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DISSOLUTION
Definition: o 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. o Dissolution is the rate determining step for hydrophobic, poorly aqueous soluble drugs. E.g. Griseofulvin, spironolactone
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2. Danckwerts model
3. Interfacial barrier model
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Solution of the solid to form a thin film or layer at the solid/liquid interface called as the stagnant film or diffusion layer which is saturated with the drug. This step is usually rapid Diffusion of the soluble solute from the stagnant layer to the bulk of the solution .this step is slower and is there for the rate determining step in drug dissolution.
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dc/dt =k(cs-cb) where dc/dt = dissolution rate of a drug, K = dissolution rate constant. Cs = concentration of drug in the stagnant layer. Cb =concentration of drug in the bulk of the solution at time t. Burner incorporated Ficks first law of diffusion and modified the Noyes Whitneys equation to
dc/ dt = DAK
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Where D A K V h
w/o
= diffusion coefficient of the drug = surface area of the dissolving solid. = intrinsic dissolution rate constant. = volume of dissolution medium. = thickness of the stagnant layer.
solid/liquid interface
intermediate concentration can exist at the interface as a result of solvation mechanism
G = Ki (Cs-Cb)
where G = dissolution rate per unit area Ki = effective interfacial transport constant Powerpoint Templates Page 10
Apparatus 6 - (cylinder)
Apparatus 7 - (reciprocating holder)
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Apparatus Classification in the European Pharmacopoeia (2002) for Different Dosage Forms
DOSAGE FORMS APPARATUS Paddle apparatus
For solid dosage forms
Basket apparatus
Flow-through apparatus
Chewing apparatus
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Flow-Through Cell
(a) Apparatus for the determination of drug release from medicated chewing gums. Powerpoint Templates (b) flow-through cell for semi-solid products. Page 13
Reciprocating Cylinder
(a) The reciprocating cylinder apparatus (Bio-Dis) and (b) reciprocating cell. Powerpoint Templates Page 14
(a) Assembly for testing timed-release preparations. (b) Continuous flow dissolution apparatus.
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A. PHARMACEUTIC FACTORS
Include the factors relating to the; 1. Physicochemical properties of the drug substance 2. Dosage form charecteristics and Pharmaceutic ingredients
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Drug stability
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1. Rate of dissolution :
eg: griseofulvin,spironolactone Hydrophobic drugs
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1. Solution of solid to form stagnant layer at the interface 2. diffusion of soluble solute from stagnant layer to bulk of solution
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solid/liquid interface
intermediate concentration can exist at the interface as a result of solvation mechanism
G = Ki (Cs-Cb)
where G = dissolution rate per unit area Ki = effective interfacial transport constant Powerpoint Templates Page 27
pressure.
Polymorphs differ from each other respect to physical factors
Amorphous form having no internal structure Greater aqueous solubility than crystalline form Energy required to transfer a molecule from
HYDRATES/SOLVATES (Pseudopolymorphism)
Solvates solvent molecules are incorporated in crystal lattice of the solid Trapped solvates can exist in different crystalline forms called as pseudopolymorphs. Hydrate In a solvate, solvent associated with the drug is water
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dissolution rate
Salt form is absorbed faster than their acid or base. The size of the counter ion influences the solubility of the salt forms of the drug. Smaller the size of the counter ion, greater the solubility of the salt
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Marked difference have been observed in rate and extent of absorption of a weak acid [H+]d = hydrogen ion concentration of the diffusion layer
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sodium
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absorbed
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administration
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is absorbed and permeation of the ionized drug is negligible pH absorption curve shift suggested that ionized forms also get absorbed, If such drugs have a large
lipophilic group
The absorption of ionized drug cause the pH absorption curve, shift to right for weak acid ,left for weak base Extent of shift depends on the relative permeability
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3. Influence of GI surface area and residence time pH-partition theory states- acidic drugs are best absorbed from stomach and basic drugs from intestine, more ionized Acidic drug reaches intestine, the remaining
layer pH shift of acidic and basic drugs shows, bulk luminal fluid is in contact with aqueous unstirred diffusion layer Increased absorption rate due to reducing thickness of layer Drug must diffuse first through aqueous barrier and then through lipoidal barrier Drugs of large partition coefficient can rapidly penetrate lipid membrane, but through diffusion layer is the rate limiting step
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bioavailability
Needs to be stable before it is absorbed in the GI fluid
2. Manufacturing Variables
Method of granulation -wet granulation -direct compression
Intensity of packing of capsule contents packing density; either inhibit or promot dissolution
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PHARMACEUTIC INGREDIENTS
Vehicles Diluents(Fillers) Binders and granulating agent Disintegrants Lubricants Coatings Colorants Powerpoint Templates
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# parameters
# influencing factors
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1. VOLUME OF MEAL
2.
COMPOSITION OF MEAL
3. VISCOSITY OF MEAL
4. TEMPERATURE OF MEAL
5. GI pH
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7. BODY POSTURE
8. EMOTIONAL STATE 9. EXERCISE 10. DISEASE STATE 11. DRUG
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INTESTINAL TRANSIT
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DISEASE STATES
GASTROINTESTINAL DISEASES ALTERED GI MOTILITY
GASTROINTESTINAL SURGERY
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HEPATIC DISEASES
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GASTROINTESTINAL CONTENTS
Food-drug interactions
Fluid volume
Interaction of drug with normal GI constituents Drug-drug interactions
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LUMENAL ENZYMES
GUTWALL ENZYMES BACTERIAL ENZYMES HEPATIC ENZYMES
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REFERENCES
JENNIFER DRESSMAN , PHARMACEUTICAL DISSOLUTION TESTING p.g.no.15 - 23
MILO GIBALDI, BIOPHARMACEUTICS AND CLINICAL PHARMACOKINETICS p.g.no 40-58 P.L. MADAN, BIOPHARMACEUTICS AND PHARMACOKINETICS , p.g.no 77 79 D.M. BRAHMANKAR,SUNIL B.JAISWAL, BIOPHARMACEUTICS AND PHARMACOKINETICS Powerpoint Templates Page 61 p.g.no 19-39
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