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Aqueous Coating with Aqueous Coating with ShinShin--Etsu AQOATEtsu AQOAT
Shin-Etsu Chemical Technical Seminar at the Seoul National University
November 17,18 2003
Current Technique in Current Technique in Aqueous Coating with ShinAqueous Coating with Shin--Etsu Etsu
AQOATAQOAT
Basics in current aqueous formulation (one component system)
3
ContentsContents
General informationCurrent aqueous formulation (one component system)An improved formulation using dual feed nozzle (two component system)
4
History of Shin-Etsu AQOATHistory of ShinHistory of Shin--Etsu AQOATEtsu AQOAT
1977 Initiated research for a new enteric coating material. 1983 Developed HPMCAS. 1985 Approval of HPMCAS in Japan.1988 Submitted Drug Master File to FDA (14272).
Listed on “Japanese Pharmaceutical Excipients.”2000 FDA inspected.2001 FDA approved. Applied for the USP.2003 Draft appeared in USP Forum.
5
Current commercial situation Current commercial situation (HPMCAS)(HPMCAS)Countries (production cite):
Japan, Korea, USA, Belgium, GermanyCommercial products appear in most of the European
countries.
Active ingredients: Antibiotics, Digestive enzymes, Anti-depressant, Anti-hypertensive, Hormones, Vitamins, Anti-inflammatory etc.
6
Chemical Structure of HPMCASChemical Structure of HPMCAS
O
O
OO
CH2OR
CH2OROR
OR OR
OR n
R = -H -CH3-CH2CH(CH3)OH-COCH3-COCH2CH2COOH
General Name: Hydroxypropyl Methylcellulose Acetate SuccinateIUPAC Name: Cellulose, 2-hydroxypropyl methyl ether, acetate
butanedioateCAS registry number 71138-97-1
7
Grades of HPMCASGrades of HPMCAS
Grade MeO HPO Acetyl SuccinoylAS-L 20.0-24.0 5.0-9.0 5.0-9.0 14.0-18.0AS-M 21.0-25.0 5.0-9.0 7.0-11.0 10.0-14.0AS-H 22.0-26.0 6.0-10.0 10.0-14.0 4.0-8.0
Substituents in wt%
AS-LG, MG, HG: Granular For organic solventsAS-LF, MF, HF: Fine powder (app. 5 mµ)For aqueous
8
Various coating methods using HPMCASVarious coating methods using HPMCAS
Coating Method Additives Advantages ProcessingTime (min)*
Required coatinglevel (%-polymer)*
Organic solution None Simple 135 7
Aqueous dispersion Current method TEC, Talc, SLS Safe 138 7
Dual feed method TEC, Talc, SLS Safe, fast 90 7 - 9
Aqueous solution Ammonia Easy 197 9
Dry coating TEC, Myvacet, Talc No water 128 9
* Lab-scale tablet coating test for 8mm tablet
9
Aqueous Coating SystemAqueous Coating System
HPMCASTECTalcSLSWater
Pump
HPMCASTalcSLSWater
Pump
Pump
Plasticizer
Current methodPolymer conc. at 7%
Dual feed methodPolymer conc. up to 15%
10
Dry CoatingDry Coating
Pump
TECMyvacet
HPMCASTalc
11
Film Formation Process in AqueousFilm Formation Process in Aqueous
AQOAT
Drying
Close-packed structure
Continuous film formation
Fused
Sprayed Water
For both current and dual feed methods
12
Basic Formulation of Current Coating Basic Formulation of Current Coating Suspension Suspension
Current formulation :
AS-MFTEC *SLS **Talc WaterTotal
* Triethyl citrate, ** Sodium lauryl sulfate ( Sodium dodecyl sulfate ).
7.0 % Enteric polymer1.96 ( 28 % ) Plasticizer0.21 ( 3% ) Wetting agent2.1 ( 30% ) Anti sticking agent
88.73100.0 %
13
Preparation of Coating Suspension Preparation of Coating Suspension
Talc AQOAT TEC SLS Water below 25˚C
Dissolving
Dispersing
Coating suspension
Keep below 25˚C with gentle stirring.
14
Dissolution of TEC
Dispersion of AQOAT powder
Coating suspension
15
Minimum Film Formation Temperature Minimum Film Formation Temperature (MFT) of AQOAT AS(MFT) of AQOAT AS--MF TypeMF Type
MFT
(˚C
)
4030201000
1020304050607080
TEC (%)
AS-MFStandard plasticizer levelfor AS-MF type
16
Heat SensitivityHeat SensitivityCoagulation Temp. vs. Conc. of SuspensionCoagulation Temp. vs. Conc. of Suspension
1210864200
10
20
30
40
Concentration (%)
Coa
gula
tion
tem
pera
ture
(˚C
)
AQOAT
AQOAT + SLS 3%
Current formulation
Old formulation
17
Heat SensitivityHeat SensitivityCoagulation Temp. vs. Amount of TECCoagulation Temp. vs. Amount of TEC
Current formulation
4030201000
10
20
30
40
Amount of TEC (%)
7% conc. SLS 3%
10% conc.
Coa
gula
tion
tem
pera
ture
(˚C
)
Old formulation
18
Summary of Heat SensitivitySummary of Heat Sensitivity
Old Current
Polymer conc. 10 % 7 %Wetting agent None SLS 3%Coagulation temp. 20˚C 28˚CGun blockage temp. 30˚C 38˚C
19
Heating Tendency of Commercial Coating Heating Tendency of Commercial Coating MachinesMachines
Exhaust air
Drying air
Mouse ringfrom front door
Water
Drying air
Exhaust air
Normal flow (parallel)
Water
Exhaust air
Drying air
Reverse flow
Water
Exhaust air
Drying airInner duct
Water
20
Heating Tendency of Commercial Coating Heating Tendency of Commercial Coating MachinesMachines
* Drying airflow system; A: normal flow, B: reverse flow, C: mouse ring (from front door), D: inner duct.Note: in every cases water temperature for spraying at 20˚C. Spray rate is indicated as that per one gun.
Coating machine Charge (kg)
System* Numberof gun
Spray rate
(g/min)
Temperature of sprayed water (˚C)80˚C 70˚C
HI-COATERHCT-MINIHCT-48N
HCT-100N
0.3556060
CCACA
11122
225253535
3938353026
3534332825
AQUACOATERAQC-48TAQC-100
560
DD
12
2535
2925
2824
DRIACOATERDRC-200
DRC-500
DRC-1200
0.30.355
100
ABAAA
11213
33132560
4936362830
4433332728
21
Tablet Coating 1Tablet Coating 1
Machine New Hi-Coater HCT-48NCharge 5 kg (placebo: 8 mm, 200 mg)Spray gun Schlick type Nozzle 1.8 mmSpray air 150 L/min, 200 kPaGun position 16 cm from tablet bed surfaceCoating quantity 8 % based on AQOATSuspension temp. 20~25˚CPost drying Supply air temp. 60˚C, 30 min
22
Tablet Coating 2Tablet Coating 2
Step 1 st 2 nd
Supply air flow 2.4 m3/min 3.0 m3/minSupply air temp. 70˚C 80˚CExhaust air temp. 47˚C 48˚CTablet temp. 45˚C 47˚CSpray feed 25 g/min 45 g/minPan revolution 16 rpm 20 rpmLiquid consumption 714 g 5000 gSpray time 29 min 111 min
23
Acid Resistance 1Acid Resistance 1
109876540
10
20
30
40Current formulationAS-MF 7% conc. SLS 3%AS-MF 10% conc.Old formulation
Coating (%)
Num
ber
of c
hang
ed
24
Acid Resistance 2Acid Resistance 2
109876540
2
4
6
8
Coating (%)
Wei
ght i
ncre
asin
g (%
)
Current formulationAS-MF 7% conc. SLS 3%AS-MF 10% conc.Old formulation
25
Current Aqueous Formulation Current Aqueous Formulation (One Component System)(One Component System)
Faster spray feeding (almost no viscosity)[optimum spray feed rate is doubled]Room temperature handlingGood film formation
Wet condition should be suitable for Shin-Etsu AQOAT.
Latest Development in Latest Development in Aqueous Coating with ShinAqueous Coating with Shin--Etsu Etsu
AQOATAQOAT
An improved formulation using dual feed nozzle (two component system)
27
ProblemProblem……..
The current formulation still has some heat-sensitivityLower polymer concentration
One solution is “Dry Coating”The other one is ….
28
Concept of Two Component SystemConcept of Two Component System
Heat sensitivity derive from the presence of plasticizer in the polymer dispersion
Polymer dispersion without plasticizer shows almost no coagulation tendencySeparation, but spraying with same spray nozzle to prevent dusting and to achieve good film formation
29
Dual Feed Concentric NozzleDual Feed Concentric Nozzle
3 mm
Concentric dual-feed nozzle
Inner for polymer suspensionOuter for plasticizer
30
Atomizing ConditionsAtomizing Conditions
Two component system has dusting tendency (polymer dispersion without plasticizer easily recover original powder)Atomizing conditions should be wet as much as possible
: Close gun position: High spray feed rate: Special device design (left
photo): Low atomizing air flow ratespiral straight
31
Formulation for Separation SystemFormulation for Separation System
Polymer dispersionAQOAT (AS-MF) 15.0 partsTalc 4.5Sodium lauryl sulfate 0.15Water 80.35PlasticizerTriethyl citrate (TEC) 100 parts
32
Tablet Coating 3Tablet Coating 3
Machine New Hi-Coater HCT-100NCharge 60 kg (placebo: 8 mm, 200 mg)Spray gun Dual feed nozzle 1.8 mm x 2Spray air 120 L/min, 400 kPaGun position 10 cm from tablet bed surface
(20 cm for current, 25 cm for Pharmacoat)Coating quantity 8 % based on AQOATSuspension temp. 20~25˚CPost drying Supply air temp. 60˚C, 30 min
33
Tablet Coating 4Tablet Coating 4
Step 1 st 2 nd
Supply air flow 13 m3/min 15 m3/minSupply air temp. 70˚C 75˚CExhaust air temp. 44˚C 35˚C
(41˚C) (40˚C)Spray feed 100 g/min 250 g/min
(110 g/min) (220 g/min)Spray feed for plasticizer 4.3 g/min 10.8 g/minPan revolution 5 rpm 10 rpmSpray time 80 min [2%] 93 min [6%]*
* Expressed as polymer consumption( ) indicate conditions for current formulation
34
Pilot TestPilot TestPolymer pump
Plasticizer pump
Hi-CoaterHCF-100NBatch size 60
kg
35
Photo (Pilot Scale Test)Photo (Pilot Scale Test)
36
Acid Resistance 3Acid Resistance 3
0
10
20
30
40
50
60
Tab
let d
efec
t (%
)
70
5 6 7 8 9Coating amount (% - polymer basis)
Dual-Pilot AS-MF 15%Current-Lab AS-MF 7%
Dual-Lab AS-MF 15%
Current-Pilot AS-MF 7%
37
Inside of Pan after CoatingInside of Pan after Coating
38
ResultsResults
Successfully achievedSlightly lower gastric resistance due to high polymer concentration (15%).
No nozzle-blocking
Reduced coating time (approx. half)
Clean inside of pan after coating