apply the rheological measurements to assess the flow properties of powders and granules and to compare the results with the standard pharmacopeial tests. Quality by design approach was utilized to better understand the compression of the solids into minitablets.Significance: Insights are provided regarding the methodology of rheological properties of powders and granules using powder flow analyzer (PFA). The 'six sigma' approach was presented as a tool for assessment of the minitablets manufacturing process.Methods: Pharmacopeial methods and rheological tests using PFA were performed to assess the flow properties of designed powder and fractionated granule mixtures - placebo and with benzodiazepines. Compression of 2.5 and 3 mm minitablets was carried out and the compression force registered during the process and weight uniformity were statistically analyzed by calculating the capability indices.Results: The flow rate measurement and cohesion test (PFA test) resulted in the best differentiation between mixtures. Higher values of capability indices were obtained for processes in which granule mixtures with better flow properties were compressed and 3 mm minitablets were produced and the usefulness of QbD tools in assessment of minitablets compression process was confirmed.Conclusion: Performed study showed that the flow properties are the critical quality attributes determining the performance of minitablets compression. The cohesion test is the most discriminative to distinguish the analyzed mixtures. Capability indices can be used to assess the manufacturing process as a useful tool in pharmaceutical development of minitablets.

Optimization of the coating process of minitablets in two different lab-scale fluid bed systems.

The optimization of the coating process for minitablets is extremely important in fluidized bed systems, and allows knowledge acquisition about the process for modern multiparticulate forms. The coating of minitablets allows the development of modified-release pediatric drugs. In our study, 3-mm minitablets with pantoprazole were coated to obtain an enteric product. The experiments were designed to evaluate the quality of the enteric product by efficiency and quality of film coating. Four process parameters at two levels were examined, and 16 experiments for two different fluid bed systems in laboratory-scale batches were performed. During analysis, the critical parameters of inlet airflow rate (X1) and coating mixture flow rate (X3) in different fluid bed coaters were examined. The findings indicate that apparatus construction has a significant effect on the different process parameters. Despite the fact that statistical analysis is directly related to the tested conditions, it creates opportunity to anticipate certain problems while scaling up, and a possibility to minimize them.