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Course Contents No Units/Topics Sub Topics List Number of Weeks 1 Introduction Introduction to physical pharmacy , Importance of 1...

Course Contents No Units/Topics Sub Topics List Number of Weeks 1 Introduction Introduction to physical pharmacy , Importance of 1 studying , physicochemical properties in drug formulation, 2 Surface and Definition of Surface and interfacial tension , 2 interfacial Measurements of surface tension , Surfactants , HLB Phenomenon System , Classification of SAAs, Critical micelle concentration(CMC) , Effect of counter ion and temperature on surface tension and temperature on CMC-values , Determination of the maximum additive (MAC( and Pharmaceutical applications of SAA 3 Adsorption Definition , Mechanism of adsorption ,Heat of adsorption 1 Types of adsorption and factors affecting on adsorption Adsorption isotherm and Pharmaceutical applications Dr. Yousef Algaradi Physical pharmacy No Units/Topics Sub Topics List Number of Weeks 4 Rheology Principles of rheology and types of flow.and Measuring 1. methods in the rheology 5 Midterm exam 1 6 State of States of Matter, Properties of solid ,Physical form (crystal & 2 Matter amorphous) polymorphism, Solvation , Gaseous States and Liquid States. 7 Solubility Definition of solubility, Types of solutions ,, Methods to 3 expression of solubility , Solubility of liquid in liquid and solid in liquids , Factors/ parameters affecting solubility , Determination of solubility based on the pH Partition theory and Partition coefficient , Drug dissolution and Pharmaceutical applications 8 Stability 2 studies No. of weeks per semester 13 Dr. Yousef Algaradi Physical pharmacy Physical pharmacy Dr. Yousef Algaradi Physical pharmacy  Introduction  Physical Pharmacy : The area in pharmacy that deals with the quantitative and theoretical principles of physiochemical science as they applied to the practice of pharmacy.  Why We Study Physical Pharmacy? 1) Proper understanding of subsequent courses in Pharmaceutics and pharmaceutical technology. 2) Integrates knowledge of mathematics, physics and chemistry and applies them to the pharmaceutical dosage form development. 3) It focus on the theories behind phenomena needed for dosage form design Dr. Yousef Algaradi Physical pharmacy  Introduction 4) Enable the pharmacist to make rational decisions on scientific basis concerning the art and technology of dosage forms. 5) provides the basis for understanding the chemical and physical phenomena that govern the in vivo and in vitro actions of pharmaceutical products 6) Aids the pharmacist ,pharmaceutical chemist in their attempt to predict the solubility, stability, compatibility, and biologic action of drug products. Dr. Yousef Algaradi Physical pharmacy  Design of dosage forms Principles of dosage form design:  Drugs:  Rarely administered as pure chemical substances alone  Formulated preparations including additives (excipients).  Drug product:(Dosage form)  Simple solution to complex drug delivery systems.  Prepared of pure drug and excipients  Excipients: formulation additives  Solubilizer, Suspending, flavoring, emulsifying agents, preservative , sweeteners etc. Dr. Yousef Algaradi Physical pharmacy  Design of dosage forms Biopharmaceutical of dosage form design:  The physicochemical properties of the drug.  The dosage form in which the drug is given.  The route of administration  Affect the rate and extent of systemic drug bioavailability Dr. Yousef Algaradi Physical pharmacy Design of dosage forms Variation in time of onset of action for different dosage forms Dr. Yousef Algaradi Physical pharmacy Physicochemical properties of the drug  Understanding the physicochemical properties is crucial for:  Drug formulation  Drug development  Optimization of drug delivery systems  Predicting the drug's behavior in the body. 1) Molecular weight:  The molecular weight of a drug affects its pharmacokinetics, including absorption, distribution, metabolism, and excretion.  Smaller molecules tend to have better absorption and distribution. Dr. Yousef Algaradi Physical pharmacy  Physicochemical properties of the drug 2) Particle size and surface area:  Dissolution and absorption :  Particle size reduction of poorly soluble drugs increase surface area which increase dissolution rate and absorption  High absorption of Inhalation aerosols ( optimum 1- 6 µm)  Stability:  Very fine powders → ↑air adsorption → wetting or agglomeration problems.  Size reduction → changes in crystallinity → chemical stability problems Dr. Yousef Algaradi Physical pharmacy Physicochemical properties of the drug 3) Solubility:  Refers to the ability of a drug to dissolve in a particular solvent.  It is an important property as it affects the drug's absorption, distribution, and bioavailability.  Drugs with poor aqueous solubility exhibit incomplete absorption.  Solubilities of weak acidic or basic drugs are pH- dependent:  Solubility enhancement: 1) Size reduction 2) Formation of complex. 3) Solubilization with excipients eg. surface active agents. Dr. Yousef Algaradi Physical pharmacy Physicochemical properties of the drug 4) Partition coefficient(o/w) :  This property describes the distribution of a drug between two immiscible phases, typically oil and water.  Indicative of drug ability to penetrate biological membranes.  The cell membrane → lipid in nature, the higher the lipid solubility of the drug, the greater is the permeability of a drug molecule. Dr. Yousef Algaradi Physical pharmacy Physicochemical properties of the drug 5) Ionization constant (pKa):  This property determines the degree of ionization of a drug at different pH levels.  It influences the drug's solubility, permeability, and binding affinity to receptors or proteins.  The importance of ionization in drug absorption → the unionized form of the drug has a greater K o/w than the ionized form → ↑ absorption. Dr. Yousef Algaradi Physical pharmacy Physicochemical properties of the drug 6) Crystal properties:  Crystalline, (i.e. high order of regular molecular arrangements),  Amorphous (i.e. without regular molecular arrangements),  Anhydrous , hydrate (various degrees of hydration)  Solvated with other entrapped solvent molecules or  Polymorphs: Drug exists in more than one form of crystal which has different physical properties such as dissolution, solid-state stability, powder flowability Dr. Yousef Algaradi Physical pharmacy Physicochemical properties of the drug 7) Melting point/boiling point:  These properties indicate the temperature at which a solid substance melts or a liquid substance boils.  They can influence formulation processes and storage conditions for drugs. Dr. Yousef Algaradi Physical pharmacy Physicochemical properties of the drug 8) Stability:  The stability of a drug is crucial for its shelf life and effectiveness.  It includes factors such as susceptibility to degradation due to light, heat, moisture, or chemical reactions  Chemical decomposition of drugs : I. Hydrolysis: Example: Aspirin II. Oxidation: Example: Ascorbic acid III. Photochemical decomposition Dr. Yousef Algaradi Physical pharmacy Surface and interfacial phenomenon Dr. Yousef Algaradi Physical pharmacy  Interface & Surface  Interface is the boundary between two phases.  Surface is a term used to describe either a solid-gas or a liquid-gas interface.  Interfacial phase is a term used to describe molecules forming the interface between two phases which have different properties from molecules in the bulk of each phase. Dr. Yousef Algaradi Physical pharmacy Why?? Dr. Yousef Algaradi Physical pharmacy  Surface & Interfacial tensions  Molecules in the bulk liquid are surrounded in all directions by other molecules for which they have an equal attraction (only cohesive forces).  Molecules at the surface can only develop cohesive forces with other molecules that are below and adjacent to them; and can develop adhesive forces with molecules of the other phase. Dr. Yousef Algaradi Physical pharmacy  Surface & Interfacial tensions  This imbalance in the molecular attraction will lead to an inward force toward the bulk that pulls the molecules of the interface together and contracts the surface, resulting in a surface tension. Dr. Yousef Algaradi Physical pharmacy  Surface & Interfacial tensions  Surface tension is the force per unit length that must be applied parallel to the surface to counterbalance the net inward pull.  It has the units of dynes/cm or N/m  Interfacial tension is the force per unit length existing at the interface between two immiscible phases (units are dynes/cm or N/m). Dr. Yousef Algaradi Physical pharmacy  Surface & Interfacial tensions  Usually the term surface tension is used when the interface is between a liquid and a gas, or a solid and a gas.  While interfacial tension is used when the interface is between two liquids or two solids or a solid and a liquid.  Interfacial tensions are weaker than surface tensions because the adhesive forces between two liquid phases forming an interface are greater than that between liquid and gas phases.  For example Mercury has surface tension of 476 dynes/cm while its interfacial tension against water is 375 dynes/cm. Dr. Yousef Algaradi Physical pharmacy  Surface free energy  In the bulk of the liquid: each molecule is pulled equally in all directions by neighboring liquid molecules (net force of Zero)  The surface layer of a liquid possesses additional energy as compared to the bulk liquid.  If the surface of the liquid increases (e.g. when water is broken into a fine spray), the energy of the liquid also increases.  Because this energy is proportional to the size of the free surface, it is called a surface free energy. Dr. Yousef Algaradi Physical pharmacy  Measurement of tensions  Methods for measuring surface and interfacial tension 1) Capillary rise method 2) Ring method 3) Drop weight 4) Drop count method  The choice of a particular method depends on: 1) Surface or interfacial tension is to be determined, 2) The accuracy and convenience desired, 3) The size of sample available, Dr. Yousef Algaradi Physical pharmacy  Capillary Rise Method  When a capillary tube is placed in a liquid contained in a beaker, the liquid rises up in the tube to a certain distance.  By measuring this rise in the capillary, it is possible to determine the surface tension of the liquid using the formula: 𝜸 =½𝒓𝒑𝒈𝒉  𝒓: radius of capillary  𝒉: height  𝒑: density of the liquid  𝒈: acceleration of gravity  This method cannot be used to obtain interfacial tensions. Dr. Yousef Algaradi Physical pharmacy Capillary Rise Method Dr. Yousef Algaradi Physical pharmacy  DuNouy Ring Method (Tensiometer)  The DuNouy tensiometer is widely used for measuring surface and interfacial tensions.  The principle of the instrument depends on the fact that the force necessary to detach a platinum–iridium ring immersed at the surface or interface is proportional to the surface or interfacial tension.  The force required to detach the ring in this manner is provided by a torsion wire and is recorded in dynes on a calibrated dial. Dr. Yousef Algaradi Physical pharmacy DuNouy Ring Method (Tensiometer) Dr. Yousef Algaradi Physical pharmacy  DuNouy Ring Method (Tensiometer)  The surface and interface tensions is given by the 𝐷𝑖𝑎𝑙 𝑟𝑒𝑎𝑑𝑖𝑛𝑔 𝑖𝑛 𝑑𝑦𝑛𝑒𝑠 equation γ= 𝑥 β 2 𝑥 𝑟𝑖𝑛𝑔 𝑐𝑖𝑟𝑐𝑢𝑚𝑓𝑒𝑟𝑒𝑛𝑐𝑒  A correction factor (β) is required before accurate results can be obtained.  Dial reading (F) = mass M of liquid (grams) x 980.665 cm / sec2 (gravity constant)  Ring circumference = 2πr Dr. Yousef Algaradi Physical pharmacy Surface active agents (Surfactants) Dr. Yousef Algaradi Physical pharmacy  Surface active agents (SAAs)  Certain molecules and ions, when dispersed in the liquid, move of their own accord to the interface.  The surface free energy and the surface tension of the system are automatically reduced.  Molecules and ions that are adsorbed at interfaces are termed surface-active agents or surfactants. Dr. Yousef Algaradi Physical pharmacy  Surface active agents (SAAs)  Are solutes that are preferentially adsorbed at the surface or interface of liquid and reduce the surface or interfacial tension and therefore termed Surface active agent.  Surface active agents consists of 2 parts: 1) A lipophilic (hydrophobic) group : Consisting of a long carbon chain which has little affinity for aqueous solvents. Dr. Yousef Algaradi Physical pharmacy  Surface active agents (SAAs) 2) A hydrophilic (or lipophobic) group: Consisting of polar group such as COOH, OH,…which has high affinity for polar solvents.  These molecules are referred to as amphiphilic or amphipathic  Thus, in an aqueous dispersion of amphiphile, the polar group is able to associate with the water molecules and nonpolar portion is rejected.  As a result, the amphiphile is adsorbed at the interface. Dr. Yousef Algaradi Physical pharmacy  HLB System  For the amphiphile to be concentrated at the interface, it must be balanced with the proper amount of water- and oil-soluble groups.  If the molecule is too hydrophilic, it remains within the body of the aqueous phase and exerts no effect at the interface.  if it is too lipophilic, it dissolves completely in the oil phase and little appears at the interface Dr. Yousef Algaradi Physical pharmacy  HLB System  The hydrophile-lipophile balance (HLB) system is an arbitrary scale for expressing the hydrophilic and lipophilic characteristics of an emulsifying agent.  In these system, each surfactant is assigned a number between 1 and 20 representing the relative proportions of lipophilic and hydrophilic parts of the molecule. Dr. Yousef Algaradi Physical pharmacy  HLB System  Depending on their HLB values, the surfactants have different uses.  Agents with HLB value of 1-8 are lipophilic and HLB values of 3-6 are suitable for preparation of w/o emulsions.  Agents with HLB value of 8-18 are hydrophilic and good for o/w emulsions. Dr. Yousef Algaradi Physical pharmacy HLB Values of Some Common SAAs Dr. Yousef Algaradi Physical pharmacy  Classification of SAAs A. According to their ionization: 1) Ionic SAA  Anionic SAA  Cationic SA 2) Non-ionic SAA 3) Ampholytic SAA Dr. Yousef Algaradi Physical pharmacy  Classification of SAAs B. According to their functions & uses: a) Wetting agents b) Detergents c) Antifoaming agents d) Emulsifying agents e) Solubilizing agents f) Antibacterial agents. Dr. Yousef Algaradi Physical pharmacy Micelles formation (OR) Micellization  When a surfactant molecules are added to water, then at low concentrations, the molecules will arrange themselves at the surface.  As the concentration of the surfactant increases, the surface becomes saturated with the surfactant molecules & will aggregate together to form is known as the critical micellar concentration ( CMC) Dr. Yousef Algaradi Physical pharmacy  Micelles formation (OR) Micellization  The CMC value is constant for each surfactant at constant temperatures.  CMC detection :  The CMC can be detected by measuring the surface tension of the surfactant solution:  The surface tension of the surfactant solution decreases as the concentration of the surfactant increases.  Because the surfactant molecules arrange themselves at the surface & hence reducing the upward force due to the surface tension.  As the surface becomes saturated with the surfactant molecules , then no further reduction in the surface tension will occur & the surface tension becomes constant. Dr. Yousef Algaradi Physical pharmacy  Micelles formation (OR) Micellization  The surfactant concentration which corresponds to the beginning of the constant reduction in the surface tension will refer to CMC. Dr. Yousef Algaradi Physical pharmacy  Explanation of micelles formation  On explanation of micelles formation is concerned with the structural organization of water molecules in aqueous solutions.  Water molecules usually possess high degree of structural organization , due to the strong hydrogen boding between water molecules.  If molecules containing a non- polar or hydrophobic group, such as surfactant molecules are added to water, then the water molecules will resist such addition (because of the strong hydrogen bonding attracting water molecules) Dr. Yousef Algaradi Physical pharmacy  Explanation of micelles formation  That attraction will push such surfactant molecules away from them in order to maintain the structural organization of the water molecules.  So at first the surfactant molecules will move to the surface & will arrange the molecules with their polar part facing the water molecule& their non-polar part away from water.  Than as the concentration of surfactants increases, the surface becomes saturated with the surfactant molecules & the surfactant molecules will migrate or move to the bulk of the solution. Dr. Yousef Algaradi Physical pharmacy  Explanation of micelles formation  Surfactant will spontaneously arrange themselves as aggregates to form micelles, with polar group to wards water & the non- polar groups directed inward facing each other & away from water molecules  Such organization will cause the minimum disturbance in the structural organization of water molecules. Dr. Yousef Algaradi Physical pharmacy  Factors Affecting Micellisation 1) Structure of the surfactant 2) Addition of electrolytes 3) Type of counterion 4) Effect of temperature Dr. Yousef Algaradi Physical pharmacy  Structure of the surfactant  Increase in length of the hydrocarbon chain results in a decrease in CMC at constant temperature and an increase in micellar size.  Branched of hydrocarbon chain causes an increase in CMC because decrease in free energy  The CMC is increase 3-4 times by the presence of double (unsaturated) bond in the compound compared to analogous saturated compound.  An increase in the ethylene oxide chain length of a nonionic surfactant makes the molecule more hydrophilic and the CMC increases.  The CMC increases as the polar group is moved from the terminal position towards the middle of hydrocarbon chain. Dr. Yousef Algaradi Physical pharmacy  Addition of electrolytes  Electrolyte addition to solutions of ionic surfactants decreases the CMC and increases the micellar size.  This is because the electrolyte reduces the forces of repulsion between the charged head groups at the micelle surface, allowing the micelle to grow.  Micellar size increases for a cationic surfactant as the counterion is changed and vesa versa for a particular anionic surfactant. Dr. Yousef Algaradi Physical pharmacy  Effect of temperature  For nonionic surfactants, Increasing temperature increases micellar size and decrease CMC.  Temperature has a comparatively small effect on the micellar properties of ionic surfactants.  The effect of temperature stops at a characteristic temperature called the cloud point where the solution become turbid due to the separation of the solution into two phases. Dr. Yousef Algaradi Physical pharmacy  Micellar solubilization  Micellar solubilization is the ability of the micelles to increase the solubility of materials that are normally insoluble, or only slightly soluble, in the dispersion medium used.  The process of bringing hydrophobic (or water insoluble) substances into solution by their incorporation (or entrapment) into micelles.  As Micellar solubilization depends on the existence of micelles; it does not take place below the CMC.  So dissolution begins at the CMC. Dr. Yousef Algaradi Physical pharmacy  Micellar solubilization Above the CMC, the amount solubilized is directly proportional to the surfactant concentration. As the number of micelles increases the extent of solubilization increases. The hydrophobic substance (which its solubility is to be increased) is known as the solubilizate & the surfactant is known as the solubilizing agent. Dr. Yousef Algaradi Physical pharmacy  Micellar solubilization  Concentration of solubilizates (MAC) The maximum additive concentration of a solubilizates (MAC) can be defined as the maximum concentration of a solubilizates that can be incorporated into a given solubilizates system at a fixed surfactant concentration above the CMC.  Determination of the MAC:  First the MAC is approximately determined by adding increasing concentrations of the solubilizates to a fixed known concentration of the surfactant above its CMC.  When turbidity starts to appear, this will correspond approximately to the MAC. Dr. Yousef Algaradi Physical pharmacy  Micellar solubilization  In order to exactly determine the MAC then:- Choose three or four solubilizate concentrations just before the concentration, which causes turbidity. Add each of these concentrations to the same fixed concentration of the surfactant. The lightest solubilizates concentration, which shows clear solution, will correspond to the MAC  Examples :  The solubility of phenolic compounds, such as cresol, chlorocresol & chloroxylenol in water can be highly increased by solubilizing them in triethanolamine oleate  Iodine is insoluble in water & its solubility can be increased by solubilizing it in an aqueous solution of tween (non-ionic surfactant) above the CMC Dr. Yousef Algaradi Physical pharmacy  Application of surfactants in pharmaceutics 1) Solid dosage forms:  Surface-active agents have been widely shown to enhance drug dissolution rates.  This may be due to wetting effects, resulting in increased surface area, effects on solubility.  Consequently surfactants have been included in tablet and capsule formulations.  Also The stainless steel molds are lubricated prior to dipping into the gelatin solution using sodium lauryl sulphate as surfactant. (gelatin capsule manufacturing) Dr. Yousef Algaradi Physical pharmacy  Application of surfactants in pharmaceutics 2) liquid dosage forms:  Formulation of Solution:  Surfactants used as solubilizing agent, which increase drug solubility.  It includes Sorbitan mono oleate and PEG.  It used in rang 0.05-0.5% to avoid toxicity.  Formulation of Suspension: (Dispersants)  Surfactants may be used to aid dispersion of the solid particles in the liquid.  This is particularly important if the powder is not readily wetted by the liquid vehicle.  Surfactants can reduce the interfacial tension between the solid particles and the liquid vehicle. Dr. Yousef Algaradi Physical pharmacy  Application of surfactants in pharmaceutics  Formulation of Emulsions:  Water-in-oil emulsions traditionally contain surfactants of low hydrophilic-lipophilic balance (HLB) (indicating high lipophilicity)  Oil in water emulsion contain surfactants of high hydrophilic-lipophilic balance (HLB) (indicating high hydrophilicity) Dr. Yousef Algaradi Physical pharmacy  Application of surfactants in pharmaceutics 3) Semisolid preparations:  Ointment and cream formulation:  Surfactants are useful for the easy removal from the skin by washing with water & also for the consistency by reduction of surface tension.  Surfactants are also used in formulation of cold cream, cleansing cream, vanishing cream, shaving cream  Suppositories:  Used as lubricants for suopsitories stainless steel molds before filing of liquefied bases.  In addition, emulsifying surfactants help to keep insoluble substances suspended in a fatty base suppository. Dr. Yousef Algaradi Physical pharmacy  Application of surfactants in pharmaceutics  Detergency of surfactants:  The displacement of dirt and debris by the use of detergents in the washing of wounds is an application of wetting agents.  The application of medicinal lotions and sprays to the surface of the skin and mucous membranes Dr. Yousef Algaradi Physical pharmacy Dr. Yousef Algaradi Physical pharmacy Adsorption Dr. Yousef Algaradi Physical pharmacy  Adsorption  Adsorption is the adhesion of atoms, ions, biomolecules or molecules of gas, liquid, or dissolved solids to a surface.  Adsorption can be defined as the accumulation or the existence of high concentration of any particular substance at the surface of a solid or a liquid Dr. Yousef Algaradi Physical pharmacy  Adsorption  Adsorption & Absorption:- The difference between adsorption & Absorption is that  Adsorption is a surface phenomena, which mean that substance only remain at the surface.  While in absorption the substance penetrates through the surface & becomes distributed through out the inner parts of the solid or liquid.  The molecular species or substance, which concentrates or accumulates at the surface is termed adsorbate and the material on the surface of which the adsorption takes place is called adsorbent. Dr. Yousef Algaradi Physical pharmacy  Mechanism of adsorption  Inside the adsorbent all the forces acting between the particles are mutually balanced but on the surface the particles are not surrounded by atoms or molecules of their kind on all sides, and hence they possess unbalanced or residual attractive forces.  These forces of the adsorbent are responsible for attracting the adsorbate particles on its surface.  The extent of adsorption increases with the increase of surface area per unit mass of the adsorbent at a given temperature and pressure. Dr. Yousef Algaradi Physical pharmacy  The heat of adsorption  Another important factor featuring adsorption is the heat of adsorption.  During adsorption, there is always a decrease in residual forces of the surface, i.e., there is decrease in surface energy which appears as heat.  Adsorption , therefore, is invariably an exothermic process.  When a gas is adsorbed, the freedom of movement of its molecules become restricted.  This amounts to decrease in the entropy of the gas after adsorption, i.e., ∆S is negative. Dr. Yousef Algaradi Physical pharmacy  The heat of adsorption  Adsorption is thus accompanied by decrease in enthalpy as well as decrease in entropy of the system.  In other words , ∆H of adsorption is always negative.  For a process to be spontaneous, the thermodynamic requirement is that, at constant temperature and pressure, Dr. Yousef Algaradi Physical pharmacy  Factors affecting on adsorption process  Adsorption on a solid is influenced by a number of factors such as, 1) Surface area 2) Nature of the adsorbate 3) Hydrogen ion concentration (pH) of the solution 4) Temperature 5) Mixed solutes 6) Nature of adsorbent Dr. Yousef Algaradi Physical pharmacy  Examples of adsorptions 1) If a gas like O2, H2, CO or SO2 is taken in a closed vessel containing powdered charcoal, it is observed that the pressure of the gas in the enclosed vessel decreases.  The gas molecules concentrate at the surface of the charcoal, i.e., gases are adsorbed at the surface. 2) In a solution of an organic dye, say methylene blue, when animal charcoal is added and the solution is well shaken, it is observed that the filtrate turns colourless.  The molecules of the dye, thus, accumulate on the surface of charcoal,(adsorbed). Dr. Yousef Algaradi Physical pharmacy  Examples of adsorptions 3) Aqueous solution of raw sugar, when passed over beds of animal charcoal, becomes colourless as the colouring substances are adsorbed by the charcoal 4) The air becomes dry in the presence of silica gel because the water molecules get adsorbed on the surface of the gel. Dr. Yousef Algaradi Physical pharmacy  Types of adsorptions  According to the type of forces or bonds which bind adsorbate molecules to the adsorbent molecules at the surface, adsorption can be classified into two types:- A. Physical adsorption B. Chemical adsorption (chemisorptions). Dr. Yousef Algaradi Physical pharmacy  Physical adsorption  In this type the adsorbate molecules are attracted around to the adsorbent molecules at the surface , by weak physical bonds such as dipole – dipole forces (or Van der weals force).  Because such bonds are weak, the powers of physical adsorption is reversible & the process is characterized by low value of heat of adsorption (0.5-1 kcal/mole)  Example of physical adsorption:  The adsorption of most substances (such as acidic carboxylic acid) onto the surface of charcoal (adsorbent) is a physical adsorption. Dr. Yousef Algaradi Physical pharmacy  Chemical adsorption  In this type the adsorbate molecules are attached or bound to the adsorbent molecules at the surface by Chemical bounds or through Chemical reactions, such as hydrogen bonding or ion-exchange reaction.  This type of adsorption is irreversible & shows high heat of adsorption because chemical adsorption involved stronger chemical bonds.  The amount of heat of adsorption is in the rage of (1-10) Kcal/mole. Dr. Yousef Algaradi Physical pharmacy  Chemical adsorption Example of chemisorptions:  Certain adsorbents such as bentonite & attapulgite have certain ion-exchange groups in their structures; consist of sodium silanolate group.  Such as cationic adsorbents can adsorb cationic drugs or basic drugs such as quaternary ammonia compounds & tertiary amines by cation-exchange mechanism. Dr. Yousef Algaradi Physical pharmacy Types of adsorptions Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm  Langmuir and Freundlich's isotherms are the most commonly used two-parameter models. 1) Freundlich is valid for multilayer adsorption on heterogeneous sites. 2) The Langmuir isotherm is applicable for monolayer adsorption on a homogeneous site. Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm Freundlich adsorption isotherm:  The variation in the amount of gas adsorbed by the adsorbent with pressure at constant temperature can be expressed by means of a curve termed as adsorption isotherm.  Freundlich adsorption isotherm: Freundlich, in 1909, gave an empirical relationship between the quantity of gas adsorbed by unit mass of solid adsorbent and pressure at a particular temperature. Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm  The relationship can be expressed by the following equation: log x/m = log k + 1/n log P Where:  x is the mass of the gas adsorbed on mass m of the adsorbent at pressure P  k and n are constants which depend on the nature of the adsorbent and the gas at a particular temperature. Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm  The relationship is generally represented in the form of a curve where mass of the gas adsorbed per gram of the adsorbent is plotted against pressure.  These curves indicate that at a fixed pressure, there is a decrease in physical adsorption with increase in temperature. These curves always seem to approach saturation at high pressure. Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm  The validity of Freundlich isotherm can be verified by plotting log x/m on y-axis (ordinate) and log p on x-axis (abscissa).  If it comes to be a straight line, the Freundlich isotherm is valid, otherwise not.  The slope of the straight line gives the value of 1/n.  The intercept on the y- axis gives the value of log k. Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm  The factor 1 can have values between 0 and 1.  Thus, above equation holds good over a limited range of pressure.  When1/n = 0, x/m = constant, the adsorption is independent of pressure. Nm  When 1/n = 1, the adsorption varies directly with pressure.  Both the conditions are supported by experimental results.  The experimental isotherms always seem to approach saturation at high pressure. Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm Langmuir adsorption isotherm:  It is a plot or a graph showing the relationship between (the amount of adsorbate which is adsorbed per unit amount of adsorbent) and the equilibrium concentrations of the unabsorbed adsorbate at a constant temperature.  In order to plot the adsorption isotherm, then adsorption experiments should be conducted as follows:- 1) A number or different adsorbate concentrations (in moles) are prepared.  These concentrations are referred to as initial concentrations (Co) Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm 2) An equal volume from each of the above concentrations is transferred to a flask containing a certain equal weight (in gm) of the adsorbent (m). 3) The flasks are then tightly closed & shaken for (½ -1) hr at constant temperature & then left for another one hour, after shaking, to equilibrate. 4) After equilibration, the content of each flask is filtered to remove the adsorbent. 5) The concentration of the filtrate is determined in each flask using any proper analytical method ( such as U.V. spectrophotometry or titration) & this concentration will be the equilibrium concentration (CE) ( in moles). Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm 5) The amount of the adsorbed adsorbate (x) ( in gm) can be calculated each time by subtracting (CE ) from (Co) & the obtained values are then multiplied by the molecular weight of the adsorbate to give you the amount ( x) in (gm). 6) Each time (x) is divided by (m) to give x/m values 7) So now we have different (x/m) values at different (CE) values & by plotting (X/M) against CE we can obtain the adsorption isotherm for the adsorbate in a specific adsorbent system. Dr. Yousef Algaradi Physical pharmacy  Adsorption isotherm  Information of Langmuir adsorption isotherms:  The determination of (x/m) mono which corresponds to the maximum amount of adsorbate (x) which can be adsorbed by a given weight of the adsorbent (m),  Where high (x/m) mono value indicate that the adsorbent is efficiency & can hold a large amount of adsorbate, while small values indicate an inefficient or poor adsorbent. Dr. Yousef Algaradi Physical pharmacy  Applications of adsorption 1) Production of high vacuum: The remaining traces of air can be adsorbed by charcoal from a vessel evacuated by a vacuum pump to give a very high vacuum. 2) Gas masks: Gas mask (a device which consists of activated charcoal or mixture of adsorbents) is usually used for breathing in coal mines to adsorb poisonous gases. 3) Control of humidity: Silica and aluminium gels are used as adsorbents for removing moisture and controlling humidity. Dr. Yousef Algaradi Physical pharmacy  Applications of adsorption 4) Removal of colouring matter from solutions: Animal charcoal removes colours of solutions by adsorbing coloured impurities. 5) Heterogeneous catalysis: Adsorption of reactants on the solid surface of the catalysts increases the rate of reaction. There are many gaseous reactions of industrial importance involving solid catalysts. 6) Separation of inert gases: Due to the difference in degree of adsorption of gases by charcoal, a mixture of noble gases can be separated by adsorption on coconut charcoal at different temperatures. Dr. Yousef Algaradi Physical pharmacy  Applications of adsorption 7) In curing diseases: A number of drugs are used to kill germs by getting adsorbed on them. 8) Froth floatation process: A low grade sulphide ore is concentrated by separating it from silica and other earthy matter by this method using pine oil and frothing agent. 9) Adsorption indicators: Surfaces of certain precipitates such as silver halides have the property of adsorbing some dyes like eosin, fluorescein, etc. and thereby producing a characteristic colour at the end point. Dr. Yousef Algaradi Physical pharmacy  Applications of adsorption 10) Chromatographic analysis: Chromatographic analysis based on the phenomenon of adsorption finds a number of applications in analytical and industrial fields. Dr. Yousef Algaradi Physical pharmacy