In Vitro Dissolution Absorption System (IDAS): Simultaneous …€¦ · Microsized Formulations of Indomethacin Using the In Vitro Dissolution Absorption System 2 (Li J, et al., J

Chris Bode, Ph.D.

VP Scientific & Corporate Communications

In Vitro Dissolution Absorption System (IDAS):

Simultaneous Dissolution and Permeation

Evaluation

In Vitro Dissolution Absorption System

© 2019 Absorption Systems 2

IDAS2

IDAS1

Biopharmaceutics Dissolution with Better In Vivo Correlation

A Closer Look at IDAS2


A Closer Look at IDAS2


Why IDAS?

Dissolution and permeability are routinely measured independently and under conditions that may have little physiological relevance

Poor discrimination, which impacts the link between in vitro drug product release characteristics and in vivo performance.

Limited utility in formulation development and optimization

IDAS enables concomitant evaluation of bio-relevant processes Improved IVIVC


Dissolution – Permeability Relationship: Class I


Dissolution – Permeability Relationship: Class II


Dissolution – Permeability Relationship: Class III


Dissolution – Permeability Relationship: Class IV


IDAS: Drug Product Dissolution and Permeation


Dissolution

0 30 60 90 1200

20

40

60

80

100Minoxidil (BCS 1)

Carbamazepine (BCS 2)

Azathioprine (BCS 3)

Time (min)

% D

iss

olu

tio

n

Permeation

0 30 60 90 1200

1

2

3

4

Minoxidil (BCS 1)*

Carbamazepine (BCS 2)

Azathioprine (BCS 3)

Time (min)

% P

erm

ea

tio

n

Application: Product Discrimination


Batch Release Data for Amlodipine - Q value was similar for different manufacturers

: p < 0.05

Data using IDAS shows marked differences in dissolution AUC and % permeated for different manufacturers

Product Dissolution AUC

(0-2 hours) % Permeation (0-2 hours)

RLD 7304.8 ± 407.1 2.33 ± 0.52

Test 1 4001.3 ± 590.1* 0.25 ± 0.13*

Test 2 2166.1 ± 756.8* 0.51 ± 0.16*

Test 3 5043.8 ± 1157.7* 0.55 ± 0.35*

Test 4 6477.0 ± 1031.9 0.51 ± 0.16*

IDAS Achieves Relevant Discrimination

2016 AAPS AM; Poster #22R1030

Product % Q

(Average of 10 tablets) SD

RLD 99.0 1.8

Test 1 96.1 7

Test 2 97.5 3.2

Test 3 99.2 1.6

Test 4 95.2 5.6

Application: Equivalence


0

20

40

60

80

100

120

0 20 40 60 80 100 120

Dis

solu

tio

n (

%)

Time (min)

Compound X Dissolution, Low Dose

Test Formulation

RLD

0

20

40

60

80

100

120

0 20 40 60 80 100 120

Dis

solu

tio

n (

%)

Time (min)

Compound Y Dissolution, Low Dose

Test

FormulationRLD

Application: Equivalence


0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

0 20 40 60 80 100 120

Cu

mu

lati

ve

Rec

eiv

er C

on

c. (

nM

)

Time (min)

Compound X Permeation (Low Dose)

RLD

Test

Formulation

0.0

20.0

40.0

60.0

80.0

100.0

120.0

0 20 40 60 80 100 120

Cu

mu

lati

ve

Rec

eiv

er C

on

c. (

nM

)

Time (min)

Compound Y Permeation (Low Dose)

RLD

Test

Formulation

Application: Dose Discrimination


IDAS Achieves Improved Dose Discrimination: Dissolution vs. permeability in fasted state simulated intestinal fluid (FaSSIF) for a tablet with different strengths

Amount Dissolved vs. Time Amount Permeated vs. Time

Application: Food Effect

15

Objective:

Evaluation of dissolution and permeation of the BCS Class 2 drug simvastatin from tablet formulation using FaSSIF (pH 6.5) and FeSSIF (pH 5.8, higher bile salt and phospholipid concentrations)

Faster and complete dissolution in FeSSIF, but permeation was not faster than in FaSSIF

0

20

40

60

80

100

120

0

100

200

300

400

500

600

700

800

900

0 30 60 90 120

Dis

s. (

%)

Co

nc.

(µ

M)

Time (min)

FeSSIF FaSSIF0.00

1.00

2.00

3.00

4.00

5.00

6.00

0 30 60 90 120

Co

nc.

(µ

M)

Time (min)

FaSSIF FeSSIF

Application: Particle Size

Objective: To determine the effects of particle size of oral indomethacin

formulation on drug dissolution and permeation using IDAS2

Methods Nano- and micro-sized indomethacin formulations were dosed at

equal API level into the dissolution chamber.

Indomethacin dissolution and permeation were measured by LC-MS/MS.

The dissolution rate constant (kD) and the permeation rate constant (kP) were determined by simultaneously modeling the concentration vs. time profiles for both dissolution and permeation.


Application: Particle Size


Application: Gastrointestinal Supersaturation

Typical (single-stage) study design: 2 dose units (tablets, capsules) in 500 mL of FaSSIF with permeation chambers immersed in the dissolution vessel

Gastric dissolution followed by emptying into the intestine modeled in vitro with a 2-stage study design: 2 dose units first exposed to SGF (pH 1.6) for 20 minutes before switching to FaSSIF (pH 6.5). The change is achieved by adding 5X FaSSIF, with only 25% dilution.

BCS Class 2 weak bases: dipyridamole, ketoconazole, itraconazole

Weak acid: warfarin

Negative controls (BCS Class 1 weak bases): minoxidil, metoprolol


Application: Gastrointestinal Supersaturation


0 20 40 60 80 100 120 1400

20

40

60

Time (min)

Dis

so

lved

Co

nc.

(

g/m

L)

0 20 40 60 80 100 120 1400

200

400

600

Time (min)

Dis

so

lved

Co

nc.

(

g/m

L)

Dissolution

0 20 40 60 80 100 120 1400

50

100

150

200

250

Time (min)

Dis

so

lved

Co

nc.

(

g/m

L)

Dipyridamole

Ketoconazole

Itraconazole

Permeation

0 20 40 60 80 100 120 1400

1

2

3

4

Time (min)

Perm

eate

d C

on

c.

(

g/m

L)

0 20 40 60 80 100 120 1400

1

2

3

4

Time (min)

Perm

eate

d C

on

c.

(

g/m

L)

0 20 40 60 80 100 120 1400.00

0.05

0.10

0.15

Time (min)

Perm

eate

d C

on

c.

(

g/m

L)

pH shift (●) and pH 6.5 (■)

More Information About IDAS


https://www.absorption.com/kc/idas/

https://www.absorption.com/kc/idas/

IDAS Resource Library

Publications Supersaturation: In Vitro and In Vivo Assessment of the Potential of Supersaturation to Enhance the

Absorption of Poorly Soluble Basic Drugs (Li J, et al., J Pharm Innov., published online 7 Sep 2019;

https://doi.org/10.1007/s12247-019-09404-5)

Particle Size: Simultaneous Analysis of Dissolution and Permeation Profiles of Nanosized and

Microsized Formulations of Indomethacin Using the In Vitro Dissolution Absorption System 2 (Li J, et

al., J Pharm Sci. 2019; 108: 2334-2340)

Viscosity: In Vitro Dissolution Absorption System (IDAS2): Use for the Prediction of Food Viscosity

Effects on Drug Dissolution and Absorption from Oral Solid Dosage Forms (Silchenko S, et al., Eur J

Pharm Sci., published online 21 Nov 2019; https://doi.org/10.1016/j.ejps.2019.105164)

Biowaivers: Innovative In VitroMmethodologies for Establishing Therapeutic Equivalence (Murray L,

et al., Rev Panam Salud Publica. 2016; 40(1): 23-28)

Generics: Near Infrared (NIR)-Spectroscopy and In-vitro Dissolution Absorption System 2 (IDAS2)

Can Help Detect Changes in the Quality of Generic Drugs. (Jimenez-Romero C, et al., Drug Dev Ind

Pharm, published online 3 Dec 2019; https://doi.org/10.1080/03639045.2019.1701004)


Documents

In Vitro Dissolution Absorption System (IDAS): Simultaneous …€¦ · Microsized Formulations of Indomethacin Using the In Vitro Dissolution Absorption System 2 (Li J, et al., J