Development of gastroretentive floating granules with gentian root extract by hot-melt granulation

Jelena Mudrić,Jelena Ðuriš,Mirjana Pajić,Dubravka Bigović

doi:10.5937/leksir2040040m

Abstract

The roots of yellow gentian, Gentiana lutea L. (Gentianaceae) are used in traditional medicine for the treatment of gastrointestinal disorders, with the literature data indicates a local gastric effect of gentian root extract (GRE) and support the use of the solid pharmaceutical forms. Gentiopicroside, as a dominant secoiridoid in the GRE, has a short elimination half-life and low bioavailability and, consequently, its bioactivity is limited. The aim of the study was to develop gastroretentive floating delivery system with GRE, and to provide prolonged release of gentiopicroside. Floating granules with dry GRE (DGRE) were prepared by the hot-melt granulation technique, while formulations included effervescent components (citric acid and sodium bicarbonate), hydroxypropyl methylcellulose (HPMC) and meltable binders (Compritol® 888 ATO and Gelucire® 50/13). The flowability of the DGRE and prepared formulations was determined by calculating the Carr index and Hausner ratio. Floating properties and in vitro dissolution rate of gentiopicroside from investigated formulations were examined. Floating granules were characterized with improved flowability (Carr index 14-22 %; Hausner ratio 1.16-1.28) in comparison to the DGRE (Carr index 28.99 %; Hausner ratio of 1.41). Furthermore, the floating granules exhibited immediate and long-lasting buoyancy and prolonged-release of gentiopicroside (over 8 h). Compritol® 888 ATO has provided sustained release of gentiopicroside from floating granules, while HPMC has decreased release rate additionally. On the other hand, Gelucire® 50/13 has increased gentiopicroside release rate. The results have shown that hot-melt granulation technique, as a green granulation method was successfully employed for obtaining gastroretentive floating granules with DGRE.

Highlights

Underground parts of yellow gentian, Gentiana lutea L. (Gentianaceae) are used in traditional medicine for the treatment of gastrointestinal disorders, such as dyspepsia, liver dysfunction, loss of appetite, while it is official in the European and many nationals Pharmacopoeias
The results have shown that hot-melt granulation technique, as a green granulation method was successfully employed for obtaining gastroretentive floating granules with dry GRE (DGRE)
Excipients used for formulation were hydroxypropyl methylcellulose (HPMC, Methocel® E5 LV, Dow®, USA), hydrophilic polymer used as a matrix forming excipient, lactose monohydrate was used as a diluent, citric acid and sodium bicarbonate as an effervescent components, while glyceryl behenate (Compritol® 888 ATO, Gattefrosse, Saint-Priest, Cedex, France) and stearoyl macrogol-32 glycerides (Gelucire® 50/13, Gattefrosse, Saint-Priest, Cedex, France) were used as meltable binders

Summary

Introduction

Underground parts of yellow gentian, Gentiana lutea L. (Gentianaceae) are used in traditional medicine for the treatment of gastrointestinal disorders, such as dyspepsia, liver dysfunction, loss of appetite, while it is official in the European and many nationals Pharmacopoeias Previous studies have shown choleretic (Öztürk et al, 2002), anti-inflamtory (Mathew et al, 2004), antiulcerogenic (Niiho et al, 2006), radioprotective (Menkovicet al., 2010), analgesic (Öztürk et al, 2002) and antimicrobial (Pontus et al, 2006) activity of gentian root extract. Beneficial health effects of gentian root extract are associated with the presence of bitter-tasting secoiridoids (gentiopicroside, sweroside, swertiamarin, loganic acid) and biphenyl derivatives (amarogentin, amaropanin and amaroswerin), as well as phenolics i.e. xanthones (isogentisin, gentioside, gentisin), and flavonoids (isovitexin, isoorientin) (Šavikin et al, 2015; Živkovicet al., 2019). Gentiopicroside is the dominant bioactive compound in the gentian root extract with choleretic, hepatoprotective, adaptogenic and anti-inflammatory activities (Wu et al, 2017). The literature data indicate a local gastric effect of gentian root extract and support the use of the solid pharmaceutical forms (EMA, 2018)

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