Buffers and Isotonic Solutions - PDF

Buffers Buffers are compounds or mixtures of compounds that, by their presence in Buffered and Isotonic solution, resist cha...

Buffers Buffers are compounds or mixtures of compounds that, by their presence in Buffered and Isotonic solution, resist changes in pH upon addition of Solutions small quantities of acid or alkali. JHON RAPHAEL M. JIMENEZ, RPh, MS Lecturer Buffers Buffer Action Solutions that have the property of resisting Buffer action is the resistance to a change in changes in the pH when acids or bases are pH added to them Koppel and Spiro published a paper on buffer Results from the presence of a buffer pair action in 1914 and suggested a number of which consists of either applications, which were later elaborated by – Weak acid and some salt of a weak acid/its conjugate base Van Slyke. – Weak base and some salt of a weak base/ its conjugate acid  Types of Buffers Buffers Generally, buffers are of two types: These are substances that resists change in pH. – Acidic buffers It is able to neutralize small amounts of added An acidic buffer is a combination of weak acid and its acid or base, thus maintain the ph of the solution. salt with a strong base Weak acid and salt with strong base (conjugate base) Examples: CH3COOH/CH3COONa; H2CO3/NaHCO3; Types of buffer systems H3PO4/NaH2PO4; HCOOH/HCOONa – Sorensen Phosphate Buffer – Basic buffers – Feldman’s Buffer System A basic buffer is a combination of weak base and its salt – Atkins and Pantin Buffer System with a strong acid – Gifford Buffer System Weak base and salt with strong acid (conjugate acid) Examples: NH4OH/NH4Cl; NH3/NH4Cl Sorensen Phosphate Buffer Borate Buffer Systems It is a modified phosphate buffer containing These are used in many pharmaceutical sodium chloride to make it isotonic with preparations containing metals which would otherwise precipitate in phosphate buffers physiological fluid Disadv: the toxic nature of boric acid and borate pH 6 - 8 restricts its use in internal preparations and injectables The pKa of boric acid is 9.2, making this system inefficient at physiological pH. Borates are weak bacteriostatics, but support mold growth when stored at room temperature.  Three Borate Buffer Systems Henderson-Hasselbach Equation Feldman’s Buffer System (pH 7.6-8.2) !"#$ Weak acids: 𝑝𝐻 = 𝑝𝐾𝑎 + log "%&' – Composed of boric acid, sodium chloride, alkaline solution with sodium borate Atkins and Pantin Buffer System (pH 7.6-11) – Composed of alkaline solution of sodium carbonate and ("!) acid buffer solution of boric acid and sodium chloride Weak bases: 𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + log !"#$ Gifford Buffer System (pH 6-7.6) – Similar to Feldman’s Buffer System but uses potassium chloride(instead of NaCl) –making it hypotonic Henderson-Hasselbach Equation Answer 𝑏𝑎𝑠𝑒 1. What is the pH of a buffer solution prepared 𝑝𝐻 = 𝑝𝐾𝑤 − 𝑝𝐾𝑏 + log with 0.025 M ammonia and 2.5x10-6 M 𝑠𝑎𝑙𝑡 ammonium chloride? Kb= 1.71x10-5 0.025 𝑀 𝑝𝐻 = 14 − 1.71x10−5 + log 0.0000025 𝑀 pH = 9.99  Sample Problem Buffer capacity Calculate the pH of the buffer solution Also known as buffer action, buffer efficiency, formed when 0.3M acetic acid (Ka= 1.8 x buffer index, buffer value 10-5) is added to 0.2 M sodium acetate Ability of a buffer solution to resist changes in pH upon addition of an acid/alkali. Buffer capacity Isotonic Solutions Koppel, Spiro and Van Slyke Equation: Hypertonic Solutions – Solution with more solutes compared to cell + concentrations 𝐾𝑎 [𝐻3𝑂 ] – Solution that freeze lower than -0.52⁰C 𝛽 = 2.3 𝐶 + 𝐾𝑎 + 𝐻3𝑂 2 – Cell effect: crenation or shrinkage Hypotonic Solution – Solutions with less solutes compared to cell Where C= total buffer concentration, that is, the sum concentrations of the molar concentrations of the acid and the salt – Solutions that freeze higher than -0.52⁰C – Cell effect: swelling and lysis  Isotonic Solutions Tonicity – Solution for which a living cells does not gain or lose water – Same synchronicity to blood – Has similar concentration as 0.9% (w/v) NaCl solution Methods of Adjusting Tonicity Methods of Adjusting Tonicity Class I: Addition of Tonicity Adjuster Class I: Addition of Tonicity Adjuster 1. Freezing Point Depression /Cryoscopic Method 2. Sodium Chloride Equivalent / E Method Freezing point determination – E-value -0.52⁰C is generally accepted freezing point of both gram of NaCl equivalent to 1 gram of substance serum and lacrimal fluid MW NaCl / i factor NaCl = MW subs / i factor subs – Isotonic NaCl conc = 0.9% (w/v) NaCl  E-Value Method E-Value Method Steps: 1. Calculate the amount of NaCl represented by the How many grams of NaCl should be used in ingredients in the prescription the compounding the following prescription? 2. Calculate the amount NaCl that would make the volume of solution (specified in the prescription) isotonic 3. Subtract the amount of NaCl represented by the ingredients Solution: in the prescription (Step 1) from the amount of NaCl that Rx NaCl needed – 30 ml x 0.009 = 0.27 would make the specific volume in the prescription isotonic Pilocarpie (E=0.22) 0.3 g NaCl available – 0.3 x 0.22 = 0.066 NaCl qs (Step 2) Purified water qs ad 30 mL NaCl to be added – 0.27 – 0.066 4. If the agent is other than NaCl is to be used to make the = 0.204 Make isotonic solution solution isotonic, divide the amount of NaCl (answer in Step Sig. for the eye 3) by the E value of the other substance. E-Value Method E-Value Method How many grams of boric acid should be used How many grams of KNO3 (E=0.58) should be in compounding the prescription? used to make the following prescription isotonic? E value of AgNO3=0.34 Solution: Solution: Rx NaCl needed – 60 ml x 0.009 = 0.54 Rx NaCl needed – 60 ml x 0.009 = 0.54 Phenacaine HCl (E=0.17) 0.6 g 0.2% Silver Nitrate Solution Cholobutanol (E= 0.18) 0.3 g NaCl available – (0.6 x 0.17) + (0.18 60ml NaCl available – 0.002 (convert 0.2% x 0.3) = 0.156 into g) x 0.34 = 0.00068 Boric Acid (E= 0.52) qs Purified water qs 60ml NaCl to be added – 0.54 – 0.156 = NaCl to be added – 0.54 – 0.00068 = 0.384 Make isotonic solution 0.53932 Make isotonic solution Boric acid to be added = 0.384 / Sig. For eye use KNO3 to be added = 0.53932 / 0.58 0.52 = 0.74 = 0.93 g Sig. 1 drop in each eye  Sample Problem Answer How many grams of dextrose monohydrate (E=0.16) should be used in compounding the NaCl needed - 50 ml x 0.009 = 0.45 prescription? NaCl available - (0.50 x 0.29) + (0.25 x 0.24) Rx NaCl available = 0.205 Ephedrine Hydrochloride (E=0.29) 0.50 g Cholobutanol (E=0.24) 0.25 g NaCl to be added – 0.45 – 0.205 = 0.245 Dextrose, monohydrate (E=0.16) q.s. Rose water ad 50 mL Dextrose to be used = 0.245 / 0.16 = 1.53 g Make isotonic solution Sig. Nose drops Methods of Adjusting Tonicity Sample Problem Class II: Addition of water, followed by dilution Determine the volume of purified water and 0.9% with a buffered isotonic vehicle. w/v sodium chloride solution needed to prepare 20 mL of a 1% w/v solution of hydromorphone White Vincent Method hydrochloride (E=0.22) using White Vincent Method. VH20 = wt x E value x 111.1 Sprowl’s Method – simplified version of White-Vincent Method VH20 = 0.3 x E value x 111.1  Answer E-Value Computation using Liso *+ , -&!. Vol of H2O = ml x E value x 111.1 𝐸 𝑉𝑎𝑙𝑢𝑒 = /0 Vol of H2O = 0.2 (get 1% of 20 ml) x 0.22 x 111.1 Calculate the approximate E-value of boric acid (MW=61.84; Liso=1.8) Vol of H2O = 4.89 ml Calculate the approximate E-value of zinc sulfate anhydrous (MW=287.56; Liso=2.5) Acid-Base Equilibria Pearson’s HSAB THEORY ACID BASE HARD ACID SOFT ACID HARD BASE SOFT BASE Small size, high Large size, small or Valence electrons Valence electrons Substance that yields H Substance that yields Arrhenius Theory or H30+ in H20 OH- in H20 positive charge, not zero positive tightly held easily distorted easily distorted, charge, several Bronsted-Lowry Theory Proton Donor Proton Acceptor polarized valence electrons (easily distorted) Lewis Theory Electron acceptor Electron donor Hard acids are electron acceptor with high positive Pearson’s HSAB charges and relatively small sizes while soft acid have positive charges and relatively large sizes.  pH & Sorensen’s pH Scale Ionization vs Dissociation pH Ionization – A measure of the acidity or alkalinity of a – The complete separation of ions in a crystal lattice solution, numerically equal to 7 for neutral when salt is dissolved. solutions, increasing alkalinity and decreasing with increasing acidity. Dissociation – The ph scale commonly in use ranges from 0 to – The separation of ions in solution when the ions 14. are associated by inter-ionic attraction.