Dissolution testing conventional and controlled release products
- 1. Dissolution Testing for Conventional and Controlled Release Products Presented by: MD.FIAZ M.Pharm.(PAQA) Guided by: Mr.R.Balaji Reddy,M.Pharm. (Department of Pharmaceutics)
- 2. Overview: • Introduction • Importance and need for dissolution testing • Theories of drug dissolution • Dosage forms requiring dissolution • Factors for designing dissolution test • Dissolution media • Official Dissolution Apparatus • Dissolution testing methods • Conclusion
- 3. Introduction 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. Rate of dissolution- It is the amount of drug substance that goes in solution per unit time under standardized conditions of, temperature, pH and solvent composition and constant solid surface area. The rate of dissolution quantifies the speed of the dissolution process.
- 4. Importance & need for Dissolution Testing Fig.-Disintegration, deaggregation, and dissolution stages as a drug leave a tablet or granular matrix. Granules or aggregates Tablet or Capsules Fine particles Drug in solution (in vitro or in vivo) Drug in blood, other fluids , and tissues Disintegration Deaggregation Dissolution Absorption (in vivo)
- 5. Dissolution testing is of utmost importance in following aspects- As reliable Predictor of in vivo dissolution performance of drug. A Rate limiting factor in determining the physiological availability of drug. As Quality control tool for monitoring the uniformity and reproducibility of production batches. As Research tool in optimizing parameters and ingredients in new drug formulation. It is widely accepted as animal experimentation has been restricted under the Act of Prevention of cruelty of animals. Importance & need for Dissolution Testing
- 6. Theories Of Drug dissolution Diffusion layer model/Film Theory. Danckwert’s model/Penetration or surface renewal Theory. Interfacial barrier model/Double barrier or Limited solvation theory.
- 7. Dosage forms requiring dissolution • Tablets (coated and uncoated). • Capsules • Suppositories • Suspensions • Topical dosage forms like creams ,gels, ointments, etc . • Transdermal patches.
- 8. Factors for designing dissolution test: 1) Factors related to the dissolution apparatus: size of container (several ml to liters ) shape of container (round bottomed or flat) nature of agitation (stirring, rotating or oscillation ) speed of agitation performance precision of the apparatus etc. 2) Factors related to the dissolution fluid (media): Composition of dissolution media (pH range 1- 8, water etc) Temperature Viscosity Volume Sink condition Non-sink condition
- 9. 3) Process parameters: Method of introduction of dosage form Sampling techniques Changing dissolution media Factors for designing dissolution test:
- 10. Dissolution media Common dissolution media used (suggested by different guidelines): Purified water. Diluted acid (o.1 N HCl ). Buffered aqueous solutions. Simulated gastric fluid (with or without enzymes). Simulated intestinal fluid (with or without enzymes) Factors effecting selection of dissolution media: Dissolved gases Composition of dissolution media ph of dissolution media Viscosity of dissolution media Surfactant Temperature
- 11. Official Dissolution Apparatus USP Type- I Basket Type USP Type- II Paddle Type USP Type- III Reciprocating Cylinder USP Type- IV Flow Through Cell USP Type- V Paddle Over Disk USP Type- VI Rotating Cylinder USP Type- VII Reciprocating Holder
- 12. Official Dissolution Apparatus USP TYPE I: BASKET TYPE APPARATUS
- 13. Official Dissolution Apparatus USP TYPE II : PADDLE TYPE APPARATUS
- 14. Official Dissolution Apparatus USP TYPE III : RECIPROCATING CYLINDER
- 15. Official Dissolution Apparatus USP TYPE- IV : FLOW THROUGH CELL USP TYPE V : PADDLE OVER DISK APPARATUS
- 16. Official Dissolution Apparatus USP TYPE VI : ROTATING CYLINDER USP TYPE VII: RECIPROCATING HOLDER
- 17. Dissolution testing methods CONVENTIONAL & PROLONGED-RELEASE DOSAGE FORMS Place the dissolution medium into the vessel(free from dissolved air) Assemble the apparatus and warm the dissolution medium to 36.5º to 37.5º. Place one dosage unit in the apparatus Allow the tablet or capsule to sink to the bottom of the vessel prior to the rotation (PADDLE TYPE APPARATUS) OR Place the tablet or capsule in a dry basket at the beginning of each test and lower the basket into position before rotation(BASKET TYPE APPARATUS) Operate the apparatus immediately at the speed of rotation specified
- 18. At each of the times stated, withdraw a specimen from a zone midway between the surface of the dissolution medium and the top of the rotating blade or basket, not less than 10 mm from the wall of the vessel. For each of the tablet or capsule tested, calculate the amount of dissolved active ingredient in solution as a percentage of the stated amount . Dissolution testing methods
- 19. ACCEPTANCE CRITERIAS CONVENTIONAL RELEASE DOGASE FORMS: *D is the amount of dissolved active ingredient specified in the individual monograph, expressed as a percentage of the labeled content. **Percentages of the labeled content. Dissolution testing methods Level Number tested Acceptance criteria S1 S2 S3 6 6 12 Each unit is not less than D* + 5 percent**. Average of 12 units (S1 +S2) is equal to or greater than D, and no unit is less than D – 15 per cent**. Average of 24 units (S1+S2+S3)is equal to or greater than D, not, More than 2units are less than D – 15 per cent** and no unit is less than D – 25 per cent**.
- 20. PROLONGED-RELEASE DOSAGE FORMS Dissolution testing methods Level Number tested Acceptance criteria L1 L2 L3 6 6 12 No individual value lies outside each of the stated ranges and no individual value is less than the stated amount at the final test time. The average value of the 12 units (L1 +L2) lies within each of the stated ranges and is not less than the stated amount at the final test time; none is more than 10per cent of labeled content outside each of the stated ranges; and none is more than 10 per cent of labeled amount below the stated amount at the final test time. The average value of the 24 units (L1 +L2 + L3) lies within each of the stated ranges, and is not less than the stated amount at the final test time; not more than 2 of the 24 units are more than 10per cent of labeled content outside each of the stated ranges; not more than 2 of the 24 units are more than 10 per cent of labeled content below the stated amount at the final test time; and none of the units is more than 20 per cent of labeled content outside each of the stated ranges or more than 20 per cent of labeled content below the stated amount at the final test time
- 21. TRANSDERMAL PATCHES Place the prescribed volume of the dissolution medium in the vessel and equilibrate the medium to the prescribed temperature. Apply the patch to the SSDA by adhesive Place the patch mounted on the SSDA flat at the bottom of the vessel with the release surface facing upwards. Immediately rotate the paddle at 100 r/min At predetermined intervals; withdraw a sample from the zone midway between the surface of the dissolution medium and the top of the blade, not less than 1 cm from the vessel wall. Dissolution testing methods
- 22. Perform the assay on each sample, correcting for any volume losses, as necessary. Repeat the test with additional patches. Dissolution testing methods
- 23. According to USP apparatus used are Dissolution testing methods USP APP. DESCRIPTION ROT. SPEED DOSAGE FORM I BASKET 50-120 rpm IR, DR, ER II PADDLE 25-50 rpm IR, DR, ER III RECIPROCATING CYLINDER 6-35 rpm IR, ER IV FLOW-THROUGH CELL N/A ER, POORLY SOLUBLE API V PADDLE OVER DISK 25-50 rpm TRANSDERMAL VI CYLINDER N/A TRANSDERMAL VII RECIPROCATING HOLDER 30 rpm ER
- 24. Conclusion • Dissolution testing has become an integral part of quality control. • Although official methods are used, there exists no standard method for evaluation of a solid dosage form. • The method and standards, which correlate well with the in- vivo data, should be utilized. • The knowledge not only acts as tool for quality control, it also assists in preformulation studies and in understanding the biopharmaceutical role of the same.
- 26. References: United State Pharmacopoeia, The National Formulary, 2002, 20th Edition, United State Pharmacopoeial Convention INC, Washington, 711, 2011. INDIAN PHARMACOPOEIA 2007 Volume 1, The Indian Pharmacopoeia Commission, Ghaziabad, 179-181. Remington, The Science And Practice of Pharmacy, Volume 1, 21st Edition, Indian Edition, B. I. Publications Pvt. Ltd., 654-665. Banakar, U.V. 2000, Pharmaceutical Dissolution Technologies , volume 49. Marcel Dekker INC, N.Y., 174-175,280. Subramanyam C.V.S. 2006, Textbook Of Physical Pharmaceutics, 2nd Edition , Vallabh Prakashan,Delhi,88-90 .