King Faisal University College of Clinical Pharmacy Department of Pharmaceutical Sciences

Pr a ct ica l N ot e Physica l Ph a r m a ce u t ics

Done by: Dr. Azza Ali Hasan Assistant professor (Pharmaceutics) First Year Second Semester
Name:___________________________________ Academic Number:______________________

CONTENTS Expt. No
1 2

Date

Experiment Name
Measurement of Density Of Unknown Liquid Experimental Determination Of Surface Tension

Page No

Solubility Of Solid In Liquid 3 4 Partition Coefficient 5 Determination Of Partition Coefficient Of Benzoic Acid And Salicylic Acid Between Chloroform And Water Determination of Partition Coefficient For The Distribution Of Iodine Between Carbon Tetrachloride And Water Preparation Of S rensens Phosphate Buffer Viscosity Measurement Of A Liquid Determination Of Rate Constant For First Order Reaction Determination Of The Reaction Rate Constant Of Saponification Of Ethyl Acetate In The Presence Of An Equal Quantity Of Sodium Hydroxide Adsorption Of Oxalic Acid From Aqueous Solutions By Activated Charcoal Dtermination Of Angle Of Repose Of Powders ` Solubilization Of Benzoic Acid In Distilled Water Solubilization Of Salicylic Acid In NonIonic Surfactant (Tween 80)

7 8 9 10

11 12

Physical Pharmaceutics (Practical)

Course Number

: 2001003

Lab. contact hours : 3 hours /week Grading Plan: 25% (Practical examinations, assignments, solving problems,) Course Description : Several related experiments on: adsorption, viscosity, surface tension, partition coefficient), and reaction kinetics and determination of reaction rate constants. Course Objectives : At the end of this practical course the student should be able to : Measure the density of unknown liquids. Calculate the amount of solid dissolved in liquid. Determine the effect of surface active agents on solubility Calculate the partition coefficient of different substances Prepare different buffers and measure the pH Measure the viscosity of different liquids Determine the order of reactions and calculate the reaction rate constant Calculate the amount of solid adsorbed on adsorbent. Measure the angle of repose of different powders Reading and recording results , performing calculations and discussion of results .

Lab. 1. Measurement of Density Of Unknown Liquid Aim: Find the density of two unknown liquids. Materials and apparatus: 50ml graduated cylinder, digital balance, 2 unknown liquids. Procedure: 1) Find the mass of the empty graduated cylinder. 2) Pour unknown liquid 1 into the graduated cylinder to the 25 ml. level. 3) Find the mass of the graduated cylinder with 25 ml of unknown liquid 1. 4) Repeat steps 1-3 for unknown liquid 2. Calculations & Results: We can calculate density of a liquid using the formula: Density= Mass/Volume To calculate the mass for the liquid (you must subtract out the mass of the graduated cylinder). Unknown Liquid Mass of empty graduated cylinder Mass of graduated cylinder with liquid Mass of the liquid Volume of liquid Density of liquid

Liquid 1 Liquid 2

What is each liquid? Using the table below it is now possible for you to determine what each liquid is. Densities for some common liquids are: Substance Water Paraffin Oil Sea Water Carbon tetrachloride Benzene Glycerin Methanol Density (gm/cm3) 1.00 0.8 1.025 1.58 0.87 1.26 0.79

Lab. 2. Experimental determination of surface tension: Drop-Number method: (By using Stalagmometer) Aim: By using stalagmometer, determine the relative surface tension of the given liquids, supplied with reference to distilled water (S.T. of distilled water= 72.8 dyne/cm at 20 C) Materials and apparatus: Stalagmometer, beaker, filter paper, different samples Procedure: 1. Wash the stalagmometer several times with water before use. 2. Introduce the flat tip of stalagmometer into a small beaker (100 ml capacity) half filled with distilled water, suck the water through the apparatus avoiding entrance of air bubbles) till the level of water becomes above the upper mark of apparatus by 1 cm) 3. Using a small filter paper remove any attached humidity on the outside of the apparatus. 4. Adjust the level of water to the upper mark and remove any suspended drop. 5. Count the number of drops falling until the level of water reaches the lower mark (undescended drop is not counted) 6. Repeat the procedure for unknown liquids after washing the apparatus twice with the liquid to be measured. 7. Record your results in the following table, and represent the data graphically.

Calculations & Results:

Sample

Number of drops n1 n2 n3 Mean n

Surface tension (dyne/cm)

Water Sample 1 Sample 2 Sample 3

where and are the surface tension of water and liquid. d1 and d2 are the densities of water and liquid, respectively. n1 and n2 are the number of drops of water and liquid.

Lab.3. Solubility Of Solids In Liquids Solubilization Of Benzoic Acid In Distilled Water Aim: Calculate the amount of Benzoic Acid dissolved In Distilled Water. Materials and apparatus: Benzoic acid, distilled water, 0.05 N NaOH solution, phenolphthalein indicator, 100 ml beaker, 250 ml conical flasks, 10 ml pipettes, 50 ml burettes, filter paper and funnels.

Procedure: 1. In clean conical flasks, place exactly 1 gm of benzoic acid. 2. Add 20 ml of distilled water to the flask. 3. Shake the flasks for 15 minutes (shaking should be efficient), set aside for another 15 minutes. 4. Filter the content of the flask. 5. Titrate 10 ml of filtrate with 0.05 N NaOH solution using phenolphthalein as indicator. (1 ml 0.05 N NaOH 6.1 mg benzoic acid). End point: faint pink. 6. Record the result and calculate the amount of benzoic acid dissolved in 20 ml. Calculations & Results: End point (mls of 0.05 N NaOH) Amount of benzoic acid dissolved =
E.P. F 20 mg/20 ml 10

Lab.4. Solubilization Of Salicylic Acid In Non-Ionic Surfactant (Tween 80) Aim: Effect of surfactants on solubility. Non-ionic surfactants may act as wetting, emulsifying , and solubilizing agents. One of the properties of surfactants is their ability to increase the solubility of a sparingly soluble compound through micelle formation. Below the CMC, as the concentration of surfactant increases, the solubility of the compound shows slower increase. At the CMC range, a sharp increase in the solubility can be observed due to micelle formation (which entraps the undissolved molecules and get them dissolved). i.e., Micellar solubilization. Materials and apparatus: Salicylic acid (solubility 1 g in 550 ml water, i.e., slightly soluble (1:100 to 1: 1000), distilled water, 6% v/v Tween 80, 0.05 N NaOH solution, phenolphthalein indicator, 100 ml beaker, 250 ml conical flasks, 10 ml pipettes, 50 ml burettes, filter paper and funnels. Procedure: 1. In clean conical flask, place exactly 0.5 gm of salicylic acid. 2. Add 20 ml of distilled water to the flask. 3. Shake the flasks for 15 minutes (shaking should be efficient), set aside for another 15 minutes. 4. Filter the content of the flask. 5. Titrate 10 ml of filtrate with 0.05 N NaOH solution using phenolphthalein as indicator. (1 ml 0.05 N NaOH . mg salicylic acid). End point: faint pink. 6. Record the result and calculate the amount of salicylic acid dissolved in 20 ml distilled water. 7. Repeat the same procedure, but instead of 20 ml of distilled water use 20 ml of surfactant solution (6% v/v Tween 80). 8. Record the result and calculate the amount of salicylic acid dissolved in 20 ml surfactant solution. 9. Comment on the result.
9

Calculations and Results: End point (mls of 0.05 N NaOH) Distilled water Amount of salicylic acid dissolved =
E.P. F 20 mg/20 ml 10

Surfactant solution

10

Lab.5. Determination of Partition Coefficient of Benzoic acid between Chloroform and Water Aim: a partition- (P) or distribution coefficient (D) is the ratio of concentrations of a compound in the two phases of a mixture of two immiscible solvents at equilibrium. Hence these coefficients are a measure of differential solubility of the compound between these two solvents. Materials and apparatus: Stoppered conical flask, bottle, separating funnel, pipette, burette, Sodium hydroxide, Benzoic acid, chloroform, phenolphthalein. Procedure: 1. Prepare 0.1 N NaoH in water and prepare the following mixture in a bottle. 30 ml water + 30 ml Chloroform + 2 gm Benzoic acid 2.Shake the contents of the bottle for 15 min. 3. Allow it to stand for 10 min in separating funnel and separate 2 layers. 4. pipette out 5 ml of lower organic layer from the funnel into separate flask using dry pipette. 5. Titrate this against 0.1 N NaoH using phenolphthalein indicator. (vigorous shaking is necessary) 6. pipette out 10 ml of upper aqueous layer separately using dry pipette. 7. Titrate against 0.1 N NaoH using same indicator. Calculations and Results: 1. Partition co-efficient of Benzoic acid between Chloroform and Water systems is

11

End point (mls of 0.1 N NaOH) In organic layer In aqueous layer

Amount of benzoic acid dissolved (mg/ ml) In organic layer C org= ml

E.P. F mg/ 5

In aqueous layer C aq=

E.P. F mg/ 10

ml

Partition Coefficient= Concentration of benzoic acid in organic layer Concentration of benzoic acid in aqueous layer Partition Coefficient= Solubility of benzoic acid in organic layer Solubility of benzoic acid in aqueous layer K (Distribution ratio) = C org C aq = S org

S aq

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Lab.5. Determination of Partition Coefficient of Salicylic acid between Chloroform and Water Materials and apparatus: Stoppered conical flask, bottle, separating funnel, pipette, burette, Sodium hydroxide, Salicylic acid, chloroform, phenolphthalein. Procedure: 1. Prepare 0.1 N NaoH in water and prepare the following mixture in a bottle. 30 ml water + 30 ml Chloroform + 2 gm Salicylic acid 2.Shake the contents of the bottle for 15 min. 3. Allow it to stand for 10 min in separating funnel and separate 2 layers. 4. pipette out 5 ml of lower organic layer from the funnel into separate flask using dry pipette. 5. Titrate this against 0.1 N NaoH using phenolphthalein indicator. (vigorous shaking is necessary) 6. pipette out 10 ml of upper aqueous layer separately using dry pipette. 7. Titrate against 0.1 N NaoH using same indicator. Results: 1. Partition co-efficient of Salicylic acid between Chloroform and Water systems is

13

Calculations & Results: End point (mls of 0.1 N NaOH) In organic layer In aqueous layer Amount of Salicylic acid dissolved (mg/ ml) In organic layer C org= ml
E.P. F mg/ 5

In aqueous layer C aq=

E.P. F mg/ 10

ml

Partition Coefficient= Concentration of Salicylic acid in organic layer Concentration of Salicylic acid in aqueous layer Partition Coefficient= Solubility of Salicylic acid in organic layer Solubility of Salicylic acid in aqueous layer K (Distribution ratio) = C org C aq = S org

S aq

14

Lab.6. Determination Of Partition Coefficient For The Distribution Of Iodine Between Carbon Tetrachloride And Water Aim: To determine the partition coefficient for distribution of iodine between CCl4 and water. Materials and apparatus: Stoppered conical flask, separating funnel, pipette, burette, iodine, carbon tetrachloride, Sodium Thiosulphate, starch. Procedure: 1. Take two stopper 250 ml iodine flasks A and B. 2. pipette out saturated solution of iodine in CCl4 and transfer 30 ml iodine solution into flask A and 25 ml iodine solution into flask B. 3. Add 5 ml of pure CCl4 into flask B only to make the volumes same. 4. pour 120 ml of water each into the two flasks. 5. Put the stoppers and shake the flasks on a mechanized shaker for 15 minutes. 6. Allow it to stand for 10 min in separating funnel so that the layers separate. While waiting, fill the burette with 0.01N Sodium Thiosulphate solution. 7. From iodine flask A, pipette out 5 ml of organic layer into a conical flask (organic layer should not be contaminated by the aqueous layer) 8. Titrate against 0.01N thiosulphate solution, without indicator till the purple colour disappear. 9. Pipette out 20 ml of aqueous layer from the same bottle into the conical flask, (adding starch at the beginning itself since the colour is light) and titrate against 0.01N thiosulphate solution (till the blue colour just disappears).
15

10. Repeat the two titrations for iodine flask B also. Calculate partition coefficient for each flask. Calculations & Results: Partition coefficient of iodine between CCl4 and water = (1) _____ (2) _____ Amount of Iodine dissolved End point Sample number (mls of 0.01 N Na S2O3) In organic layer C org= ml A
E.P. F mg/ 5

In aqueous layer C aq=

E.P. F mg/ 20

ml

Partition Coefficient= Concentration of Iodine in organic layer Concentration of Iodine in aqueous layer Partition Coefficient= Solubility of Iodine in organic layer Solubility of Iodine in aqueous layer K (Distribution ratio) = C org C aq = S org

S aq

16

Lab.7.

Preparation Of S rensens Phosphate Buffer; PH 5.88.0, PKA = 7.20

Aim:

To prepare and measure pH of different buffer solutions.

Materials and apparatus:

pH meter Beakers Glass rod Measuring cylinder Monobasic sodium hydrogen phosphate Dibasic sodium hydrogen phosphate

Procedure:

Mix appropriate volumes of stock and add an equal volume of distilled water to make a final 0.1 M S rensens phosphate buffer solution (S rensen, 1909; Gomori, 1955). Keep in mind that high levels of phosphate may be somewhat toxic to plant cells (Sabatini, et al., 1962) and thus S rensens buffer may not be appropriate for some experiments.
17

Stock solutions: A 0.2 M NaH2PO4 B 0.2 M Na2HPO4 A (ml) 92.0 87.7 81.5 68.5 62.5 56.5 51.0 45.0 39.0 33.0 28.0 23.0 19.0 16.0 8.5 5.3 B (ml) 8.0 12.3 18.5 31.5 37.5 43.5 49.0 55.0 61.0 67.0 72.0 77.0 81.0 84.0 91.5 94.7 pH 5.8 6.0 6.2 6.5 6.6 6.7 6.8 6.9 7.0 7.1 7.2 7.3 7.4 7.5 7.8 8.0

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Lab.8. Viscosity measurement of a liquid

Aim: The viscosity of two liquids can be compared by making use of an Ostwald Viscometer (Capillary viscometer) which consists of two

bulbs, one attached with a capillary tube and U-tube below the capillary tube while other bulb is attached to the other arm of U-tube at a level lower than the other bulb. The liquids of known densities are allowed to flow through the capillary maintaining the same differences of levels in the limbs and the time equation which governs the flow lead to the relation:

where and are viscosity coefficients of the liquid and water, respectively and d1 and d2 are the densities of liquid and water, respectively. Knowing the value of viscosity of one liquid, one can calculate the viscosity of other liquid.
19

Materials and apparatus: Viscometer, beaker, pipette, stopwatch, different samples. The procedure for measurement of viscosity is as follows. 1. The viscometer is fixed vertically on the stand and 15 mL of water is pipetted into the lower bulb. The volume of water (15 mL) is chosen so that the liquid can be conveniently sucked into the upper bulb leaving some in the lower bulb. 2. Water is sucked up into the other bulb to a point about the mark above the bulb. 3. Now it is released and stop clock is started when the meniscus crosses the mark. 4. The clock is stopped when the mark below the bulb is passed. 5. The time is recorded at the moment. 6. The same procedure is repeated twice or thrice and their average is used in calculations. 7. Similarly, the experiment is repeated with the given liquid. 8. Then calculate the viscosity. The viscosity of water at room temperature is used from the tables (usually water, i.e. 1.0019 cps).

20

Calculations & Results: Sample Water Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 T1 T2 T3 Mean

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Lab.9. "Determination Of Rate Constant For First Order Reaction" Aim: To follow the reaction by a titrimetric method and determination of the first order rate constant by a graphical treatment of the data. CH3COOC2H5 + HCL -------------- CH3COOH+ C2H5CL The reaction depends on the concentration of ethyl acetate. The decomposition of ethyl acetate follows 1st order reaction kinetics:
K 2.303 V log t V V , where Vt

K t

is the first order reaction rate constant, and is the time.

Materials and apparatus: Conical flask, measuring cylinder, pipette, test tube, stopwatch, water bath, burette, thermometer, Hydrochloric acid, sodium hydroxide, phenolphthalein, ethyl acetate. Procedure: 1. Measure 100 ml of 0.5 N HCL into a conical flask, keep in a water bath. 2. Measure 10 ml of ethyl acetate into a clean test tube and keep in the same water bath for equilibrium. 3. After equilibrium temperature is attained, mix them thoroughly and start the stop watch. 4. Quickly withdraw 5 ml of mixture (i.e. at 0 min) with pipette and transfer to a conical flask containing 10 ml of ice cold water. 5. Add phenolphthalein indicator and titrate with standard 0.5 N NaoH solution, the volume of NaoH consumed is noted as V . 6. Repeat the titration by withdrawing samples of 5 ml periodically at 10, 20, 30, 40, 50, 60, 70 and 80 min intervals. 7. There values shall be taken as Vt. 8. The reaction is accelerated to completion by heating to 60 C for 20 min in water bath. During this time the flask must be stoppered to avoid changes in concentration due to evaporation.
22

9. Cool to room temperature, pipette out 5 ml of solution into conical flak containing 10 ml of ice cold water and repeat the titration. 10. The volume of NaoH consumed shall be taken as V . 11. Plot a graph of log (V -Vt) against time. 12. The slope gives the reaction rate constant. Calculations & Results: The initial ethyl acetate concentration is proportional to (V - Vo), where V is the final titre volume and Vo is the initial titre volume. The concentration of ethyl acetate at time t is proportional to (V - Vt) where Vt is the titre volume of the sample at time t. Time (min) 0 10 20 30 40 50 60 70 80 Volume of NaoH added (ml) Vt V -Vt Log V -Vt
K 2.303 V log t V V Vt

23

L o g c o n c e n tr a ti o n

Time

Slope = -k/2.303

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Lab.10. Determination Of The Reaction Rate Constant Of Saponification Of Ethyl Acetate In The Presence Of An Equal Quantity Of Sodium Hydroxide Aim: to determine the rate of reaction CH3COOC2H5 + NaOH -------------- CH3COONa + C2H5OH The reaction depends on the concentration of both ethyl acetate and sodium hydroxide. In this experiment, the concentration of both reactants are equal (a = b). The decomposition of ethyl acetate follows 2nd order reaction kinetics:
x a (a x) Kt , where

a x

is the initial concentration of either reactant, is the concentration of the decomposed reactant,

a-x is the concentration of the remaining reactant, K t is the second order reaction rate constant, and is the time.

Materials and apparatus: Conical flask, measuring cylinder, pipette, test tube, stopwatch, water bath, burette, thermometer, Hydrochloric acid, sodium hydroxide, phenolphthalein, ethyl acetate. Procedure: 1. In two separate conical flasks, place 50 ml of 0.05 N ethyl acetate and 50 ml of 0.05 N sodium hydroxide. 2. Add the solutions of # 1 to one another, shake and quickly withdraw 10 ml to the titration flask containing 10 ml of ice cold water. 3. Add few drops of phenolphthalein and titrate against 0.05 N HCl. 4. The titration value corresponds to the initial concentration "a".
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5. Similarly withdraw 10 ml samples at 5, 10, 15, 20, 25 and 30 min intervals titrate the samples as earlier. 6. The titration values denote the amount of sodium hydroxide/ethyl acetate remain unreacted i.e. "a-x" 7. Substituting these values in 2 nd order reaction. 8. Reaction gives the reaction rate constant or specific rate constant. 9. Plot a graph of
x a(a x)

Vs time "t" and calculate the slope.

Calculations & Results: Plot a curve for

x a(a x)

against time and calculate the K value.

The K value equals to the slope of the obtained line. The unit of K value is (mole. L -1.min-1).

EP (ml) Time volume (min) of HCL added

Conc. NaoH (a-x)

Amount decomposed x

x a (a x)

K=

1 x t a (a x)

0 5 10 15 20 25 30
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Lab.11. Adsorption of Oxalic acid from aqueous solutions by Activated Charcoal Adsorption: it is applied to more or less uniform accumulation of a substance at a substance or interface. Adsorbent: it is the solid on its surface adsorption takes place. Adsorbate: the substance which is adsorbed on the surface of adsorbent. Aim: To determine the adsorption of oxalic acid from solutions of various concentrations using activated carbon. Freundlich isotherm: Log (x/m) = (1/n) Log C +Log K where: X/m Weight of adsorbate in grams, adsorbed by g of the adsorbent K, n Constants. C Equilibrium concentration of the adsorbate A plot of log X /m against log C should be linear, with an intercept of log K and a slope of 1/n. Materials and apparatus: Stoppered conical flask, measuring cylinder, pipette, test tube, stopwatch, burette, filter paper, Charcoal, Oxalic acid, sodium hydroxide, phenolphthalein. Procedure:
1. 2.

In each 5 stoppered flask, place 2 gm of finely divided Charcoal. Add 50 ml standard oxalic acid solutions to each of the 5 flasks changing the concentration from 0.1, 0.2, 0.3, 0.4 and 0.5 N as given. Shake the flasks at least 4 times, 2 min every 10 min, and then set aside for 10 minutes to attain equilibrium. Filter the contents of the flask separately through filter paper and reject the first portion of the filtrate after washing the receiver with it.
27

3.

4.

5.

Titrate accurately measured portion (10 ml) of each filtrate with 0.5 N NaoH using phenolphthalein as indicator. Calculate the amount unadsorbed of oxalic acid in each and tabulate your results. Plot log X /m against log C according to Freundlich adsorption isotherm.

6.

7.

Calculations & Results: E.p

blank:

volume of 0.5 N NaOH corresponding to the initial amount

of oxalic acid in the 10 ml sample.

E.P

experiment

: volume of 0.5 N NaOH corresponding to the free

amount of oxalic acid (unadsorbed ) in the 10 ml sample. 1 ml of 0.5 N NaoH = 0.0225 g = 22.5 mg C (mg/ ml) = E.P experiment x F 10 Where C: unadsorbed concentration of oxalic acid at equilibrium. X/ m (mg/g) = (E.p blank E.P experiment) x F x Total volume (50) Sample volume (10) x weight of adsorbent (2 g)

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Normali ty of Oxalic acid 0.1 0.2 0.3 0.4 0.5

Blank E. P (ml )

Experime Free nt E. P (ml ) oxalic C (mg/ml)

(x/m) (mg/g )

Log C

Log (x/m)

29

Lab.12. DTERMINATION OF ANGLE OF REPOSE OF POWDERS (sodium chloride, lactose, and lactose +2 % talc)

Aim: Determination of flow properties of powder: Angle of repose: is the maximum angle between the surface of a pile of powder and the horizontal plane. tan then, As = h / r (h: the height, r: the radius) = tan -1 h / r

decreases, the flow property increased.

Materials and apparatus: Sodium chloride (crystalline) Lactose Talc Acetyl salicylic acid starch Funnel

30

Procedure: 1. A quantity of the supplied powder is allowed to flow carefully through a funnel, whose tip is adjusted at 2 cm from a horizontal surface beneath (see the diagram), so that the apex of the pile just touch the lower tip of the funnel. 2. Mark the base of pile. Then remove the powder. 3. Measure the diameter of the formed circle (take the average of two diameters). 4. Repeat the process three times and calculate the average diameter (d). And the radius (r = d / 2). 5. The height of the pile (the distance between the horizontal surface and the lower tip of the funnel) is called (h). 6. Tan the angle of repose (tan = h / r), get tabulate your results. 7. Comment on the results. ( = tan -1 h / r), and

31

Calculations & Results: Tabulate the results as shown in the table: powder Sodium chloride (crystalline) Acetyl salicylic acid starch Height (h) Radius (r) Angle of repose ( )

Comment on the results

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