K.-J. Steffens Application of Starches, Modified Starches ...Modified Starches, Pregelatinated Starches: ... Amylose and amylopectine is partially degraded. Until usage retrogradation

University of Bonn Klaus-J. Steffens

K.-J. Steffens

Application of Starches, Modified Starches andStarch Derivatives in Pharmaceutical Products

57. Starch Convention, Detmold, April 26 - 28, 2006


Starches, Pharmaceutical Applications_____________________________________________________________

Starches used in pharmaceutical preparations:

Corn StarchPotatoe StarchRice StarchWheat StarchPea Starch (soon in Pharmacopoeia)

Native starches are mainly used as fillers and disintegrants in tablets and capsules,sometimes as fillers in dermatological powders.



Modified Starches, Pregelatinated Starches:

Dextrins and Maltodextrins are used as fillers and binders in tablets,as thickeners in liquid preparations.

Starch paste is widely used as binder in tablets.



Starch Derivates:

Hydroxyethyl-starch (HES) plasma expander

Na-Carboxymethyl-starch, crosslinked „super-disintegrant“ in tablets

Hydroxypropyl-beta-cyclodextrin complexing agent in several preparations


Starches as Binder for Wet Granulation____________________________________________________________

pharmapedia.com :

Freshly prepared starch paste is used as a binder.

- Its method of preparation is very crucial.


Potatoe Starch, Water, 20 °C____________________________________________________________


Swelling of Potatoe Starch, Water, 75 °C____________________________________________________________


Swelling of Potatoe Starch, Water, 95 °C____________________________________________________________


Swelling of Starch in Water, 95 °C_____________________________________________________________

Starch paste is not a complete solution.

It is a dispersion of swollen starch grains.

A part of amylose is in solution insidethe swollen „sacks“ and can leave them by diffusion.

Amylose and amylopectine is partiallydegraded.

Until usage retrogradation occurs

All these phenomena are influenced bytemperature, kinetics of cooking and timeuntil usage.

A starch paste with constant propertiescan hardly be achieved.

Solution: Pregelatinzed or modified starches


Comparison Lycatab DSH versus Kollidon 30 ____________________________________________________________


Comparison Lycatab DSH versus Kollidon 30 ____________________________________________________________


Starches and Modified Starches as Binders for Wet Granulation____________________________________________________________

Properties (compared to other binders):

Sufficient binding capacity

Extremely low potential of incompatibilities

Stable properties during shelf life of tablets

Positive influence on tablet disintegration

Positive influence on dissolution of actives

Low concentrations of lubricants for tableting

Long service life for tableting tools

Sensitive to magnesium stearate film forming


Continuous Wet Granulator, based on a Planetary Roller Extruder____________________________________________________________


powderblendgranulation

liquidnitrogen

vacuum

GRANULATIONDRYING

SIEV

ING

Continuous Wet Granulator, based on a Planetary Roller Extruder____________________________________________________________


Planetary Roller Extruder, side view____________________________________________________________


Planetary Roller Extruder, front view____________________________________________________________


Formulation

Ibuprofen 92.0 %Cellulose Powder 3.0 %

GranulesStarch (Eurylon 7)Water

5.0 %14.0 %

Final Blend Magnesium Stearate 0.5 %

Sodium CarboxymethylStarch (Explotab) 5.0 %

Starch is completely gelatinizedTemperature: < 40 °CFinal Tablet contains 87.6 % of ibuprofen

Formulation of Ibuprofen Tablets with Starch as a Wet Binder___________________________________________________________


Ibuprofen Tablets, Compression Profile____________________________________________________________

0,5

1

1,5

2

2,5

3

3,5

0 20 40 60 80 100 120 140 160 180 200

Compression Presssure (MPa)

Tens

ile S

treng

th (N

/mm

²)

Ibuprofen Granules: Bohle 28.09.2004+ 0.5% Mg-Stearate+ 5.0% Explotab

- P1200, 24 Eu19 Punch 9.0 mm, Radius 15 mm- Speed: 30 Rpm- Tablet Weigt: 200 mg, Filling Depth: 7 mm- Precompression:~10% of Maincompression

Disintegration > 20 min

Disintegration > 5 min

Disintegration > 1.5

Disintegration < 30


1. Conclusion____________________________________________________________________

Especially modified starches deserves serious consideration

as binders in solid dosage forms wet granulation.


Co-Processed Excipient, StarLac, 85% Lactose, 15% Corn Starch____________________________________________________________________


StarLac, 85% Lactose, 15% Corn Starch (coprocessed)____________________________________________________________________


Disintegration time (+1.0% Mg-stearate)

00' 00''

00' 30''

01' 00''

01' 30''

02' 00''

02' 30''

03' 00''

03' 30''

8 10 12 14 16 18 20 22

compression force [kN]

disi

nte

gra

tion

tim

e

Starlac corn starch + Flowlac

StarLac, Disintegration Time of Tablets versus Compression Force____________________________________________________________________

StarLac

PhysicalMixture


00' 00''

00' 17''

00' 35''

00' 52''

01' 09''

01' 26''

01' 44''

02' 01''

02' 18''

02' 36''

02' 53''

0 20 40 60 80 100 120 140 160 180

Tablet Crushing Strength [N]

Dis

inte

grat

ion

Tim

e [s

]

StarLac 0,5% Mg-Stearat StarLac 0,1 Mg-Stearat%

Physikalische Mischung 0,5% Mg-Stearat Physikalische Mischung 0,1% Mg-Stearat

StarLac, 0.5 % Mg-StearateStarLac, 0.1 % Mg-Stearate

Physical Mixt., 0.5 % Mg-Stearate

Physical Mixt., 0.1 % Mg-Stearate

StarLac, Influence of Magnesium Stearate____________________________________________________________________


StarLac, Orodispersible Tablets____________________________________________________________

Orodispersible tablets:

Tablets to be placed in the mouth

where they disperse rapidly before swallowing


StarLac, Orodispersible Tablets, Measurement of Functionality (Roquette)____________________________________________________________

Tablet ist placed in a metal beaker

A piston (5 mm) presses on the Tablet ( 5 N)

2 ml water is added

Force versus time curve is measured)



Porosity controlled: swelling and collapseViscosity controlled: continous melting






Lycoat, Film-Former for Coated Tablets ____________________________________________________________

Lycoat:

Pea Starch with ideal amylose content

Hydroxypropylated to avoid starch retrogradation


Lycoat, Film Properties ____________________________________________________________


Conclusions ____________________________________________________________

Starch, modified starches and starch derivates

deserves more attention regarding their outstanding

functionalities beyound their classical usage as

binder and disintegrant in pharmaceutical preparations.

Documents

K.-J. Steffens Application of Starches, Modified Starches ...Modified Starches, Pregelatinated Starches: ... Amylose and amylopectine is partially degraded. Until usage retrogradation