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

Abstract

Liqui-pellet is a new dosage form stemming from pelletisation technology and concept from liquisolid technology. In spite of liqui-pellet overcoming a major hurdle in liquisolid technology through achieving excellent flow property with high liquid load factor, the formulation requires to be optimised in order to improve drug release rate. Liqui-pellets of naproxen containing Tween 80, Primojel, Avicel and Aerosil were extruded and spheronised. Flowability test confirmed that all liqui-pellet formulations have excellent-good flow property (Carr's index between 3.9-11.17%), including liqui-pellets with a high liquid load factor of 1.52, where 38% of the total mass is co-solvent. This shows a relatively high liquid load factor can be achieved in liqui-pellet without compromising the flowability, which is one of the key novelty of this work. It was found that the improved drug release rate was due to the remarkably improved disintegration of the supposedly non-disintegrating microcrystalline-based pellet; the optimised liqui-pellet seems to explode into fragments in the dissolution medium. At pH 1.2, the optimised formulation had ~ 10% more drug release than non-optimised formulation after 2 h, and at pH 7.4, the drug release of the optimised pellet was nearing 100% at ~ 15 min, whereas the none-optimised pellet only achieved ~ 79% drug release after 2 h. DSC and XRPD indicated an increase in the dissolution rate could be due to molecularly dispersion of naproxen in the pellets. Overall results showed that liqui-pellet exhibited an enhanced drug release and the capacity for high liquid load factor whilst maintaining excellent flowability, rendering it a potentially commercially feasible drug delivery system.

Keywords: Dissolution enhancement; Extrusion-spheronisation; Liqui-pellet; Liquid vehicle; Liquisolid; Liquisolid pellet; Solid-state analysis.

Fig. 1

Diagram summarising the novel liqui-mass system which is used to make liqui-pellet

Fig. 2

Particle size distribution of LP-8 (top), LP-11 (middle) and physical mixture pellet (bottom)

Fig. 3

Images from SEM of physical mixture pellet, LP-7, LP-8 and LP-11; (I) × 80 magnification, (II) × 200 magnification and (III) × 800 magnification

Fig. 4

Dissolution profile of pellets in capsule for naproxen 25 mg with different concentrations of Primojel (5, 10 and 15% w/w) with and without Tween 80 (pH 1.2)

Fig. 5

Dissolution profile of pellets in capsule for naproxen 25 mg with various modifications in attempt to improve dissolution rate (pH 1.2)

Fig. 6

An image of LP-8 liqui-pellet disintegrate explosively in acidic dissolution medium. Note the small white specks are fragments of the liqui-pellet

Fig. 7

Dissolution profile of formulations containing naproxen 25 mg with the fastest dissolution rate after modifications, formulation containing Tween 80 as liquid vehicle with Primojel 5% w/w, and physical mixture pellets (pH 7.4)

Fig. 8

DSC thermogram of naproxen

Fig. 9

DSC thermograms of Avicel, Aerosil, Primojel physical mixture pellet, LP-8 and LP-11. Note the scales of Avicel, Aerosil and Primojel are the same but different from physical mixture, LP-8 and LP-11

Fig. 10

Diffractograms of naproxen, Avicel, Aerosil, Primojel, physical mixture pellet, LP-8 and LP-11