THE FACTOR AFFECTING DISSOLUTION RATE

THE FACTOR AFFECTING DISSOLUTION RATE

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  The Factor Affecting Dissolution Rate PresentedBy Mohammad Zishan Ibrahim
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  What is Dissolution? Dissolutionis a process in which a solid substance solubilizes in a given solvent to yield a solution i.e. mass transfer from the solid surface to the liquid phase.
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  Importance of Dissolutionin Solid Dosage Form
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  Dissolution Rate Dissolution rateis the amount of drug substance that converts into solution per unit time under standardized condition of temperature and pressure. *The rate of dissolution is given by Noyes and Whitney: 𝒅𝒄 𝒅𝒕 = 𝒌 𝑪𝒔 − 𝑪𝒃
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  Factors Affecting DissolutionRate • Factor related to Physicochemical Properties of Drug • Factors related to Drug Product Formulation • Processing Factor • Factors Relating Dissolution Apparatus • Factors Relating Dissolution Test Parameters
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  Particle Size Surface areaincreases with decrease in particle size, higher dissolution rates may be achieved through reduction of particle size. Factor related to Physicochemical Properties of Drug
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  Drug Solubility • Aqueoussolubility of drug leads to the higher dissolution rate. • Dissolution rate is directly proportional to their respective solubility. Example : • Poorly Soluble drug ; griseofulvin, spironolactone • Hydrophilic drug : neomycin
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  Solid State Characteristics Anhydrous: forms dissolve faster than hydrated from because they are thermodynamically more active than hydrates. E.g. Ampicillin anhydrate faster dissolution rate than trihydrate. Amorphous : forms of drug tend to dissolve faster that crystalline materials. E.g. Novobiocin, Grisefulvin.
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  Salt Formation • Itis one of the common approaches used to increase drug solubility and dissolution rate. E.g. sodium and potassium salts of penicillin G, phenytoin, barbiturates, tolbutamide, etc
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  Binders • The hydrophilicbinders like gelatin increase dissolution rate of poorly wettable drug. • Non aqueous binders such as ethyl cellulose retard the drug dissolution. • Phenobarbital tablet granulated with gelatin solution provide a faster dissolution rate in human gastric juice than those prepared using Na – carboxy methyl cellulose or polyethylene glycol 6000 as binder. FACTORS RELATED TO DRUG PRODUCT FORMULATION
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  Disintegrates: “Disintegrating agent addedbefore & after the granulation affects the dissolution rate.“ A Microcrystalline cellulose is a very good disintegrating agent but at high compression force, it may retard drug dissolution.
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  Lubricants • Lubricants arehydrophobic in nature (metallic stearates) and prolong the tablet disintegration time by forming water repellent coat around individual granules. This retarding the rate of dissolution of solid dosage forms. • Both amount and method of addition affect the property. It should be added in small amount (1% or less) and shouldbe tumbled or mixed gently for only very short time. Prolonged mixing affect the dissolution time.
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  Surfactants • They enhancethe dissolution rate of poorly soluble drug. This is due to lowering of interfacial tension, increasing effective surface area, which in turn results in faster dissolution rate. E.g Non-ionic surfactant Polysorbate-80, increases dissolution rate of phenacetin granules. • The increase was more pronounced when the surfactant was sprayed on granules than when it was dissolved in granulating agent.
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  Complexing Agents • Acomplexed drug may have altered stability, solubility, molecular size, partition coefficient and diffusion coefficient. E.g. Enhanced dissolution through formation of a soluble complex of ergotamine tartarate-caffeine complex and hydroquinone-digoxin complex.
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  Granulation • Wet granulationhas been shown to improve the dissolution rate of poorly soluble drugs by imparting hydrophilic properties to the surface of granules. • A newer technology called as APOC “Agglomerative Phase of Comminution” was found to produce mechanically stronger tablets with higher dissolution rates than those made by wet granulation. A possible mechanism is increased internal surface area of granules produced by APOC method. PROCESSING FACTORS
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  Agitation • Speed ofagitation generates a flow that continuously changes the liq/solid interface between solvent and drug. • In order to prevent turbulence, The sustain reproducible laminar flow, which is essential for obtaining reliable results, agitation should be maintained at a relatively low rate. Thus, in general relatively low agitation should be applied. 1. BASKET METHOD- 100 rpm 2. PADDLE METHOD- 50-75 rpm24 FACTORS RELATED TO DISSOLUTION APPARATUS
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  Temperature • Drug solubilityis temperature dependent, therefore careful temperature control during dissolution process is extremely important. FACTORS RELATING DISSOLUTION TEST PARAMETERS Vibration • The excessive vibration of dissolution apparatus increases dissolution rates. pH of Medium • Weak acids, dissolution rate increases with increase in pH where as for weak beses, increase with decrease in pH
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