Pharmaceutical Technology Lecture 1 PDF

Lecture 1 Pharmaceutical Technology 3 rd Stage Dispersed system Dispersed system is a mixture of two phases (dispersed phase and dispersion medium), which consist of dispersed part of one or two substances in a dispersion medium.The dispersed phase ma...

Lecture 1 Pharmaceutical Technology 3 rd Stage Dispersed system Dispersed system is a mixture of two phases (dispersed phase and dispersion medium), which consist of dispersed part of one or two substances in a dispersion medium.The dispersed phase may called solute or internal phase, while the dispersion medium called solvent or external phase. Classification of dispersed systems 1. According to physical state of both phases dispersed system can be classified into nine types as: 2. According to the interaction between the two phases, dispersion system can be classified as Lyophilic dispersion e.g. sugar in water, alcohol in water, and Lyophobic dispersion e.g. benzene with water, oil with water. 3. According to the particle size of the dispersed phase, dispersion can be divided into: Molecular dispersion Colloidal dispersion and  Coarse dispersion. Molecular dispersion can be defined as a homogenous system of two or more substances; this system may be called true solution, because the solute completely dissipated into solvent. Whereas other dispersions are heterogeneous system-as exemplified by suspension and emulsion-where the dispersed phase, typically a particle of some type, is physically distinguishable from the medium in which it is dispersed. Molecular dispersions 1. Molecular dispersion is a true solutions of a solute phase in a solvent. 2. The dispersed phase (solute) is in form of separate molecules homogeneously distributed throughout the dispersion medium (solvent). 3. The molecule size is less than 1 nm. Examples of molecular dispersions: 1. air (a molecular mixture of Oxygen, Nitrogen and some other gases), 2. electrolytes (aqueous solutions of salts), 3. metal alloys solid solution. Colloidal dispersion (colloids) 1. Colloids are micro-heterogeneous dispersed systems, in which the size of the dispersed phase particles is within the range 1 - 1000 nm. 2. The colloids phases can not be separated under gravity, centrifugal or other forces. Dispersed phase of colloids may be separated from the dispersion medium by micro-filtration. Examples of colloids: 1. Milk (emulsion of fat and some other substances in water), 2. Fog (aerosol of water micro-droplets in air), 3. Silica aerogel monolith, 4. Alumina aerogel monolith Coarse dispersions (suspensions) 1. Coarse dispersions are heterogeneous dispersed systems, in which the dispersed phase particles are larger than 1000 nm. 2. Coarse dispersions are characterized by relatively fast sedimentation of the dispersed phase caused by gravity or other forces. Dispersed phase of coarse dispersions may be easily separated from the continuous phase by filtration. Other solutions, because of their composition or use, may be classified as other pharmaceutical dosage forms. 1. For example, aqueous solution containing sugar are classified as syrups. Whereas, sweetened hydroalcoholic solutions are termed elixirs. 2. On the other hand solutions of aromatic materials are termed spirits if the solvent is alcohol and aromatic water if the solvent is aqueous Solutions prepared by extracting active constituents from crude drugs are termed tincture or fluid extracts, depending on their method of preparation and concentration. Tinctures may also be solutions of chemical substances dissolved in alcohol or in a hydroalcoholic solvent.  Certain solutions prepared to be sterile and pyrogen free and intended for parenteral administration are classified as injections. The prefer dosage form is solution but sometimes we use suspension instead of solution because: 1. To get more stability 2. To change the drug taste 3. Large quantity of the drug will be in the dispersed form and not precipitate. Solutes other than the medicinal agent are usually present in orally administered solutions. These additional agents usually are included to provide color, flavor, sweetness or stability. In formulating or compounding a pharmaceutical solution, the pharmacist must use information on the solubility and stability of each solute present with regard to the solvent or solvent system employed. Solution: One phase system of two or more substances e.g. addition of sucrose to water produce a single phase system that is physically homogenous system result in a true solution. This system may be:  Solid  Liquid (the pharmacist most frequently used )  Gas *Liquid solution: The solvent is liquid while the solute may be liquid, solid or gas. If water is one component of the system it is considered to be the solvent. *Usually larger component is solvent but when solid is dissolved in liquid the solid is solute and the liquid is solvent regardless of proportion of one to other. Note: True solution is type of dispersion (molecular dispersion ) ,partical size is less than 1 nm. Types of solutions: 1. Solution of liquid in liquid a) Two liquids such as water/ alcohol, water/glycerin and water /aceton. Are mixed homogenous system is formed irrespective of the proportions in which the two are taken. Such pairs of liquid are said to be miscible. b) Liquefied phenol/water or ether /water are formed homogenous system only when mixed in a certain proportion.Such liquids are said to be miscible in certain proportion. c) Water/mineral oil is in soluble in each other in any proportion so they are immiscible. 2. Solution of gas in liquid The solubility of gas in liquid is described by Henry,s Law which state that the solubility of gas is very nearly proportional to the pressure if the temperature remain constant provided that the gas is only slightly soluble. The great solubility of certain gases such as ammonia and hydrogen chloride may be due to either chemical reaction between gas and solvent or to cohesive influences which the molecule exerts on one another. Increase the pressure in this case has little or no effect on their solubility. Effect of temperature on solubility of gas: Increase the temperature lead to decrease the solubility, e.g CO2 is twice as soluble 0 oC as it at 20 oC. So the gaseous solutions should be stored at cool place (refrigerator).Containers holding strong ammonia solution should be cooled before they are opening order to reduce libration and expansion of gas since on cooling the solubility of gas increase. Note: When a salt is added to a liquid containing dissolved gas, libration of gas occurs due to the decrease solubility. This effect is referred to salting out of the gas. 3. Solution of solid in liquid Most of true solutions are example of solid in liquid solution. Solubility: The solubility of an agent in a particular solvent indicates the maximum concentration to which a solution may be prepared with that agent and that solvent. When a solvent at a given temperature has dissolved all of the solute.Possible, it is said to be saturated. When excess of solid (solute) is shaken with liquid (solvent) for a period of time a maximum amount of it will be dissolved, the solvent is then saturated by solute resulting in saturated solution at a given tempreture. When excess amount of solute is added to saturated solution and the temperature is increased more of solute will be dissolved.  If such solution is filtered and cooled to the original temperature it will often retain the extra solute that dissolved at higher temperature. The resulting solution is called super saturated solution, e.g.Na thiosulfate and K acetate solution. Factors affecting solubility:  Temperature: Solids are usually more soluble in hot than in cold water. In the process of solution we have three cases: a) Endothermic reaction: Increase in the temperature lead to increase solubility. b) Exothermic reaction: Increase in the temperature result in decrease solubility, e.g methyl cellulose and Ca salts are more soluble in cold water than in hot water. Solution of methyl cellulose become cloudy when heated and give flaky precipitate which redissolves as the solution cools. c) When heat is neither absorbed nor given off in the process of solution: Increase or decrease in the temperature results in no effect on the solubility e.g. NaCl have the same solubility in water at 25 oC and in boiling water. Solubility against rate of solution: The solubility of an agent in a particular solvent indicates the maximum concentration to which a solution may be prepared with that agent and that solvent. A distinction should be made between degree of solubility and rate of solution, increase rate of solution doesn’t mean an increase in the amount of solute dissolved. Rate of dissolution is the speed at which the solute goes into solution it's unit is equal to unit of concentration/ unit of time = ΔC/Δt = mg/ml/min.  Rate of dissolution depends on: i. Particle size of solute: Reduction in particle size results in increase S.A. and increase rate of solution. 1 𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒 𝑠𝑖𝑧𝑒 ∝ surface area The finer the powder, the greater the surface area, which comes in contact with the solvent, and the more rapid the dissolving process. ii. Agitation: Increase agitation result in increased rate of solution by removing the more concentrated solution from the surface of solute and bringing in less concentrated solvent. i.e agitation results in reduce the thickness of stagnant layer and increase the penetration of solvent and increase solubility. iii. Heating: Results in increase solubility by increase the frequency with which solvent molecule collides with the surface of dissolving material. Factors affecting solubility:  Effect of molecular structure : The more nearly solute and solvent are alike molecular structure the greater the solubility of one in the other. The solubility of substance in water is linked to the dipole nature of water molecule:  Water is composed of covalent molecules which are described as polar structures with strong dipole characteristics (negative and positive regions).  Molecules having dipoles show a tendency to join into group of molecules and to associate with other polar substances. This attraction in case of water molecules is by H-bounding.  In general it may be stated that the polar solvents like water will dissolve salts and other electrolyte readily so they are poor solvents for non polar substances. Polar liquids may act as solvent when it and solute are capable of complexation by H-bound formation e.g. water and alcohol of low M.wt.As the M wt of alcohol increased resulted in decrease polarity and decrease the solubility in water. Carbon tetrachloride (CCl4 ) is non polar.Such solvate ions of salt like NaCl since they don’t supply attractive force (solvent force) which is required to overcome the force that holds the ions of the salt together. So non polar liquids don’t dissolve polar or slightly polar substance. Ethyl alcohol molecule Have:  5 non polar carbon –Hydrogen bond  1 C-C bond (non polar)  C-O bond & H-O bond (polar) So it is considered as good solvent for some polar and non-polar substances due to the presence of distinct polar and non-polar regions.  Although there are exceptions to any specific rules which might be formulated for the selection of solvents, the following generalizations should be of some value in predicting solubilities:  The more nearly solvents and solutes are alike structurally, the more rapidly solution takes place.  Polar liquids dissolve electrovalent compounds readily, but they are poor solvents for non-polar substances. On other hand, non-polar liquids are required for non-polar solutes.  Polar liquids should be miscible with other polar liquids. Conversely non polar liquids dissolve only slightly in polar solvents, but they dissolve readily in solvents that are non-polar.  Complex organic compounds which have polar and non-polar groups in their molecules may dissolve in polar liquids ,but their solubility in such solvents tends to decrease in proportion to the number of non-polar groups  Semi polar liquids, such as ethyl alcohol process some of properties of both polar and nonpolar solvents.  Effect of pH on solubility: Organic substances are either weak acids or weak bases. Their aqueous solubility depends on pH of solvent. These substances are dissociated very slightly and the undissociated forms are slightly soluble in water. Within certain pH range they exist in ionic or dissociated forms which are very soluble in water. a) The solubility in water of weak organic acids such as barbiturates & sulfonamides is increased as the pH increased by addition of base.This increase in solubility is due to the formation of water soluble salts. For  example solubility of Phenobarbital (free acid) in water at 25 oC is 1.25 g /1000 mL and the pH is 5.5.while the solubility of Phenobarbital sodium (salt) in water at 25oC is 1000 g/1000 mL, pH 9.3. So:  If the pH of Phenobarbital solution is increased above 5.5 by addition of strong base the solubility will increase.  If the pH of Phenobarbital solution is decrease by addition of strong acid Phenobarbital (free acid) will precipitate. b) The solubility in water of weak organic base (alkaloids and local anesthetic) increase as the pH decrease by addition of acid due to the formation of water soluble salts. e.g. Temperature Solubility pH Atropine(free base) 25 oC 2.2g/1000 mL >10 Atropine Sulfate (Salt) 25 oC 2500g/1000 mL 5.4 If the pH of aqueous solution of salt is increased by addition of base atropine (free base will be precipitate). At a given pH the degree of ionization weakly acid or basic drug depends on its pka value which is the –ve Log of its dissociation constant.  For weak acidic drugs: S - So pH = pKa +Log --------------- So S = molar concentration of drug (dissociated and undissociated) species in solution. So=molar solubility of undissociated species. This equation derived from Handerson –Hasselbach equation. For weak basic drug: So pH= pKw – pKb + log -------------- S - So Note: These equations may be used to calculate the pH at which a weak acids or bases will precipitate from solution of its salt. Importance of pH on absorption and excretion: The unionized form can pass the biological membrane due to its lipid solubility and since the membrane is lipoprotein in nature. The ionized form can also pass the biological membrane by carrier mediated mechanism. If toxic acidic substance is taken by patient, we give him basic compound to change it to ionized form that are more soluble and cannot be reabsorbed by kidney tubules and will be excreted by kidney out of body, and vice versa if we have basic compound.  Effect of other substances on solubility: The solubility of substance is depends on the type and concentration of other substance in the solution. In general the solubility of slightly soluble electrolytes is reduced by addition of second salt which contain a common ion for example when NaCl is added to a saturated solution of silver chloride AgCl, some of AgCl is precipitates from the solution due to the presence of common ion (Cl-). AgCl Ag + Cl NaCl Na + Cl The common ion may form complex with slightly soluble electrolyte may lead to increase the solubility of salts.e.g. Mercuric iodide is insoluble in water yet it dissolved by solution of soluble iodideds. Note: Most volatile oils such as peppermint, rose and citrus oils are only very slightly soluble in water but they may be solubilized by the use of certain nonionic surfactant. Expression of solubility: The solubility of substance may expressed in various ways but usually it is designated as the number of mL of solvent required to dissolve 1 g of solute or 1 mL of substance that are liquids at 25oC.  If the solubility of substance has been determined accurately it may be used as an index of purity for that substance. Relative terms of solubility The solubility of a substance in a given solvent may be determined by preparing a saturated solution of it at a specific temperature and by determining by chemical analysis the amount of chemical dissolved in a given weight of solution. The amount of solvent required to dissolve the amount of solute can be determined by a simple calculation. The solubility may then be expressed as grams of solute dissolving in milliliters of solvent; for example, “1 g of sodium chloride dissolves in 2.8 mL of water.” When the exact solubility has not been determined, general expressions of relative solubility may be used. These terms are defined in the USP and presented in the following table. Solvents for pharmaceutical use: The choice of suitable solvent for pharmaceutical use depends on: a) Toxicity: Not toxic mean there is no harmful effect on body. b) Volatility: In case of volatility, so it is volatile, so it evaporates and so lead to precipitate the active ingredient and it may become toxic or  harmful. Therefore, it should store in cool place and in a well closed container. c) Stability: In case of stability, it should not interact with active ingredient or the added substances and should be stable on storage condition and protect the active ingredient stable.