SOLUBILITY

SOLUBILITYANDDISSOLUTION : 

SOLUBILITYANDDISSOLUTION Prepared by: SIDDHARTH GUPTA M.PHARM 1ST SEM. Dr. Y.S.Tanwar and Kamal Singh Rathore

CONTENTS : 

DEFINATIONS(SOLUBILITY+DISSOLUTION) BCS CLASSIFICATION INTRINSIC SOLUBILITY METHODS FOR DETERMINING SOLUBILITY FACTORS AFFECTING SOLUBILITY SOLUBILITY CLASSIFICATION METHODS OF IMPROVING SOLUBILITY HANSEN SOLUBILITY PARAMETERS. IMPORTANCE OF SOLUBILITY STUDIES DISSOLUTION,THEORIES DISSSOLUTION APPARATUS (ACC. TO USP) CONTENTS

DEFINATIONS: : 

Solubility: The amount of substance that passes into the solvent in order to establish the equilibrium at constant temperature and so as to produce a saturated solution is k/- as Solubility. or It can also be said as the spontaneous interaction of two or more substance to form a homogenous molecular dispersion. Now if some of the solute molecule strike the bulk solute surface and redeposit on them, Than initially when the conc. Of solute mol. Is low in the solution the no of mol leaving the bulk solute surface is much higher DEFINATIONS:

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However, At saturation: Rate of mol = Rate of mol leaving the surface redepositing Hence the conc. of solution at which this equilibrium is reached is c/- Thermodynamic Solubility and the rate at which this equilibrium is reached is c/- as DISSOLUTION RATE Therefore we can say Solubility as EQUOLIBRIUM phenomena. Dissolution as Kinetic phenomena.

BCS classification and solubility : 

Class I - High Permeability, High Solubility Example: Metoprolol Those compounds are well absorbed and their absorption rate is usually higher than excretion. Class II - High Permeability, Low Solubility Example: Glibenclamide The bioavailability of those products is limited by their solvation rate. A correlation between the in vivo bioavailability and the in vitrosolvation can be found. Class III - Low Permeability, High Solubility Example: Cimetidine The absorption is limited by the permeation rate but the drug is solvated very fast. If the formulation does not change the permeability or gastro-intestinal duration time, then class I criteria can be applied. Class IV - Low Permeability, Low Solubility Example: Hydrochlorothiazide Those compounds have a poor bioavailability. Usually they are not well absorbed over the intestinal mucosa and a high variability is expected. BCS classification and solubility

The Biopharmaceutics Classification System is a guide for predicting the intestinal drug absorption provided by the U.S. Food and Drug Administration . The fundamental basis for the BCS was established by Dr. Gordon Amidon : 

The drugs are classified in BCS on the basis of following parameters:1. Solubility2. Permeability3. Dissolution The Biopharmaceutics Classification System is a guide for predicting the intestinal drug absorption provided by the U.S. Food and Drug Administration . The fundamental basis for the BCS was established by Dr. Gordon Amidon

Intrinsic solubility : 

It is defined as the maximum amount of solute that can be dissolved in solvent under standard condition of temperature, pressure and ph. If the solubility of a new drug increases in acidic solii compared to its aqueous solii suggests W.Base and in alkaline suggests W.acid Solubility shtd ideally be measured at 2 temp.: a)4-5ºC to ensure- good physical stability. -to extend short term storage-chemical stability. b) at37ºC – to support biopharmaceutical evaluation Intrinsic solubility

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Supression by common ion effect, salting out Self association,complexation,solubiolization by impurities Pure –no interaction Phase solubility diagram. Deviation from horizontal indicates presence of impurity which suppresses or promote solubility.

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Factors affecting solubility

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CLASSIFICATION OF SOLUBILITY

Methods of improving solubility : 

Methods of improving solubility

Hansen solubility parameter:  were developed by Charles Hansen as a way of predicting if one material will dissolve in another and form asolution.They are based on the idea that like dissolves like where one molecule is defined as being 'like' another if it bonds to itself in a similar way : 

each molecule is given three Hansen parameters:  The energy from dispersion bonds between molecules  The energy from dipolar intermolecular force between molecules  The energy from hydrogen bonds between molecules. Combining this with the interaction radius(Ro) gives the relative energ y difference (RED) of the system: Ra(distance b/w hansen parameters) Hansen solubility parameter:  were developed by Charles Hansen as a way of predicting if one material will dissolve in another and form asolution.They are based on the idea that like dissolves like where one molecule is defined as being 'like' another if it bonds to itself in a similar way RED < 1 the molecules are alike and will dissolve RED = 1 the system will partially dissolve RED > 1 the system will not dissolve

Method of determining solubility : 

Acc to Kalpen (1972) the solubility of a compound are determined by exposing excess of drug sample to liquid in question and assaying after equilibrium is established. 1.) If a compound have aqueous solubility of 1% (10mg/ml) over the pH range of1-7 at 37ºC than potential Bioabsorption problem may occur. 2.) If dissolution rate is less than 0.1mg/ml than the Dissolution rate limited absorption occurs. 3.) Solubility less than 1mg/ml indicates the need of salt formation Method of determining solubility

Importance of solubility studies : 

i) To develop a method of making the solution of drug. ii) To check the solubility of drug in solution form for example: Penicillin are very unstable in aqueous solution, hence they are stabilized by making insoluble salts of Pn and or formulating the as suspension. iii) To study the solubility of drug in media having ions and acidic ph to understand the drug solubility profile and to choose salts to achieve good bioavailability. Importance of solubility studies

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DISSOLUTION

What is meant by dissolution : 

1.A process in which a solid substance is solubilised in a given solvent that is mass t transfer from solid surface to liquid phase. 2. It is a process by which drug released from solid dosage form and immediately goes into molecular solution. What is meant by dissolution

Why do we study dissolution ? : 

DYNAMIC PROCESS. Why do we study dissolution ? SOLID DOSAGE FORM DISINTEGRATION SOLID DRUG PARTICLE DISSOLUTION DRUG IN SOLUTION FOR ABSORPTION RATE DETERMINING STEP FOR LIOPHILIC DRUGS

Theories of dissolution : 

1. Diffusion layer model or film theory 2. Danckwert’s model or Surface renewal theory 3. interfacial barrier model. Theories of dissolution

Diffusion layer model: : 

1. Simplest and most common. 2. Absence of reactive/ chemical forces, involves 2 steps i) formation of stragnated film/diffusion layer ii) diffusion-slower, rate determining step. Noyes and Whitney equation  dc/dt = DAKw/o (Cs - C)/Vh or dc/dt = K(Cs – Cb) Diffusion layer model:

Danckwert’s model: : 

1. Did not approve existence of stagnant layer. 2. Turblance in dissolution medium exist at solid-liquid interface. 3. Packet of Eddy currents absorb the solute by diffision. Vdc/dt=dm/dt=A(cs-cb)√YD M =mass 0f solid dissolved. Y= rate of surface renewal. Danckwert’s model:

Interfacial barrier layer model: : 

1. Assumption of previous models.(RDS in disso is mass transfer, solid-solii equib; is achived at s/l interface.) 2. intermediate conc. Exist at the interface as a result of solvation mechanism it is function of solubility rather than diffusion. G=Ki(Cs-Cb) G=disso rate /area Ki=effective interfacial transport constant. Interfacial barrier layer model:

Factors affecting and process influnced by Dissolution: : 

Factors affecting and process influnced by Dissolution:

Goals of predective disolution test : 

To accessing therapeutic efficacy. Monitoring batch to batch consistency. High cost of in vitro dissolution test. Assessment of bioequiovalance Goals of predective disolution test

Based on sink and non sink condition dissolution apparatus are calssified as: : 

1. Closed compartment apparatus 2. open compartment apparatus Based on sink and non sink condition dissolution apparatus are calssified as:

TYPES OF DISSOLUTION APPARATUS : 

TYPES OF DISSOLUTION APPARATUS USP dissolution apparatus(official) 1. Apparatus1:Basket type 2. Apparatus2:Paddle type 3.Apparatus3:Reciprocating cylinder 4. Apparatus4:Flow through cell 5. Apparatus5:paddle over disc 6. Apparatus6:Rotating cylinder 7. Apparatus7; Reciprocating disc USP dissolution apparatus(non-official) 1.Rotating bottle method 2. Diffusion cell 3. Peristalasis method 4. Intrinsic dissolution method

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BP dissolution apparatus: Apparatus1: basket type Apparatus2: paddle type Apparatus3: flow through cell IP dissolution apparatus: Apparatus 1: Paddle Type Apparatus 2: Basket Type

USP apparatus 1: Basket type : 

Design A) Vessel:-Made up borosilicate glass. -semi hemispherical bottom - capacity 1000ml. B) Shaft:- Stainless steel 316 - Rotates smoothly without significance wooble. C) Basket:- Stainles steel 316 - Gold coating upto 0.0001 inch. D) Water Bath: Maintained at 37± 0.5 C USE: Capsules, Tablets, Delayed release, Suppositories,Floating dosage forms. USP apparatus 1: Basket type

USP apparatus 2:Paddle type : 

Design: A) Vessel: Made up borosilicate glass. -semi hemispherical bottom - capacity 1000ml. B) Shaft:-The blade passes through the sahft so that bottom of blade fuses with bottom of shaft. C) Stirring elements:- Made of Tefflon -For Laboratory purpose -stainless steel 316 D) Water bath: Maintain at 37±0.5ºC E) Sinkers:- Platinum wire used to prevent caps/tab. From floating. USP apparatus 2:Paddle type

Dissolution apparatus and uses : 

Type 3(Reciprocating cylinder)-useful in bead type modified release dosage form. Type4 (Flow through cell)- used for mod.dosage form that contain active ingredient with limited solubility. Inaddition 3&4 can also be used for- Soft gelatin capsule and suppositories. Type 5 &6(paddle over cylinder and rotating disc) are used for Transdermal dosage form Type 7 (Reciprocating disc)- for non disintegrating oral modified release dosage form+transdermal dosage form. Dissolution apparatus and uses

References:1. USP2. Indian pharmacopiea3.Bharmarkar.4.Lachman5.Internet : 

References:1. USP2. Indian pharmacopiea3.Bharmarkar.4.Lachman5.Internet