In-vitro Dissolution apparatus and equation used for dissolution.pptx

apparatus/equation used in in-vitro dissolution

1. IN VITRO DISSOLUTION AND DRUG RELEASE ANKIT RAJ M.PHARM 2 ND SEM. AMITY UNIVE RSITY, HARYANA

2. CONTENT I ntroduction Mechanism of dissolution Theories of dissolution Apparatus used in dissolution Factor affecting dissolution Problem of variable Control in dissolution testing performance of drug product.

3. INTRODUCTION DISSOLUTION A process in  which a solid substance is solubilized in a given solvent i.e., mass transfer from solid surface to liquid phase. (i.e., from solid to liquid) It is a Rate Determining Step Rate of dissolution is the amount of drug substance that goes in solution per unit time under standardized conditions of liquid/solid interface, temperature and solvent composition.

4. 2. MECHANISM OF DISSOLUTION • Wetting of dosage form • Penetration of dissolution medium • Disintegration • Dissolution

5. 3. THEORY OF DISSOLUTION Diffusion Layer Model/ Film theory Danckwerts’s Model/ Penetration or Surface Renewal Theory Interfacial Barrier Model/ Double Barrier Theory

6. A. DIFFUSION LAYER THEORY OR FILM THEORY Solution of the solid to form a thin layer at the solid/liq. interface is called Stagnant film • This step is Rapid Soluble solute form diffuses from the stagnant layer to the bulk of the solution. This step is slower and rate-determining step in drug dissolution. • This rate of dissolution if the process is diffusion controlled and invovles no chemical reaction. • It can be explained by Noyes – Whitney Equation . dC /dt = k(Cs- Cb ) where , dC /dt = dissolution rate of drug Cs = conc. of drug in stagnant layer Cb = conc. of drug in bulk of the solution at time t. k = dissolution rate constant. (First order)

7. B. DANCKWERT’S MODEL This  model suggest that turbulence in dissolution medium exists at the solid/liquid interface. Danckwert takes into account the eddies or packets that are present in the agitated fluid which reach the solid-liquid interface, absorb the solute by diffusion and carry it into the bulk of solution. These packets get continuously replaced by new ones and expose to new solid surface each time, thus the theory is called as surface renewal theory.

8. C. INTERFACIAL BARRIER MODEL An intermediate concentration can exist at the interface as result of solvation mechanism and function of solubility rather than diffusion. When considering the dissolution of a crystal, each face of the crystal will have a different interfacial barrier such a concept is given by the following equation : G =Ki (cs - cb ) • where, G= dissolution rate per unit area. Ki =effective interfacial transport constant. Cs = Concentration of drug in the stagnant layer Cb =Concentration of drug in the bulk of the solution at time t In this theory, the diffusivity D may not be independent of saturation concentration cs. Therefore the interfacial model can be extended to both diffusion layer model and Danckwerts model.

9. 4. CLAASIFICATION OF DISSOLUTION APPARATUS IN DIFFERENT PHARMACOPEIAS TYPES I.P USP B.P E.P TYPE 1 PADDLE TYPE BASKET TYPE BASKET TYPE PADDLE TYPE TYPE 2 BASKET TYPE PADDLE TYPE PADDLE TYPE BASKET TYPE TYPE 3 RECIPROCATING CYLINDER FLOW THROUGH CELL FLOW THROUGH CELL TYPE 4 FLOW THROUGH CELL TYPE 5 PADDLE OVER DISC TYPE 6 CYLINDER TYPE 7 RECIPROCATING HOLDER

10. 1 .  DISSOLUTION APPARATUS-1 (ROTATING BASKET) Design: Vessel: -Made Of Borosilicate Glass. Semi Hemispherical Bottom-capacity 1000ml Shaft : -Stainless Steel 316 -Speed 50-100 Rpm. Water Bath :-Maintained At 37±0.5ºc Dosage Form Is Kept In Basket. Use: tablets, capsules, floating dosage forms.

11. 2.   DISSOLUTION APPARATUS-2 (PADDLE) Design: Vessel:  -Same As Basket Apparatus Shaft: - Fused With Blade At Bottom Stirring Elements:- Coated With Teflon For Laboratory Purpose Stainless Steel Is Used Rotation Speed:- 25-50 Rpm Water-bath: -Maintains At 37±0.5°c Sinkers : -Platinum Wire Used To Prevent Tablet/Capsule From Floating. Dosage Form Should Remain At The Bottom Center Of Vessel U se : Orally Disintegrating Tablets, Chewable Tablets Etc. 

12. 3.   DISSOLUTION APPARATUS-3 (RECIPROCATING CYLINDER) Design: Vessel: -Set Of Cylindrical Flat Bottom Glass Vessels -Set Of Reciprocating Cylinders -Stainless Steel Fittings. Agitation Type: -Reciprocating (Upward & Downward) Volume Of Dissolution Medium:-200-250ml Water Bath:- Maintain At 37±0.5°c Dosage Form Is Placed In Cylinder Use: Tablets, Beads, Controlled And Extended Release Formulations

13. 4. DISSOLUTION APPARATUS-4 (FLOW THROUGH  CELL) D esign: R eservoir :- For Dissolution Medium P ump :- Forces Dissolution Medium Through Cell (Upward Direction) -Flow Rate 10-100ml/Min -Laminar Flow Is Maintained -Centrifugal Pumps Are Not Recommended W ater Bath:- Maintained At 37±0.5°c Use: Low Solubility Drugs, Micro Particulate, Implants, Suppositories, Controlled Release Formulations

14.  5. DISSOLUTION APPARATUS-5 (PADDLE- OVER-DISK) Design   Vessel & Shaft:- Same As Paddle Apparatus Rotation Speed:- 25-50 Rpm Sample Holder:-disk Assembly That Holds Product In Such A Way That Release Surface Is Parallel With Paddle Blade -Distance 25 ± 2 Mm -Samples Are Drawn Between Surface Of The Medium & The Top Of The Paddle Blade Temperature:32 ± 0.5°C Use : Transdermal Products, Emulsions. 

15. 6 . DISSOLUTION APPARATUS-6 (ROTATING CYLINDER)   Design: Vessel:- Same As Of Basket Apparatus Shaft & Cylinder:- Stainless Steel Sample :- Mounted To Cuprophan (Inner Porous Cellulosic Material) An Entire System Is Adhered To Cylinder. - Dosage Unit Is Placed In Cylinder And Release From Side Out. Rotation Speed:- 25-50 Rpm Water-bath: Maintained At 32±0.5°c Use : Mainly Transdermal Products 

16. 5. COMMONLY USED DISSOLUTION  MEDIA Purified water Dilute acid (0.001N – 0.1N HCl) Stimulated gastric fluid Stimulated intestinal fluid Surfactants (e.g. Polysorbate, SLS) Aqueous buffers (pH 5-7)

17. 6. FACTORS AFFECTING DISSOLUTION  RATE Factors Related To Physicochemical Properties Of Drug Particle size of drug Drug solubility Salt formation :- sodium salt faster than their corresponding Factors Related To Drug Product Formulation Binder :- hydrophilic binder increase the dissolution rate. Disintegrating agent :- added before and after the granulation directly affect the dissolution Lubricant :- hydrophobic in nature , prolong the disintegration Surfactant :- enhance the dissolution rate of poorly soluble drug

18. 3. Processing Factor Method of granulation :- wet granulation shown to improve dissolution rate Compression force :- Influence density, porosity hardness of tablet. Storage condition Factors Relating Dissolution Apparatus Agitation :- speed of agitation Stirring element alignment Factors Relating Dissolution Test Parameters Temperature :- Drug solubility is temperature dependent, therefore temperature control during dissolution process is extremely important. Design of vessel :- Plastic vessels provide more perfect hemisphere than glass vessels

19. 6. PROBLEMS OF VARIABLE CONTROL IN DISSOLUTION TESTING PERFORMANCE OF DRUG PRODUCT The Source Of Deviation From Accurate Results In Dissolution Test Can Be Broadly Classified Into Following Categories: Equipment Related Factors Process Related Factors Drug Substance Properties Related Factors Drug Product Properties Related Factors Miscellaneous Factors

20. A. EQUIPMENT RELATED FACTORS The initial quality of the device and its subsequent care and maintenance with influence both operational reliablity and product dissolution rate result. A discussion of dissolution equipment is important as the dissolution rate is generated by the string mechanism interacting with the dosage form in the media. The environment in which it operates will also affect the performance and in need to running properly at all time. Some of the parameter associated are :- dissolution test vessels Paddle/ baskets shaft vibration use of filters calibration of dissolution vessels.

21. B. PROCESS RELATED FACTOR Various factor associated with dissolution test procedure may lead to errors. use of water as dissolution media. Sample introduction single point versus multi point sampling control Release doses form. C. DRUG SUBSTANCE PROPERTIES RELATED FACTOR Knowledge of drug properties like solubility of drug effect of PH change, crystalline structure is important. One could anticipate precipitation of drug as the pH change in solution, or if release from the dosage from lead to supersaturation of the test media. Example, preparation of the standard solution may is an important step. It is customary to use a small amount of alcohol to dissolve the standard completely.

22. D. DRUG PRODUCT PROPERTIES RELATED FACTOR Dissolution profile may help in identifying trains and effect of formulation changes when the result are highly variable. It indicate that the method is not robust. Two major casual factor influence viability. mechanical :- Mechanical causes can arise from the dissolution condition chosen. E.g :- an apparatus or speed change may change the result. Formulation :- e.g The film coating may cause sticking to the vessel wall.