RPD21203 Basic Pharmaceutical Chemistry PDF

RPD21203 Basic Pharmaceutical Chemistry INTRODUCTION TO ANALYTICAL PHARMACEUTICAL CHEMISTRY Definition of Analytical Chemistry Analytical Chemistry. oseparation ·...

RPD21203 Basic Pharmaceutical Chemistry INTRODUCTION TO ANALYTICAL PHARMACEUTICAL CHEMISTRY Definition of Analytical Chemistry Analytical Chemistry. oseparation · identification of the determination the Analytical chemistry is the relative amounts of up a Mengasingkan componenty making separation, identification, and sample. knantifi determination of the relative amounts of the components making up a sample. Applications of analytical chemistry in pharmacy sciences. F Pharmaceutical chemistry. Pharmaceutical industry (quality control). S Analytical toxicology is the detection, identification and measurement of drugs and other foreign compounds. Natural products detection, isolation, and structural determination. Chemical analysis Chemical analysis is the chemical& ( characterization of matter of qualitative analysis and quantitative analysis O Qualitative analysis: An analysis in which we determine the identity of the constituent species in a sample. ⑳ Quantitative analysis: An analysis in which we determine how &much of a constituent species is present in a sample. Imeasure how much  Steps in Chemical Analysis Select Defi n e bl e r h D /efre problem Define the problem i sampling electretul a Select a method. amplig 3) Sampling (obtain sample). sampleprpat essay prepar ample Analysi e te results cherichopatr the 4) afform any occo. Sample preparation (prepare sample for analysis). Amusin 5) Perform any necessary chemical separations calcante pe Analysis (perform the measurement). 7) Calculate the results and report. Do Precision & Accuracy Meca Justify or 2Precision( - If you measure a quantity several times and the values agree ~ closely with one another, your measurement is precise. If the values vary widely, your measurement is not very precise. Accuracy describes how close a measured value is to the “true” value. If a known standard is available, accuracy is how close your value is to the known value. 9 it lose to each other - not close b b because each other b) the % if close b, becaus the valane to torne isclose to each oh as not close to true lye. the LVa  ↑ good accurate Types of errors and precise = no error There are 2 types of errors in analytical laboratory: 1. ① ⑪(systematic errors) - errors that affect the accuracy of results. Determinate en ⑪measurement. # 2. Indeterminate errors (random errors) - errors that affect the precision of value - true notrate ↑ · X accurate ↑ precise & X = systematic random errors error Determinate/systematic errors min-purata ❑ Error that were known to have occurred or at least were determined later ❑ This type of error causes the mean of a set of data to differ from the accepted value um ❑ Poor accuracy > - be its close to notthe value There are three types of systematic errors:- 1. Instrumental errors are caused by the imperfections in measuring devices and instabilities in their components. 2. Method errors arise from non ideal chemical or physical behavior of analytical systems. 3. Personal errors results from the carelessness / inattention Indeterminate/ random errors zetich gibe ↳ ❑ Due to unknown causes/not specifically identified ❑ Poor precision ❑ Cannot be corrected by any method of calibration or other known method of control. ❑ Maybe avoided by increasing the number of reading and using statistical means to obtain the best approximation results/average results.  (2)PHYSICAL ANALYSIS ⑤ ① ② ③ ④ ⑳ 1  LEARNING OUTCOME At the end of the lesson, student should be able to: 1. List the methods that can be used to determine physical properties of a substance. 2. Name the instruments that can be used for measuring these parameters. 3. Discuss the applications of the instruments. 2  TYPES OF PHYSICAL ANALYSIS 1. Melting point - 2. Boiling point & 3. Density hetumpatan 4. Viscosity + /3 ↑ G 5. Optical rotation 6. Disintegration & Dissolution 7. Particle size 3 MELTING POINT The melting point (mp) of a pure solid organic compound is a characteristic physical property. Mp determination helps to characterize a compound and indicate purity (mp range). Mp determined using a Mel-Temp apparatus and a capillary tube to hold the sample. The Mp is the temperature at which a substance changes from a solid to a liquid state BOILING POINT The boiling point of a pure liquid compound is also a characteristic physical property. Bp determination does not help to indicate purity, as bp is affected less by impurities. * takboleh MCC & efect impurities Kalan liquid bolch brat test boiling point  * masn & density a 3. DENSITY volume densite b The density, ρ, is elementary physical property of matter high M3 temp) ⑲ ρ = m/V (the ratio of its mass to volume) ~ The SI unit of density is kg/m³ = However, g/cm³ is another unit commonly used = in laboratory - The density of an object depends on its temperature, with higher temperature resulting in lower density. 6 4. VISCOSITY The viscosity of a fluid is a measure of its resistance to flow For liquids, it corresponds to the informal notion of “thickness”. Ex: honey has higher viscosity than water. A liquids viscosity depends on the size and shape of its - particles. 7 5. OPTICAL ROTATION - The optical rotation is the angle through which the plane of polarization is rotated when polarized light passes through a layer of liquid Dextrorotatory (+) or levorotatory (-) according to whether the plane of polarization is rotated clockwise or counterclockwise respectively The measurement of optical activity is used for pharmacopoeia purposes mainly to establish the identity/purity of the substance 8  6. DISINTEGRATION & DISSOLUTION T kene perah & Tablets/capsules/suppositories must disintegrate to attain good absorption of its active ingredient. rese ↑ For a drug to be readily available to the body, it must be in solution For most tablets, the first important step toward solution is breakdown of the tablet into smaller particles/granules, a process called disintegration. The disintegration is the breaking up of tablets in water or simulated gastric/intestinal fluid at 37˚c to the point that the particles pass through a 10 mesh - screen. - 9 DISSOLUTION TEST To show that the release of drug from the tablet is close to 100% To show that the rate of drug released is uniform Most often performed on products that have poor solubility or absorption problem hite nat handle sability and absorption 10 7. PARTICLE SIZE ANALYSIS Particle size can affect Final formulation: performance, appearance, stability Pharmacological behavior of a drug product 11  2 Marks METHODS TO ANALYZE PARTICLE SIZE in MLC either in StQ. 1. Sieving ayak Sieve analysis is performed using a nest or stack of sieves where each lower sieve has a smaller aperture size than that of the sieve above it. (number of wires per linear inch. Approx. size range : 5µm - ~3mm) 12  (5) Complexometric Titration Learning Outcome To define complexometric and chelation. um To list out the types of ligands. um Define endpoint detection. - Introduction Complexometric titration is a form of- chemical analysis in which O metal ions react with a ligand to form complex. The will disappear as they form complex ions. - metal ions - If colored complex form, it is used to indicate the end point of a titration without indicator. o Complexometric titration is also referred to as EDTA titrations. -  COMPLEXOMETRIC TITRATION Ligand Ve - Complex The anion or neutral Formed by the molecule, donate which The metal ion election reaction of metal acts as Lewis base Known as central ~ that can bind with a ion (Mn+) with metal atom, which (f) charge metal ion through anion by forming acts as Lewis acid. one or several dative bond. ~ atoms to form a a cept electron large complex. (adaclea mi + 1 = )  Dative bond Dative bond is similar to covalent bond (formed of2 - - & but two electrons), in dative bond the electrons pair are donated from one atom to the - other. The atom gives electron pair is known as donor, while the atom accept electron pair is known as acceptor. The bond is represented by an arrow (⎯→) from donor to acceptor. donater Ligand acceptor Metal Examples of ligand Ligand possess lone = pair (unpaired - electrons) readily donate - electrons to metals F ion. > - = Chelation Chelation: is the process of forming chelate. resear Chelate : It is a complex formed between the ligand and metal to form ring - - structure. (heterocyclic rings or chelate rings). => Chelates are usually insoluble in water but soluble in organic solvent Chelating agents: agent/organic molecules containing two or more donor groups which combine with metal to form complex having ring structure. Sequestering agent : Ligands which form water soluble chelates e.g. EDTA. EDTA insetttje x pedu ranjang' ( Ethylene diamine tetra acetic acidS(EDTA) has 6 donor sites - Ethylene diamine tetra acetic acid (EDTA) has 6 donor sites hah join metal EDTA EDTA is important sequestering agents to soluble metal ions. It able to solubilize metal ions. Is the widest general application in analysis because: a) Low price b) Special structure – 6 ligand atoms – more stable c) Forms strainless five-membered rings Types of complexing agent/ ligand Classification of= ligands according to the number of sites of - - attachment to the metal ion - - - - O siteh 1 1) Monodentate I nos L : > - M ↳ Bidentate 2) not &:: -M2 3) Tridentate 1 >no -m :: 4) Multidentate - I 8 W M Monodentate Ligand The ligand attached to metal at one site e.g. H2O , NH3 , CN - , Cl - , I - , Br - , (i.e. forming one dative bond) Metal 1 binding site die basi metal or ligat pastn hone luhin acceptor donour die atampin Inhib , namala [Cu(NH3)4] Bidentate Ligand The ligand attached to metal at two sites. Ligand binding site L NH2 NH2 H 2N H2C M H2C CH2 2 + Cu2+ Cu H2C H2C CH2 Metal NH2 NH2 H 2N Ethylene diamine [Cn(nitz (HCH-N)]' Tridentate Ligand The Ligand attached to metal at 3 sites S Ligand binding site Y Sites und 3 Diethylene triamine [cu(HCHzCH2NHCHuCHzNHu)]2t Mutidentate Ligand Ethylene diamine tetra acetic acid (EDTA) – has 6 sites Endpoint detection – metal ion indicator (pM indicators) pM indicator is a O dye. It is capable of acting as a chelating agent/ ligand to give a - dye-metal complex. Dye-metal complex has different colour from the dye itself. Lower stability than the chelate-metal complex. When there is slight excess of ligand in the solution, the metal-dye complex decompose to produce free dye. This cause changes in colour. > yellow colour indicatio final alone Eyellow lemon colour to Lemon colony pM indicator or inabiacamper  (6) Chemical Analysis: Redox titration Office : A 9051(New building) Prepared by: Ms. Puvana Devi. S  Redox Titration REDOX-(Oxidation and Reduction): A chemical reaction that involves reduction and oxidation simultaneously, in which a change in the valency of reacting elements or ions takes place. Oxidation: is a loss of electrons, Reduction: is a gain of electrons, Leo the Lion! L E GER O L ossof Electrons is oxidation LEO the lion saysGER (donation), Gain of Electrons is Reduction (acceptance)  Oxidation- Reduction Oxidation Terms Reduction Loss electron Electron Gains electron Loss Hydrogen Hydrogen Gains Hydrogen Gains Oxygen Oxygen Loss Oxygen Increases in Oxidation Oxidation Number Decreases in Oxidation Number Number  Oxidation- Reduction Oxidation means an increase in oxidation state, increase in positive valency or decrease in negative valency of an element - lose electrons. Fe ++ Fe ++ + + e Reduction means a decrease in oxidation state, decrease in the positive valency or increase in the negative valency - gain electrons. Fe +++ + e Fe++ The substance that is oxidized is called the reducing agent. The substance that is reduced is called the oxidizing agent  Difference between oxidizing and reducing agents OXIDIZING AGENTS REDUCING AGENTS ❖ Cause the oxidation of another ❖ Cause the reduction of another elements/ elements/compound compound ❖ Is reduced (undergo reduction) ❖ Is oxidized (undergo oxidation) ❖ Use to analyze the concentration of reducing agent ❖ Use to analyze the concentration of oxidizing agent Example Potassium Permanganate, KMnO4 Example Potassium Dichromate, K2Cr2O7 The active metals sodium, magnesium, aluminum, and zinc Ferrous Ammonium Sulfate (FAS or Mohr’s salt) (NH4)2Fe(SO4)2 Sodium Thiosulfate, Na2S2O3 Na Oxidation number De The charge the atom would have in a molecule (or an R H2 ionic compound) if electrons were completely transferred. H H 1. Free elements (uncombined state) have an oxidation - #10 > - 0 X boleh number of zero. Na, Be, K, Pb, H2, O2, P4 = 0 mono - Lit 2. In monatomic ions, the oxidation number is equal 04 - - 2 to the charge on the ion. 0 = - 2 Li+, Li = +1; Fe3+, Fe = +3; O2-, O = -2 2 always - 3. The oxidation number of oxygen is usually –2. In H2O2 and O22- it is –1. - H = + 1 4. The oxidation number of hydrogen is +1 except - when it is bonded to metals. In these cases, its oxidation number is –1. - 5. Group 1 metals are +1, Group 2 metals are +2 and Ne app fluorine is always –1. 6. The sum of the oxidation numbers of all the atoms in a molecule or ion is equal to the charge on the molecule or ion. #300p2- 3H + p + 48 = - 2  Practice problem Determine the oxidation number of each element in these compounds: a) CaO (s) (a 0 2 Nalt50p 20a = + 2 = - b) KNO3 (s) Na 1 4 + 40 0 + + = (a + 0 = 0 c) NaHSO4 (aq) + 1 + + 1 + 3 + 4) 2) - = 0 +2 + - 2 = 0 d) CaCO3 (s) 4 = + 6 e) N2 (g) f) H2O (l)  Practice problem Identify the oxidizing agent and reducing agent in each of the following: snOc = 0 - Sn + 2) 2) - = 0 single E Sn + NO3¯ ---> SnO2 + NO2 metal butt - (n 4 = 0 - HClO + Co ---> Cl + Co 2+ ridul a and X + 2 Sn = 4 , In Reducing Agent = Nos - Oxidizing Agent  Balancing Redox Reaction. When balancing redox reactions, = electrons lost by the reducing agent = the number of electrons gained by - - = the oxidizing agent. Method used : Half-reaction method (acidic/basic solution) A half-reaction is simply one which shows either reduction OR oxidation, but not both. the acidic of basic Balancing redox reaction 10 marke sampai basic zmarne  Practice problem - - 2CrEO- -2 so malan mana tan e =cr = - z + 14 + - St Cr + 6 croz--crstamyt = diereduction , so reduct were hina. HNO2 -NOS- [O] Cr2872 [R] - > - 2 crit HNOL [O] -NOS 70 - 3H ,0 Cr20f" - + > 2(r> + 7H20 gainrection & be + 14H" + (07" - LC3IH2O [R] + 14 + ( - 2) + + 0 H2 + C - 1 = + 6 b = - 6  -[ [ J - & commorthing : // S e-A +, H20 olerpots) 5H + ↑H 20 III  Practice problem - - +2 O [R] Ag > - Ag. 0 + 2nd > 2n - [R] tuperlu balance 2 Age Agro- Int2 In  Cair oada 7 So tambal. #20 satu ↑ H-0 + 2Ag- + +g : 0 In't + 2n +2 emcnetambanse #20 2A8 Ag20 + + > - + 24 Ink+ > In - ze dganze takyah balance , H20 + 2Ag -Aseo e) potong je + a + ex Ind ++ > - In Int + He0 + 2 Ag > - &20 + 2+ + In  20H + + 20H- / & & Co H20 3H + + 30H - 3H20 T  Redox indicator A redox indicator is a compound that changes color when it goes from oxidized to a reduced state Type of redox indicator: ❑ Self indicator ❑ External indicators  take perm indicator asitf - Self indicator meswh Many a times the titrant itself may be so strongly colored that after the equivalence point, a single drop of the titrant produces an intense color in the reaction mixture. E.g. potassium permanganate. so stop = reaction =. The disappearance of the violet color of KMnO4 is due to its reduction to the colorless Mn2+. - - When all the reducing sample (Fe2+) has been oxidized (equivalence point), the first - - drop excess of MnO4- colors the solution a distinct pink. - seffisstor External indicator In titration of Fe2+ by Cr2O72- The reaction & proceeds until all Fe2+ is converted into Fe3+ use The end point is reached when the drop fails to give a blue coloration with the indicator (on plate) Less accurate method and may lead to loss or contamination of sample.  dan Ibabic Clos -3(1 - + H20 25 - 1 L 7 ↑  9) Clos + (1 - [R] base - + Gl + + 105 - 372 + (1 - + 3H - 0 + 60H - O I I [O] - > - 3120 C10s - - > 11- to + 61- + 1105 9312 + Cl + 50 + 60H- ② 21 - > In 3H20 +6 + + 205 -312 + C - + 60H - - ③ Clos x + 3H20 21 I' - > - : + be = - 1 = +5 1 + 6 - 1 - O & + - + 6H + + Cl03 21 3H20 = + 4 - Stro 6H 1103 + + 6 - (21 + 2e > - 12) x3 - 61 > 312 + ey + 6H (10n + ye + - - C + 3H20 [GE - + anid + 6H + -] 7 M - 10x10 = acidic solution + ] 1 0x10 - 9M (H j + = CH =. [H + 2 [OH -3 = [OH-] > [H + ] neutral = basic x nw = CH + ] SOH-] 1 0x10. - 14 = COH-] - 15 M 1 0 x 10 COH-]. = [H + 7 > [OH-] aridin The pH Scale NO UNIT The pH of a solution is defined as: pH = -log [H3O+] or pH = -log [H+] The pOH of a solution is defined as: pOH = -log [OH-] pH + pOH = 14 Practice Problem 1) A solution with hydronium ion concentrations of 1.0 × 10-4 M Find the pH value. 2) Calculate pH and pOH for each of the following solutions at 25°C. a. 1.0 × 10−3 M OH− b. 1.0 M H+ 3) Calculate [H3O+], pH, [OH–], and pOH for each solution at 25°C: a. 0.30 M HNO3 b. 0.0042 M Ca(OH)2  H + 2 > - H + + [H ) = 1 0x10- 4 M. - Oca + OH "OH- pH = -log (H ] + b) 2(0. 0042m) = OH T) log (1 9) [H - 0 x 10 j 0 3M 0004M = =. + =. > (OH 0 = =. 4 PH -log (0 3) - =. = 0. 527 [OH-] [H + ] = um POR + PH = 14 pot = 14-0 517. = 13 47. [H ] + M 1 0 M (OH-] 1 -3 b) =. a) =. 0x10 + ] - 10g [10x10 - 3] PH = -log (n POH = -log (OH-1 POH = IOH -1 0] -log 109 [1 = 3. 1 3. 47 = = = PH + POH = 14 = 0 = 3. 350x10-14 14 - 3 PH = PA pOH 14 = + = I 14 + POH = 14 14 polt = Ionization Constant The ionization of an acid or base in H2O can be quantified using its ionization constant. Ka = acid ionization constant Kb = base ionization constant  Acid – ionization constant, Ka - - - USE RICE TABLE unir ❑pKa = −logKa PhArenda ❑Smaller pKa = stronger acid stronger acid.  Practice Problem Reaction Initial Conc Changes cone equib- Acetic acid has a Ka = 1.8 x 10-5.Determine the pH of a 0.2 M acetic acid solution,CH3COOH. + #30 - H 0 > CH3100 t R CH3C00 I t = O O 8 I 0. 2 + U + U C - U M I N E u N 0. 2 - I Rag neglect A - NHpT + Of 3 O O Kb value for NH3 = 1.8 x 10-5 O 6.. 82x10- sh + U [D) - [NH3] undistimated. - H + U > - 1 82 x 10-3 - x it U N [N1s] = 1. 82x 10.3 - u = 1. 82x 10 - 3 - 1 81x10-. 4 RD= CNO =Nothing 1x10-5 3 = 1. 639x10- M 1. 8 x165 =52x10- = 1 81. x 10 - ↑ M Relationship between Ka & Kb  CB Young Practice Problem irnice dalam water Suppose a 0.1 mole solution sodium acetate is dissolved in 1 liter of water. What is the pH of the solution? Ka of acetic acid = 1.76 x 10-5  A B - Salt + 120 Salt + - Find the pH, pOH, [OH-], [H+] of 0.050 M NaCN. HIN NEOH- > NaCN + He = ↓ HCN (Ka = 6.2 x 10-10) A Natu congupate chalb = nw base Ub - ACN + OH Ub 14 CN - + H20 - = 1. 0x10 - O ⑧ O - 10 0. 05 6. 2 X 10 rel + 1 - 5 - U N = 1. 61x10 M 1 PH + POH = 14 0. 05 - xi PH = 10. 95 [Rb) 1. 61x10-5 - [H + ] = antilog ( -10 95) SHWO - : "M - = 1. 114 X 10 - 4M x = 8. 900X10 M 05- x 10 - 4 0 neglect (OH =7 0 900. =. -10g98 90x10 45 - = 23 047 · POH. Acid – base indicator The acid-base indicator indicates : The endpoint of the titration by changing color. Are substances which change color with pH. They are usually weak acids or bases The acid and its conjugate base have different colors How indicator works (litmus) Y base How indicator works (litmus) : Cntnue If the concentrations of HLit and Lit - are equal : At some point during the movement of the position of equilibrium, the concentrations of the two colors will become equal. The color you see will be a mixture of the two. & purple How Indicators Work Methyl Orange Phenolphthalein Methyl orange is one of the Phenolphthalein is another indicators commonly used in commonly used indicator for titrations. In an alkaline -> base titrations, and is another solution, methyl orange is weak acid : ⑭into mmm yellow ~ad volutioa solation ↓ basil -birn pH range for indicators m - - - X X I & ⑤ ↓