PHT 463

Lubna Ashry

Quality Control of Capsules

Capsules are preparations with hard or soft shells, of various shapes and capacities, usually containing a single dose of medicament. Types of capsules: hard, soft, enteric, and modified-release capsules. Quality Control Tests for Capsules: I. Standard for content of active ingredients in capsules: This test determines the amount of active ingredient by the method in the assay. II. Disintegration: Disintegration is the state in which no residue except fragments of capsule shell, remains on the screen of the test apparatus or adheres to the lower surface of the disc. The disintegration test determines wither tablets or capsules disintegrate within a prescribed time when placed in a liquid medium under the prescribed experimental conditions. Method: According to the B.P. and applies to hard and soft capsules. Introduce one capsule into each tube and suspend the apparatus in a beaker containing 600 ml water @ 37oC. If hard capsules float on the surface of the water, the discs may be added. Operate the apparatus for 30 minutes; remove the assembly from the liquid. The capsules pass the test if o No residue remains on the screen of the apparatus or, o If a residue remains, it consists of fragments of shell or, o Is a soft mass with no palpable core.

o If the disc is used, any residue remaining on its lower surface should only consist of fragments of shell.

PHT 463

Lubna Ashry

III. Uniformity of Weight: This test applies to all types of capsules and it is to be done on 20 capsules. Method: Limit: Not more than two of the individual weights deviate from the average weight by more than the percentage deviation shown in the table below, and none deviates by more than twice that percentage.
Average Weight of Capsule Content Less than 300 mg 300 mg or more Percentage Deviation 10 7.5

Weigh an intact capsule. Open the capsule without losing any part of the shell and remove the contents as completely as possible. Weigh the shell. The weight of the contents is the difference between the weighing. Repeat the procedure with a further 19 capsules selected at random. Determine the average weight.

Record your results in the following table:

Capsul e Numbe r 1 2 -up to 20 Total weight Weight of intact capsules (A) Weight of empty shell (B) Weight of contents =A-B

Average weight = X / 20 Upper limit = average weight + (Average weight * % error) Lower limit = average weight - (Average weight * % error)

PHT 463

Lubna Ashry

Quality Control of Tablets

(Hardness, Friability, Wt. Variation, Disintegration)

When a patch of a certain medication is received, we should check many of its properties to make sure that it is suitable for human use. Some of these tests include the following: 1. General Appearance: It is the visual identity and overall elegance which is essential for consumer acceptance. This includes: Size, shape, and thickness: this is important to facilitate packaging and to decide which tablet compressing machine to use. Organoleptic properties: which include color and odor of the tablets. Tablet color is important because it affects rapid identification of the medication, and odor is important to identify any stability problems. An example is Aspirin which gives the odor of acetic acid if any stability problem occurred. 2. Official and unofficial tests. Official Tests: Weight variation, disintegration, dissolution, drug content. Non-Official Tests: hardness, friability.

I- Non official tests:

Hardness (crushing strength):

It is the load required to crush the tablet when placed on its edge.
Why do we measure hardness? Hardness determinations are made throughout the tablet runs to determine the need for pressure adjustments on the tableting machine. Hardness can affect the disintegration. So if the tablet is too hard, it may not disintegrate in the required period of time. And if the tablet is too soft, it will not withstand the handling during subsequent processing such as coating or packaging. In general, if the tablet hardness is too high, we first check its disintegration before rejecting the patch. And if the disintegration is within limit, we accept the patch. 3

PHT 463 If H. is high + disintegration is within time accept the patch. Factors Affecting the Hardness: 1. Compression of the tablet and compressive force. 2. Amount of binder. (More binder more hardness)

Lubna Ashry

3. Method of granulation in preparing the tablet (wet method1 more hardness than direct method2 Slugging method3 gives the best hardness). 4. Characteristics of the drug. Limits: 5 kilograms minimum and 8 kilograms maximum. Make hardness test on 5 tablets and then take the average hardness. Friability: It is the tendency of tablets to powder, chip, or fragment and this can affect the elegance appearance, consumer acceptance of the tablet, and also add to tablets weight variation or content uniformity problems. Friability is a property that is related to the hardness of the tablet. An instrument called friabilator is used to evaluate the ability of the tablet

to withstand abrasion in packaging, handling, and shipping. Roche Friabilator: Subjects a number of tablets to abrasion and shock by utilizing a plastic chamber that revolves at 25 rpm, dropping the tablets a distance of 6 inches with each revolution. After a given number of rotations the tablets are weighed and the loss in weight indicates the ability of the tablets to withstand this type of wear.

Wet method is by mixing the powder with some alcohol, make it into granules, then perform a size reduction, then compress it to tablets. This gives harder tablets. 2 Direct method is to compress the powder directly into tablets.
3

In this method, the powder made into granules just as the wet method, then is compressed to large tablets in the slugging machines size reduction compress again to tablets.

PHT 463

Lubna Ashry

Procedure: 1. Weigh 20 tab altogether = W1 2. Put these tablets in the friabilator and adjust the instrument at 100 rpm (i.e. = 25 rpm for 4 min) 3. Weigh the 20 tablets (only the intact ones) = W2 4. Friability (% loss) = ( w1 w2) *100 w1

It must be 1% but if more we do not reject the tablets as this test is non-official. Perform this test using 20 tablets that were used first in the weight variation test

II- Official Tests:

Disintegration: It is the time required for the tablet to break into particles, the disintegration test is a measure only of the time required under a given set of conditions for a group of tablets to disintegrate into particles. In the present disintegration test the particles are those that will pass through a 10-mesh screen. Complete disintegration occurs when no residue of the tablet still present on the screen except the insoluble ingredients as the shell or the coat of the tablet. .Explain the disintegration device Liquids used in disintegration: Water, simulated gastric fluid (PH = 1.2 Hcl), or Simulated intestinal fluid (PH = 7.5, KH2PO4 (phosphate buffer) + pencreatin enzyme +NaoH) Limits: Uncoated tablets: According to U.S.P According to B.P. Medium Simulated gastric fluid Water Temperature 37oC 37oC Time limit Not exceed 30\ Not exceed 15\

PHT 463

Lubna Ashry

U.S.P: 1. Start the disintegration test on 6 tablets. 2. If one or two tablets from the 6 tablets fail disintegrate completely within 30\ repeat the same test on another 12 tablet. (i.e. the whole test will consume 18 tablets). 3. Not less then 16 tablets disintegrate completely within the time if more then two tablets (from the 18) fail to disintegrate, the patch must be rejected. Coated tablets: To be given as a homework to the students. 1. To remove or dissolve the coat, immerse the tablet in distilled water for 5\. 2. Put the tablet in the apparatus in water or HCL for 30\ at 37oC (according to the U.S.P). If not disintegrated, put in intestinal fluid. 3. To calculate the disintegration time: 5\ (in water) +30\ (in simulated gastric fluid) + distinct time in monograph4 + 30\. If one or two tablets fail to disintegrate, repeat on 12 tablets. So 16 tablets from the 18 must completely disintegrate within the time if two or more not disintegrated the patch is rejected. Enteric-coated tablets: To be given as a homework to the students. According to the U.S.P: 1. Put in distilled water for five minutes to dissolve the coat. 2. Then put in simulated gastric fluid (0.1M HCL) for one hour. 3. Then put in simulated intestinal fluid for two hours. If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. So 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate the patch must be rejected.

Sometimes the time is specified for each substance individually in the pharmacopoeia.

PHT 463

Lubna Ashry

According to B.P. 1. Put in distilled water for five minutes to dissolve the coat. 2. Put in simulated gastric fluid for two hours (emptying time). 3. Put in phosphate buffer (PH 6.8) for one hour. 4. If one or two tablets fail to disintegrate repeat on 12 tablets. So 16 tablets should disintegrate. If more than two tables fail to disintegrate reject the patch. N.B. -A plastic disc could be placed over the tablet. This disk has a V shape mark where it must be pointing up word as the liquid pass more easily. -For enteric-coated tablets, the disc is put over the tablet when placed in simulated intestinal fluid. Explain the disintegration device for students. The test is performed on 6 then 12 tablets .((18 tablets total

Other Different Forms: Not to be given to the students. For buccal tablets as for uncoated tablets, but omit the use of disc. Disintegration time is four hours. Sublingual and hard gelatin are as for uncoated tablets but omit the disc. Chewing, effervescent, sustained release tablets: as part disintegrate in stomach then in duodenum then in the intestine. Hypoderm tablets, soft caps. Use 18 tablets in this test.

PHT 463

Lubna Ashry

Weight Variation (uniformity of weight): 1. Weigh 20 tablet selected at random, each one individually. X1, X2, X3 Xz 2. Determine the average weight. X= (X1+X2 +X3++ Xz)/20 Limits according to U.S.P: To be memorized by students. Limit: Upper limit = average weight + (average weight * %error) Lower limit = average weight - (average weight * %error) The individual weights are compared with the upper and lower limits. Not more than two of the tablets differ from the average weight by more than the % error listed, and no tablet differs by more than double that percentage. In general, first we calculate double % error and if one tablet is out of the range, we calculate the % error, if more than two tablets are out of the range, we reject the patch. This test is done on 20 tablets that will later be used in the friability test. Weight of tablet 130 mg or less %error = 10% Weight of tablet 130-324 mg %error = 7.5% Weight of tablet 324 mg or more %error = 5%

PHT 463

Lubna Ashry

Suppositories Evaluation I. Uniformity of weight (weight Variation) (B.P. 1980): 1. 2. 3. 4.

Weigh 20 suppositories individually. w1, w2, w3.w20 Weigh all the suppositories together = W. Calculate the average weight = W/20. Limit: not more than 2 suppositories differ from the average weight by more than 5%, and no suppository differs from the average weight by more than 10%. Upper limit = average weight + Lower limit = average weight 5 * avg.wt. 100 5 * avg.wt. 100

Not more than two of the suppositories differ from the average weight by more than the % error listed. If more than two suppositories are different from the average weight by 5%, calculate double the percent error as follows: Upper limit = average weight + Upper limit = average weight 10 * avg.wt. 100 10 * avg.wt. 100

1.

No suppository differs by more than double that percentage.

II. Hardness of Suppositories (Breaking Test)

1. The suppository is placed in the instrument. 2. Add 600 g; leave it for one min. (use a stop watch). 3. If not broken, add 200 g every one min. until the suppository is broken. Calculations: The hardness of the suppository is calculated by adding the weights together. But if the suppository is broken before the end of the last min. the last weight is canceled.

PHT 463

Lubna Ashry

Results: Using polyethylene suppositories H = 1.7 kg. Using Indocid suppositories _ H = 4 kg. Using Glycerin suppositories H = 1.4 kg.

III. Melting Range Test:

This test is also called the Macromelting range test and is a measure of the time it takes for the entire suppository to melt when immersed in a constant-temperature (37oC) water bath. The apparatus commonly used for measuring the melting range of the entire suppository is the USP Tablet Disintegration Apparatus. Procedure: The suppository is completely immersed in the constant temperature water bath, and the time for the entire suppository to melt or disperse in the surrounding water is measured. The suppository is considered disintegrated when: 2. It is completely dissolved or 3. Dispersed into its component part. 4. Become soft change in shape with formation of core which is not resistant to pressure with glass rod.

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PHT 463

Lubna Ashry

General notes on concentration calculations:

To calculate the concentration of a drug in a solution one of the following methods could be used: Method #1: Mwt 10

= E11 *

(1)

Where = molecular extinction coefficient or molecular absorbitivity coefficient. E11 = A1% = the absorbance of a solution having a concentration of 1% w/v.

E = CL

or

A= absorbance = CL

(2)

Where C = concentration (mole/liter). L = 1 cm path length.

Method #2: Concentration = Absorbance Number of incremints * dilution factor * A1% 100

And this is the way we are using in some of the assay labs.

Method # 3: The standard calibration curve method. The construction of a curve or straight line by plotting observed or experimental data on a graph is an important method of visualizing relationships between variables. Fitting a curve to the points on a graph implies that there is some sort of relationship between the variables x and y. Moreover, the relationship is not confined to isolated points but is a continuous function of x and y. In many cases a hypothesis is made concerning the relationship between the variables x and y. Then an empirical equation is formed that best describes the hypothesis. This empirical equation must satisfactorily fit the experimental or observed data. 11

PHT 463

Lubna Ashry

Physiologic variables are not always linearly related. However, it may be possible to arrange or transform the data to express the relationship between the variables as a straight line. Straight lines are very useful for accurately predicting values for which there are no experimental observations. The general equation of a straight line is: y = a + bx Where a = y intercept. b = slope. y = dependent variable. x = independent variable. Straight line equation could be obtained by the ruler method, the least-squares method, calculator, excel etc. The linear regression calculation using the least-squares method is used for calculation of a straight line through a given set of points. Using the least-squares method we can calculate the slope and the intercept by using the following equations, where n = number of data points: b=

( x) ( y ) n ( xy)
[( x)] - n (x )

a=

( x) ( xy) n ( x ) ( y)
[( x )] - n (x )

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PHT 463 Standard Calibration Curve of Aspirin

Always use volumetric flasks

Lubna Ashry

1. Grind a small amount of aspirin powder into very fine powder. 2. Stock solution #1: 50 mg aspirin powder in 50 ml acetate buffer pH 4.5 (1mg/ml). 3. Solution # 2: Take 10 ml (10mg) of solution #1 and complete to 100 ml with acetate buffer (0.1mg/ml). 4. Solution # 3: Take 10 ml (1mg) of solution # 2 and complete to 100 with acetate buffer. Read the absorbance at max = 265nm for aspirin. 5. Make other dilutions from solution # 2 to get the best fit line and determine the equation the best describes it: 5ml (0.5mg) in 100ml acetate buffer. 15ml (1.5mg) in 100ml acetate buffer. 20ml (2mg) in 100ml acetate buffer. 25ml (2.5) in 100ml acetate buffer.

6. Read the absorbance of all dilutions at 265nm. 7. Plot absorbance VS concentration (mg/100ml) which is the standard calibration curve, and then estimate the slope of the line B and the y intercept A using both the ruler and the calculator.

Results: Concentration X (mg/100ml) 0.5 1 1.5 2 2.5 y 2 y1 . x 2 x1 Absorbance Y 0.025 0.027 0.050 0.075 0.091

Slope=B = Y=A+BX

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PHT 463

Lubna Ashry

Dissolution of Aspirin Tablets USP

Conditions: Apparatus: Media: Speed: Procedure: 1. Put one tablet into each basket and start the apparatus at the above conditions. 2. Withdraw 5 ml sample with the pipet (using polyethylene tube to filter the sample) at different time intervals (5, 10, 15, 20, 30, 45, and 60 min.). 3. Dilute one ml of the samples in a test tube with 9 ml acetate buffer i.e dilution factor = 10. 4. Replace the withdrawn amount with 5 ml fresh acetate buffer. 5. Read the absorbance of the diluted samples at 265 nm, against acetate buffer as blank. 6. Tabulate your results as follows:
Time (min) Abs Dilution factor (df) Concentration
From the straight line equation last lab or =

Apparatus I Basket 500 ml acetate buffer pH 4.5 50 rpm

Temperature: 37oC 0.5

% released =
Amount released dose * 100

abs E1%

* dissolution vol. * df

5 10 15 20 30 45 60

7. Plot the % released VS time. From the curve determine the time required for 80% of the dose to be released. Limit: The tablets should release 80% of its contents within 30 minutes. Where E1% = 0.036.

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PHT 463

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Assay of Indomethacin Suppository (B.P)

1. 2.

Take 10 suppositories and weigh = W. Cut the suppositories into small pieces then take a mass equivalent to 100 mg Indomethacin: 10 suppositories * 100 mg per one W (known) 100 mg Indomethacin X

3. 4. 5.

Put in a V.F. 50 ml, complete to volume with Methanol and shake for complete dispersion. If the suppository is not dispersed use a water bath at around 50o C Filter if necessary to get rid of the base, but reject the first portion of filtrate. Take 2 ml filtrate, add a sufficient of mixture of equal volumes of methanol and phosphate buffer pH 7.2 (e.g. 60 ml methanol + 60 ml phosphate buffer) to produce 100 cc (in V.F. 100 ml) mix.

6.

Measure the absorbance at 318 nm, knowing that E% = 0.193 (against blank mixture of equal volume of phosphate buffer + methanol).

Limit = 90 110 % of the prescribed amount (B.P.). Calculations: Concentration = Abs 100 * E % 100

100 mg Indomethacin 50 ml methanol X X = 4mg % of drug = Results: Abs. = 0.701 Actual conc. * 100 theoretical (4) 2 ml taken

Conc. =

0.701 100 * =3.63mg/100ml 0.193 100

% of drug =

3.63 * 100 = 90.8% 4

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PHT 463

Lubna Ashry

Assay of Indomethacin Capsules

Procedure: Limit: 90-110 % of the labeled amount. To a quantity of the mixed contents of 20 capsules equivalent to 50 mg of Indomethacin, add 10 ml of water in a vol. flask 100ml. Stand for 10 minutes, swirling occasionally. Add 75 ml of methanol shake well and add sufficient methanol to produce 100 ml and filter if necessary. To 5 ml of the filtrate, add sufficient of a mixture of equal volumes of methanol and phosphate buffer (pH 7.2) to produce 100 ml in a vol. flask. Measure the absorbance of the resulting solution at max = 318 nm. Calculate the content of Indomethacin, taking 0.193 as the value of E1%.

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PHT 463 Calculations: Weight of 20 capsules = W1 Weight of empty shells = W2 Weight of contents = W1-W2=W3 Amount of drug = 20 capsule* 25 mg each W3 50 mg Abs. = 0.452 X

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Concentration =

Abs. * volume of last flask 0.452 100 = * = 2.34 mg% E1% * 100 0.193 100

Theoretical amount of Indomethacin: 50 X 100ml 5 ml

X = 2.5 mg% because we completed the volume to 100 Concentration *100 Amount..of ..Indomethacin

% of drug =

2.34 * 100 = 93.6 % 2.5

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PHT 463

Lubna Ashry

Assay of Chloramphenicol Ointment 1%

BP 1980 (P.572 Vol. II)

Procedure:
1. Weigh an amount of ointment containing 10 mg chloramphenicol. We are provided with 4g ointment each contains 10 mg of chloramphenicol, so weigh 1 g of the ointment. (1%: 1g 1000mg100g so 10mgx). try to weigh it on a small piece of wax paper. 2. Put in a separating funnel together with the wax paper to remove all the quantity of the ointment then add 50 ml petroleum ether, shake for complete dispersion. 3. Extract with successive quantities of 50, 50, 50 and 30 ml of warm watershake. 4. Collect the extract water layer each time in a 200 ml volumetric flask and adjust to volume with distilled water mix well. 5. Filter through filter paper discard the first portion 10-20 ml. 6. Take 10 ml of the filtrate with pipette in a 50 ml volumetric flask and adjust to volume with distilled water shake. 7. Measure the absorbance at max = 278 nm and A1%=0.297. Limit 95-105%. Calculations: % of drug = Concentration * 100 Amount 0f drug Abs. * volume of last flask E1% * 100

Concentration =

Theoretical amount of drug = 10 mg 200 ml X 10 ml X= 0.5 mg

Result: Absorbance = 0.225

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PHT 463

Lubna Ashry

Assay of Aspirin Tablets

(B.P. 1988) C9H8O4

:Procedure
Aspirin + NaoH Hydrolysis Sodium acetate + Salicylic acid + excess NaoH
back titrated with Hcl

.Weigh and powder 20 tablets .1 Take a quantity of the powder containing 0.5 g aspirin .2 tablets * 0.3 g aspirin W 20 g aspirin X 0.5 Place in a conical flask .3 (Add 30 ml 0.5 M NaOH (using a burette .4 .Boil gently for 10 minutes. Cover the flask to prevent evaporation. Cool .5 .Titrate the excess of alkali with 0.5 M HCl using Phenol Red indicator .6 End point: Red (violet in alkaline medium)yellow (in acidic medium). (Repeat the same procedure without the substance being examined (blank .7 i.e. Boil 30 ml NaOH for 10min. Cool Titrate with HCl. The difference between the two titrations represents the amount of sodium hydroxide .8 .consumed to change Aspirin to sodium acetate and salicylic acid F = each ml of NaOH 0.04504 g of aspirin * :Limit Content of Aspirin: 95-105% of the prescribed (labeled) amount.

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Calculations:
%of the drug = (blank exp eriment ) * F * f * 100 starting weight

Where F= equivalent factor f = standardization factor of titrant (HcL) and it is usually written on the titrant bottle, if it was not there, use f =1. (B E) * F * f * 100 0.5

Results for Aspirin-Bayer: (27.7 16.7) * 0.04504 * 1 * 100 0.5

%of aspirin

Results for Aspirin tablets compressed by direct compression before the lab: (24 15) * 0.04504 * 1 *100 0.5

%of aspirin =

= 81.072%

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Lubna Ashry

Assay of Phenoxy Methyl Penicillin

(B.P.) 1. Weigh 20 tablets = W (each containing 0.3 g Phenoxy Methyl Penicillin). 2. Powder and take an amount equivalent to 0.1g Phenoxy Methyl Penicillin. 20 tablet * 0.3 g each W 0.1 g X

3. 4.

Put in a 100 ml volumetric flask, add 80 ml (by measure) distilled water, shake for 5 minutes then adjust volume to 100 ml with distilled water, filter. Experiment: Take 10 ml filtrate (in stoppered conical flask) + 5 ml 1N NaOH (by pipet) and stand for 20 min. to confirm that all phenoxy methyl penicillin is hydrolyzed by NaOH.

5.

Add 20 ml acetate buffer + 5 ml 1 M HCl ( to stop the reaction between NaOH and the drug) + 25 ml 0.01 M I2 and stand for another 20 min. and protect from light.

6.

Titrate with 0.02 M sodium thiosulfate Na2S2O3 using starch as indicator Note: Titrate until I2 becomes light brown; add 3 drops of starch indicator after shaking it well. The color of the solution will become blue; titrate until the solution become colorless. (End point = straw yellow colorless).

7.

Blank: In another stoppered flask put 10 ml filtrate + 20 ml acetate buffer + 25 ml 0.01M I2, stand for 20 min. in a dark place. (The exact procedure as the experiment but without the addition of NaOH and HCl). Titrate using 0.02 M Na2S2O3 using starch as indicator.

F= each ml of 0.01M I2 = 0.875mg phenoxy .methyl penicillin. Limit = 92.5- 107.5% Calculations:
% of drug =

(blank exp eriment ) * F * f * 100 sample volume

Where: F= equivalent factor f = standardization factor of titrant Na2S2O3.

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PHT 463 Volume of the sample = 10 ml Results: Blank = 26.3 Experiment = 13.7

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===================================goooooo d
Assay of Chloramphenicol 0.5% Ophthalmic Solution B.P.
Limit: According to the B.P. content of chloramphenicol should be 90- 110 % of the prescribed or stated amount. Calculations: 500 mg 25 mg X= 100 X 100 * 25 = 5 ml 500 Absorbance * (volume of last flask/100) E1% 0.316 * 100 = 1.215 0.297 * 100 Absorbance X 100 100 (last dilution) Dilute a volume containing 25 mg of chloramphenicol to 250 ml with water. Dilute 10 ml of the mixture to 100 ml with water. Measure the absorbance of the resulting solution at the maximum at 278 nm. Calculate the content of chloramphenicol taking 297 as the value of A (1%, 1cm) at the maximum at 278 nm.

Concentration = =

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PHT 463 Concentration * 100 Amount..of ..drug 1.215 * 100 = 121.5% 1

Lubna Ashry

% of drug = =

Amount of drug: 25 mg 250 X mg 10 ml X = (25*10)/250 = 1 mg

Assay of Aminophylline Injection (B.P.) The trade name for aminophylline injection that we are using is Euphyllin (0.24g) where 1 ampoule of 10 ml injection contains: Theophylline monohydrate 0.1932 g Ethylenediamine 0.0468 g This drug is used in acute and severe dyspnea due to airway obstruction e.g. bronchial asthma. To calculate the content of Theophylline (0.1932 g): 1. Take a volume of injection equivalent to 80 mg (0.08g) of Euphyllin. 0.24 g 0.08 g 10 ml ampoule x ml

x = 3.33 ml taken by a syringe 2. Put in a 200 ml volumetric flask and complete to volume with 0.01M NaoH and mix. 3. Take 5 ml of this mixture using a pipet and put in a 250 ml volumetric flask, and complete to volume with 0.01M NaoH. 4. Measure absorbance at 275 nm where E1% = 650.

Calculations:

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PHT 463 Euphyllin 0.24 g 0.08 g x = 3.33 ml 10 ml from the package. x ml

Lubna Ashry

To calculate the actual amount of Theophylline we can use one of the two following ways: 1. We took 80 mg Euphyllin X mg Euphyllin
in in

200 ml 5 ml that was withdrawn.

X = 2 mg = 0.002 g Euphyllin 0.24 g Euphyllin 0.002 g Euphyllin 0.1932 g Theophylline W

W = 1.61 * 10 3 g Theophylline present in 5 ml. 2. The second way of calculating the actual amount of Theophylline is: 0.24 g Euphyllin 0.08 g Euphyllin x = 0.0644 g Theophylline 0.0644 g Theophylline x g Theophylline 200 ml solution 5 ml withdrawn 0.1932 g Theophylline x g Theophylline

x = 1.61 * 10 3 g of Theophylline

Then we calculate the concentration of the drug: Concentration = * 250 Absorbance * 250 0.291 = = 1.1 * 10 3 g / 250 ml E1% * 100 650 * 100

% of drug =

Concentration *100 Amount..of ..Theophylline

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= (1.1* 10 3 * 100) / (1.61*10-3) = 68.32 %, which is very low either because of expiration or because the drug was not protected from light while stored. Limit: According to the B.P. the content of anhydrous Theophylline 73.25 - 88.25% of the prescribed or stated amount of Aminophylline. To calculate the content of Ethylenediamine: 1. Take a volume of injection equivalent to 0.5 g Euphyllin 0.24 g 0.5 g with a pipette or a syringe}. 2. Add sufficient amount of distilled water to produce 20 ml we may not need that because the volume is more than 20 ml. 3. Add 2 drops of Bromocresol green indicator and titrate using 0.05 M sulfuric acid H2SO4, where the end point is when the blue green. 10 ml from the package x ml

x = 20.8 ml {we take two whole ampoules 20 ml and the rest 0.8 ml is taken

Calculations: 0.24 g Euphyllin 0.5 g Euphyllin X = 20.8 ml Each ml of 0.05 M H2SO4 is equivalent to 0.003 g Ethylenediamine. Concentration = E.P. * F * f Where E.P. is the end point F = equivalence factor = 0.003. And f = standardization factor 25 10 ml ampoule X ml

PHT 463 So the concentration = 31.5 ml * 0.003 * 0.95 = 0.0897 g 0.24 g Euphyllin o.5 g 0.0468 g Ethylenediamine xg x = 0.0975 g of Ethylenediamine Note: % of drug = concentration*100/x 0.0897 * 100 / 0.0975 = 92 %

Lubna Ashry

The total amount of Ethylenediamine (C2H8N2) should not exceed 0.295 g for each g of anhydrous Theophylline (C7H8N4O2) present.

Leakers Test: This test is made to detect the incompletely sealed ampoules. Procedure: Put the ampoule in a beaker and add any dye such as methylene blue (we make a ve pressure to make the dye inter the ampoule if there is any cavity in it) wash and see if there is any color inside.

Powdered Glass Test

Rinse 6 or more containers with purified water then dry them with clean air. Crush the containers into fragments about 25mm in size. Take 100 g of the coarsely crushed glass and divide them into three approximately equal portions. Place one of the portions in the special mortar. Crush the glass further using a hammer while the pestle is still in place. Nest the sieves and empty the mortar into No. 20 sieve. Repeat the operation on each of the two remaining portions of glass.

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Shake the sieves for a short time then remove the glass from the Nos. 20 and 40 sieves. Repeat again this crushing and sieving operation. Empty the receiving pans. Reassemble the nest of sieves, and shake on a mechanical sieve shaker for 5 minutes. Transfer the portion retained on the No. 50, which should weigh in excess of 10 g, to a closed container, and store in a desiccator until used for the test. Spread the specimen on a piece of glazed paper, and pass a magnet through it to remove particles of iron that may be introduced during the crushing. Transfer the specimen to a 250-ml conical flask of resistant glass. Wash it with six 30-ml portions of acetone, swirlinhg each time for about 30 seconds and carefully decanting the acetone. After washing, the specimen should be free from agglomerations of glass powder. Dry the flask and contents for 20 minutes at 140oC. Transfer to a weighing bottle, and cool in a desiccator. Use the test specimen within 48 hours, after drying. transfer 10.00 g of the prepared specimen, accurately weighed, to a 250-ml conical flask that has been aged previously with High-purity water in a bath at 90oC for at least 24 hours or at 121oC for 1 hour.

Procedure:

Add 50 ml of High-purity water to this flask and to one similarly prepared to provide a blank. Cap all flasks with borosilicate glass beaker that previously have been treated as described for the flask and that are of such size that the bottoms of the beaker fit snugly down on the top rims of the containers.

Place the containers in the autoclave, and close it securely, leaving the vent cock open. Heat until steam issues vigorously from the vent cock, and continue heating for 10 minutes.

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PHT 463 Close the vent cock and adjust the temperature to 121oC. Hold the temperature at 121 2oC for 30 minutes.

Lubna Ashry

Reduce the heat so that the autoclave cools and comes to atmospheric pressure in 38 to 46 minutes being vented as necessary to prevent the formation of a vacuum. Cool the flask at once in running water. Decant the water from the flask into a suitably cleansed vessel. Wash the residual powdered glass with four 15-ml portions of High-purity Water, adding the decanted washings to the main portion. Add 5 drops of Methyl Red Solution. Triturate immediately with 0.020 N sulfuric acid. Record the volume of 0.020 N sulfuric acid used to neutralize the extract from 10 g

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