(USP1092)溶出度试验的开发和验证

1092

USP

1.

1.1 Performing Filter Compatibility

1.2

1.3

1.4

2.

2.1

2.2

2.3

2.4

2.4.1

2.4.2

2.4.3

2.4.4

2.52.6

3.

3.1

3.2

3.3

3.4

3.5

3.6HPLC

4.

4.1

4.2 4.3

4.4

4.5

4.6

5.

5.1 /

5.2

5.3 /

5.4

5.4.1

5.4.2

5.4.3

5.55.6

5.7

6.

6.1

6.2

6.3

6.4

6.5

6.5.1

6.5.2

6.5.3

7.

1.

1.1

frits 0.20 70 m

USP 4

1.2

pH 37 37 25 pH pHpH 1.2-7.5

SDS

CMC 1 CMC - FDA - 1

SDS HPLC 80

pH SDS 0.5mol/L SDS1

CMC

SDS,SLS 0.18%-0.23% 2-4

0.2% 3

0.16% 3

0.12% 3

CTAB

0.033%-0.036%

0.92-1.0mM

5,6 1622 0.18%(4mM) 2

20 20 0.07%-0.09% 3,7

80 80 0.02%-0.08% 3.7

Labrasol

0.01% 4 35 Cremophor

EL

0.02% 8 Brij

35 0.013% 9 Triton

X-100 0.01%-0.03% 3,10

N-

LDAO

0.023% 11

pH pH pH

37

1.3

711 Capsules–Dissolution Testing and RelatedQuality Attributes 1094 5

IR

711 A B 10%

1 2 500 1000 2 4

3 7

4 100-200

1.4

2 1 1 2

3

44 beaded products

5

6

7 see Semisolid Drug Products—Performance Tests <1724>

40 10 20 80 <711>

2.

10 12 RSD

20% RSD 10%

2.1

<711>USP RS 6 /

2.2

2

<711> 2a

316 0.032 /20 2 ;

cm

#0 12 0.8 4

#1 #2 10 0.7 3

#3 #4 8 0.55 2<711> 2a

2.3

1 50~100 rpm

2 50 75 rpm 25 rpm 150 rpm

25rpm~50rpm

50rpm 75 rpm 100rpm IVIVC

3 5 30

4 ( )

2.4

<711>

2.4.1

30~60 min FDA 15 85% 30~45 85%~100%5 10 60

15 85% f2 f2 85% n=12 85%

>80% B according to In Vitro and In Vivo Evaluation of Dosage Forms <1088> 100%

2 pH <711>

2 PH

15~60 100%

2.4.2

/

[

]

2.4.3

/

<711> 50

4

2.4.4

/

4.4

2.5

1 2 4 4

1

2

1 C t 1

2 4

2 An example of a plot of theobserved concentration of the sample taken for an interval that is negligiblysmall in relation to the time of the overall dissolution process. Thisconcentration is propostional to the instantaneous or fractional dissolution rate(dc/dt). This type of plot is readily observed in continuous-flowdissolution systems, such as Apparatus 4 in openloop configuration.

2.6

85% 85% 15 f2

±10%~20%

3.“ ”

5

3.1

3.2

1.1

3.3

3.4

HPLC

3.5

0.02cm~1cm

100% Q

=A/bc

A= b= cm c= mg/ml

AU• / AU

.

3.6 HPLC

HPLC >100

100

4.

711

4.1

pH 2.1

4.2

±2%

4.3

1 2

1% 2.5

4.4

pH

5.7

2.4.3 ,

PTFE PP HDPE

4.4

2.4.4

4.5

21 CFR11 17

4.6

•

•

•

•

5.

<1225> ICH 3 / <1225>

SOP 1.1

5.1 /

37

= (A P/A S)×Cs ×(V/L)×100A P A S

Cs mg/ml V ml

L mg

2%

1% 1%

2% HPLC

2%

5.2

/ 5 <1225> 5% v/v r2 0.98 , y 0 common stock

5.3 /

/

5% 95%~105%

<711> 10%

5.4

5.4.1

/ / RSD RSD ICH

100% 6 RSD<2% +

5.4.2 /

HPLC85% 10% 85% 5%

5.4.3

5.5

3 6 .

pH DOE ,

1225 HPLC pH

5.6

98%-102%

98%-102%

5.7

711/

<85% 10% >85% 5%

6.

19

6.1

10 20 30 40

50 60 15 30 45 60

Q Q 75%-80% Q 80%

6.2

<711> <711> NMT 0.1n 2 0.05M pH=6.8. ph 45

Q6.3

20 1-2 20

19,20 / 19,20 L2 L3 2 L1 <711>

6.4

4.10.10 1 21 2 2 22,23

6.5

<711>

6.5.1

Q S1 6 Q +5

30

NLT80%(Q) “ ” 80%

200mg Q LC 80% 30 170mg 30 NLT85%

2 S2 6 s2 12 Q LC80% 160mg Q-15% LC 80% 130mg .

3 S3 12 s3 2

4 Q LC80% 160mg 1) LC65% 130mg ,2 . Q-25% LC55% 110mg

6.5.2

10% 1 A1 A1 6 2 A2 A2 12 NMT 10 25 10%

Q B1 B2

B3 B1 B2 B3 S1 S2 S3

6.5.3

1 4 8

1 LC 24 44

4 LC 56 76

8 NLT85

USP-NF 33.L1

h

1 24-44%

4 56%-76%

8 NLT85%

1 L1 6 1

1 L1 ; 1 L1 6

2 L2 L2

1 1

2 NLT

2 12 >10

3 12 >10

L2 12 4

4.L2

1h 4h 8h 24-44% 56%-76% NLT85%

14%-54% 46%-86% NLT75%

12 3 L3 L3

1 24 NLT

2 24 NMT2 >10

3 2

4 NMT2 >10

4 24 >20

5 24 >20

5.L3

1h4h8h

NMT2 14 -

54

4 -

NMT2

46 -86

36 -

96

NMT2

<75