IMPORTANCE, OBJECTIVES &EQUIPMENTS OF DISSOLUTION STUDY

PREPARED BY: JAYDIP VASOYA M.PHARM 1st SEM GUIDED BY: SUNNY SHAH, ASSISTANT PROFESSOR M.PHARM PHARMACEUTICS

CONTENTS..
DEFINITION IMPORTANCE & OBJECTIVES APPARATUS

Questions
REFERENCES

DEFINITION: Dissolution is a process in which a solid substance solubilise in a given solvent i.e mass transfer from solid surface to liquid phase.

DISSOLUTION RATE: Amount of substance that solubilise in a given solvent in unit time is termed as dissolution rate

Applications of in vitro dissolution study

Importance Of Dissolution Study

As a most powerful and valuable tool to guide formulation development. Important in monitoring of the manufacturing process, assess product quality, To predict in vivo performance of solid oral dosage forms. As a surrogate measure for bioequivalence (be) and to provide biowaivers Need for further studies relative to scale-up and post-approval changes (SUPAC), where it functions as a signal of bioequivalence To achieve an in vitro/in vivo correlation. Is also employed for evaluating other non-oral (special) dosage forms such as topicals and transdermals, suppositories, implants, etc.

Instruments for dissolution

Main two types
Official apparatus
Beaker methods Open flow-through compartment system Dialysis concept

Non official apparatus

Rotating filter method Rotating flask disc method Rotating & static disc method

Official apparatus
Closed compartment apparatus : It is a limited volume apparatus operating under non sink condition. The dissolution fluid is restrained to the size of the container, e.g. rotating basket and rotating paddle apparatus. Open compartment apparatus : In this dosage form is contained in a column which is brought in continuous contact with fresh dissolution medium .It operates under sink condition, e.g. flow through cell apparatus. Dialysis system : For very poorly aqueous soluble drugs sink condition would be difficult to maintain and it require large volume of dissolution fluid.

Various Official Dissolution Test apparatus

I.P. USP B.P. E.P.

Type I
Type II Type III Type IV

paddle apparatus basket apparatus

Type V
Type VI Type VII

basket apparatus paddle apparatus Reciprocating cylinder flow through cell apparatus Paddle over disk cylinder
reciprocating holder

basket apparatus paddle apparatus flow through cell apparatus

paddle apparatus basket apparatus flow through cell apparatus

Dissolution apparatus & type of dosage form

DOSAGE FORM
Solid dosage form (IR,MR Products) Bead type MR dosage form

APPARATUS (USA)
Type 1-basket Type 2-paddle Type3-Reciprocating cylinder

MR release dosage form that contain Type4-flow through cell apparatus active ingredients with limited solubility
Soft gelatin capsules, suppositories, poorly soluble drugs Transdermal dosage form Non disintegrating oral modified dosage form as will as traditional dosage form Type 3 & 4 Type5-Paddle over disk Type6-cylinder Type7-reciprocating holder

Usp dissolution apparatus

Type 1 Rotating basket apparatus
Simple beaker type closed type apparatus The vessel is cylindrical, with a hemispherical bottom. A fitted cover may be used to retard evaporation. shaft is positioned so that its axis is not more than 2 mm at any point from the vertical axis of the vessel and rotates smoothly and dont create wobble allows the shaft rotation speed to be selected and maintained at 4%. gold coating of about 0.0001 inch (2.5 m) thick may be used. The distance between the inside bottom of the vessel and the bottom of the basket is maintained at 25 2 mm

Used for mainly.. For.. Tablets , Capsules Beads Floaters

Standard volume
900/1000 ml 1, 2, 4 liter vessels

Type -2 Rotating paddle apparatus.

Use the assembly from Apparatus 1. A paddle formed from a blade and a shaft is used as the stirring element. Dosage form should remain at the bottom centre of the vessel Sinkers used for floaters pH change by media addition Useful for: Tablets Capsules delayed release / enteric

Paddles

Both The USP Apparatus 1 And 2 Share Some Common Advantages And Disadvantages.

Advantages include:
Widely Accepted Apparatus For Dissolution Test, Apparatus Of First Choice For Solid Oral Dosage Forms, Standardized, Easy To Operate, Robust And Broad Experience.

Disadvantages include:
Limited Volume Of The Dissolution Media, Simulation Of The Gastrointestinal Transit Is Not Possible And Hydrodynamic Conditions Are Not Known. Dissolution Results Obtained With Usp Apparatuses 1 And 2 May Be Significantly Affected By Shaft Wobble, Location Centering, And Coning

Sinkers
JP/ USP / EP Sinker

a small loose piece of nonreactive material can be used not more than a few turns of wire helix may be attached to dosage units that would otherwise float other validated sinker devices may be used

3) Apparatus 3-Reciprocating cylinder

The assembly consists of a set of cylindrical, flatbottomed glass vessels; a set of glass reciprocating cylinders; inert fittings (stainless steel type 316 or other suitable material), and screens that are made of suitable nonsorbing and nonreactive material and that are designed to fit the tops and bottoms of the reciprocating cylinders. A motor and drive assembly to reciprocate the cylinders vertically inside the vessels. the reciprocation rate to be selected and maintained at the specified dip rate given in the individual monograph within 5%.

Reciprocating cylinder
Useful for Tablets Beads Controlled release formulations USP Apparatus 3 offers advantages like Programmed for dissolution in various media for various time, Prevents the cone formation May start at pH 1 and then pH 4.5 and then at pH6.8 and Attempts to mirror pH changes and transit times in the GI tract. But it has got some disadvantages too, i.e. Disintegrating dosage forms show too low results, Surfactants cause foaming and Volume of dissolution media is too small

Apparatus 4 Flow through cell

The assembly consists of a reservoir and a pump for the pumping of Dissolution Medium; a flow-through cell; and a water bath that maintains the Dissolution Medium at 37 0.5C The pump has delivery range between 240 and 960 mL per hour, with standard flow rates of 4, 8, and 16 mL per minute. It must deliver a constant flow (5% of the nominal flow rate); the flow profile is sinusoidal with a pulsation of 120 10 pulses per minute.

Continue
Useful for
:

Low solubility drugs Rapid degradation Implants

Advantages
No limitation regarding the volume of media used for the dissolution test, Suitable for low soluble drugs, Gentle hydrodynamic conditions, Simulation of the gastrointestinal transit,Suitable for special dosage forms such as powder and granules, implants.

Disadvantages includes
i) Pump precision may influence the results and

Tablets 12 mm

Tablets 22 mm Powders / Granules Implants

Suppositories /soft gel cap

Flow through cell apparatus

5) Paddle-over-Disk Apparatus (USP Apparatus 5)

This uses the paddle apparatus (USP 2) with the sample, usually a transdermal delivery system, being attached to a stainless steel disk, which is then placed on the bottom of the vessel, directly under the paddle.

Useful for:
Transdermal patch Ointments

Floaters Emulsions Bolus Advantages Standard equipment (paddle) can be used, only add a stainless steel disk assembly. Disadvantages Disk assembly restricts patch size.

6) Cylinder method (USP Apparatus 6)

Same as apparatus 1,except to replace the basket and shaft with a S.S. cylinder stirring element. Temperature - 32 0.5
Useful for:

Transdermal patches

7) Reciprocating Holder method (Apparatus 7)

The assembly consists of a set of calibrated solution containers, a motor and drive assembly to reciprocate the system vertically. Various type of sample holder are used.
Useful for: Transdermal patches Solid dosage forms Small volumes.

Manual sampling cannula.

Spacers and centering tools

Example of extended release dosage forms that uses different dissolution apparatus
Dissolution
Example Apparatus Apparatus I

Cefaclor extended release tablets

Acetaminophen extended release tablets Nifedipine extended release tablets

Apparatus II

Apparatus VII

Non official methods

THE ROTATING FILTER METHOD

It consists of a magnetically driven rotating filter assembly and a 12 mesh wire cloth basket. The sample is withdrawn through the spinning filter for analysis.

ROTATING FLASK DISSOLUTION METHOD

This consists of a spherical flask made of glass and supported by a horizontal glass shaft that is fused to its sides. The shaft is connected to a constant speed driving motor.
The flask is placed in a constant temperature water bath and rotates about its horizontal axis.

ROTATING AND STATIC DISK METHODS

The compound is compressed into non disintegrating disc
Mounted One surface is exposed to medium Assumption Surface area remains constant Used to determine the intrinsic dissolution rate

Automation in dissolution apparatus

In-situ dissolution testing using UV fiber optics has attracted much attention in the pharmaceutical industry. These instruments employ different types of spectrometers and the probes differ in shape, light beam path, and sampling window. These differences may have significant impact on the dissolution operations and results.

U.V. Fiber Optic System

UV DISSOLUTION APPARATUS

Dissolution Acceptance Criteria

For Immediate-Release Dosage Forms

The requirements are met if the quantities of active ingredient dissolved from the dosage units tested conform Acceptance Table1. The quantity, Q, is the amount of dissolved active ingredient specified in the individual monograph , expressed as a percentage of the labeled content of the dosage unit.

Extended release dosage form

Limits on the amount of active ingredients dissolved are expressed in term percentage of labeled content. Limits embrace each value of Q , the amount dissolved at each specified fractional dosing interval
NO. TEST ED 6 6

LEV EL LI L2

CRITERIA
No individual value lies outside each of the stated range and no individual value is less than the stated amount at the final test time. The avg. value of 12 units lies within each of the stated range and is not less than the stated amount at the final test time; none is more than 10% of labeled content outside each of the stated range; and none is more than 10% of labeled content below the stated amount at the final test time. The avg. value of the 24 unit lies within each of the stated range, and is NLT stated amount at the final test time; NMT 2 of the 24 units are more than 10% of labeled content outside each of the stated range; NMT 2 of the 24 units are more than 10% of labeled content below the stated amount at the final test time; and none of the unit is more than 20% of labeled content outside each of the stated range or more than 20% of labeled content below the stated amount at the final test time.

L3

12

Delayed release dosage form

LEVEL A1 NO. TESTED 6 CRITERIA No individual value exceeds 10 % dissolved Avg. of 12 units is NMT 10% dissolved and no individual unit is greater than 25% dissolved Avg. of 24 units is NMT 10% dissolved and no individual unit is greater than 25 % dissolved.

A2

A3

12

Buffer stage
LEVEL B1 B2 NO.TESTED 6 6 CRITERIA Each unit is NLT Q+5% Avg. of 12 units is equal to or greater than Q and no unit is less than Q15%. Avg. of 24 units is equal to or greater than Q, NMT 2 units are less than Q-15%. And no unit is less than Q-25%

B3

12

Questions
What is the significance of dissolution testing? Describe dissolution test for unconventional and novel dosage forms? FEB 2011. Write about Usp dissolution apparatus in brief. Describe use of dissolution apparatus for different dosage forms.

References
Pharmaceutical dissolution testing, by Jennifer Dressman and Johannes Krammer , Taylor & Frances page no. 81-89 The science and practice of pharmacy by Remington, 20th edition vol. 1 Chapter-35 United State Pharmacopeia 30, <711> Encyclopedia of pharmaceutical technology by James swabrick,3 rd edition, Page no 909-930 In-Situ Dissolution Testing Using Different UV Fiber Optic Probes and Instruments Xujin Lu Ruben Lozano, Pankaj Shah, Dissolution Technologies November 2003. Asian Journal of Pharmacy and Life Science Vol. 2 (1), JanMarch,2012 Asian Journal of Biochemical and Pharmaceutical Research Issue 1 (Vol. 1) 2011