SOLUBILITY & SOLUBILIZED SYSTEM

SOLUBILITY & SOLUBILIZED SYSTEM : 

SOLUBILITY & SOLUBILIZED SYSTEM PRESENTED BY: Mr.MAHESH LIMBACHIYA M.Pharm (Pharmaceutics) Sem - 1 GUIDED BY: Mrs.SUNITA A.CHAUDHARY M.Pharm ( Ph.D ) SARASWATI INSTITUTE OF PHARMACEUTICAL SCIENCES AT & PO- DHANAP DIST: GANDHINAGAR

CONTENT: 

CONTENT 1.Aim Of Studying Solubility 2.Introduction Definition Of Solubility Intrinsic Solubility Determination of solubility 3.Process Of Solubilization 4.Factors Affecting Solubility 5.Solubility Enhancement Techniques 6.Applications 7.Questions References

Aim Of Studying Solubility:: 

Aim Of Studying Solubility: To choose t he best solvent medium for a drug or combination of drugs. To overcome certain difficulties that arises in the preparation of pharmaceutical solution. And further more, can serve as a standard test of purity.

PowerPoint Presentation: 

INTRODUCTION: Solubility : Solubility is defined as the number of milliliters of solvent in which 1 gm of solute will dissolve. Descriptive term Approximate volume of solvent in milliliters per gram of solute very soluble less than 1 freely soluble from 1 to 10 Soluble from 10 to 30 sparingly soluble from 30 to 100 slightly soluble from 100 to 1000 very slightly soluble from 1000 to 10,000 insoluble or practically insoluble more than 10,000

PowerPoint Presentation: 

Intrinsic solubility(Co) When the purity of the drug sample can be assured, the solubility value obtained in acid for a weak acid or alkali for a weak base can be assumed to be intrinsic solubility(Co) The presence of impurities could either increase or decrease the solubility(or alternatively have no effect). A reasonably accurate estimation of this crucial solubility can be made by phase-solubility diagram.

EXAMPLE: Compound is a base in 0.1 M NaOH . Four solution of 3 mL can be set up containing, 3, 6, 12 and 24 mg of drug. The vials should be agitated continuously overnight and then the concentration in solution determined. : 

EXAMPLE: Compound is a base in 0.1 M NaOH . Four solution of 3 mL can be set up containing, 3, 6, 12 and 24 mg of drug. The vials should be agitated continuously overnight and then the concentration in solution determined. Any deviation from the horizontal is indicative of the presence of impurities. A large amount of drug, with its inherent impurities, will either promote or suppress solubility.

PowerPoint Presentation: 

The Henderson- Hasselbalch equations are used to find the intrinsic solubility for weak acid and base For weak acids: For weak bases:

DETERMINATION OF SOLUBILITY : 

DETERMINATION OF SOLUBILITY There are two method for solubility determination: 1. Modified Shake Flask method: 2. Potentiometric Titration method:

1. Modified Shake Flask method: : 

1. Modified Shake Flask method: The drug is added to a standard buffer solution until the saturation occur. The pH is measured and if necessary readjusted with dilute acid or alkali. The flask shaken for 24 hours The amount of dissolved drug is determined by suitable assay of the solution after filtration . This method is time consuming

2. Potentiometric Titration method: : 

2. Potentiometric Titration method: Titrations are performed using dilute acid or base titrants in 0.15 M KCl ionic strength buffered solutions. Solubility of the salt is not determined with this technique, The solubility-pH profile provide over the entire pH range excluding the onset of salt precipitate. The potentiometric method requires an accurately measured pKa

PROCESS OF SOLUBILISATION:: 

PROCESS OF SOLUBILISATION: Step 1: Holes opens in the solvent Step 2: Molecules of the solid breaks away from the bulk Step 3:The freed solid molecule is intergrated into the hole in the solvent

FACTORS AFFECTING SOLUBILITY: 

FACTORS AFFECTING SOLUBILITY POLARITY CRYSTAL STRUCTURE PARTICLE SIZE MOLECULER SIZE PRESSURE pH TEMPERATURE SOLUBILITY

PARTICLE SIZE: 

PARTICLE SIZE The size of the solid particle influences the solubility because as a particle becomes smaller, the surface area to volume ratio increases. The larger surface area allows a greater interaction with the solvent. The effect of particle size on solubility can be described by Where, S is the solubility of infinitely large particles S 0 is the solubility of fine particles V is molar volume is the surface tension of the solid r is the radius of the fine particle

TEMPERATURE: 

TEMPERATURE ENDOTHERMIC REACATION: If the solution process absorbs energy then the solubility will be increased as the temperature is increased. EXOTHERMIC REACATION: If the solution process releases energy then the solubility will decrease with increasing temp. Generally, an increase in the temperature of the solution increases the solubility of a solid solute.

PH: 

PH 1.NONIONIZABLE SUBSTANCES Little effect of pH on nonionizable substances. Solubility can be increased by change of dipole moment. 2. IONIZABLE SUBSTANCES Depends on HEDERSON-HESSELBALCH equation. For Acidic drug pH= pKa+log [(S-S0)/S0 ] S=Over all solubility of substance For basic drug So=solubility of unionized species pH= pKa+log [S0/(S-S0) ] S-So=solubility of ionized species

PowerPoint Presentation: 

The effect of pH on a weak acid (A) and a weak base (B)

PRESSURE: 

PRESSURE For gaseous solutes, an increase in pressure increases solubility and a decrease in pressure decrease the solubility. For solids and liquid solutes, changes in pressure have practically no effect on solubility . MOLECULAR SIZE The larger the molecule or the higher its molecular weight the less soluble the substance.

POLARITY: 

POLARITY Non-polar solute molecules will dissolve in non-polar solvents and polar solute molecules will dissolve in polar solvents. The polar solute molecules have a positive and a negative end to the molecule. If the solvent molecule is also polar, then positive ends of solvent molecules will attract negative ends of solute molecules. This is a type of intermolecular force known as dipole-dipole interaction.

CRYSTAL STRUCTURE: 

CRYSTAL STRUCTURE Amorphous form of drugs are more soluble than Crystalline form. Amorphous form having no internal crystal structure. They have greater aqueous solubility than the crystalline forms because they require less energy to transfer a molecule into solvent.

TECHNIQUES OF SOLUBILITY ENHANCEMENT: : 

TECHNIQUES OF SOLUBILITY ENHANCEMENT: PHYSICAL MODIFICATIONS A. Particle size reduction : a. Micronization b. Nanosuspension B. Modification of the crystal habit C. Drug dispersion in carriers : a. Eutectic mixtures b. Solid dispersions c. Solid solutions D. Complexation E. Solubilization by surfactants F. Solubilization by salt formation G. Nanotechnology approaches II. CHEMICAL MODIFICATIONS

OTHER TECHNIQUES: 

OTHER TECHNIQUES Co- crystallisation Cosolvency Hydrotrophy Solubilizing agents Microemulsion Use of Clathrates Use of buffers

A. PARTICLE SIZE REDUCTION: 

A. PARTICLE SIZE REDUCTION

a.Micronization: 

a.Micronization Micronization is reduction of particle size upto micron level. Micronization increases the dissolution rate of drugs through increased surface area. Micronization of drugs is done by milling techniques using jet mill, rotor stator colloid mills etc.

b.Nano suspension: 

b.Nano suspension Nanosuspensions are sub-micron colloidal dispersion of pure particles of drug Techniques for the production of nanosuspensions a) Homogenization: The suspension is forced under pressure through a valve that has nano aperture. This causes bubbles of water to form which collapses as they come out of valves. This mechanism cracks the particles.

PowerPoint Presentation: 

Three types of homogenizers are commonly used: Conventional homogenizers, Sonicators , and High shear fluid processors. b) Wet milling: Active drug in the presence of surfactant is defragmented by milling.

Other Techniques For Reduction Of the Particle size: : 

Other Techniques For Reduction Of the Particle size: 1. Sonocrystallisation 2. Supercritical fluid process(SCF)

1. Sonocrystallisation : 

1. Sonocrystallisation The novel approach for particle size reduction on the basis of crystallisation by using ultrasound. Sonocrystallisation utilizes ultrasound power characterised by a frequency range of 20–100 kHz for inducing crystallisation . Size reduction and controlling size distribution of the active pharmaceutical ingredients (API) occur in sonocrystallisation .

2.Supercritical fluid process(SCF) : 

2.Supercritical fluid process(SCF) Supercritical fluids are fluids whose temperature and pressure are greater than its critical temperature ( Tc ) and critical pressure ( Tp ). The most widely employed methods of SCF process: Rapid Expansion Of Supercritical Solutions (RESS) Gas Antisolvents Recrystallisation (GAS) , Both are employed by the pharmaceutical industry using carbon dioxide (CO 2 ) as the SCF due to its favourable characteristics like,low critical temperature ( Tc = 31.1C) and pressure (Pc = 73.8 bar).

Rapid Expansion Of Supercritical Solutions (RESS) : 

Rapid Expansion Of Supercritical Solutions (RESS)

PowerPoint Presentation: 

Solute Dissolved in SCF Pass it through a nozzle at sonic speeds Rapid expansion Due to rapid expansion Density and solvation power of the SCF decreases, resulting supersaturation and subsequent precipitation of solute occcur , Higher the expansion, Smaller the particle size

Gas Antisolvents Recrystallisation (GAS): 

Gas Antisolvents Recrystallisation (GAS)

PowerPoint Presentation: 

It is possible to induce rapid crystallisation by introducing the antisolvent gas into a solution containing dissolved solute. In this process,the size reducation depends on the rate of addition of the SCF in the solution. The most important requirement for this technique is that the carrier solvent and the SCF antisolvent must be atleast partially miscible.

B. MODIFICATION OF THE CRYSTAL HABIT: : 

B. MODIFICATION OF THE CRYSTAL HABIT: Some drugs can exist in amorphous form( i.e.having no internal crystal structure). They have greater aqueous solubility than the crystalline forms because they require less energy to transfer a molecule into solvent. Melting followed by a rapid cooling or recrystallization from different solvents can be produce metastable forms of a drug. Metastable forms are associated with higher energy and thus higher solubility. Thus, the order for dissolution of different solid forms of drug is: Amorphous> Metastable polymorph >Stable polymorph

PowerPoint Presentation: 

C.DRUG DISPERSION IN CARRIERS DRUG DISPERSION IN CARRIERS EUTECTIC MIXTURE SOLID DISPERSION SOLID SOLUTION Hot Melt method Solvent Evaporation Method Hot-melt Extrusion Melting solvent method According to molecular size of two molecules /crystalline structure According to the extent of miscibility of two components Continuous Discontinuous Substitutional Interstitial

EUTECTIC MIXTURE : 

EUTECTIC MIXTURE The word “Eutectic" comes from Greek and means “ easily melted ” Eutectic mixture is a mixture at such proportions that the melting point is as low as possible. Thermodynamically, such a system is intimately blended physical mixture of two crystalline components EXAMPLE: PCM-Urea Griseofulvin-succinic acid

Phase diagram of Eutectic mixture: 

Phase diagram of Eutectic mixture 1. The liquidus line separates The all melt phase from the melt+crystal phase. 2.The solidus line separates the melt+crystal phase from the all crystal phase. 3.The eutectic is the point at which all three phases can exist simultaneously. When the eutectic mixture is exposed to water, it dissolves leaving the drug in a microcrystalline state which solubilises rapidly.

SOLID DISPERSION : 

SOLID DISPERSION The term “Solid dispersions” refers to the dispersion of one or more active ingredients in an inert carrier in a solid state Methods of preparation of solid dispersion 1. Hot Melt method 2. Solvent Evaporation Method 3. Hot-melt Extrusion 4. Melting –solvent method

1. Hot Melt method : 

1. Hot Melt method Drug and carrier were melted together and then cooled in an ice bath. The resultant solid mass was then milled to reduce the particle size. Cooling leads to supersaturation , but due to solidification the dispersed drug becomes trapped within the carrier matrix. An important requisite for the formation of solid dispersion by the hot melt method is: The miscibility of the drug and the carrier in the molten form. The thermostability of the drug and carrier.

2. Solvent Evaporation Method : 

2. Solvent Evaporation Method Both the drug and the carrier Dissolved in a common solvent SOLID DISPERSION Evaporate the solvent The solvent can be removed by various methods like by spray-drying or by freeze-drying. Temperatures used for solvent evaporation generally lie in the range 23-65 C.

3. Hot-melt Extrusion : 

3. Hot-melt Extrusion The preparation of solid dispersions in a single step. Melt extrusion of miscible components results in amorphous solid solution formation. Whereas,extrusion of an immiscible component leads to amorphous drug dispersed in crystalline excipient .

4. Melting –solvent method : 

4. Melting –solvent method

Evaluation of s.d : 

Evaluation of s.d To characterize & determine Amorphous / Crystalline content in S.D: X-ray diffraction Differential scanning calorimetry (DSC) FTIR To observe the solubility of drug: Dissolution study

SOLID SOLUTION : 

SOLID SOLUTION DEFINATION: “ A solid solution is a binary system comprising of a solid solute molecularly dispersed in a solid solvent. Since the 2 components crystallize together in a homogenous one phase system, solid solutions are also called as, MOLECULAR DISPERSIONS OR MIXED CRYSTALS OR MELTS

Classification of Solid solution: 

Classification of Solid solution

BASED ON EXTENT OF MISICIBILITY OF 2 COMPONENTS : 

BASED ON EXTENT OF MISICIBILITY OF 2 COMPONENTS CONTINUOUS SOLID SOLUTION In this type of solid solution the two components are miscible in the solid state in all proportion. DISCONTINUOUS SOLID SOLUTION In contrast to the continuous solid solution, there is only a limited solubility of a solute in a solid solvent in this group of solid solution

BASED ON MOLECULAR SIZE OF 2 MOLECULES : 

BASED ON MOLECULAR SIZE OF 2 MOLECULES 46 /60 SUBSTITUTIONAL INTERSTITIAL Drug molcule Crystal lattice of carrier molecule This happens when the drug and carrier molecules are same size This happens when the size of drug molecule is 40% or less than the size of carrier molecule

QUESTIONS: 

QUESTIONS Janu / feb 2011: (a)What is intrinsic solubility? How is it determined? How intrinsic solubility differs from dissolution rate? (b)Discuss various techniques for drug solubilization with mechanisms. January 2010: (a)What do you mean by intrinsic solubility? Enlist various solubilization techniques with their mechanisms. April 2010: (a)What is solubility? How solubility is predicted mathematically. Describe any two practical methods for solubility determination.

REFERENCES:: 

REFERENCES: Aulton M.E, Pharmaceutics,The science of dosage form design,2nd edition; page no:338-340. D.M.Brahmankar,Biopharmaceutics and Pharmacokinetics, 2nd edition. vallabh prakashan ; page no:349-357 Leon Lachman,Herbert A.Liberman , Joseph L.King , The theory and practice of Industrial Pharmacy, 3rd edition. Varghese publication; page no:457-466 Remington,The science and Practice of Pharmacy, 21st edition; Volume I; page no:211-216;229-230 Anil.J.Shinde, Solubility enhancement techniques, IJPRD, 2010; Volume I; page no.76-104

: 

?

THANK YOU: 

THANK YOU

D. COMPLEXATION: : 

D. COMPLEXATION: Two specific classes useful for the increasing the solubility: STACHING COMPLEXATION INCLUSION COMPLEXATION

STACHING COMPLEXATION : 

STACHING COMPLEXATION Organic drug + water → Squeezed out by strong water-water interaction force. Forms aggregates Reduces the contact b/w nonpolar hydrocarbon moieties & the polar water molecule Large nonpolar regions Opposed by entropy Random arrangement Complexes stached can be homogeneous or mixed Self association complexation

PowerPoint Presentation: 

Some compounds that are known to form staching complexes are as follows: Nicotinamide , Anthracene , Methylene blue, Benzoic acid, Salicylic acid, Ferulic acid, Gentisic acid, Purine , Theobromine , Caffeine, Naphthalene etc.

INCLUSION COMPLEXATION : 

INCLUSION COMPLEXATION Inclusion complexes are formed by the insertion of the nonpolar molecule or the nonpolar region of one molecule (known as guest) into the cavity of another molecule or group of molecules (known as host). The cavity of host must be large enough to the guest and small enough to eliminate water, so that the total contact between the water and the nonpolar regions of the host and the guest is reduced. The most commonly used host molecules are cyclodextrins

structure of cyclodextrin   : 

structure of cyclodextrin  -CD  -CD  -CD  -CD Molecular formula C 36 H 60 O 30 C 42 H 70 O 35 C 48 H 80 O 40 - Optical rotation[  ]d +150.5 +160.0 177.4 - GP units 6 7 8 9 Molecular weight 972 1135 1297 1459 Cavity diameter(A) 4.7-5.3 6-6.5 7.5-8.3 10.3-11.2 Solubility(g/100ml)25`c 14.5 18.5 23.2 -

WHY CYCLODEXTRINS USED? : 

WHY CYCLODEXTRINS USED? To increase aqueous solubility of drugs. To increase chemical stability of drugs. To enhance drug delivery to and through biological membranes. To increase physical stability of drugs. To convert liquid drugs to microcrystalline powders. To prevent drug-drug and drug-excipient interactions. To reduce local irritation after topical or oral administration .

Cyclodextrin inclusion complex: : 

Cyclodextrin inclusion complex:

The formation of inclusion complex with CD occur in following step: : 

The formation of inclusion complex with CD occur in following step: Approach of the guest or substrate molecule to CD molecule Loss of the water structure within the cavity with removal of some water molecules Break down of water structure and transport of some water molecules in solution. Interaction of the substituent groups of substrate inside the cyclodextrin ring Possible formation of bonds between the CD and the substrate. Re-establishment of water structure around the external parts of substrate after the inclusion has occurred. Cyclodextrin complexes are relatively stable their water solubility compared to pure cyclodextrin

PowerPoint Presentation: 

CALCULATION: K . So . [ Ct ] - K . So . [D C ] K . So . [ Ct ] = [ D C ] Х [ 1 + K . So ] K = Binding constant [ D ] = Concentration of free Drug [ C ] = Concentration of free Cyclodextrin [DC] = Concentration of Complex So = Intrinsic solubility of Drug [Ct ] = Total concentration of Cyclodextrin Where,

PowerPoint Presentation: 

Total Solubility = Intrinsic Solubility + Drug in Complex St = So + [ D C ] If Dt = Dose of Drug CDt = Total amount of Cyclodextrin V = Volume available for dissolution Therefore, Total Concentration of Cyclodextrin , Now, Concentration of Drug in solution ≤ Total Solubility of Drug

PowerPoint Presentation: 

From equation ( 1 ), ( 2 ) and ( 3 )… Now multiply with V / Dt , So . V/ Dt = Inverse of dose No. For poorly soluble drugs So . V / Dt values is less than 1, so that Negligible

ADVANTAGES OF -CYCLODEXTRINE: : 

ADVANTAGES OF  -CYCLODEXTRINE: Liquid component can be transformed into a crystalline form that is suitable for manufacture of tablet. Volatile component can be stabilized against losses through evaporation Molecules can be protect against oxidation. It can be used for taste and smell masking. Incompatible drug can be mixed together if one of them is protected by formation of cyclodextrine complex. Solubility in water as well as the rate of dissolution of poorly soluble drug can be increased.

DISADVANTAGES: : 

DISADVANTAGES: Most impotent limitation is that an elementary nature, whether the drug can form any complex at all. The most impotent parameter that determines the formation of inclusion complex of the molecule is its hydrophobicity and geometry in relation to those of cyclodextrine cavity. Another limitation related to the stochiometry of complex. CD-drug complexes usually have 1:1, 1:2, 3:2 stochiometry . The majority drug have much lower molecular weight than CD this difference and the stochiometry of complex limit the amount of drug that can be supplied conveniently by using this method

Application of -cyclodextrin: 

Application of  - cyclodextrin

E. SOLUBILIZATION BY SURFACTANTS: : 

E. SOLUBILIZATION BY SURFACTANTS: Surfactants are molecules with distinct polar and nonpolar regions. Most surfactants consist of a hydrocarbon segment (aliphatic chain segment) connected to a polar group. The polar group can be anionic,cationic,zwitter - ionic or nonionic

PowerPoint Presentation: 

In the water, As the concentration of surfactant increases above a critical value, its molecules self associate into soluble structures called micelles. The concentration at which they begin to form is called the critical micelle concentration (CMC).

F. SOLUBILIZATION BY SALTS : 

F. SOLUBILIZATION BY SALTS Salt have improved solubility and dissolution characteristics in comparision to the original drug. It is generally accepted that a minimum difference of 3 units between the pka value of the group and that of its counterion is required to form stable salts. eg . Alkali metal salts of acidic drugs like penicilins and strong acid salts of basic drugs like atropine are more water-soluble than the parent drug. Factors that influence salt selection are physical and chemical properties of the salt,safety of counteron,therapeutic indications and route of administration.

Salt formation have limitation: : 

Salt formation have limitation: It is not feasible to form salts of neutral compounds. It may be difficult to form salts of very weak bases or acids. The salt may be hygroscopic,exhibit polymorphism or has poor processing characteristics. Conversion of salt to free acid or base form of the drug on surface of solid dosage form that prevents or retards drug release. Precipitation of unionized drug in the GI milieu that has poor solubility.

G. NANOTECHNOLOGY APPROACHES: : 

G. NANOTECHNOLOGY APPROACHES: a). NANOCRYSTAL: A nanocrystal is a  crystalline material with particles the size range of 1-1000 nanometers . methods used for producing nanocrystals Milling Precipitation High pressure homogenization Cryo -vacuum method Bottom-up Bottom-down

PowerPoint Presentation: 

Milling : In ball mills, particle size reduction is achieved by using both impact and attrition forces. The most common models are a tumbling ball mill and a stirred media mill. One problem of this method is the degradation of mill surfaces and subsequent suspension contamination.

High pressure homogenization:: 

High pressure homogenization: An aqueous dispersion of the crystalline drug particles is passed with high pressure through a narrow homogenization gap with a very high velocity. Homogenisation can be performed in water or alternatively in non-aqueous media or water-reduced media The static pressure exerted on the liquid causes the liquid to boil forming gas bubbles. When exiting from the gap, gas bubbles collapse under normal air pressure. This produces crystals collide, leading to particle disintegration. The particle size obtained during the homogenization process depends on the nature of the drug, the pressure applied and the number of homogenization cycles.

Precipitation: 

Precipitation Dissolving the substance in a solvent where its dissolution is good. The solution with the drug is then injected into water, which acts as a bad solvent. At the time of injection, the water has to be stirred efficiently so that the substance will precipitate as nanocrystals . Nanocrystals can be removed from the solution by filtering and then dried in air.

Cryo-vacuum method:: 

Cryo -vacuum method: The method is based on sudden cooling of a solvent by immersing the solution in liquid nitrogen (-196 ºC). The solvent must be completely frozen before the vessel is removed from the liquid nitrogen. Next the solvent is removed by sublimation in a lyophilization chamber where the temperature is kept at constant -22 ºC . Cryo -assisted sublimation makes it possible to remove the solvent without changing the size of the particles produced, so they will remain crystalline. The method yields very pure nanocrystals

b). NANOMORPH : 

b). NANOMORPH The Nanomorph technology is to convert drug substances from coarse Crystalline state to Amorphous nanoparticles . A suspension of drug substance in solvent is fed into a chamber, where it is rapidly mixed with another solvent & converted into a true molecular solution. The admixture of an aqueous solution of a polymer induces precipitation of the drug substance. The polymer keeps the drug substance particles in their nanoparticulate state. e.g. spray-drying.

II. CHEMICAL MODIFICATIONS: : 

II. CHEMICAL MODIFICATIONS: An alkaloid base is, generally, slightly soluble in water, but if the pH of medium is reduced by addition of acid, the solubility of the base is increased as the pH reduced. The reason for this increase in solubility is that the base is converted to a salt, which is relatively soluble in water. (e.g. Tribasic calcium phosphate). The solubility of slightly soluble acid increased as the pH is increased by addition of alkali, the reason being that a salt is formed. (e.g. Aspirin, Theophylline , Barbiturates).

OTHER TECHNIQUES FOR SOLUBILITY ENHANCMENT: : 

OTHER TECHNIQUES FOR SOLUBILITY ENHANCMENT: Co- crystallisation Cosolvency Hydrotrophy Solubilizing agents Microemulsion Use of Clathrates Use of Buffers

Co-crystallisation : 

Co- crystallisation A co-crystal may be defined as a crystalline material that consists of two or more molecular (and electrically neutral) species held together by non-covalent forces. Co-crystals can be prepared : By evaporation of a heteromeric solution or By grinding the components together. Another technique for the preparation of co-crystals includes sublimation, growth from the melt, and slurry preparation. The formation of co-crystals is important to salt formation, particularly for neutral compounds or those having weakly ionizable groups.

Cosolvency : 

Cosolvency Weak electrolytes and nonpolar molecules have poor water solubility and it can be improved by altering polarity of the solvent.This can be achieved by addition of another solvent.This process is known as cosolvency . Solvent used to increase solubility known as cosolvent . Cosolvent system works by reducing the interfacial tension between the aqueous solution and hydrophobic solute.It is also commonly referred to as solvent blending.

Hydrotrophy : 

Hydrotrophy Hydrotrophy designate the increase in solubility in water due to the presence of large amount of additives. The mechanism by which it improves solubility is more closely related to complexation involving a weak interaction between the hydrotrophic agents (sodium benzoate, sodium acetate, sodium alginate, and urea) and the solute. Example: Solubilisation of Theophylline with sodium acetate and sodium alginate

Solubilizing agents: 

Solubilizing agents The solubility of poorly soluble drug can also be improved by various solubilizing materials. EXAMPLE: PEG 400 is improving the solubility of hydrochlorthiazide . Modified gum karaya (MGK), a recently developed excipient was evaluated as carrier for dissolution enhancement of poorly soluble drug, nimodipine . The aqueous solubility of the antimalarial agent halofantrine is increased by the addition of caffeine and nicotinamide .

Microemulsion: 

Microemulsion A microemulsion is a four-component system composed of external phase, internal phase, surfactant and cosurfactant . The addition of surfactant, which is predominately soluble in the internal phase unlike the cosurfactant , results in the formation of an optically clear, isotropic, thermodynamically stable emulsion. It is termed as microemulsion because of the internal or dispersed phase is < 0.1 μ droplet diameter.

Preparation Of Microemulsion : 

Preparation Of Microemulsion The drug is be dissolved in the lipophilic part of the microemulsion i.e. Oil and the water phases can be combined with surfactant and a cosurfactant is then added at slow rate with gradual stirring until the system is transparent. EXAMPLE: Etoposide emulsion Methotrexate emulsion

Advantages of microemulsion over coarse emulsion: 

Advantages of microemulsion over coarse emulsion Thermodynamic stability Transparent and elegant appearance Increased drug loading Enhanced penetration through the biological membranes Increased bioavailability, and Less inter- and intra-individual variability in drug pharmacokinetics

Use of Clathrates: 

Use of Clathrates Definition: A special type of inclusion compound in which the host molecules form a crystal lattice containg spaces into which guest molecules can fit. The macrocyclic molecule is called the HOST. The small included molecule is the GUEST. The inclusion process gives rise to HOST-GUEST CHEMISTRY.

PowerPoint Presentation: 

Speciality of the clathrates :- chemical bonds are not involved & only the molecular size of the encaged component is of importance. Ideal requirement: Host molecule-must be hydrophilic yet able to bind the lipophilic guest molecule by means of hydrophobic interactions. Stability of a clathrate due to the strength of the structure.

Use of Buffers: 

Use of Buffers The practical use of a buffer is to simply maintain the pH of the system over time & reduce or eliminate the precipitation of the drug upon dilution Selection of buffer The buffer must have adequate capacity in desired pH range. Biologically safe for intended use. No Deleterious effect on stability of the final product. Should permit the use of other excipients like flavoring or coloring agents.

PowerPoint Presentation: 

A very small change in pH may result in 30% more drug going into the solution. So, by observing pH solubility profile; it helps in selection buffer for optimum pH range

Buffers used in pharmaceutical : 

Buffers used in pharmaceutical

APPLICATIONS OF SOLUBITITY: : 

APPLICATIONS OF SOLUBITITY : Fundamental importance in a large number of scientific disciplines and practical applications, to the use of medicines, and the transport of pollutants. Represents a fundamental concept in fields of research such as chemistry, physics, food science, pharmaceutical, and biological sciences. Controls the bioavailability of a drug substance. Solubility of a substance is useful when separating mixtures. solubility and solubility-related properties provide important information regarding the structure of drug substances , and in their range of possible intermolecular interactions.

THANK YOU: 

THANK YOU