Liquisolid systems: Evaluation of the influence of formulation variables on the optimum liquid load

Abstract

Liquisolid systems represent an emerging approach in the preparation of solid dosage forms with liquid lipophilic drug or poorly water-soluble drug solution/suspension in suitable liquid vehicle. This study addresses the lack of data regarding the compaction behavior of liquisolid systems, with the aim to investigate the influence of liquid load, carrier to coating ratio, carrier type (microcrystalline cellulose vs. spray dried calcium hydrogen phosphate, anhydrous (Fujicalin®)) on flowability and compaction properties of liquisolid systems and to determine the optimum liquid loads. Liquisolid admixtures with Fujicalin® showed notably better flowability than those with microcrystalline cellulose. An increase in carrier to coating ratio led to enhanced flowability of the admixtures. Compacts with Fujicalin® had good mechanical properties up to 24.7% liquid, while those with microcrystalline cellulose had acceptable mechanical strength up to 16.2% liquid. Liquisolid systems with Fujicalin® showed similar tabletability profiles as those with microcrystalline cellulose, despite having higher liquid content. The ejection stress values indicated that the addition of lubricant might be needed in the case of liquisolid systems with Fujicalin®. Superior properties of Fujicalin® as a carrier for liquisolid tablets were revealed, and dynamic compaction analysis was found to be a valuable tool for the assessment of compaction behavior of liquisolid systems.

Liquisolid systems as a novel approach in formulation and manufacturing of solid dosage forms: Challenges and perspectives

“…The proposed mathematical equations allow the calculation of the excipient specific formulation parameters that could further facilitate the calculation of the optimum quantities for a certain system. These equations, as well as the criteria for the acceptably compressible admixture, were based on the properties of common excipients, such as microcrystalline cellulose and silica, and should be reconsidered in the case of novel excipients with considerably higher specific surface area and adsorption capacity (8). However, the idea behind the proposed formulation approach, i.e., the importance of considering both flowability and compaction properties of the admixtures at the same time, is of utmost importance for a wider applicability of the LS technology.…”

“…Although highly promising, this technique is accompanied by certain challenges calling for future research efforts, and some of them involve (7,8,22):…”

“…Studies addressing the lack of knowledge regarding compaction behavior of liquisolid systems are still scarce. Apart from several studies reported in the last years that involve the analysis of mechanical properties (resistance to crushing, friability) of liquisolid tablets (18,(27)(28)(29)(30)(31)(32), there are only a few recent studies dealing more thoroughly with factors influencing compaction behavior of liquisolid systems (14,19), including recent papers of our research group (8,9). These studies revealed that the influence of different formulation and process parameters can significantly affect compaction behavior of LS systems and that the use of dynamic compaction analysis and mathematical models for the evaluation of compression properties could contribute to a better understanding and facilitate the optimization of the formulation and production process of LS tablets.…”

Application of Machine-Learning Algorithms for Better Understanding the Properties of Liquisolid Systems Prepared with Three Mesoporous Silica Based Carriers

“…The mechanical characteristics of LS tablets, such as friability and resistance to crushing, have been investigated in several studies over the years [ 5 , 20 , 21 , 22 , 23 ]. However, few recent studies have discussed the influence of formulation factors on the behavior of LSS during compaction [ 24 , 25 , 26 , 27 ] and a more detailed insight into the complex relationship between the formulation of LSS and the process parameters during all stages of compaction is still lacking. Therefore, the application of this technology requires not only a good understanding of the LS formulation and an accurate calculation of the required amounts of excipients but also an understanding of the tableting process and all its stages.…”