Application of Starches, Modified Starches and Starch Derivatives in Pharmaceutical Products

Transcription

1 57. Starch Convention, Detmold, April 26-28, 2006 K.-J. Steffens Application of Starches, Modified Starches and Starch Derivatives in Pharmaceutical Products

2 Starches, Pharmaceutical Applications _ Starches used in pharmaceutical preparations: Corn Starch Potatoe Starch Rice Starch Wheat Starch Pea Starch (soon in Pharmacopoeia) Native starches are mainly used as fillers and disintegrants in tablets and capsules, sometimes as fillers in dermatological powders.

3 Starches, Pharmaceutical Applications _ 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.

4 Starches, Pharmaceutical Applications _ Starch Derivates: Hydroxyethyl-starch (HES) Na-Carboxymethyl-starch, crosslinked Hydroxypropyl-beta-cyclodextrin plasma expander super-disintegrant in tablets complexing agent in several preparations

5 Starches as Binder for Wet Granulation pharmapedia.com : Freshly prepared starch paste is used as a binder. - Its method of preparation is very crucial.

6 Potatoe Starch, Water, 20 C

7 Swelling of Potatoe Starch, Water, 75 C

8 Swelling of Potatoe Starch, Water, 95 C

9 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 inside the swollen sacks and can leave them by diffusion. Amylose and amylopectine is partially degraded. Until usage retrogradation occurs All these phenomena are influenced by temperature, kinetics of cooking and time until usage. A starch paste with constant properties can hardly be achieved. Solution: Pregelatinzed or modified starches

10 Comparison Lycatab DSH versus Kollidon 30

11 Comparison Lycatab DSH versus Kollidon 30

12 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

13 Continuous Wet Granulator, based on a Planetary Roller Extruder

14 Continuous Wet Granulator, based on a Planetary Roller Extruder vacuum nitrogen granulation liquid powder blend DRYING GRANULATION SIEVING

15 Planetary Roller Extruder, side view

16 Planetary Roller Extruder, front view

17 Formulation of Ibuprofen Tablets with Starch as a Wet Binder Formulation Ibuprofen 92.0 % Granules Cellulose Powder 3.0 % Starch (Eurylon 7) 5.0 % Water 14.0 % Final Blend Magnesium Stearate 0.5 % Sodium Carboxymethyl Starch (Explotab) 5.0 % Starch is completely gelatinized Temperature: < 40 C Final Tablet contains 87.6 % of ibuprofen

18 Ibuprofen Tablets, Compression Profile 3,5 3 Tensile Strength (N/mm²) 2,5 2 1,5 Disintegration > 20 min Disintegration > 5 min Disintegration > 1.5 Ibuprofen Granules: Bohle % Mg-Stearate + 5.0% Explotab 1 Disintegration < 30 - 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 0, Compression Presssure (MPa)

19 1. Conclusion Especially modified starches deserves serious consideration as binders in solid dosage forms wet granulation.

20 Co-Processed Excipient, StarLac, 85% Lactose, 15% Corn Starch

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

22 StarLac, Disintegration Time of Tablets versus Compression Force Disintegration time (+1.0% Mg-stearate) 03' 30'' 03' 00'' 02' 30'' Physical Mixture disintegration time 02' 00'' 01' 30'' 01' 00'' 00' 30'' StarLac 00' 00'' compression force [kn] Starlac corn starch + Flowlac

23 StarLac, Influence of Magnesium Stearate 02' 53'' 02' 36'' Physical Mixt., 0.5 % Mg-Stearate 02' 18'' Disintegration Time [s] 02' 01'' 01' 44'' 01' 26'' 01' 09'' 00' 52'' 00' 35'' 00' 17'' Physical Mixt., 0.1 % Mg-Stearate StarLac, 0.5 % Mg-Stearate StarLac, 0.1 % Mg-Stearate 00' 00'' Tablet Crushing Strength [N] StarLac 0,5% Mg-Stearat Physikalische Mischung 0,5% Mg-Stearat StarLac 0,1 Mg-Stearat% Physikalische Mischung 0,1% Mg-Stearat

24 StarLac, Orodispersible Tablets Orodispersible tablets: Tablets to be placed in the mouth where they disperse rapidly before swallowing

25 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)

26 StarLac, Orodispersible Tablets Porosity controlled: swelling and collapse Viscosity controlled: continous melting

27 StarLac, Orodispersible Tablets

28 StarLac, Orodispersible Tablets

29 Lycoat, Film-Former for Coated Tablets Lycoat: Pea Starch with ideal amylose content Hydroxypropylated to avoid starch retrogradation

30 Lycoat, Film Properties

31 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.