Dissolution testing conventional and controlled release products

Dissolution Testing for Conventional

and Controlled Release Products

Presented by:MD.FIAZ

M.Pharm.(PAQA)

Guided by:Mr.R.Balaji Reddy,M.Pharm.

(Department of Pharmaceutics)

Overview:

• Introduction

• Importance and need for dissolution testing

• Theories of drug dissolution

• Dosage forms requiring dissolution

• Factors for designing dissolution test

• Dissolution media

• Official Dissolution Apparatus

• Dissolution testing methods

• Conclusion

Introduction

Dissolution is a process in which a solid substance solubilizes

in a given solvent i.e. mass transfer from the solid surface to

the liquid phase.

Rate of dissolution- It is the amount of drug substance that

goes in solution per unit time under standardized conditions

of, temperature, pH and solvent composition and constant

solid surface area.

The rate of dissolution quantifies the speed of the dissolution

process.

Importance & need for Dissolution Testing

Fig.-Disintegration, deaggregation, and dissolution stages as a drug leave a tablet or granular matrix.

Granules or aggregates

Tablet or Capsules

Fine particles

Drug in solution

(in vitro or in vivo)

Drug in blood, other fluids , and

tissues

Disintegration

Deaggregation

Dissolution Absorption

(in vivo)

Dissolution testing is of utmost importance in following aspects-

As reliable Predictor of in vivo dissolution performance of drug.

A Rate limiting factor in determining the physiological availability of

drug.

As Quality control tool for monitoring the uniformity and reproducibility of production batches.

As Research tool in optimizing parameters and ingredients in new drug formulation.

It is widely accepted as animal experimentation has been restricted under the Act of Prevention of cruelty of animals.

Importance & need for Dissolution Testing

Theories Of Drug dissolution

Diffusion layer model/Film Theory.

Danckwert’s model/Penetration or surface renewal Theory.

Interfacial barrier model/Double barrier or Limited solvation theory.

Dosage forms requiring dissolution

• Tablets (coated and uncoated).

• Capsules

• Suppositories

• Suspensions

• Topical dosage forms like creams ,gels, ointments, etc .

• Transdermal patches.

Factors for designing dissolution test:

1) Factors related to the dissolution apparatus:

size of container (several ml to liters )

shape of container (round bottomed or flat)

nature of agitation (stirring, rotating or oscillation )

speed of agitation performance precision of the apparatus etc.

2) Factors related to the dissolution fluid (media):

Composition of dissolution media (pH range 1- 8, water etc)

Temperature

Viscosity

Volume

Sink condition

Non-sink condition

3) Process parameters:

Method of introduction of dosage form

Sampling techniques

Changing dissolution media

Factors for designing dissolution test:

Dissolution media

Common dissolution media used (suggested by different guidelines):

Purified water.

Diluted acid (o.1 N HCl ).

Buffered aqueous solutions.

Simulated gastric fluid (with or without enzymes).

Simulated intestinal fluid (with or without enzymes)

Factors effecting selection of dissolution media:

Dissolved gases

Composition of dissolution media

ph of dissolution media

Viscosity of dissolution media

Surfactant

Temperature

Official Dissolution Apparatus

USP Type- I Basket Type

USP Type- II Paddle Type

USP Type- III Reciprocating Cylinder

USP Type- IV Flow Through Cell

USP Type- V Paddle Over Disk

USP Type- VI Rotating Cylinder

USP Type- VII Reciprocating Holder


USP TYPE I: BASKET TYPE APPARATUS


USP TYPE II : PADDLE TYPE APPARATUS


USP TYPE III : RECIPROCATING CYLINDER


USP TYPE- IV : FLOW THROUGH CELL

USP TYPE V : PADDLE OVER DISK APPARATUS


USP TYPE VI : ROTATING CYLINDER

USP TYPE VII: RECIPROCATING HOLDER

Dissolution testing methodsCONVENTIONAL & PROLONGED-RELEASE DOSAGE

FORMSPlace the dissolution medium into the vessel(free from dissolved air)

Assemble the apparatus and warm the dissolution medium to 36.5º to 37.5º.

Place one dosage unit in the apparatus

Allow the tablet or capsule to sink to the bottom of the vessel prior to the rotation

(PADDLE TYPE APPARATUS)

OR

Place the tablet or capsule in a dry basket at the beginning of each test and lower the

basket into position before rotation(BASKET TYPE APPARATUS)

Operate the apparatus immediately at the speed of rotation specified

At each of the times stated, withdraw a specimen from a zone midway

between the surface of the dissolution medium and the top of the rotating

blade or basket, not less than 10 mm from the wall of the vessel.

For each of the tablet or capsule tested, calculate the amount of dissolved

active ingredient in solution as a percentage of the stated amount .

Dissolution testing methods

ACCEPTANCE CRITERIASCONVENTIONAL RELEASE DOGASE FORMS:

*D is the amount of dissolved active ingredient specified in the individual monograph, expressed as a percentage of the labeled content.

**Percentages of the labeled content.


Level Number tested Acceptance criteria

S1

S2

S3

6

6

12

Each unit is not less than D* + 5 percent**.

Average of 12 units (S1 +S2) is equal to or

greater than D, and no unit is less than D –

15 per cent**.

Average of 24 units (S1+S2+S3)is equal to

or greater than D, not, More than 2units are

less than D – 15 per cent** and no unit is

less than D – 25 per cent**.

PROLONGED-RELEASE DOSAGE FORMS


Level Number tested Acceptance criteria

L1

L2

L3

6

6

12

No individual value lies outside each of the stated

ranges and no individual value is less than the

stated amount at the final test time.

The average value of the 12 units (L1 +L2) lies

within each of the stated ranges and is not less than

the stated amount at the final test time; none is

more than 10per cent of labeled content outside

each of the stated ranges; and none is more than 10

per cent of labeled amount below the stated amount

at the final test time.

The average value of the 24 units (L1 +L2 + L3)

lies within each of the stated ranges, and is not less

than the stated amount at the final test time; not

more than 2 of the 24 units are more than 10per

cent of labeled content outside each of the stated

ranges; not more than 2 of the 24 units are more

than 10 per cent of labeled content below the stated

amount at the final test time; and none of the units

is more than 20 per cent of labeled content outside

each of the stated ranges or more than 20 per cent

of labeled content below the stated amount at the

final test time

TRANSDERMAL PATCHESPlace the prescribed volume of the dissolution medium in the vessel and

equilibrate the medium to the prescribed temperature.

Apply the patch to the SSDA by adhesive

Place the patch mounted on the SSDA flat at the bottom of the vessel with the

release surface facing upwards.

Immediately rotate the paddle at 100 r/min

At predetermined intervals; withdraw a sample from the zone midway

between the surface of the dissolution medium and the top of the blade, not

less than 1 cm from the vessel wall.


Perform the assay on each sample, correcting for any volume losses, as

necessary. Repeat the test with additional patches.


According to USP apparatus used are


USP

APP.

DESCRIPTION ROT.

SPEED

DOSAGE FORM

I BASKET 50-120 rpm IR, DR, ER

II PADDLE 25-50 rpm IR, DR, ER

III RECIPROCATING

CYLINDER

6-35 rpm IR, ER

IV FLOW-THROUGH

CELL

N/A ER, POORLY

SOLUBLE API

V PADDLE OVER

DISK

25-50 rpm TRANSDERMAL

VI CYLINDER N/A TRANSDERMAL

VII RECIPROCATING

HOLDER

30 rpm ER

Conclusion• Dissolution testing has become an integral part of quality

control.

• Although official methods are used, there exists no standard

method for evaluation of a solid dosage form.

• The method and standards, which correlate well with the in-

vivo data, should be utilized.

• The knowledge not only acts as tool for quality control, it also

assists in preformulation studies and in understanding the

biopharmaceutical role of the same.

References: United State Pharmacopoeia, The National Formulary, 2002, 20th Edition, United

State Pharmacopoeial Convention INC, Washington, 711, 2011.

INDIAN PHARMACOPOEIA 2007 Volume 1, The Indian Pharmacopoeia

Commission, Ghaziabad, 179-181.

Remington, The Science And Practice of Pharmacy, Volume 1, 21st Edition, Indian

Edition, B. I. Publications Pvt. Ltd., 654-665.

Banakar, U.V. 2000, Pharmaceutical Dissolution Technologies , volume 49. Marcel

Dekker INC, N.Y., 174-175,280.

Subramanyam C.V.S. 2006, Textbook Of Physical Pharmaceutics, 2nd Edition ,

Vallabh Prakashan,Delhi,88-90 .