Dissolution control of direct compression tablets in ... · 7 . Dissolution Control of Direct Compression Tablets Generally, dissolution profile of direct compression (DC) tablets

1

Dissolution control of direct compression tablets in different test media using novel

pregelatinized starch, SwelstarTM MX-1

ASAHI KASEI CHEMICALS CORPORATION

CEOLUS R&D DEPARTMENT

2

CONTENTS

General Characteristics of SWELSTARTM MX-1

Special Properties of SWELSTARTM MX-1

Application Fields of SWELSTARTM MX-1

Mechanism of Dissolution Control by

SWELSTARTM MX-1

Conclusions

3

General Characteristics of SWELSTARTM MX-1

Developed by Asahi Kasei Chemicals and Sanwa Cornstarch.

Produced by physical modification of potato starch.

Performs as matrix agent to control sustained drug release.

Applicable for CR of drugs with various water solubilities.

Dissolution controllable tablets in different media.

Conformable to USP/NF, EP and JPE [Pregelatinized Starch].

4

Water soluble and insoluble elements

- Resistant to alpha-amylase

High swelling ability by rapid hydration

- Gel matrix structure

- Independent of ionic strength in test media

Strong gel matrix structure having resistance to erosion

- Resistant to digestive tract motions

Controllable gel strength with addition of water soluble material

- Dissolution control

- Zero-order release profile

Low reactivity

- High storage stability

Special Properties of SWELSTARTM MX-1

5

Powder Properties of SWELSTARTM MX-1

MX-1 consists of water soluble and insoluble substances. The insoluble part keeps the raw starch-like crystalline structure, contributing to its resistance to alpha-amylase. MX-1 forms gel matrix structure after swelling by rapid hydration.

a) Dry state (SEM) b) Wet state (OM *1 )

Particle morphology

*1 Optical microscope

Typical properties of MX-1

Bulky density

[g/cm3]

0.27

Repose angle [°] 36

Av. particle diameter

[μm]32

Water holding capacity

[%]800

Swelling volume

[cm3/g]

9

Water soluble content

[%]60-85

Viscosity [mPa･s]

2% solution at 25 ºC70

6

Application Fields of SWELSTARTM MX-1

Controlled release gel-matrix tablets

Dissolution control of direct compression tablets

- various drugs with different water solubilities

- various media with different pH

- different rotation speeds

- storage stability of the drug release profile

7

Dissolution Control of Direct Compression Tablets

Generally, dissolution profile of direct compression (DC)

tablets is faster than that of wet-granulation (WG) tablets.

Therefore, it is not easy to adjust the dissolution profile

of DC tablets to that of WG tablets in various test media

required by the guideline for the bioequivalence tests of

generic drugs.

Purpose of this study

It was investigated whether it is possible to adjust the

dissolution profile of DC tablets in different test media by

using a small amount of MX-1 to the original dissolution

profile of WG tablets.

8

Benefits of DC Method

granule Powder Tablet Tableting Granulation and drying

DC method has no granulation and drying process, therefore it can give an effective cost reduction.

WG method

DC method

Powder Tablet Tableting

9

Rotating paddle (50, 100 rpm) method with 900 ml medium: Water, Artificial gastric buffer pH 1.2 (1st fluid in JP XIV) and Artificial intestinal buffer pH 6.8 (2nd fluid in JP XIV)

SSA※1

MCC※2

Lactose※3

CS※4

HPC-L※5

70 wt%

10 wt%

15 wt%

5 wt%

0.75 wt%*

(*Of total of above)

Single press (MODEL-1321DW CREEP, AIKOH Engineering)

180 mg, φ8 mm, round-face (Tablet hardness: about 60N)

Experiment Procedure - Highly Water Soluble Drug -

Tableting

Evaluation

WG method

Granulation

Drying

Granule

High shear granulator VG-10 (Powrex Corporation), Load: 1600g, Binder: 200g (6% HPC-L aq.), Impeller: 280rpm, Cross screw: 3000rpm, Granulation time: 3min

1410 μm

Fluidized bed granulator MP-01 (Powrex Corporation)

※1 Sodium salicylic acid, Yoshitomi (Solubility in water: 1250 mg/ml) ※2 Microcrystalline cellulose, Ceolus™ PH-101, ASAHI KASEI ※3 Pharmatose 200M, DMV-Fonterra ※4 Corn starch, ST-C, Nippon Starch Chemical ※5 Hydroxypropyl cellulose, Type L

Dissolution test

10

Experiment Procedure - Highly Water Soluble Drug -

Tableting

Evaluation

※1 Sodium salicylic acid, Yoshitomi ※2 Microcrystalline cellulose, Ceolus™ UF-711, ASAHI KASEI ※3 Super-TabTM, DMV-Fonterra ※4 Silica, Aerosil® 200, Nippon Aerosil ※5 Hydroxypropyl cellulose, Type L

SSA※1

MCC※2

Lactose※3

SiO2※4

70 wt%

20 wt%

10 wt%

0.5 wt%*

(*Of above total)

SSA※1

MCC※2

Lactose※3

MX-1 or HPC-L※5 SiO2※4

70 wt%

18-20 wt%

0-7 wt%

3-12 wt%

0.5 wt%*

(*Of above total)

DC-1 method

Mixing

DC-2 method

for 3 min in PE bag



Rotating paddle (50, 100 rpm) method with 900 ml medium, Water, Artificial gastric buffer pH 1.2 (1st fluid in JP XIV) and Artificial intestinal buffer pH 6.8 (2nd fluid in JP XIV)

Dissolution test

11

Dissolution Profiles from WG Tablets and DC Tablets - Highly Water Soluble Drug -

Only 5% MX-1 demonstrates the same sustained release profile of SSA from DC tablets as the WG tablets, however HPC could not sustain release of SSA even at 12%. 0

20

40

60

80

100

0 20 40 60 80 100 120

時間[min]

溶出率

[%]

HPC-L 3%

HPC-L 6%

HPC-L 9%

HPC-L 12%

湿打処方

直打処方 DC-2 Tablets (HPC-L)

DC-1 Tablets

WG Tablets

Dis

solu

tion[

%]

Time[min]

0

20

40

60

80

100

0 20 40 60 80 100 120

時間[min]

溶出率

[%]

MX-1 3%

MX-1 5%

MX-1 6%

湿打処方

直打処方 DC-2 Method (MX-1) DC-1 Tablets

WG Tablets

Dis

solu

tion[

%]

Time[min]

DC-2 Tablets (MX-1)

0

20

40

60

80

100

0 20 40 60 80 100 120

時間[min]

溶出率[%]

湿打処方

直打処方DC-1 Tablets

WG Tablets

Dis

solu

tion[

%]

Time[min]

pH Buffer 1.2

12

0

20

40

60

80

100

0 20 40 60 80 100 120

Time[min]

Dis

solu

tion[

%]

DC-1 TabletsWG TabletsDC-2 Tablets (5% MX-1)DC-2 Tablets (12% HPC-L)

Buffer pH 1.2

The Influence of Different Test Media

- Highly Water Soluble Drug -

MX-1 could adjust the dissolution profile of DC tablets in different test media to that of WG tablets.

0

20

40

60

80

100

0 20 40 60 80 100 120

Time[min]

Dis

solu

tion[

%]


Buffer pH 6.8

0

20

40

60

80

100

0 20 40 60 80 100 120

Time[min]

Dis

solu

tion[

%]


Water

pH Buffer 1.2 pH Buffer 6.8

Water

13

The Influence of Different Rotating Speeds - Highly Water Soluble Drug -

MX-1 shows the same dissolution profile as WG tablets at both conditions of 50 rpm and 100 rpm.

0

20

40

60

80

100

0 20 40 60 80 100 120

時間[min]

溶出率[%]

HPC-L 12% 50rpm

HPC-L 12% 100rpm

湿打処方/50rpm

湿打処方/100rpm

0

20

40

60

80

100

0 20 40 60 80 100 120

時間[min]

溶出率[%]

湿打処方/50rpm

湿打処方/100rpm

100rpm

50rpm

Dis

solu

tion[

%]

Time[min]

WG Tablets

0

20

40

60

80

100

100rpm

50rpm Dis

solu

tion[

%]

Time[min] 0 20 40 60 80 100 120

DC-2 Tablets (5% MX-1)

50rpm

100rpm

DC-2 Tablets (12% HPC-L)

Dis

solu

tion[

%]

Time[min]

pH Buffer 1.2

14

0

20

40

60

80

100

0 20 40 60 80 100 120

Time[min]

Dis

solu

tion[

%] DC-1 Tablets

WG Tablets

DC-2 Tablets (5% MX-1)

DC-2 Tablets (12% HPC-L)

Water

Disintegration of Tablets - Highly Water Soluble Drug -

Disintegration Time [min]

7

25

12

14

MX-1 could sustain release of SSA from DC tablets without delaying the disintegration time compared to WG tablets.

15

-Dissolution test Rotating paddle (50 rpm) method with 900 ml medium, Water, Artificial gastric buffer pH 1.2 (1st fluid in JP XIV), Artificial intestinal buffer pH 6.8 (2nd fluid in JP XIV) and buffer pH 4.0



Experiment Procedure - Water Insoluble Drug -

Tableting

Evaluation

WG method

Granulation

Drying

Granule

High shear granulator VG-10 (Powrex Corporation), Load: 1050g, Water: 140g, Impeller: 280rpm, Cross screw: 3000rpm, Granulation time: 3min

COMIL (Powrex Corporation), Screen: 1.14mmφ, Spacer: 250mm, Frequency: 40Hz, -1410μm

Fluidized bed granulator MP-01 (Powrex Corporation)

※1 Ethenzamide, Yoshitomi (Solubility in water: 0.97 mg/ml) ※2 Pharmatose 200M, DMV-Fonterra ※3 Hydroxypropyl cellulose, Type L

Etz※1

Lactose※2

HPC-L※3

30 wt%

70 wt%

5 wt%*


16

-Dissolution test Rotating paddle (50 rpm) method with 900 ml medium, Artificial gastric buffer pH 1.2 (1st fluid in JP XIV)


180 mg, φ8 mm, round-face (Tablet hardness: about 60N) Tableting

Evaluation

※1 Ethenzamide, Yoshitomi ※2 Super-TabTM, DMV-Fonterra ※3 Microcrystalline cellulose, Ceolus™ UF-711, ASAHI KASEI ※4 Hydroxypropyl cellulose, Type L

Etz※1

Lactose※2

MCC※3

30 wt%

50 wt%

20 wt%

Etz※1

Lactose※2

MCC※3

MX-1 or HPC-L※4

30 wt%

35-44 wt%

20 wt%

6-15 wt%

DC-1 method

Mixing

DC-2 method

for 3 min in PE bag


17

Dissolution Profiles from WG Tablets and DC Tablets - Water Insoluble Drug -

Only 8% MX-1 demonstrates the same sustained release profile of Etz from DC tablets as the WG tablets, however HPC could not sustain the release of Etz even at 15%. 0

20

40

60

80

100

0 30 60 90 120 150 180

Time[min]

Dis

solu

tion[%

]

HPC-L：10%

HPC-L：15%

DC-2 Tablets (HPC-L)

DC-2 Method (MX-1)

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[%

]

MX‐1：6%

MX‐1：8%

DC-2 Tablets (MX-1)

0

20

40

60

80

100

0 30 60 90 120 150 180

Time[min]

Dis

solu

tion[%

]

DC-1 Tablets

WG Tablets

pH buffer 1.2

18

The Influence of Different Test Media on WG Tablets - Water Insoluble Drug -

The dissolution profiles of WG tablets in pH buffer 6.8 and water show the biggest difference.

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

WG （pH 1.2）

WG （pH 6.8）

WG （water）

WG Tablets

Dissolution tests of DC tablets with either 5% MX-1 or 5% HPC were performed in pH buffer 6.8 and water.

19

The Influence of Different Test Media on DC Tablets - Water Insoluble Drug -

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

WG （pH 6.8）

WG （water）

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

DC with 5%HPC （pH 6.8）

DC with 5%HPC （water）

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

DC with 5%MX-1 （pH 6.8）DC with 5%MX-1 （water）

※1 Ethenzamide, Yoshitomi ※2 Pharmatose 200M, DMV-Fonterra ※3 Hydroxypropyl cellulose, Type L ※4 Super-TabTM, DMV-Fonterra

Etz※1

Lactose※4

MX-1 or HPC-L※3

30 wt%

70 wt%

5 wt%*


DC tablets with either 5% MX-1 or 5% HPC-L WG tablet

Etz※1

Lactose※2

HPC-L※3

30 wt%

70 wt%

5 wt%*


Both WG tablets and DC tablets which contain 5% HPC showed faster dissolution in pH buffer 6.8 than in water. To the contrary, DC tablets which contain MX-1 showed the reverse action. Therefore HPC was used in order to enhance the dissolution in pH buffer 6.8 together with a main matrix agent, MX-1.

WG Tablets DC Tablets (5% HPC-L) DC Tablets (5% MX-1)

20

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

WG

DC with 5% MX-1 + 5% HPC-L

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

WG

DC with 5% MX-1 + 5% HPC-L

pH buffer 6.8

Water

The Influence of Different Test Media on DC Tablets - Water Insoluble Drug -

DC tablets with 5% MX-1 and 5% HPC-L WG tablet

Etz※1

Lactose※2

HPC-L※3

30 wt%

70 wt%

5 wt%*


※1 Ethenzamide, Yoshitomi ※2 Pharmatose 200M, DMV-Fonterra ※3 Hydroxypropyl cellulose, Type L ※4 Super-TabTM, DMV-Fonterra ※5 Microcrystalline cellulose, Ceolus™ UF-711, ASAHI KASEI

Etz※1

Lactose※4

MCC※5

MX-1 HPC-L※3

30 wt%

40 wt%

20 wt%

5 wt%

5 wt%

By using 5% MX-1 and 5% HPC, the dissolution profiles are closer to that of WG tablets, but not the same. It needs to be promoted in the later stage of the dissolution.

21

The Effect of PEG on Drug Release Profile - Water Insoluble Drug -

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

5%MX-1+5%HPC

5%MX-1+5%HPC+10%PEG

Water

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

5%MX-1+5%HPC

5%MX-1+5%HPC+10%PEG

BufferpH 6.8

※1 Ethenzamide, Yoshitomi ※2 Super-TabTM, DMV-Fonterra ※3 Microcrystalline cellulose, Ceolus™ UF-711, ASAHI KASEI ※4 Hydroxypropyl cellulose, Type L ※5 Polyethylene glycol, Macrogol 6000, Sanyo

Etz※1

Lactose※2

MCC※3

MX-1 HPC-L※4

PEG※5

30 wt%

30 wt%

20 wt%

5 wt%

5 wt%

10 wt%

DC tablets with 5% MX-1 and 5% HPC-L and 10% PEG

By adding 10% PEG, the dissolution was restrained in the early stage and then it was promoted in the later stage.

pH buffer 6.8

Water

22

-Dissolution test Rotating paddle (50 rpm) method with 900 ml media, Water, Artificial gastric buffer pH 1.2 (1st fluid in JP XIV), Artificial intestinal buffer pH 6.8 (2nd fluid in JP XIV) and Buffer pH 4.0

Rotary Press (Clean Press, Kikusui Seisakusho Ltd.), 12punches, 54rpm

180 mg, φ8 mm, round-face Tableting

Evaluation

※1 Ethenzamide, Yoshitomi ※2 Super-TabTM, DMV-Fonterra ※3 Microcrystalline cellulose, Ceolus™ UF-711, ASAHI KASEI ※4 Hydroxypropyl cellulose, Type L ※5 Polyethylene glycol, Macrogol 6000, Sanyo

Etz※1

Lactose※2

MCC※3

MX-1 HPC-L※4

PEG※5

30 wt%

30 or 33 wt%

20 wt%

5 wt%

5 wt%

7 or 10 wt%

DC-3 method

Mixing for 3 min in PE bag


0.5% Mg-St※6 ※6 Magnesium Stearate, Taihei Chemical Industrial Co. Ltd.

23

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

Buffer pH 1.2

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

WG TabletsDC-1 TabletsDC-3 Tablets (7% PEG)DC-3 Tablets (10% PEG)

Water

Dissolution Profiles in Different Media - Water Insoluble Drug -

It was possible to adjust the dissolution profile of DC tablets in different test media by using 5% MX-1 in combination with 5% HPC and 7-10% PEG to that of WG tablets. MX-1 acted as a sustained-release matrix and PEG was used to specifically control the dissolution profile. HPC was effective to enhance the dissolution in pH buffer 6.8, in which the WG tablet shows faster dissolution than in the other media.

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

Buffer pH 6.8

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%]

Buffer pH 4.0pH Buffer 1.2 pH Buffer 6.8 pH Buffer 4.0

24

0

20

40

60

80

100

0 30 60 90 120 150 180Time[min]

Dis

solu

tion[

%] DC-1 Tablets

WG Tablets

DC-3 Tablets (7% PEG)

DC-3 Tablets (10% PEG)

Water

Disintegration of Tablets - Water Insoluble Drug -

Disintegration Time [min]

2

45

32

37

MX-1 could sustain release of Etz from DC tablets without delaying disintegration time compared to WG tablets.

25

Storage Stability of Drug Release

under Accelerated Conditions - Water Insoluble Drug -

The release profiles of Etz from DC-3 tablets with 7% PEG hardly changed under accelerated conditions for 6 months.

Etz/Lactose/MCC/MX-1/HPC/PEG =30/33/20/5/5/7

Buffer pH 6.8

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

Storage for 6 months under the condition of 40˚C75%R.H. in sealed glass bottles

Buffer pH 1.2

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

Buffer pH 4.0

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

Water

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

純水・40℃75%RHオープン

0

20

40

60

80

100

0 30 60 90 120 150 180

時間[min]

溶出率[%]

湿打－initial

直打－initial

直打－2week

直打－1month

直打－3month

直打－6month

WG Tablets-initial DC-3 Tablets (7% PEG)-initial DC-3 Tablets (7% PEG)-2 weeks DC-3 Tablets (7% PEG)-1 month DC-3 Tablets (7% PEG)-3 months DC-3 Tablets (7% PEG)-6 months

pH Buffer 1.2 pH Buffer 6.8 pH Buffer 4.0 Water

26

Storage Stability of Drug Release

under Accelerated Conditions - Water Insoluble Drug -

The release profiles of Etz from DC-3 tablets with 10% PEG hardly changed under accelerated conditions for 6 months.

Etz/Lactose/MCC/MX-1/HPC/PEG =30/30/20/5/5/10

Storage for 6 months under the condition of 40˚C75%R.H. in sealed glass bottles

純水・40℃75%RHオープン

0

20

40

60

80

100

0 30 60 90 120 150 180

時間[min]

溶出率[%]

湿打－initial

直打－initial

直打－2week

直打－1month

直打－3month

直打－6month

WG Tablets-initial DC-3 Tablets (7% PEG)-initial DC-3 Tablets (7% PEG)-2 weeks DC-3 Tablets (7% PEG)-1 month DC-3 Tablets (7% PEG)-3 months DC-3 Tablets (7% PEG)-6 months

Buffer pH 1.2

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

Buffer pH 6.8

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

Water

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

Buffer pH 4.0

0

20

40

60

80

100

0 30 60 90 120 150 180時間[min]

溶出率

[%]

pH Buffer 1.2 pH Buffer 6.8 pH Buffer 4.0 Water

27

How could SWELSTARTM MX-1 Specifically Control the Dissolution Profile?

In combination with PEG, MX-1 could restrain the

dissolution of the DC tablets in the early stage and then

promote dissolution in the later stage.

The mechanism of the dissolution control by MX-1 and PEG

was investigated.

28

APAP※1

MX-1 or HPMC※2

MCC※3 PEG※4

-Dissolution test Rotating basket (100 rpm) method with 900 ml medium Artificial intestinal buffer (2nd fluid in JP XIV) , pH: 6.8, α-amylase 5 μg/L -Tablet weight & water absorbing capacity (WAC) Tablet being removed during dissolution test

※1 Acetaminophen, Yoshitomi (Solubility in water: 15.8 mg/ml)

※2 Hydroxypropyl methylcellulose, Viscosity of 2% solution: 100mpa・s

※3 Microcrystalline cellulose, Ceolus™ KG-802, ASAHI

※4 Polyethylene glycol, Macrogol 6000 , Sanyo

10 wt%

60 wt%

20-30 wt%

0-10 wt%


180 mg, φ8 mm, round-face, Compression force 6 kN

TWwet: Tablet weight in wet state TWdry: Tablet weight after drying

WAC= (TWwet – TWdry) / TWdry × 100

Experiment Procedure - The Effect of PEG -

Mixing

Tableting

Evaluation

for 3 min in PE bag

29

0

20

40

60

80

100

0 2 4 6 8 10Time (hr)

% D

isso

lutio

n

0 5 10

PEG(%)

0

20

40

60

80

100

0 2 4 6 8 10Time (hr)

% D

isso

lutio

n

0 10

PEG(%)

Dis

solu

tion r

ate

[%

]

In combination with 10% PEG, MX-1 restrained the dissolution of matrix tablets in the early stage and then promoted dissolution in the later stage, whereas HPMC showed no change of the dissolution with PEG.

Dis

solu

tion r

ate

[%

]

60% MX-1 60% HPMC

Dissolution Profiles of Matrix Tablets - The Effect of PEG -

30

0

50

100

150

200

250

300

350

0 1 2 3 4 5 6 7 8 9

Time（hr）

Wet

weig

ht

(mg)

0

50

100

150

200

250

300

350

0 1 2 3 4 5 6 7 8 9

Time（hr）W

ater

abso

rbin

g cap

acity(

%)

Tablet weight in wet state Water absorbing capacity

Both MX-1 and HPMC swelled in the first 2 hours, and then eroded. Tablet weight in wet state showed that MX-1 experienced less erosion than HPMC especially without PEG. Addition of PEG increased water absorbing capacity and accelerated erosion for MX-1 after 5 hours. PEG did not affect swelling or erosion patterns of HPMC.

swelling erosion

Swelling and Erosion of Matrix Tablets

during Drug Dissolution - The Effect of PEG -

Time [hr] Time [hr]

Table

t w

eig

ht

in w

et

state

[m

g]

Wate

r abso

rbin

g c

apaci

ty

[%]

MX-1 PEG 0% MX-1 PEG10% HPMC PEG 0% HPMC PEG10%

MX-1 PEG 0% MX-1 PEG10% HPMC PEG 0% HPMC PEG10%

31

0

20

40

60

80

100

0 2 4 6 8 10Time (hr)

% D

isso

lutio

n

PEG: 0 %PEG: 10 %

Hydration of MX-1 particles was promoted, then strong gel layer was formed.

Excess water absorption decreases gel strength.

Drug diffusion was restrained effectively.

Diffusion of drugs and erosion of gel layer were promoted remarkably.

1st stage

2nd stage 1st stage 2nd stage

Hydration of HPMC particles was not largely affected by promoting water penetration, because hydration rate was very high originally.

0

20

40

60

80

100

0 2 4 6 8 10Time (hr)

% D

isso

lutio

n

PEG: 0 %PEG: 10 %

Assumed Mechanism: How could SWELSTARTM MX-1 Specifically Control the Dissolution Profile with PEG?

Time [hr]

Time [hr] D

isso

lution r

ate

[%

] D

isso

lution r

ate

[%

]

Water penetration was promoted by adding PEG

Matrix Tablet

Matrix Tablet

60% MX-1

60% HPMC

32

It is assumed that tablets containing 5% MX-1 disintegrate into fragments, and each fragment forms gel layer ( ) on its surface, which sustains the release of drug.

Assumed Mechanism: How could SWELSTARTM MX-1 Sustain Release of Drug without Delaying Disintegration Time?

5% MX-1

Water Penetration

Swelling Disintegration Tablet

Gel Layer

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MX-1 can sustain the release of drugs from DC tablets at low doses without

delaying disintegration time, and adjust the dissolution profile to the

original dissolution profile of WG tablets in combination with other

excipients such as PEG.

MX-1 is a sustained-release excipient which is applicable to varying

conditions such as drugs with different water solubilities, various

media with different pH and different rotation speeds.

Tablets containing MX-1 show stable drug release profiles under

accelerated conditions.

CONCLUSIONS

MX-1 can perform as an effective and useful sustained-release excipient to control dissolution profiles of DC tablets.

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Thank you for your attention !

Documents

Dissolution control of direct compression tablets in ... · 7 . Dissolution Control of Direct Compression Tablets Generally, dissolution profile of direct compression (DC) tablets