Dissolution

This presentation describes detailed about Dissolution

1. Md. Abdul Karim Mia Analyst National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh Dissolution

2. Dissolution? Academic Definition Dissolution is the process by which a solid substance enters into a solvent to form a solution. Pharmaceutical Definition Dissolution is a test used throughout the life cycle of a pharmaceutical product to evaluate the rate of release of a drug substance from the dosage form. National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

3. History of Dissolution The first dissolution studies were reported in the literature in 1897 by Noyes and Whitney where they studied the dissolution of two sparingly soluble compounds, namely benzoic acid and lead chloride. Edwards in 1951 postulated that the rate-limiting step in the absorption of aspirin in the bloodstream was its dissolution. In 1957 Nelson was the first scientist to explicitly relate the blood levels of orally administered theophylline to its dissolution. However , in the mid 1960s realization of the impact of dissolution on the therapeutic effect of orally administered drugs began . National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

4. Why do we study dissolution? Disintegration Dissolution Absorption Drug in the blood and the body National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

5. Dissolution Apparatus National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

6. Link of dissolution Protractor Thermometer Paddle Basket Sinker Protractor Wobble Guage Vessel National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh Cannula

7. Goal of the dissolution It asses the performance of drug products To be effective the test should be predictive, comparative, disseminatory and reproducible. Predict the bioavailability- surrogate the parameter of the therapeutic efficacy Indicate the robustness of the dosage form of drug product related safety Sensitivity variation of the manufacturing process which have a critical influence on the dosage form performance. National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

8. Principle Th e main principle is to crate an environment in the GIT tract of human body where tablets or capsules or other preparation of drugs are dissolved and absorbed . We use this method to see the dissolving content in percentage of a product within a certain time at specific condition in GIT. Based on measuring the rate and extent of dissolution or release of the drug substance from a drug product, usually in an aqueous medium under specified conditions National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

9. Dissolution apparatus Apparatus   Name Drug Product Apparatus 1 Rotating basket Tablets Apparatus 2 Paddle Tablets, capsules, modified drug products, suspensions Apparatus 3 Reciprocating cylinder Extended-release drug products Apparatus 4 Flow cell Drug products containing low-water-soluble drugs Apparatus 5 Paddle over disk Transdermal drug products Apparatus 6 Cylinder Transdermal drug products Apparatus 7 Reciprocating disk Transdermal drug products Rotating bottle (Non-USP-NF) Extended-release drug products (beads) Diffusion cell (Franz) (Non-USP-NF) Ointments, creams, transdermal drug products National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

10. Dissolution vs Solubility Dissolution Solubility The amount of substance that goes into solution per unit time under standard condition of temperature, pH, solvent composition and constant surface area. The maximum amount of solute dissolved in given solvent standard condition of temperature, pressure and pH. It is a dynamic process It is a static process National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

11. Dissolution/ Drug release test Tablets Capsules Suspensions Ointments Creams Suppositories Transdermal Implants Medicated gums And Others National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

12. Dissolution Procedure Dissolution condition: Method : HPLC/ UV spectrophotometer Apparatus : paddle II Medium : Phosphate buffer 6.8 Volume : 900 ml Temperature : 37 °c (±0.05) Time : 45 Min National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

13. Dissolution Procedure Set the dissolution tools: Check the bath level by protractor Set the vessel (According to serial number) Set the paddle (According to serial number) Verify the vessel surface checked by verticality tester. RPM : Check by Tachometer Time : Stop watch ±02 sec Temp: Thermometer National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

14. Dissolution Procedure Media preparation: 6.8 gm potassium Dihydrogen orthrophosphate and 0.91 gm sodium Hydroxide is added to 950 water. Adjust pH 6.8 ( ±0.05) using diluted sodium hydroxide or orthrophosphoric acid. Finally make the volume to 1000 ml with water . (Filter and sonicate if specified) Sample Solution preparation: Set the dissolution parameters of the instrument as mentioned above Individually place one tablet ( pre-weighed) in 6 dissolution vessel, 900 ml of dissolution medium which has been equilibrated to the temperature of 37 ± 0.5°c immediately start the apparatus and run for 30 (specified in STP) minutes. At the end of specified time withdraw few ml solutions from zone midway between the surfaces to the dissolution medium and top of the rotating blade not less than 1 cm from the vessel wall. Filter the solution through 0.45 micron filter paper. National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

15. Dissolution Procedure Calculate % of content Sample dissolved in 45 minutes by using following formula — AT x Ws x 10 x 900 x P x 0.752 x100 -------------------------------------------- AS x100x 50 x LC x100 AT= Area of sample As = Area of standard preparation Limit: Not less than 75% (Q) Ws = Weight of standard preparation P = Standard potency LC = Label claim Factor: Ws x 10 x 900 x P x 0.752 x100 -------------------------------------- AS x100x 50 x LC x100 National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh Sample: Factor x area of sample%

16. Dissolution Procedure Stage Number of Unit Tested Acceptance criteria S1 6 Each unit is not less than Q+5% S2 6 Average of 12 units ( S1+S2) equal to or greater than Q. and no unit is less than Q -15% S3 12 Average of 24 units (S1+S2+S3) Is equal to or greater than Q. Not more than two units are less than Q- 15%and no unit is less than Q-25% Interpretation of dissolution results: Immediate dosage form Acceptance table; National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

17. Dissolution Procedure Precautions: Wear appropriate PPE (gloves, face-mask, goggles etc.) while working with dissolution tester. Do not run the pump dry. Do not force the paddle while inserting. This might increase the wobble in the paddle. Do not hold the stirrer while in operation or do not try to remove the shaft/paddle while stirring. The water bath should be filled with demineralized or distilled water only. While filling the bath, make sure that water should not fall on the stirrer until & on the heater cover. Do not press the lift-up switch, while the paddles/baskets are rotating. Stop the rotation first then move the lift. Before starting analysis, make sure that the dissolution vessel, paddle or basket & shaft are clean. In case of power failure, do not resume the test. Start the analysis from the very beginning to get the authentic result . National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

18. Factors Affecting Dissolution Apparatus choice Agitation, temperature, volume Media composition & pH Surface area & undissolved solid Formulation of drug product Excipients (lubricants, suspending agents, etc ) Coherent masses may reduce total surface area available  overcome by using wetting agent. Presence of pores. E.g. dissolution of phenacetin (hydrophobic) is enhanced by adding diluent gelatin ( hydrophilic) during granulation. National Control Laboratory (NCL), DGDA, Dhaka, Bangladesh

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