Kollicoat IR. The application of Kollicoat IR as a Zero Peroxide Binder for use in Solid Oral Dosage Forms. ExcipientFest.

Transcription

1 Kollicoat IR The application of Kollicoat IR as a Zero Peroxide Binder for use in Solid Oral Dosage Forms ExcipientFest Nigel Langley

2 Market Need Platforms Instant & Modified Release Solubilization Skin Softgels Biologics Delivery Solutions. Focus on Excipient Functionality 2

3 Market Need Platforms Instant & Modified Release Solubilization Skin Softgels Biologics Delivery Solutions. Kollicoat IR Instant Release Coating Polymer Focus on Excipient Functionality 3

4 Kollicoat IR - Elongation at Break 4

5 Kollicoat IR Impact of Viscosity on processing steps Preparation of the coating suspension Film coating Process Kollicoat IR s low viscosity over all leads to a shortened process time and an increase of production efficiency (through-put) through all these factors

6 PRODUCT TEMPERATURE [ C] Process Parameter for IR Film Coating Kollicoat IR formed film is very flexible extremely wide range of usable parameters very short process time PROCESS TIME [m inutes] film coating impossible, sticking of the cores film coating principally possible, surface not acceptable clearly separated quality zones optimum film coating process, surface acceptable optimum film coating process, best results in surface quality

7 Process Parameter for IR Film Coating Comparison to Competitor Products film coating impossible, sticking of the cores film coating principally possible, surface not acceptable optimum film coating process, surface acceptable optimum film coating process, best results in surface quality

8 elongation at break [%]. Properties of the isolated Films Pigment Binding Capacity Kollicoat IR HPMC type 3 mpas HPMC type 6 mpas talc concentration [%]

9 Market Need Platforms Instant & Modified Release Solubilization Skin Softgels Biologics Delivery Solutions. Kollicoat IR Instant Release Coating Polymer Wet Binder Focus on Excipient Functionality 9

10 Kollicoat IR Instant release binder options from BASF Ready-to-use Direct compression Granulation Regular ODT Dry (roller compaction) Wet CL-M Ludiflash Ludipress VA64 Fine Kollidon VA64 Fine Kollidon CL-M Peroxides Aqueous Solventbased Low volume, high binding VA64 Kollidon VA64 Kollidon CL-SF Extended protection Kollidon VA64 K25 / K30 Peroxeal Kollidon 90 Peroxeal Superior protection K30 LP Peroxeal Maximum protection Kollicoat IR 10

11 Kollicoat IR Market trend towards the use of low-peroxide binders Need for low peroxide formulations Examples for peroxidesensitive APIs New sensitive APIs Low dosage formulations Product lifecycle mgmt OTC packaging (no blister) Cost efficiency Hormones Estrogen Gestagen Antivirals / Anti-HIV Saquinavir Coronary Verapamil Diltiazem 11

12 Peroxide Kollicoat IR does not show peroxide buildup! After production Batch No Peroxide level, meq/kg * at release < < < < < < < < < <1 During stability storage Months at 40 C/75% r.h. Peroxide level, meq/kg * 0 month <1 3 months < 1 6 months < 1 12 months 1 18 months 1 30 months 1 12

13 Chemical Structure Kollicoat IR Graft polymer consisting of PEG 6000 and Polyvinyl alcohol Spray dried product Molecular weight approx Dalton ph-value 5 to 8 (solution 20% solids)

14 Log. dynamic visscossity [mpas] Viscosity Kollicoat IR, Kollidon 25, 30, VA64 & solutions can be processed with acceptable low viscosities 1,E+07 1,E+06 1,E+05 1,E+04 1,E+03 Viscosity of binder solutions Batch size: 400g Water: 50g Polymer (solution): 6g 10.7% 12g 19.4% 20g 28.6% 1,E+02 1,E+01 1,E Polymer content [%] Polymer (granules): 1.5% 6g 3.0% 12g 5.0% 20g Kollidon 25 Kollidon 30 Kollidon 90F Kollidon VA64 HPMC 3 mpas HPMC 6 mpas HPMC 15 mpas Kollicoat IR 14

15 Kollicoat IR. Processability in fluid bed and high shear granulation Granulation Dry granulation Wet granulation Melt granulation Roller compaction Vertical granulation Fluid bed* Extrusion High shear Top spray Low shear Bottom spray *applicable as binder solution or using water for powder-blends 15

16 Kollicoat IR In fluid bed granulation, Kollicoat IR shows outstanding tensile strength at low binder content* Tablets with 10% Binder Tablets with 20% Binder** 8 Tensile Strength [N/mm²] 8 Tensile Strength [N/mm²] 6 Kollicoat IR 6 Kollidon 30 (Batch A) 4 4 Kollidon 30 (Batch B) Kollicoat IR HPMC 6 mpas kn 10 kn 18 kn 0 5 kn 10 kn 18 kn *formulated with Ca-Phosphate as filler **HPMC 6mPas hardly processable in high-shear granulation due to impact of high viscosity 16

17 Kollicoat IR In high-shear granulation, Kollicoat IR performs comparable to PVP With 10 kn compression force** With 18 kn compression force** 8 Tensile Strength [N/mm²] 8 Tensile Strength [N/mm²] Kollidon K30 (Batch A) Kollidon K30 (Batch B) Kollicoat IR 0 Kollidon K30 (Batch A) Kollidon K30 (Batch B) Kollicoat IR *formulated with Ca-Phosphate as filler **HPMC 6mPas hardly processable in high-shear granulation due to impact of high viscosity 17

18 Drug release [%] Drug release [%] Kollicoat IR API release comparable to PVP Fluid bed granulation with 10% Binder Fluid bed granulation with 20% Binder Kollidon Time [min] Kollidon 30 Kollicoat IR HPMC 6mPas Time [min] HPMC 6mPas not processable as granulation liquid to viscous 18

19 Kollicoat IR No API degradation products formed Formulation Sr. No Ingredients 3% binder 6% binder mg/tab % content mg/tab % content 1 Raloxifene hydrochloride Binder DCP (Calipharma A) Aerosil Magnesium Stearate Total Degradation products of Raloxifene in stability (Raloxifene-N-oxide) Binder type/-quantity Unit Initial 1 month 3 month 6 month Kollicoat IR - 6% Kollidon 30 LP - 6% area-% Competitor Povidone - 6% Competitor product - 6%

20 Kollicoat IR Allows peroxide-free binding using low binder content with a wide processing window Kollicoat IR is one of the binders where a minimum of binder content is optimal for the granulation. PVP K25 PVP K30 PVP K90 better results worse results HPMC 3mPas HPMC 6mPas HPMC 15mPas VA-VP worse better Kollicoat IR Recommended binder content [%] 20

21 Kollicoat IR Is peroxide free along the full lifecycle Excipient Finished dose Closed/resealed Open Sealed Whole lifetime Kollidon 25/30/90F in Peroxeal Kollidon 30 LP in Peroxeal Kollicoat IR 21

22 Kollicoat IR Is solely suited for aqueous wet binding. 22

23 Functionality Kollicoat IR Powerful binding. No peroxides. Kollidon 25 / 30 Kollidon 90F Cellulose derivatives Native starch Kollicoat IR Viscosity ( aq. solution) low high medium/high high low Binding power high very high medium medium high Processing window wide wide small small wide Pre-processing no no no yes no Organic solvents yes yes yes no no Peroxides yes yes no no no Kollicoat IR has the benefits of PVP and cellulosic derivatives in 1 Binder 23

24 Kollicoat IR FDA Inactive Ingredient Database, IID Inactive Ingredient POLYVINYL ALCOHOL GRAFT POLYETHYLENE GLYCOL COPOLYMER (3:1; MW) Route Dosage Form CAS Number UNII Maximum Potency ORAL TABLET ZQ42JZZH 5.37MG POLYVINYL ALCOHOL GRAFT POLYETHYLENE GLYCOL COPOLYMER (3:1; MW) ORAL TABLET, EXTENDED RELEASE ZQ42JZZH 19MG 24

25 Regulatory Kollicoat IR Powerful binding. No peroxides. Pharma Dietary supplements Ph.Eur (EU) USP/NF (USA) Europe - Use as binder in food supplements covered by E1209 US self-affirmed GRAS JPE (Japan) TGA (Australia) 25

26 Summary Kollicoat IR Powerful binding. No peroxides. Binding power No peroxide formation Low viscosity Binding performance at least as good as Kollidon 30 No evidence for peroxide formation at any time Easy processing due to low viscosity in solution What s next? Kollicoat IR Fine - In development Low peroxide dry binder 26