Presented byMr. MAYUR R. KHINVASARA

(M. Pharm. Sem. I)Roll No. A-11

Guided byDr. SANJAY B. PATIL( M. Pharm., Ph.D.)

Department of PharmaceuticsS. S. D. J. COLLEGE OF PHARMACY,CHANDWAD

DISSOLUTION TESTING : A HEART OF PHARMACEUTICS

2 CONTENTS Introduction Dissolution Dissolution testing Need of dissolution USP dissolution apparatus

OfficialUnofficial

Factors ConclusionReferences

3 INTRODUCTION Dissolution tests are one of the most commonly used tests in

the characterization of drugs and in the quality control of certain dosage forms.

During the late 1960s, it was accepted that dissolution data should be determined by studying the rate at which dosage forms allow their formulated drug to dissolve.

Dissolution tests for seven products were introduced into the USP 18.

Dissolution tests become especially important if dissolution is the rate-limiting step in drug absorption.

Dissolution is considered today as one of the most important quality control procedure performed on pharmaceutical dosage forms.

4DISSOLUTION

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.

Dissolution process of solid dosage Forms

5DISSOLUTION TESTING

Dissolution and drug release tests are in-vitro tests that measure the rate and extent of dissolution or release of the drug substance from a drug product, usually aq. medium under specified conditions.

It is an important QC procedure for the drug product and linked to product performance in vivo.

NEED FOR DISSOLUTION TESTING: Evaluation of bioavailability. Batch to batch drug release uniformity. Development of more efficacious and therapeutically optical

dosage forms. Ensures quality and stability of the product. Product development, quality control, research and

application.

6Dissolution testing apparatus from

different official Compendia

7 OFFICIALUSP dissolution apparatus

8APPARATUS-1 (ROTATING BASKET)

DESIGN: Vessel: Made of borosilicate glass. -hemispherical bottom -Capacity 1000 ml Shaft: Shaft and basket made of SS 316. -Cylindrical basket made of 22 mesh,

-Shaft must be rotate smoothly without significant wobble.

Speed :- 25-150 rpm Water bath:- Temp. Maintained at 37±0.5ºC USE: Tablets, capsules, delayed release dosage forms, suppositories, floating dosage forms.

9APPARATUS-2 (PADDLE)

DESIGN: Vessel: -Made of borosilicate glass. -Semi hemispherical bottom -Capacity 1000ml Paddle:-Made of Teflon coated and Stainless steel 316

-The metallic, suitably inert, rigid blade. Waterbath:- Maintains at 37±0.5°C Sinkers:-Platinum wire used to prevent tablet/capsule from floating.

10 DESIGN: Vessel: -Set of cylindrical flat bottom glass

vessels -Set of reciprocating cylinders -fittings of SS 316 and screens made of nonsorbing or non-reactive materials. Agitation type: -Reciprocating -5-35 rpm Volume of medium:-200-250ml Water bath:- Maintain at 37±0.5°C USE: Tablets, beads, controlled and extended release formulations

APPARATUS-3(RECIPROCATING CYLINDER)

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DESIGN: Reservoir : -For dissolution medium Pump : -Forces dissolution medium through cell Holding a sample -Flow rate 10-100ml/min -Laminar flow is maintained -Peristaltic/centrifugal pumps are not

recommended Water bath:- Maintain at 37±0.5°C USE: Low solubility drugs ,micro particulates ,implants,

suppositories controlled release formulations

APPARATUS-4 (FLOW THROUGH CELL)

12CELL TYPES

Tablets 12 mm Tablets 22.6 mm Powders / Granules Implants Suppositories /

Soft gelatin capsules

13APPARATUS-5(PADDLE-OVER-DISK)

DESIGN: Vessel:- Made of borosilicate glass, Capacity 1000ml Shaft :- Stainless steel 316 and Teflon coated. Stirring elements- rotating speed 25-50 rpm Sample holder:

-disk assembly that hold a product in such a way that release surface is parallel with paddle

-Paddle is directly attached over disk assembly -Samples are drawn between surface off the

medium and top of the paddle blade. Volume:900ml Temperature: 32 ± 0.5°C USE: Transdermal patches, ointments, floaters ,

emulsions etc. Modification: Disk design and volume

14APPARATUS-6(ROTATING CYLINDER)

DESIGN: Vessel:- same as apparatus 1. Shaft :-Stainless steel 316, basket is replaced with cylinder is used Sample :- Mounted to inner porous cellulosic material and adheres to

cylinder. - Dosage unit is placed in cylinder and release from side out. Water-bath: maintained at 32±0.5°C USE: Transdermal patches cannot be cut into small size. Solid dosage forms,

15APPARATUS-7(RECIPROCATING-DISK)

DESIGN: Vessel:-Flat bottomed cylindrical vessel -Volume of dissolution medium 900 mL. Sample : -Placed on disk shaped holders Agitation :-Reciprocation -Reciprocating frequency 30 cycle/min Water-bath:-Maintain at 32 ± 0.5°C USE: Transdermal patches The assembly consists of a set of volumetrically calibrated solution

containers made of glass or suitable inert material, a motor , a drive assembly used to reciprocate the system vertically.

The samples are placed on the disk shaped holders using cuprophan supports

The test is carried out at 32°C. The reciprocating frequency is 30cycles/min.

shaft

disk

dissolution medium

constant temp water bath

16Figure of Reciprocating Disk sample holder

17Figure of Reciprocating Disk sample holder

18 UNOFFICIAL METHODS

1. ROTATING/ STATIC DISK METHOD Developed by late Eino nelson and described by Levy and Sahli. In this method ,the drug is compressed in a non-disintegrating disc

without excipients. The disc is mounted in a holder so that only one face of the disc is

exposed to the dissolution medium. The holder and disc are immersed in medium and held in a fixed

position as in static disc method and rotated at a given speed in rotating disc method.

Samples are collected at predetermined times. Surface area of the drug through which dissolution

occurs is kept constant –intrinsic dissolution rate.

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2.BEAKER METHOD: Reported by Levy and Hayes (1960). Dissolution medium, 250 ml of 0.1N HCl at 37°C placed

in a 400 ml beaker. Agitation by three blade polyethylene stirrer,5cm diameter and rotates at 60 rpm. Stirrer immersed to a depth of 2.7 cm in medium and in the center. Tablets are placed in a beaker and test was carried out. Samples are removed and assayed for the content.

3.FLASK STIRRER METHOD Developed by Poole (1969).It includes RBF and a stirring element similar to that

of beaker method. RBF used to avoid the formation of moulds of particles in different positions on

the flat bottom of a beaker.

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4.PERISTALSIS METHOD: To stimulate hydrodynamic condition of GIT tract in an in-vitro dissolution

device. It consists of rigid plastic cylindrical tubing fitted with septum and rubber

stopper at both ends. Dissolution chamber consists of a space between septum and lower stopper. Dissolution medium is pumped with peristaltic action through the dosage

form.

5.ROTATING BOTTLE METHOD: It consists of rotating rack to hold sample drug products in bottles and they

are capped tightly & rotated in 37°C temperature bath. Sample are decanted through a 40 mesh screen and residue are assayed.

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6.DIALYSIS METHOD: Cell consist of 32mm inflated membrane. Plugged at the lower end by tight fitting cylindrical perspex box. Upper end of the tube held by thin perspex ring inserted into the tube

and secured by an elastic band. The cell suspended , from the arm of the tablet disintegration

apparatus and containing the dosage form in 150ml of distilled water at 37°C.

The cell is raised or lowered 30times a min, into 150ml of distilled water at same temperature.

Agitation by slight flexing and stretching of the dialysis membrane as it enters and leaves the bath. Rotated at 60rpm.

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Diffusion cell

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FACTORS RELATED TO THE APPARATUS Size and shape Agitation device Speed of agitation Temperature

FACTORS RELATED TO DISSOLUTION MEDIA pH of dissolution media Surface tension Viscosity Volume

24 CONCLUSIONBy studying various factors influencing the rate of

dissolution, we can optimize the different properties of the formulation. By conducting dissolution studies we can know the batch to batch reproducibility. We can estimate the solubilty profiles of the drug. The best available tool today which can atleast quantitatively assure about the biological availability of drug from its formulation is its in vitro dissolution.

25REFERENCES

1. Brahmankar D.M.; Jaiswal S.B., Biopharmaceutics and Pharmacokinetics- A Treatise, Vallabh Prakashan, New delhi, India. (2009) pp 325-329.

2. Aulton M.E., Pharmaceutics The Science of Dosage Form Design, 2nd Ed.; Churchill Livingstone. (2011) 20-25.

3. Encyclopedia of Pharmaceutical Technology, Vol-I third edition, Edited by James Swarbrick pp 907-909.

4. Remington- The Science and Practise of Pharmacy, Vol- 1, 21st edition, Lippincott Williams and Wilkins. pp 662-680.

5. United States Pharmacopeia and National Formulary ,United States Pharmacopeial Convention Inc., Rockville, MD.

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