Dissolution Testing for IR Products

Drug product

Preapproval

Postapproval
BE study Dissolution

New drug

Generic drug

BE BA Dissolution

Class 1 HS/HP/RD

Class 1 HS/HP Class 2,3,4

Higher Strength BE study Dissolution

Dissolution for Biowaivers

Lower strength

Dissolution Testing for IR Products

NDA - If in-vivo BA of formulation established during IND period waivers of

subsequent in-vivo BE studies may be possible for BCS class 1 drugs based on dissolution testing data
Dissolution testing development report recommendations

pH solubility profile of drug Profiles at different agitation speeds e.g.

100-150 rpm for USP apparatus I (basket)

50-100 rpm for USP apparatus II (paddle)

Profiles generated on all strengths in at least three dissolution media

pH 1.2,4.5 and 6.8 buffer

Dissolution Testing for IR Products

BCS class I (HS/HP/RD) biowaivers for BE studies Rapidly dissolving(RD)- not less than 85% of drug dissolves within 30 min

using USP I (100rpm) or USP II (50 rpm) in each media:

0.1 N HCl/ Simulated gastric fluid USP without enzymes

pH 4.5 buffer pH6.8 buffer/ Simulated intestinal fluid USP without enzymes

Dissolution Testing for IR Products

In-vivo BE Studies can be waived based on dissolution tests and in-vivo studies on

highest strength if

Drug product has same dosage form Active and inactive ingredient in the drug product are proportionally similar with respect to strength

If appropriate dissolution method has been established and dissolution results

indicate that dissolution characteristics of product are not dependent on product strength then dissolution profile in one medium is sufficient to support biowaivers
If appropriate dissolution method is not available then dissolution data in three

media (pH 1.2,4.5.6.8 buffer)

Dissolution Testing for IR Products

ANDA BCS based biowaivers for IR (HS/HP/RD) test products provided

reference listed drug product is also rapidly dissolving and having similar dissolution profile that of refernce listed drug product ANDA
No

USP method available

Yes

FDA recommended method available

Yes Follow FDA recommended method

No

New dissolution method development

Follow USP method

Postapproval changes
Level 1 change Dissolution testing enough (No BE)

Level 2 change - Dissolution testing enough (No BE)

Site change Level 3- Dissolution testing enough (No BE) Level 3 changes- Dissolution testing and BE studies are necessary

However BE study may be waived with an acceptable IVIVC which must be

validated

Dissolution testing for MR Products

Drug product Preapproval Postapproval

New drug BA studies for each strength Food effect studies Multiple dose studies Dissolution

Generic drug

Higher Strength

Lower strength
Beaded capsule

Tablets

BE study Food effect study Dissolution

Dissolution profile

Dissolution profile in additional media

Dissolution testing for MR Products

In case of MR products like beaded capsules biowaivers for lower strengths

formulation may be granted depending on BE studies on higher strength such that the various strength varies only in no. of beads containing active moiety
Similar dissolution profile between highest and lower strengths based on the

f2 test in at least three dissolution media (Ph 1.2,4.5,6.8)

ANDA Extended release product

USP method Single strength Multiple strengths

USP method adequately discriminatory

Capsules
Yes

Tablets
No

Common blend

USP method only

USP method Additional dissolution testing using three media

ANDA Extended release product

If USP method not available then follow FDA recommended method

For capsules- if different strength s has been produced from common

blend then additional dissolution testing on highest strength only in three different media

For tablets additional dissolution testing on all strength in three different

media

Post approval changes for MR products

Level 1 change- No BE study standard dissolution testing may be

enough Level 2 change -

Established IVIVC available

Dissolution profile with only standard dissolution method is recommended

Additional dissolution profiles besides standard dissolution method are recommended

Post approval changes for MR products

Level 2 change related to components and composition release controlling excipients

Narrow therapeutic range drug

Non narrow therapeutic range drug

Established IVIVC available No Single dose BE study Yes

Yes

Established IVIVC available No

Dissolution profile with only standard dissolution method

Additional dissolution profiles besides standard dissolution method

Post approval changes for MR products

Level 3 change
Established IVIVC available

No

Yes

Single dose BE study

Dissolution profile with only standard dissolution method

Dissolution testing and alcohol induced dose dumping

Drugs(MR) which are highly soluble in ethanol for e.g. Office of generic drugs recommends assay

Compare dissolution performance of generic (test product) and reference

listed drug

0.1 N HCl media with differing amounts of ethanol (0%, 5%, 20%, 40%)