Dissolution - Selection of Dissolution Media

Is the processes by which solid substance enters the solvent phase to yield a solution i.e. mass transfer from solid surface to liquid phase.

1. Selection Of Dissolution Media Mr . Sagar Kishor Savale [Department of Pharmaceutics] [email protected] 2015-2016 6/3/2016 1 sagar kishor savale

2. Content 6/3/2016 2 sagar kishor savale

3. DefinItion 1 Is the processes by which solid substance enters the solvent phase to yield a solution i.e. mass transfer from solid surface to liquid phase. 6/3/2016 3 sagar kishor savale

4. Importance Of Dissolution Test 1 Dissolution testing is mainly used to confirm product quality and batch to batch consistency. Find problems in Bioavailability. In R &D department ,comparing in vitro dissolution data with in vivo bioavailability . 6/3/2016 4 sagar kishor savale

5. SELECTION OF DISSOLUTION MEDIA: 1 The selection of an appropriate dissolution medium is a fundamental stage of the dissolution test. It is more important that the test closely simulate the environment in the GI tract than necessarily produce sink condition. SINK CONDITION : The dissolution rate may be given by Novey-Whitney equation. Where, S : surface area t : time Cs-Ct: concentration gradient between the concentration of solute in the stagnant layer 6/3/2016 5 sagar kishor savale

6. dW / dt = K This represents that the dissolution rate is constant under sink conditions. We have to maintain sink condition in in-vitro. This is can be achieved by, Bathing the dissolving solid in fresh solvent from time to time. Increasing the volume of dissolution fluid. Adding a water miscible solvent such as alcohol to the dissolution medium. By adding selected adsorbent to remove the dissolved drug. 6/3/2016 6 sagar kishor savale

7. APPRATUS RECOMMENDED BASED ON DOSAGE FORM TYPE : 1 Type of dosage form Recommended Apparatus Solid oral dosage forms Basket , paddle, reciprocating, cylinder, or flow-through cell (conventional) Oral suspensions Paddle Oral disintegrating tablets Paddle Chewable tablets Basket, paddle, or reciprocating, cylinder with glass beads Transdermal —patches Paddle over disk Topical —semisolids Franz cell diffusion system Suppositories Paddle, modified basket, or dual, chamber flow-through cell Chewing gum Special apparatus [European Pharmacopoeia ( PhEur )] Powders and granules Flow-through cell (powder/granule sample cell) Microparticulate formulations Modified flow-through cell Implants Modified flow-through cell 6/3/2016 7 sagar kishor savale

8. OPERATING PARAMETERS : 1 1 . VOLUME: The recommended volume of dissolution medium is 900ml when using the basket or paddle apparatus. The volume can be raised to between 2 and 4 L, depending on the concentration and sink conditions of the drug solution. 2. TEMPERATURE: The standard temperature for the dissolution medium is 37±0.5°C for oral dosage forms. Slightly increased temperatures such as 38±0.5°C have been recommended for dosages forms such as suppositories. Lower temperatures such as 32±0.5°C are utilized for topical dosage forms such as transdermal patches and topical ointments. 6/3/2016 8 sagar kishor savale

9. 3.DEAERATION : Air bubbles can interfere with the test results. Bubbles on the dosage unit may decrease the dissolution rate by decreasing the available surface area. Some formulations will be sensitive to the presence of dissolved air in the dissolution. Media containing surfactants are not usually deaerated after the surfactant has been added to the medium. Media containing surfactants are not usually deaerated after the surfactant has been added to the medium because of excessive foaming. 6/3/2016 9 sagar kishor savale

10. 1.COMPENDIAL DISSOLUTION MEDIA : Simulated Gastric Fluid : The traditional medium to simulate gastric conditions in the fasted state has been simulated gastric fluid (SGF). This medium contains HCL and Nacl , as well as pepsin and water, and has a pH of 1.2. Although the medium addresses many of the qualities of gastric juice . For example, most studies of gastric pH indicate that the across-the-board average gastric pH usually lies in the range1.5–1.9 . Types Of Dissolution Media 1 6/3/2016 10 sagar kishor savale

11. Water is an attractive medium that because of its simplicity has been widely used for quality control purposes. It could even be argued that it is physiologically relevant since many formulations are intended to be ingested with a glass of water. However, the pH of water may vary with its source, and water has no buffer capacity. Water 6/3/2016 11 sagar kishor savale

12. A frequently used medium for the simulation of small intestinal (SI) conditions in the fasted state is simulated intestinal fluid (SIF) A medium that was first described as standard test solution in the USP more than 50 years ago. The only parameter that has been changed is the pH of the medium. As it was assumed that the pH in the small intestine is very close to blood plasma, the pH of SIF was initially set at 7.5. Simulaed Intestinal Fluid 6/3/2016 12 sagar kishor savale

13. As per above the 7.5 is mainly seen at the distal part so the we can ’ t predict the whole intestine . The dissolution characteristics of oral formulations should be evaluated over the physiologic pH range of 1.2 -6.8. 6/3/2016 13 sagar kishor savale

14. From above  we can say than the main difference seen in the Stomach pH, this is due to the secreation of the gastric juice mainly HCl . For very poorly soluble compounds, aqueous solutions may contain a percentage of a surfactant (e.g., sodium lauryl sulfate, Tween 80, Cremophor, Triton, terigitol , cyclodextrin or Span 80) that is used to enhance drug solubility. The surfactant is added to mimic the action of the Bile salts 6/3/2016 14 sagar kishor savale

15. 2.BIORELEVENT  MEDIA : Biorelevant is short for ‘ biologically relevant ’ . Biorelevant media are virtually the same as intestinal juices. They contain key natural surfactants (bile salts, phospholipids) present in intestinal juices. These are missing from ordinary dissolution media. They are virtually the same as the fluids inside the body, it can provide a much more accurate picture of how drugs and their formulations are likely to dissolve in vivo. 6/3/2016 15 sagar kishor savale

16. Fasted State Gastric Conditions: FaSSGF : Several attempts have been made to improve simulation of fasting conditions in the stomach. In most of these media, particular attention was given to the simulation of the surface tension measured in human gastric aspirates. However, in these media, non-physiologically relevant surface active agents, lower than physiological pH values or by far too high concentrations of pepsin or bile salts, were utilized. Recently, a fasted state simulated gastric fluid ( FaSSGF ) containing pepsin and low amounts of bile salt and lecithin was developed by Vertzoni . 6/3/2016 16 sagar kishor savale

17. Specifically fasted state simulating intestinal fluid ( FaSSIF ) was developed to simulate fasting conditions in the proximal small intestine. The addition of a stable phosphate buffer system that results in a pH representative to values measured from the mid-duodenum to the proximal ileum. This medium contains bile salts and phospholipids (lecithin). From pharmacokinetic studies of drug absorption in the fasted state , ingesting 200–250 ml of water with the dosage form, a maximum total volume of about 300–500 ml will be available in the proximal SI. Therefore, for dissolution tests, a volume of  ≤500 ml is recommended. Fasted State Small Intestinal Conditions: FaSSIF : 6/3/2016 17 sagar kishor savale

18. Fed State Gastric Conditions: Milk and Ensure® Plus : Is the fed state, the luminal composition in the stomach will be highly dependent on the composition of the meal ingested. The composition and the amount of the food is different in the every people , so we can’t get correlation. The ideal medium representing initial gastric conditions in the fed state should have similar nutritional and physicochemical properties to that of a meal, e.g., the standard breakfast recommended by the USFDA to studying the effects of food in BA and bioequivalence studies. Milk was first investigated as a dissolution medium about 20 years ago, the use of Ensure® Plus has been established only a few years ago. Ensure® Plus have a similar composition to a breakfast meal with respect to the ratio of carbohydrate/fat/protein. In addition, as the stability of fresh milk at 37°C is a problem, heat-treated milk must be used. 6/3/2016 18 sagar kishor savale

19. REFERENCE http://www.pharmatutor.org/articles/review-selection-of-dissolution-media?page=0,2 6/3/2016 19 sagar kishor savale

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