Fructans of Agave tequilana – A new pharmaceutical excipient? · 2019. 7. 2. · Physico-chemical properties 2.1 X-ray diffraction 2.2 Dynamic water vapour sorption 2.3 Determination

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Fructans of Agave tequilana –A new pharmaceutical excipient?

M. L. NguyenDr. H. Rein, Dr. W. Praznik*

Pharmazeutische Technologie Rheinische Friedrich-Wilhelms-Universität Bonn

*Boku Wien

Vortrag Nr. 5.5

Index

1. General information on agavefructans2. Physico-chemical properties

2.1 X-ray diffraction2.2 Dynamic water vapour sorption2.3 Determination of adherence properties

3. Possible useability3.1 Influence on the glass transition temperature3.2 Granulation and tablet compaction

4. Conclusion5.5: M. L. Nguyen, H. Rein, Dr. W. Praznik:

Fructans of Agave tequilana:– A new pharmaceutical excipient?

1. General information on Agavefructan

• Agave tequilana Weber, Var. azul• Watersolubale oligo- and polysaccherides• Structure is made of several fructose- and

one glucose units• Unique carbohydrate with a content of

about 17 %

5.5: M. L. Nguyen, H. Rein, Dr. W. Praznik: Fructans of Agave tequilana:– A new pharmaceutical excipient?

Structure Fructan vs. Starch

Agavenfructan

Amylose

Amylopectin

Extracton of the Agavefructans

• 6 to 8 years old plant, before flowering• Stem is ground up to pulp• Pulp is extracted with water• Resulting juice is cleaned with charcoal, evaporated to a

syrup with a concentration of 70 %• Syrup processed by spray drying


SEM-pictures


Index






2.1 X-ray diffraction

• X-ray diffraction analysisamorphous structure

2.2 Dynamic Vapour Sorption

Dynamic VapourSorption (DVS)

hygroscopic

DVS Agavenfructan vs. SorbitolDVS Isotherm Plot

0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105

Target RH (%)

Cha

nge

InM

ass

(%)-

Dry

Cycle 1 Sorp Cycle 1 Desorp

DVS Isotherm Plot

0

10

20

30

40

50

60

70

80

90

100

110

120

0 20 40 60 80 100 120

Target RH (%)

Cha

nge

InM

ass

(%)-

Dry


Thermogravimetrics

• Thermogravimetryabsolute water content ca. 5 %

2.3 Adherence properties

• Agavefructan + Water ! sticky mass• Pharmaceutical useability of adhesive substances:

- TTS- Binding granulation- Bioadhesive medical formulas


Adherence strength determination

• Adherence calculationvia texture analyzer

• Water solubleagavenfructan solutionvs. water soluble PVP-solution

• Observation of adherence strenght afterdifferent time intervals


Force-time-diagram

Declining peak withneg. strength

Helt strength of 10 N

Interpreted peakwith pos. strength


Maximum adherence strength results 1

• Agavenfructan-solution (30 %) 3,40 N after 75 min drying time

• PVP-solution (30 %) 2,25 N after 45 min drying time

• Adherence strength of the agavenfructan-solutionstays the same for more than 180 min

• Adherence strength of the PVP-solution only staysthe same for 60 min


Maximum adherence strength results 2

• Storage of the sample in the conditioning cabinet of 25 °C and 60 % RH

• Adherence strength of the agavenfructan sampleremained at ca. 2 N

• No measureable adherence strength of the PVP samples

• Agavenfructan binds moistureadherence strength stays stable


Index






3.1 Influence on the glasstransition temperature

• Platisizerglass transition temperature ↓

• Production of water soluable gelatinfilms withdifferent quantities of agavefructan

• Determination of glass transition temperature via differential scanning calorimetry (DSC)


Declining glass transitiontemperature via DSC

40

50

60

70

80

0 10 20 30 40 50 60 70 80 90 100

Fructanratio [%]

Gla

ss tr

ansi

tion

tem

pera

ture

[°C

]

Declining glass transition temperature

• Glass transition temperature delines with increasingconcentration of agavefructan

• Usable for softener• Possible usage to reduce brittelness e.g. in extrusions• Possible increase in flexibility of polymers


3.2 Granulation with agavefructan

• Usage as binder and filler• Sorptions- und Desorptions behaviour• Scanning electron microscope (SEM) observation• Granulation recipes

1: Fructan (20), Baldrian (20), Granulac 200 (60)2: Avicel (20), Baldrian (20), Granulac 200 (60)

(Lehmann&Voss, Hamburg)


Dynamic water vapoursorption of the granulatesDVS Isotherm Plot

0

10

20

30

40

50

60

70

0 20 40 60 80 100 120

Target RH (%)

Cha

nge

InM

ass

(%)-

Dry


DVS Isotherm Plot

0

10

20

30

40

50

60

70

80

0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105

Target RH (%)

Cha

nge

InM

ass

(%)-

Dry


SEM of the granules

Tablet making with agavenfructan

• Compression of the granules withpneumohydraulic tablet press (Flexitab, punch: 10 mm biplan)

• Pressure-break resistance profile of tabletscontaining agavenfructan vs. avicel


Pressure-break resistance profile

01020304050607080

0 5 10 15 20 25 30 35

Preßkraft [kN]

Bruc

hfes

tigke

it [N

]

Tablettiermischung 1 Tablettiermischung 2

Tablettiermischung 1: Baldrian (20), Agavenfructan (20), Granulac 200 (60)Tablettiermischung 2: Baldrian (20), Avicel (20), Granulac 200 (60)

Tablet making with agavenfructan

• Good compression of the granules without bindingagents

• Stable tablets possible even under low pressure• Even tablet surface, homogenous consistency


Surface of the fructan tablet

• plastic deformable• homogenous


Surface of the starch tablet

• rebound afterpressure removed(elastic)

• deep cracks remain

10 % potato starch90 % Sorbitol

Agavenfructan for hydrolysis protection

• Usage in formulas with hydrolysis sensitive activeagent such as phanacetin(Expl.: Aspirin-CaCO3)

• Hygroscopic agavenfructan binds moisture out of theair

• Liberation/follow up examinations to provehydrolysis protection are still to be done


Conclusion

• Usable as plastisizer• Shows good glue properties• Useable as binder in granulation• Useable as filler in tablet making• Compromised by hydroscopic properties


Thank you very much for yourattention


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Fructans of Agave tequilana – A new pharmaceutical excipient? · 2019. 7. 2. · Physico-chemical properties 2.1 X-ray diffraction 2.2 Dynamic water vapour sorption 2.3 Determination