Dissolution

Dissolution Apparatus
Mayur R. Khinvasara
M. Pharm in Pharmaceutics
SSDJ College of Pharmacy, Chandwad.

1. Presented by Mr. MAYUR R. KHINVASARA ( M. Pharm. Sem. I ) Roll No. A-11 Guided by Dr. SANJAY B. PATIL ( M. Pharm., Ph.D.) Department of Pharmaceutics S . 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 Official Unofficial Factors Conclusion References 2

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. 3

4. DISSOLUTION 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. 4 Dissolution process of solid dosage Forms

5. DISSOLUTION 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. 5

6. 6 Dissolution testing apparatus from different official Compendia

7. OFFICIAL USP dissolution apparatus 7

8. APPARATUS-1 ( ROTATING BASKET) 8 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 :- T emp. Maintained at 37±0.5ºC USE : Tablets, capsules, delayed release dosage forms, suppositories, floating dosage forms.

9. APPARATUS-2 (PADDLE) 9 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 10 APPARATUS-3(RECIPROCATING CYLINDER)

11. 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 11 APPARATUS-4 (FLOW THROUGH CELL)

12. CELL TYPES 12 Tablets 12 mm Tablets 22.6 mm Powders / Granules Implants Suppositories / Soft gelatin capsules

13. APPARATUS-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 13

14. APPARATUS-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, 14

15. APPARATUS-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. 15 shaft disk dissolution medium constant temp water bath

16. 16 Figure of Reciprocating Disk sample holder

17. 17 Figure 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. 18

19. 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. 19

20. 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 . 20

21. 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. 21

22. Diffusion cell 22

23. 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 23

24. CONCLUSION By 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. 24

25. REFERENCES 25 Brahmankar D.M.; Jaiswal S.B., Biopharmaceutics and Pharmacokinetics- A Treatise, Vallabh Prakashan , New delhi , India . (2009) pp 325-329. Aulton M.E., Pharmaceutics The Science of Dosage Form Design, 2 nd Ed.; Churchill Livingstone . (2011) 20-25. Encyclopedia of Pharmaceutical Technology, Vol -I third edition, Edited by James Swarbrick pp 907-909. Remington- The Science and Practise of Pharmacy, Vol - 1, 21 st edition, Lippincott Williams and Wilkins. pp 662-680. United States Pharmacopeia and National Formulary ,United States Pharmacopeial Convention Inc., Rockville, MD.

26. 26 Thank You