Liqui-Pellet: the Emerging Next-Generation Oral Dosage Form Which Stems from Liquisolid Concept in Combination with Pelletization Technology

Abstract

In spite of the major advantages that the liquisolid technology offers, particularly in tackling poor bioavailability of poorly water-soluble drugs ( i.e. , BCS Class II drugs), there are a few critical drawbacks. The inability of a high liquid load factor, poor flowability, poor compactibility, and an inability to produce a high dose dosage form of a reasonable size for swallowing are major hurdles, hampering this technology from being commercially feasible. An attempt was therefore made to overcome these drawbacks whilst maintaining the liquisolid inherent advantages. This resulted in the emerging next generation of oral dosage forms called the liqui-pellet. All formulations were incorporated into capsules as the final product. Solubility studies of naproxen were conducted in different liquid vehicles, namely polyethylene glycol 200, propylene glycol, Tween 80, Labrafil, Labrasol, and Kolliphor EL. The scanning electron microscopy studies indicated that the liquid vehicle tends to reduce the surface roughness of the pellet. X-ray powder diffraction (XRPD) indicated no significant differences in the crystalline structure or amorphous content between the physical mixture and the liqui-pellet formulation. This was due to the presence of a high concentration of amorphous Avicel in the formulation which overshadowed the crystalline structure of naproxen in the physical mixtures. Flowability and dissolution tests confirmed that this next-generation oral dosage form has excellent flowability, whilst maintaining the typical liquisolid enhanced drug release performance in comparison to its physical mixture counterpart. The liqui-pellet also had a high liquid load factor of 1, where ~ 29% of the total mass was the liquid vehicle. This shows that a high liquid load factor can be achieved in a liqui-pellet without compromising flowability. Overall, the results showed that the poor flowability of a liquisolid formulation could be overcomed with the liqui-pellet, which is believed to be a major advancement into the commercial feasibility of the liquisolid concept.

Optimising the release rate of naproxen liqui-pellet: a new technology for emerging novel oral dosage form

“…The previous studies by the authors demonstrated that liqui-pellets achieved a high liquid load factor of 1, whilst maintaining excellent flow property [1]. In fact, before the development of liqui-pellet, it has been proven very difficult to achieve such mentioned results, due to the cohesive nature of liquid powder admixture, which is shown in various studies [36][37][38].…”

“…It stems from liquisolid technology; however, liqui-pellet comes under liqui-mass system, which is different from liquisolid system. This liqui-mass system is combined with pelletisation technology, producing liqui-pellet [1]. In recent years, the advancement on the high-throughput screening has indicated an increased number of drug candidates to be either poorly water soluble or insoluble [2].…”

“…Other technologies include conversion of crystalline drug into its amorphous state [7], solid dispersion [8]; micronisation [9][10][11][12], nanosuspension [13,14], co-grinding [15][16][17], self-emulsifying drug delivery system [18,19] and inclusion of drug solution in soft gelatin capsule [20]. It is claimed that the liqui-pellet is highly commercially feasible and has the potential to play a major role in the future oral dosage form [1].…”

“…This is done by confronting the major drawbacks in liquisolid technology, such as poor flow property, poor compactibility and inability to produce high-dose drug without being too bulky and heavy for real-life use [3,5]. In the authors' previous studies, it is shown that liqui-pellet can achieve excellent flow property whilst having a high liquid load factor of [1]. Liqui-pellet not only contains the advantages of liquisolid technology, but it also has the inherent advantages of being in a pellet form.…”

“…The aim of the present study is to optimise liqui-pellet formulation in order to improve the drug release rate of naproxen, which is a nonsteroidal anti-inflammatory drug (NSAID), belonging to BSC class II. The chosen liquid vehicle used in the investigation is Tween 80, as it was considered the most suitable liquid vehicle from previous studies [1]. Tween 80 solubilises the API as well as acting as a surfaceactive agent which reduces interfacial tension and improve water penetrating into the dosage form.…”