Dissolution Test Apparatus

The slide has detailed description about dissolution theories and dissolution test apparatus used in pharma industry.

1. DISSOLUTION TEST APPARATUS Guided by :- Prof. Dr. H. S.Mahajan H.O.D. Pharmaceutics Prepared by :- Nilesh K. Bornare M.Pharm 1 st year R.C.PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH, SHIRPUR. 1

2. Contents Introduction : Need For Dissolution Testing Theories of dissolution Types Of Dissolution Test Apparatus Conclusion References 2

3. INTRODUCTION Dissolution is the physicochemical process by which a solid substance enters the solvent phase to yield a solution. Dissolution rate : the amount of solid substance that goes into solution per unit time under standard condition of temp, pH,& solvent composition and constant solid surface area. 3

4. Need For Dissolution Testing Batch to batch drug release uniformity . Development and optimization of dosage forms . Ensures quality, safety, efficacy and stability of the product . Evaluation of IVIVC correlation / bioavailability. To support waiver for bioequivalence requirement. For assessing pre and post approval changes in manufacturing process or formulation . 4

5. THEORIES OF DRUG DISSOLUTION Three type of dissolution model are proposed depending on the relative significance and the means by which the transport is effected . these models which can be used to describe the dissolution rate mechanism . The three models are: 1.Diffusion layer model / film theory. 2.Danckwert’s model / penetration or surface renewal theory . 3.Interfacial barrier model /double barrier or limited solvation theory. 5

6. 1.DIFFUSION LAYER MODEL / FILM THEORY: The process of dissolution of solid particle in a liquid, in the absence of reactive or chemical forces consist of two steps : Solution of the solid to form a thin film or layer at the solid / liquid interface called stagnant film or diffusion layer.(Rapid step) Diffusion of the soluble solute from the stagnant layer to the bulk of the solutio n. (Slower step &RDS) 6

7. The rate of dissolution when the process is diffusion controlled and involves no chemical reaction was given by noyes and whitney equation Dc/d t = k (cs - cb) Where, Dc/ dt = dissolution rate of the drug . K = dissolution rate constant . (cs –cb) =conc gradient for diffusion of drug. Nernst and brunner ( fick’s first law diffusion ) modified the noyes and whitney equation I.E. Dc/d t = dakw/o ( cs –cb)/vh Where, D = diffusion coefficient (diffusivity) of drug . A= surface area of dissolving solid . kw/o = water/oil partition coefficient. V = volume of dissolution medium. H = thickness of the stagnant layer. 7

8. 2.DANCKWERT’S MODEL (PENETRATION OR SURFACE RENEWAL THEORY ) Danckwert’s Did Not Approve Of The Existence Of A Stagnant Layer And Suggested That Turbulence In The Dissolution Medium Exists At The Solid/Liquid Interface. Danckwert’s Model Is Expressed By Equation : Vdc/D T=d M/D T=a( Cs-Cb).   √(γ. D) Where, M =mass Of Solid Dissolved. Γ =rate Of Surface Renewal . 8

9. 3 . Interfacial barrier model (double barrier or limited solvation theory) According to the interfacial barrier model ,an intermediate conc can exist at the interface as a result of solvation mechanism and is a function of solubility rather than diffusion. When dissolution of a crystal ,each face of the crystal will have a different interfacial barrier. G = Ki (Cs –Cb) Where, G = dissolution rate per unit area. Ki = effective interfacial transport constant. 9

10. USP apparatus (compendial method) 1.Rotating basket apparatus 2.Rotating paddle apparatus 3.Reciprocating cylinder apparatus 4.Flow through cell apparatus 5.Paddle over disc apparatus 6.Cylinder apparatus 7.Reciprocating holder apparatus 10

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13. 1. Rotating basket apparatus: Design : Vessel : -made of borosilicate glass semi hemispherical bottom capacity 1000ml. Shaft :-made of ss 316 Rotates smoothly without significance wobble(100). Speed regulator . Water bath: maintained at 37 ±0.5 ℃ Use :tablet, capsule, chewable tablet ,delayed release formulations. 13

14. Advantages : Full pH change during the test . can be easily automated which is imp for routine investigation . Disadvantages: Basket screen is clogged with gummy particle . degassing is particularly important . mess gets corroded by HCL solution . 14

15. 2.Rotating paddle apparatus: Design: Vessel:-same as basket apparatus. Shaft :-the blade passes through the shaft so that the bottom of the blade fuses with bottom of the shaft. Stirring elements:-made of tefflon (for laboratory purpose)and ss316. Water bath: maintained at 37 ±0.5℃. Sinkers: platinum wire used to prevent tablet/capsule from floting. 15

16. Use : tablet, orally disintegration tab, chewable tab, controlled release products, suspension. Advantages : Easy to use Robust pH change possible can be easily automated which is imp for routine investigation. Disadvantages : Sinkers for floating dosage form Hydrodynamic are complex ,they vary with site of the dosage form in the vessel(sticking, floting)and therefore may significantly affect drug dissolution . 16

17. 3.Reciprocating cylinder Design: Vessel:-set of cylindrical flat bottom glass vessels Set of reciprocating cylinders Stainless steel fitting(316) and screen made of non- sorbing or nonreactive materials. Agitation type: reciprocating 5 -35 rpm Volume of dissolution medium: 200-250ml Water bath:maintained at 37±0.5℃ 17

18. Uses: tablets, controlled release bead(pellet) type formulations. Advantages:-easy to change the pH Hydrodynamic can be directly influenced by varying the dip rate. Disadvantage:-small volume (max .250ml) Little experience Limited data 18

19. 4.Flow through cell 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:- maintained at 37±0.5℃ 19

20. Uses: low solubility drugs, powders and granules, microparticles, implants . advantages: Easy to change media pH PH profile possible sink condition maintained different mode i.e. open system and closed system. Disadvantages: De-aeration necessary high volume of media Labor intensive 20

21. 5.Paddle over disk Design: Vessel, shaft : same as apparatus 2 . stirring elements:-rotating speed 25-50rpm 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 of the medium and top of the paddle blade. Volume: 900ml Temperature:32℃ 21

22. Uses : transdermal formulations ,ointments , emulsion. Advantages : Easy to handle sink condition are maintained membrane effect is minimum i.e. drug is placed on the disc at the bottom. Disadvantages: Disk assembly restrict the patch size 17 mesh is standard . accommodates patches up to 90mm. 22

23. 6.Rotating cylinder Design: Vessel : in place of basket, cylinder is used. Shaft: ss 316 Sample: Mounted to cuprophan(inner porous cellulosic material) an entire system adhere to cylinder Dosage unit is placed in cylinder and release from side out. Water bath: maintained at 32±0.5℃ 23

24. Uses : transdermal formulations Advantages : -Equipment (apparatus 1) available with the manufactures can be used with modification as apparatus 6. Disadvantages : Large volume of medium is required Drug gets diluted and causes difficulties in analysis Difficult to clean the cylinder 24

25. 7.Reciprocating HOLDER Design: Vessel: Flat bottomed cylindrical vessel volume of dissolution medium Sample:- placed on disk shaped holders Agitation:- reciprocation Reciprocating frequency 30cycles/min Water bath: maintain at 32℃ 25

26. SAMPLE HOLDERS FOR DISSOLUTION TESTING OF DIFFERENT DOSGAE FORMS 26

27. Uses : controlled release formulations ,non disintegration and transdermal formulations. Advantages : -Convenient method for selecting the volume of the medium -Sink conditions can be maintained -More sensitivity Disadvantages : investment is high because the design is totally different from standard equipment already available in industry. 27

28. conclusion Dissolution research started to develop in 1897 when N oyes and Whitney derived their equation in the course of their dissolution studies on benzoic acid and lead chloride. The goal of dissolution testing is to assure the pharmaceutical quality of the product (manufacturing of product, release property and biopharmaceutical characteristics e.g. Rate and extent of absorption ). Dissolution testing is a routine work for pharmaceutical quality control for oral solid dosage forms like tablets, capsules and transdermal drug delivery systems. The science of dissolution testing is developing every day. 28

29. REFERENCES G.S. Banker And C.T. Rhodes “ Modern Pharmaceutics Revised And Extended 4 th Edition, Page No 53-101. Lachman And Liberman The Theory And Practice Of “Industrial Pharmacy 4 th Edition, Page No 182-213. D.M. Brahmankar And S.B. Jaiswal “Biopharmaceutics And Pharmacokinetics –A Treatise” 3 rd Edition, Page No 328-345 C.V.S. Subrahmanyam “Biopharmaceutics And Pharmacokinetics -Concept And Applications , 3 rd Edition, Page No 152-165. 29

30. THANK YOU ! 30