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. 2020 Dec;28(2):567-579.
doi: 10.1007/s40199-020-00362-9. Epub 2020 Aug 5.

Factors affecting performance and manufacturability of naproxen Liqui-Pellet

Matthew Lam  1 , Ali Nokhodchi  2
Affiliations

Factors affecting performance and manufacturability of naproxen Liqui-Pellet

Matthew Lam et al. Daru. 2020 Dec.

Abstract

Aim: Liqui-Pellet is potentially an emerging next-generation oral pill, which has shown promising results with unique advantages as well as displaying potential for commercial feasibility. Since Liqui-Pellet technology is still in its infancy, it is important to explore the parameters that can affect its performance, particularly the drug release rate. Therefore, the aim of this study is to investigate thoroughly the effect of Avicel PH101 (carrier) and Aerosil 300 (coating material) ratio (R-value) in Liqui-Pellet.

Methods: Key parameter for Liqui-Pellet formulation in this study was the ratio of carrier and coating material. Tests were carried out to assess the physicochemical properties of different formulations. This involved looking into particle size, robustness, flowability, solid-state and drug release profile. The morphology of Liqui-Pellet was investigated by SEM.

Results: It is found that R-value does not have a major effect on the success of Liqui-Pellet production. However, R-value does seem to have an effect on Liqui-Pellet size at a certain water content level and a slight effect on the drug release rate. A decrease in Avicel PH101 concentration and an increase in Aerosil 300 concentration in Liqui-Pellet formulations can reduce Liqui-Pellet size and slightly increase drug release rate by 9% after 2 h. The data shows Liqui-Pellet is resistant to friability, able to achieve exceptional flow property and have smooth surfaces, which is critical for applying coatings technology. Such properties are ideal in terms of commercial manufacturing. The XRPD and DSC both show the reduction in formulation crystallinity, which is expected in Liqui-Pellet formulation as a result of solubility of the drug in the co-solvent used in the preparation of Liqui-Pellets.

Conclusion: Overall it seems that R-value can affect Liqui-Pellet drug release rate and size but not on the production success rate.

Keywords: Dissolution enhancement; Liqui-Mass system; Liqui-Pellet; Liquisolid technology; Naproxen; Solid-state analysis.

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Conflict of interest statement

Matthew Lam and Ali Nokhodchi declare the following regarding conflicts of interest as they filed an International (PCT) Patent Application no. PCT/GB2019/052065 on 24 July 2019 and published on 30 January 2020 International Publication Number WO2020/021254 A1) entitled Pharmaceutical Methods and Compositions (PEL). The authors confirm that there is no significant financial support associated with this publication, which could have influenced its results.

Figures

Fig. 1
Fig. 1
Particle size distribution of physical mixture pellet and formulation LP-9 to LP-14
Fig. 2
Fig. 2
SEM images of physical mixture pellet and all successful formulation; I. × 80 magnification and II. × 800 magnification
Fig. 3
Fig. 3
Dissolution profile of all successful Liqui-Pellet formulation containing 25 mg of naproxen in capsule (pH 1.2)
Fig. 4
Fig. 4
Dissolution profile of all successful Liqui-Pellet formulation containing 25 mg of naproxen in capsule (pH 7.4)
Fig. 5
Fig. 5
Diffraction peaks of naproxen, avicel, aerosil, primojel, physical mixture pellet and formulation LP-9 to LP-14
Fig. 6
Fig. 6
DSC thermograms of naproxen
Fig. 7
Fig. 7
DSC thermograms of Aerosil 300, Avicel PH101, Primojel, physical mixture and all successful Liqui-Pellet formulations
See this image and copyright information in PMC

References

    1. Lam M, Ghafourian T, Nokhodchi A. Liqui-pellet: the emerging next-generation Oral dosage form which stems from Liquisolid concept in combination with Pelletization technology. AAPS PharmSciTech. 2019;20(6):231. doi: 10.1208/s12249-019-1441-9. - DOI - PMC - PubMed
    1. Lam M, Ghafourian T, Nokhodchi A. Optimising the release rate of naproxen liqui-pellet: a new technology for emerging novel oral dosage form. Drug Deliv Transl Res 2019;1–16. - PMC - PubMed
    1. Lam M.: The making of liqui-pellet and liqui-tablet, the next generation oral dosage form. Unpublished PhD thesis. University of Sussex, Brighton, UK. 2018
    1. Spireas S, Sadu S. Enhancement of prednisolone dissolution properties using liquisolid compacts. Int J Pharm. 1998;166(2):177–188. doi: 10.1016/S0378-5173(98)00046-5. - DOI
    1. Nokhodchi A, Hentzschel CM, Leopold CS. Drug release from liquisolid systems: speed it up, slow it down. Expert Opin Drug Deliv. 2011;8(2):191–205. doi: 10.1517/17425247.2011.548801. - DOI - PubMed

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