The crucial effect of water and co-solvent on Liqui-Pellet pharmaceutical performance

Abstract

Liqui-Pellet is considered to be the next generation oral dosage form. It is highly commercially feasible unlike its predecessor, liquisolid formulation. Liqui-Pellet uses Liqui-Mass system, allowing the formulation to overcome some of the critical drawbacks in liquisolid technology, which persisted more than two decades. These drawbacks include poor flowability, poor compressibility and inability for high dose without product being too heavy and bulky for swallowing. The investigation is an extension of the previous work on the Liqui-Pellet. In order to make this novel oral delivery system a commercial product, it is prudent to further understand the parameters affecting its drug release rate. Two major parameters affecting the dissolution rate that is investigated are water and liquid vehicle (Tween 80) contents. It is found out that reducing water content (from 8.62 ml to 4.76 ml which is 1.9 ml/0.95 ml per 20 g of API and excipients) and increasing Tween 80 concentration (from 28% w/w to 32 or 36% w/w) in naproxen Liqui-Pellet results to an increase in drug release rate; however, there is a limit of how much water and Tween 80 can be employed. Outside of this range limit, the formulation would fail to produce Liqui-Pellet due to agglomeration. The range limit of granulation liquid and liquid vehicle content are dependent on one another. In the successful formulation where Liqui-Pellets are formed, the excellent-good flow properties, resistant to friability and narrow size distribution makes it ideal for commercial production. SEM of the Liqui-Pellet shows a smooth surface which is ideal for coating. The solid state analysis via XRPD and DSC indicated reduced crystallinity of the drug which is expected.