PHT 261

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King Saud University
College of Pharmacy Department of Pharmaceutics

FLOW PROPERTIES OF POWDERS The flow property of a material results from many forces that can act between the solid particles, such as: the frictional forces, surface tension forces, mechanical forces caused by interlocking of particles of irregular shapes, and cohesive or Vander Waals forces. Importance: 1. The ability of powder to flow is one of the important factors involved in mixing different materials to form a powder blend. Mixing is an important pharmaceutical operation involved in the preparation of many dosage forms, including tablets and capsules, and in the studying of dusting powders. 2. The internal flow and granule demixing (the tendency of the powder to separate into layers of different sizes), during flow through the hopper contribute to a decrease in tablet weight during the latter portion of the compression period. 3. The flow rate of a tablet granulation increase with an increase in the quantity of fines added to the granulation. Also, an increase in the lubricant added will raise the flow rate. Factors affecting the flow properties of powders:  Particle size: smaller particles have bad flow because the cohesive forces between the particles are of the same magnitude as gravitational force. So, as particle size increases, the flow is facilitated (improved).

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Shape of the particles: flat or elongated particles tend to Porosity and density: particles with a high density and Texture: surface roughness can lead to poor flow

pack. So, round shape particles are better.  low internal porosity tend to possess free-flowing properties.  properties due to friction and cohesiveness.
 To improve flow characteristics of powders, materials termed

GLIDANTS are frequently added to granular powders.
 Glidant: is a material that improves the flow properties of granulations by

reducing the interparticulate friction and eliminating the problems associated with the flow of materials.
 Examples of commonly used glidants include: magnesium stearate (0.2-

2%), starch (2-5%), and talc (0.3-1%).
 Two of the most common methods to determine the flow properties of

powders are: 1. 2. angle of repose method, and Hopper flow rate measurements.

DTERMINATION OF ANGLE OF REPOSE OF POWDERS (sodium chloride, lactose, and lactose +2 % talc) Angle of repose: is the maximum angle between the surface of a pile of powder and the horizontal plane. tan θ = h / r (h: the height, r: the radius) then, θ = tan -1 h / r As θ decreases, the flow property increased.

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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 heap just touch the lower tip of the funnel. 2. Mark the base of heap. 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 heap (the distance between the horizontal surface and the lower tip of the funnel) is called (h).
6. Tan the angle of repose θ (tan θ = h / r), get θ (θ = tan -1 h / r), and

tabulate your results. 7. Comment on the results. Results: Tabulate the results as shown in the table: powder Sodium chloride (crystalline) Lactose Lactose + 2 % talc Height (h) Radius (r) Angle of repose (Θ)

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Comment on the results PARTICLE SIZE ANALYSIS  Clinically, the particle size of a drug can affect its release from dosage forms that are administered orally, parenterally, rectally, and topically.
 The successful formulation of suspensions, emulsions, and tablets also

depends on the particle size achieved in the product.  In the area of tablets and capsules manufacture, control of the particle size is essential in: Achieving the necessary flow properties, and proper mixing of granules and powders. Methods of particle size analysis: Sieving method: This method is the simplest and most widely used method of determining particle size and size distribution. Results are obtained on weight basis. This method utilizes a series of standard sieves calibrated by the National Bureau of Standards. According to the method of USP, a definite mass of the sample is placed on the proper sieve in a mechanical shaker. The powder is shaken for a definite period of time, and the material that passes through one sieve and is retained on the next finer sieve is collected and weighed. Optical microscopy method: Sedimentation method: Methods of data presentation: 1. Tables: 2. Graphs: Histograms: A histogram is a plot of the frequency of occurrence as a function of the size range. The ordinate, frequency, can represent the weight, surface area, or any other weighing process, in the specific size interval. Size frequency curve:

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This is a smooth curve drawn through the mid points of the bars of a histogram. Cumulative plots: Cumulative plots can be described as those which involve plotting the percent of particles greater than (or less than) a given particle size against the particle size. Thus, the limiting values of the ordinate vary from 0 to 100%. The ordinate can represent different weighing processes. DETERMINATION OF PARTICLE SIZE BY SIEVING METHOD Procedure: 1. Weigh accurately 100 g of the supplied powder, then place on the top sieve of the stack of sieves, cover and shake (mechanically) for 15 minutes. 2. Weigh the remaining powder on each sieve. 3. Tabulate your results. 4. Plot the required curves (histogram, normal distribution curve, and cumulative curves). Table of results: Sieve diameter (particle size), mm Weight retained on the sieve (g)

Mean particle size (mm)

%weight retained (frequency)

Cumulative % Under-size Over-size

Σ=
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Graphs: Using graph papers, plot the following: Histogram. (frequency vs. the particle size range) Size distribution curve. (frequency vs. the mean particle size) Cumulative curves. (% cumulative vs. the mean particle size)

Problem: Particle size analysis by sieving method A sample of granules having different particle size was analyzed utilizing a series of standard sieves placed in a mechanical shaker. The sample is shaken for a definite period of time, and the material that passes through one sieve and retained on the next finer sieve was collected and weighed. The following data were obtained: Particle size range 1.25-1.00 mm 1.00mm-800μm 800-710μm 710-600 μm 600-500 μm 500-400 μm 400-315 μm 315-250 μm 250-125 μm Weight retained on the finer sieve (g) 10.35 14.50 23.71 32.62 45.61 30.21 21.62 13.92 7.40

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EFFERVESCENT GRANULES
 The effervescent granules are preparations for oral administration of salty

bitter drugs. Also, they form a pleasant method for the administration of saline substances.  The effervescent granules are composed of: sodium bicarbonate, citric acid, tartaric acid, and sometimes sugar (to overcome the nauseous taste) in addition to the medicament and the granulating agent (ethanol 96%).  They are taken by dissolving the directed quantity in water and drinking whilst in state of effervescence.  The amounts of acids (citric acid and tartaric acid) are used in slight excess over the neutralization of sodium bicarbonate, so the final solution becomes slightly acidic for more pleasant taste.  The equation of the reaction: CH2COOH 3 NaHCO3 + HO-C-COOH . H2O COONa CH2COOH a. b. c. d. It masks the bitter and nauseous taste. It promotes gastric secretions. It acts as a carminative. It has psychological impression at the patient. Solid medicaments must be dried at 100-105 oC for constant CH2COONa  The liberated carbon dioxide has the following advantages: CH2COONa 4 H2O +3 CO2 + HO-C-

 For the medicament:
a.

weight to liberate any water of crystallization which can interfere with the partial interaction, giving rise to dead granules. b. liquid medicaments, as extracts, require special treatment:  Aqueous extracts (e.g., liquid extract of liquorice) must be concentrated to a soft mass.

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 Alcoholic extracts (e.g., tincture of belladonna) are used as the granulating agent, and alcohol 96% is then added if the amount of the extract is not enough for granulation. c. Some drugs like iron ammonium citrate and potassium iodide need special treatments (e.g., the use of a glass mortar).  Methods of the preparation of the granules: 1. Wet method:  This method is used in hot countries due to the ability of liberation of water of crystallization from citric acid.  Suitable for heat sensitive materials.  Alcohol is used as the granulating agent (its water content enhances the interaction between alkali and the acids).  Steps: All powders are dried to a constant weight at a temp. 100-105 oC. Pulverize each powder separately. Pass the pulverized powder through sieve No. 90, and weigh the calculated amount from each powder separately. Mix the powder together and by the aid of alcohol 96% (drop adding) make the mass coherent between your fingers and the mixing is continued until the mass retains its shape when molded into a ball. The mass is forced through sieve No. 10, then dry in oven at temp. not exceeding 50 oC. After drying, the granules are sieved through sieved No. 20 to leave the fine particles, and then packed in well closed wide mouth bottles. 2. Dry method (fusion method): This is based on the release of water of crystallization from citric acid by the aid of heat using a boiling water bath. Steps: Finely powder all of the ingredients and pass each, separately, through sieve 90.

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Mix the powders homogenously in a porcelain dish and raise over a boiling water bath. The mixture of the powders is continuously triturated, while on water bath. When the mass adjacent to heat seems doughy, turn over so as to allow for the release of all water of crystallization of citric acid. The point, at which the mass seems doughy, is considered critical. At such time, the dish is removed from heat and the dough is quickly forced through sieve No. 10. The collected granules are dried in a hot air oven at 40 oC. The dried granules are shaked gently over a sieve (No. 20) and the nonpassed granules are collected for packing.  Packaging and storage of the effervescent granules: a. The granules should be packed in wide mouth bottles (to permit the entering of the teaspoon). b. Bottles are covered with wax or paraffin film to prevent the absorption of moisture from the atmosphere. c. Store in cool, dry place.

Practical example # 1: Prepare 25 g of sodium sulfate effervescent granules containing 5% liquid extract of hyoscyamus : Rx Sodium sulfate Tartaric acid Citric acid Sig. : MDS. 500 g 240 g 210 g Sodium bicarbonate 500 g *F

N.B., sodium sulfate loses 50% of its weight on drying.

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Calculations:
1. Add 20% excess to the required amount to compensate for the

mechanical loss (loss arised from handling the materials and during the preparation) and the chemical loss (arised from liberation of CO2 & H2O, the chemical loss is nearly equals to 1/7 of the formula). So, the total weight = 2. Weight of sod. Sulfate = 3. Amount of hyosyamus extract = 4. amount of base =
5. F = base = totalRx

Procedure: 1. Weigh the required amount of each ingredient. 2. Powder each ingredient alone (in mortar with pestle) to a very fine powder. 3. Mix the powders geometrically in a mortar using the pestle.
4. Add hyoscyamus extract and triturate with the pestle to form the wet mass

which can be pressed against the sieve. (If the amount of the extract is not enough to form the paste, add alcohol 96% (drop adding), gradually, to make a wet mass that retains its shape on handling). 5. Screen the wet mass formed on mesh-12 sieve to get the granules.
6. Leave the granules to dry, (open air drying if the humidity is low), or dry

in an oven at a temp. not exceeding 50oC. 7. Pack the granules in a well – closed, wide mouth bottle. Fix a white label. Label: White

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Use: Sodium sulfate is used as a saline laxative to prompt watery evacuation of the bowel (in the treatment of constipation). While, hyoscyamus extract is an antispasmodic.

Practical example # 2: Prepare 25 g of sodium phosphate effervescent granules containing 5% iron ammonium citrate : Rx sodium phosphate Tartaric acid Citric acid Sig. : MDS. Calculations:
1. Add 20% excess to the required amount to compensate for the

*F 500 g 240 g 210 g

Sodium bicarbonate 500 g

N.B., sodium phosphate loses 60% of its weight on drying.

mechanical loss (loss arises from handling the materials and during the preparation) and the chemical loss (arises from liberation of CO2 & H2O, the chemical loss is nearly equals to 1/7 of the formula). So, the total weight = 2. Weight of sod. Phosphate = 3. Amount of iron ammonium citrate = 4. amount of base =
5. F = base = totalRx

Procedure: 1. Weigh the required amount of each ingredient.

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2. Powder each ingredient alone (in mortar with pestle) to a very fine powder. 3. Powder iron ammonium citrate (in a glass mortar with pestle) to a very fine powder. 4. Mix the powders geometrically in a mortar using the pestle.
5. Add alcohol 96% (drop adding), gradually, to make a wet mass that

retains its shape on handling. 6. Screen the wet mass formed on mesh-12 sieve to get the granules.
7. Leave the granules to dry, (open air drying if the humidity is low), or dry

in an oven at a temp. not exceeding 50oC. 8. Pack the granules in a well – closed, wide mouth bottle. Fix a white label. Label: White

Use: Sodium phosphate is used as a saline laxative, while iron ammonium citrate is used in the treatment of iron deficiency anemia.

EVALUATION OF CAPSULE DOSAGE FORMS (B.P) 1. disintegration test:

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 The disintegration test determines whether tablets or capsules disintegrate within a prescribed time when placed in an aqueous medium under the prescribed experimental conditions.  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, if a disc has been used.  Method: 1. Introduce one capsule into each tube and suspend the apparatus in the beaker containing water. 2. If the hard capsule floats on the top of water, the disc may be added. 3. Operate the apparatus. Record the time. Remove the assembly from the liquid. The capsules pass the test if no residue remains on the screen of the apparatus. 4. The capsules should disintegrate within 30 minutes, unless otherwise justified. 2. uniformity of weight:  This test is to be done on 20 capsules.  Method: 1. Weigh an intact capsule. 2. Open the capsule without losing any part of the shell and remove the contents as completely as possible. Weigh the shell. 3. The weight of the contents is the difference between the two weightings. 4. Repeat the procedure for further 19 capsules selected at random. 5. Determine the average weight. 6. Compare the average weight to the table below, to determine the % deviation permitted. 7. Calculate the upper and lower limits at the % deviation stated, and at double that percentage.
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8. Compare the individual weights of the capsule contents to the upper and lower limits calculated at the % deviation stated, and at double that %. 9. Limit: not more than two capsules of the individual weights deviate from the average weight by more than the % deviation listed in the table, and none deviates by more than twice that %. Table: Average weight of capsule content (mg) Less than 300 300 or more % deviation 10 7.5

Results of disintegration test:  Time recorded for the capsules to break into particles and pass to the liquid medium = ----------------- minutes.  Comment: Results of weight variation test: • Average weight of the contents = (total wt. of the contents / 20) = • % deviation permitted (from the table) = • Upper limit (at % deviation) = av. Wt. + (%/100 x av.wt.) = • Lower limit (at % deviation) = av. Wt. - (%/100 x av.wt.) = • Upper limit (at double % deviation) = av. Wt. + (double%/100 x av.wt.) = • Lower limit (at double % deviation) = av. Wt. - (double%/100 x av.wt.) =

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Caps . No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Wt. Of intact capsule

Wt. Of the empty shell

Wt. Of the content

Comparison Comparison at % deviation at double % deviation

Σ=  comment: SUPPOSITORY DOSAGE FORMS
 Suppositories are defined as solid products of various weights and shapes

intended for introduction into the rectum, vagina or urethra where they melt, dissolve or disperse and exert a local or systemic effect. Characteristics of an ideal suppository base:
1. It should melt, dissolve or disperse at 37 oC.

2. Non- irritant, and non-toxic. 3. Physically stable during manufacture or storage.

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4. Convenient to handle by the patient and does not break or melt on handling. 5. Does not leak from the rectum or vagina. 6. Compatible and chemically stable with drugs. Types of suppository bases: 1. oleaginous bases: Cocoa butter and Cocoa butter substitutes. 2. water – soluble bases: Polyethylene glycol mixture and Glycerinated gelatin 3. water dispersible bases: Polyethylene glycol derivatives, and Cocoa butter substitutes (with surfactants), e.g., Witepsol, Massa estranium, Massupol. Methods of preparation: 1. Hand rolling method: 2. compression method: 3. fusion method:

Lubrication of moulds: 1. 2. Lubrication of the cavities of the mould is helpful to prevent the adhesion of the suppository to the sides of the mould. the lubricant must be: • different in nature from the base otherwise it will become absorbed, and fail to provide a film between the mass and the metal (i.e., it should be immiscible with the base) , and • Compatible with the drugs and any other additives.

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Consequently, an oily lubricant is useless for CB base but used in glycerogelatin base, e.g., liquid paraffin, olive oil and almond oil, and for CB base and other fatty bases we must use an alcoholic lubricant as soap liniment. Containers and special labeling instructions: The prepared suppositories should be wrapped individually in metal foil (or waxed paper, if the medicament interacts with metal). Glass or plastic screw-capped jars are suitable containers for products that are hygroscopic. Commercially prepared suppositories are supplied in strips of sealed semi-rigid moulds prepared from polyvinyl alcohol. Special labels: Store in a cool place. For rectal use only. For vaginal use only. Calibration of the mould: Calibration of the mould is carried out to determine the exact capacity of the mould by using cocoa butter. Procedure: Make sure that the two halves of the suppository mould given are having the same number. Lubricate the mould with soap lubricant by means of a cotton piece; invert the mould on a porcelain slab to allow the excess of lubricating solution to drain. Weigh an amount of CB (5 g if you are supplied with a mould of one gram and 10 g if you are supplied with a mould of 2 g capacity) to prepare 3 suppositories (there is a slight excess for mechanical loss) and melt it in a porcelain dish by exposing the crucible for few seconds to steam of a water bath, remove the crucible away from steam and triturate with a

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glass rod, repeat until a uniform cream, which is easily poured, is formed. Pour gradually into a continuous stream the melted CB into the lubricated mould and allow the melted mass to over-fill to avoid the formation of holes after cooling (due to contraction of the mass). Cool the filled mass for about 10 minutes, and after cooling remove the excess CB by a sharp knife. Weigh accurately certain number of suppositories and then calculate the average weight. Calculate the correction factor (F): Average weight of one suppository Correction factor = ------------------------------------------------------------Nominal capacity of the mould (written on the mould).

Example: calculate the correction factor for a mould of 2 g capacity in which 5 suppositories weighing 10.5 g were prepared.

CALCULATION OF THE DISPLACEMENT VALUE OF SOLID MEDICAMENT IN SUPPOSITORIES (USING COCOA BUTTER)
 Displacement value: ‘is the amount of medicament which displaces one part

of cocoa butter’.

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 If the medicament you are going to incorporate in CB base has a density of

approximately that of CB, the weight of medication may replace an equal weight of the oil. If, however, the medication is heavier, it will replace a proportionally smaller amount of CB. Practical: Determine the displacement value of 10% ZnO in cocoa butter base. Calculations: To prepare 3 plain and medicated suppositories: 1. Plain suppositories: • No. of supp. = • Amount of CB (total weight) = 2. Medicated suppositories: • No. of supp. = • Amount of drug = (10/100) x (total wt.) = Or • • • • Amount of base = [(no. of supp. X mould capacity) – drug] = Or = Procedure: 1. preparation of plain CB suppositories: Lubricate the mould with soap lubricant, invert on a glass slab to drain the excess lubricant. g CB ----------- (in mould 1 g) g CB ---------- (in mould 2 g) = g ZnO ----- (in mould 1g) g ZnO ----- (in mould 2 g) =no. of supp. X mould capacity

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Weigh the required amount of CB, and cut into small pieces by a knife (or use shredded CB). Place in a porcelain dish and expose it carefully to the steam of a water bath until a creamy mass which can be easily poured is produced (use a glass rod instead of the pestle to aid melting and mixing and to avoid loss in weight). Pour (in a continuous stream) the melted mass into the lubricated mould and allow over-filling of the cavities (to avoid formation of holes that could take place due to contraction of the base on cooling). Cool in an ice bath (or in the refrigerator) for 10 min. Remove the excess of the base by means of a knife, take out the supp. From the mould. Weigh the suppositories and calculate the average weight (= a). 2. Preparation of the medicated CB suppositories: a. Use the same mould utilized in the preparation of the plain CB suppositories and prepare it as mentioned before (Lubricate the mould with soap lubricant, invert on a glass slab to drain the excess lubricant).
b.

Weigh the required amount of CB, and cut into small pieces by a knife

(or use shredded CB). Place in a porcelain dish and expose it carefully to the steam of a water bath until a creamy mass which can be easily poured is produced (use a glass rod instead of the pestle to aid melting and mixing and to avoid loss in weight). c. Add the calculated amount of pulverized and sifted medicament (ZnO) to the melted CB, and mix until a uniform and homogenous mixture is produced. d. Pour (in a continuous stream) the homogenous mixture (step # c) into the lubricated mould and allow over-filling of the cavities (to avoid formation of holes that could take place due to contraction of the base on cooling). e. f.
g.

Cool in an ice bath (or in the refrigerator) for 10 min. Remove the excess of the base by means of a knife, take out the supp. Weigh the suppositories and calculate the average weight (= b).

From the mould.

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Procedure for Calculation of the displacement value of 10% ZnO in CB base: The average wt of the plain supp. = a. The average wt of the medicated supp containing 10% of the drug = b. calculate the amount of theobroma oil (CB) in the medicated supp: CB = b x (90/100) = c Medicament = b x (10/100) = d calculate the amount of CB displaced by the medicament = a – c calculate the displacement value (DV) of the medicament: wt. Of medicament Wt. Of CB displaced by the medicament d a–c D.V. = ---------------------------------------------------- = ------------

Results:

OLEAGINOUS SUPPOSITORY BASES COCOA BUTTER BASE Cocoa butter is a natural fat, yellowish-white solid with an odor of chocolate. It is composed of a mixture of glyceryl esters of stearic acid, palmitic acid, oleic acid, and other fatty acids. Advantages of CB as a suppository base: It has a melting point of range of 30 – 36 oC (i.e., solid at room temp. but melts at the body temp.). Non toxic and non irritant. Miscible with many ingredients. Readily melts on warming and rapid setting on cooling.

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Disadvantages of CB: Polymorphism: when CB is melted and cooled, it solidifies in different crystalline forms, depending on the temperature of melting and rate of cooling. If it is melted at not more than 36 oC and slowly cooled, it forms stable beta crystals with normal melting point. However, if it is over-heated and suddenly cooled, it may produce the δ form and the α form is obtained by sudden cooling of the melted CB to 0 oC. Adherence to the sides of the mould, so it needs lubrication of the mould. Rancidity on storage due to oxidation of unsaturated glycerides. Leakage from the body cavities (rectum and vagina),so CB is rarely used as a pessary base. It contracts forming a hole at the top of the suppository, so pouring is made by excess. Expensive. Poor water absorbing ability and this can be improved by the addition of emulsifying agents. When the melting point is reduced by soluble ingredient (e.g., chloral hydrate), additives such as bees wax or spermaceti may be incorporated to counteract the effects of medicaments and/or climates. Practical: Prepare 3 aminophyllin suppositories each having the following formula: Rx Aminophyllin Cocoa butter Fiat: supp. Sig.: MDU. DV of aminophyllin = 1.59
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gr V Q.S. Mitte: III

Calculations: 1. No. of supp. = 2. amount of drug = 3. amount of base = [No. of supp. X mould capacity – (drug / DV)] x CF = = Procedure: 1. Prepare the mould (clean, dry, lubricate with soap lubricant then invert on a glass slab to drain the excess lubricant).
2. Weigh the required amount of CB, and cut into small pieces by a knife (or

g --------- for mould 2 g g --------- for mould 1 g

use shredded CB). Place in a porcelain dish and expose it carefully to the steam of a water bath until a creamy mass, which can be easily poured, is produced. (Avoid overheating, to avoid polymorphism). 3. Powder the drug (if necessary) in a mortar with a pestle, then weigh the required amount. 4. Add the calculated amount of pulverized and sifted medicament (aminophyllin) to the melted CB, and mix well with a pestle until a uniform and homogenous mixture is produced. 5. Pour (in a continuous stream) the homogenous mixture (step # 3) into the lubricated mould and allow over-filling of the cavities (to avoid formation of holes that could take place due to contraction of the base on cooling). 6. Cool in an ice bath (or in the refrigerator) for 10 min. 7. Remove the excess of the base by means of a knife, take out the supp. From the mould. 8. Wrap the suppositories in aluminum foil paper, and then fix a red label.

Label:

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Use: Treatment of bronchial asthma.

SOLUBLE SUPPOSITORY BASES 1. MACROGOLS (POLYETHYLENE GLYCOLS):


These are polymers of ethylene oxide, H(CH2-O-CH2)n OH, with different molecular weights ranging from 200 to 20000.

• At room temperature, the lower members of the series are liquids, while the PEG 1000 and PEG 1450 are soft solids and the higher members are wax-like. • Advantages: 1. No laxative effect is produced. 2. Not susceptible to microbial contamination. 3. No lubricant is to be used with these bases because they do not adhere to the mould.
4. Melting points (37-63 oC ) are above body temperature, so cool

storage is not so critical, and therefore, they are suitable for areas with hot climate. Moreover, they do not melt on handling. This high
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melting point means that the base doesn’t melt but dissolve in rectal fluids at body temperature, and disperse the medicament. 5. They produce high viscosity solutions. This means that after dispersion in the body fluid, leakage is less likely to occur. 6. They give products with clean smooth appearance. 7. They do not alter by overheating. • Disadvantages: 1. Hygroscopic: so they may cause irritation to the rectal mucosa. This can be overcome by incorporation of 20% of water in the mass, or by instructing the patient to dip the preparation in water before insertion. 2. Incompatibilities: macrogol bases are incompatible with some drugs (e.g., bismuth salts, ichthammol, benzocaine, and phenol). Also, they interact with some plastics which limits the choice of containers. 3. Brittleness: macrogol bases may be brittle unless poured at as low a temperature as possible. • The following mixtures of polyethylene glycols of varying hardness have been described for the use as suppository bases:

Macrogol PEG 6000 PEG 4000 PEG 1540 PEG 1000 PEG 400 Water

1 47% 33% ----20% ---

2 47% 33% ------20%

Mixture 3 47% --33% ----20%

4 --25% --75% -----

5 --4% --96% -----

Practical: Prepare 3 paracetamol suppositories each having the following formula:

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Rx Paracetamol Carbowax Carbowax base: *F PEG 6000 PEG 4000 PEG 400 Fiat: supp. Sig.: one supp. P.r.n. N.B.: CF of the base =1 DV of paracetamol = 1.5 Calculations: 1. 2. 3. CF = 4. F = Procedure: 1.
2.

200 mg QS to 2g

47% 33% 20%

Mitte:III

No. of supp. = amount of drug = amount of base = [No. of supp. X mould capacity – (drug / DV)] x g -------- for mould 2 g

Prepare the mould (clean and dry, no need for lubrication). Weigh the required amounts of PEGs. Place in a porcelain dish and

expose to the steam of a water bath (starting with the higher mol.wt. polymer , high melting point) until complete melting is achieved. 3. 4. Powder the drug (if necessary) in a mortar with a pestle, then weigh Add the calculated amount of pulverized and sifted medicament the required amount. (paracetamol) to the melted base, and mix well with a pestle until a uniform and homogenous mixture is produced.

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5.

Pour (in a continuous stream) the homogenous mixture (step # 4)

into the dry mould and allow over-filling of the cavities (to avoid formation of holes that could take place due to contraction of the base on cooling). 6. 7. 8. Cool in an ice bath (or in the refrigerator) for 10 min. Remove the excess of the base by means of a knife, smooth the Wrap the suppositories in aluminum foil paper, and then fix a red

surface then take the supp. out the mould. label. Label:

Use: Analgesic and antipyretic.

2. GLYCEROGELATIN BASE:  This base is a mixture of glycerin and water gelled by the addition of gelatin.  Glycerol suppository mass usually contains 70% glycerol and a minimum of 14% gelatin. Higher concentrations of gelatin may be required for use in hot countries or to counteract the softening effect of any liquid ingredients included in the product.
 Gelatin is derived from the hydrolysis of animal collagenous tissues

including skin and bones.
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Type A gelatin is prepared by acid hydrolysis at p H: 3.2, while Type B gelatin is prepared by a alkaline hydrolysis at pH: 7-8.  Disadvantages: 1. It has a laxative effect. 2. Unpredictable solution time: this varies with the batch of gelatin and the age of the base. 3. Hygroscopic: the base needs protection from heat and moisture. Also, it has a dehydrating effect on the rectal or vaginal mucosa leading to irritation. 4. Microbial contamination is likely: this base may require the addition of preservatives, which may lead to problems of incompatibilities. 5. Long preparation time, compared to fatty bases. 6. Difficult to remove from the mould: so lubrication of the mould is essential.  The specific gravity of glycerogelatin base is much higher than that of cocoa butter and this depends upon the proportion of the glycerin used in the formula. Thus the capacity of the mould must be corrected when glycerogelatin base is to be prepared.
 The mould should be lubricated with liquid paraffin or any other oil by

means of a cotton piece, then invert the mould on a glass slab to drain the excess of the lubricant.
 The mass doesn’t contract on cooling. So, take care just to fill the

cavities of the mould on pouring.

 Different formulae for the glycerogelatin base include: 1. The B.P. formula: (glycerin suppositories) Rx Gelatin Water 14 g QS Glycerin 70 g

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 This base is suitable for medicated suppositories and pessaries containing solid medicaments or not more than 20% of semi-solid or liquid medicaments. With more than this, the mass becomes too soft. 2. The U.S.P. formula: (glycerinated gelatin suppositories) Rx Gelatin 20 g Glycerin 70 g Water to 100 g

Practical : Prepare 3 suppositories of zinc oxide in glycerogelatin base having the following formula: Rx zinc oxide Glycerogelatin base Glycerogelatin base: *F Gelatin Glycerol Fiat: supp. 14 g 70 g Mitte: III Sig. MDU. 0.2 g q.s.

Water to 100 g N.B.: D.V. of zinc oxide = 4 CF of the base = 1.2 Calculations: 1. No. of supp. = 2. amount of water = 3. amount of drug =

30

4. amount of base = [(No. of supp. X mould capacity) – Drug/DV ] x CF = = 5. F = Procedure: 1. Prepare the mould (clean, then lubricate with liquid paraffin and invert on a glass slab to drain the excess lubricant). 2. in a porcelain dish, soak gelatin powder in the calculated amount of water, for about 5-10 minutes until it is completely wetted (hydrated) and swelled. Then transfer the dish over water bath.
3. Add glycerin to the soaked gelatin. Leave on water bath, stir gently (in

-------- for mould 2 g --------- for mould 1 g

cross lines) to avoid air entrapment, until complete solubility of gelatin and the formation of a translucent mass (free of air bubbles).
4. Powder zinc oxide finely, and then add to the base. Stir gently with a

glass rod (to avoid air entrapment) until a smooth mass results and a drop of the solution becomes a line or a thread. 5. Pour the mass into the lubricated mould, and just fill the cavities of the mould (no overfilling). 6. Cool in an ice bath (or in the refrigerator) for 10 min. 7. Remove the supp. out the mould. 8. Wrap the suppositories in aluminum foil paper, and then fix a red label. Label: Red

Use: Astringent.

31

3. SOAP GLYCERIN SUPPOSITORIES:  Stearin soap (curd soap) has certain advantages over gelatin for making glycerin sufficiently hard for suppositories.  A larger quantity of glycerin can be incorporated actually up to 95% of the mass.  Soap assists the action of glycerin, whereas gelatin does not.  This base is very hygroscopic and requires to be wrapped immediately (in foil paper) and protected from light. Practical: Prepare 3 soap glycerin suppositories having the following formula: Rx Glycerol Sodium carbonate Stearic acid Fiat: supp. Sig. MDU. Calculations: 1. No. of supp. = 2. amount of base (total weight) = [No. of supp. X mould capacity ] x CF = =
32

*F 90 g 2.5 g 7.5 g

Mitte: III

g --------- for mould 2 g g --------- for mould 1 g

3. F = Procedure: 1. Prepare the mould (clean, then lubricate with liquid paraffin and invert on a glass slab to drain the excess lubricant).
2. Heat glycerin in a small beaker over a sand bath until it reaches 70 oC.

(Check with a thermometer). 3. When glycerin reaches the assigned temperature, add sodium carbonate, stir with a glass rod until complete dissolving of the solid. 4. Add stearic acid powder and stir until all effervescence ceases and the solution is complete (clear solution). 5. Skim the surface with a spatula or a glass rod to remove the remaining froth. 6. Pour the solution into the lubricated mould, and allow for overfilling. 7. Cool in an ice bath (or in the refrigerator) for 10 min. 8. Remove the excess, smooth the surface and take the supp. out the mould. 9. Wrap the suppositories in aluminum foil paper, and then fix a red label. Label:

Use: Laxative (in the treatment of constipation).

33

Another formula for soap glycerin suppositories: Prepare 3 soap glycerin suppositories having the following formula: Rx Glycerol Sodium stearate Water Fiat: supp. Sig. MDU. Calculations: 1. No. of supp. = 2. amount of base (total weight) = [No. of supp. X mould capacity ] x CF = = g 3. F = Procedure: Prepare the mould (clean, then lubricate with liquid paraffin and invert on a glass slab to drain the excess lubricant). Heat glycerin in a small beaker over a sand bath until it reaches 70 oC. (Check with a thermometer). When glycerin reaches the assigned temperature, add sodium stearate, stir with a glass rod until complete dissolving of the solid. Add water. Pour the solution into the lubricated mould, and allow for overfilling. Cool in an ice bath (or in the refrigerator) for 10 min. Remove the excess, smooth the surface and take the supp. out the mould. g --------- for mould 2 g g --------- for mould 1 Mitte: III 91 g 9g 5g *F

34

Wrap the suppositories in aluminum foil paper, and then fix a red label. Label:

Use: Laxative (in the treatment of constipation).

COMPRESSED TABLETS Compressed tablets are solid dosage forms prepared by compaction of a formulation containing the drug and certain excipients selected to aid the .processing and improve the properties of the product :Tablets excipients
1.Bulking agents (diluents):

These are used to increase the bulk of the tablet. :Examples a. Soluble: lactose, sucrose, mannitol, sorbitol. b. Insoluble: calcium sulphate, dicalcium phosphate, tricalcium phosphate, calcium carbonate, starch. 2. Binders (adhesives):

35

• The substances that glue the powders together and cause them to form granules are binders or adhesives. • Binders are added either dry or in a liquid form during wet granulation to form granules or to promote cohesive compacts for directly compressed tablets. • A list of binders used in wet granulation is shown in the following table: :Table : some commonly used binders and granulating liquids comments

Binder Water Ethanol Acacia mucilage Tragacanth nucilage Gelatin solution Starch mucilage Glucose syrup Sucrose syrup PVP Cellulose derivatives 3. a.

Strength

----------- ------------------------------------------------- --------------------------------------10-20% Hard, friable granules 10-20% 2-10% 2% 25-50% 65-83% 3-15% 5-10% Same as acacia .Strong adhesive, use warm .One of the best general adhesives, use warm Strong adhesive, tablets may soften in high .humidity .Same as glucose --------------------------------------------------------------------------------------------

Lubricants, glidants, and anti-adherents: Lubricants:

Are those agents that reduce the friction between the tablet edges and die .wall during the ejection cycle, e.g., magnesium stearate b. Glidants: Are materials that improve the flow characteristics of granulation by .reducing friction between the particles, e.g., talc c. Anti-adherents: These function to prevent tablet granulation from sticking or adhesion to .the faces of the punches and the die walls, e.g., talc

36



Lubricants, glidants and antiadherents are added at the very last

step before compression, since they must be present on the surface of the granules and in between them and in the parts of the tablet press. 4. Disintegrants: Disintegrant is a term applied to substances added to a tablet granulation for the purpose of causing the compressed tablets to break apart when placed into an .aqueous environment :Methods of adding disintegrant Disintegrants could be added in the first step before granulation, or in the last step just before compression. However, it is better to add it in two portions, one half is added to the powdered components before the wet granulation process and the other remaining portion is added to the finished granulation just prior to compression. This method holds that a disintegrant is required between the .granules as well as within them :Some of the commonly used disintegrants are listed in the table :Table: disintegrants: typical amounts used Disintegrant Starch Avicel Algenic acid Veegum Bentonite (Concentration (% w/w 5-20% 5-20% 5-10% 5-15% 5-15%

METHODS OF MANUFACTURE 1. Direct compression method:

37

 Direct compression method involves compressing the tablet from

powdered material without modifying the physical nature of the material itself.  Drugs characterized by high dose, poor compressibility and poor fluidity (flow) do not lend themselves to direct compression method. On the other hand, small doses can be mixed with direct compressible vehicle before compression into a tablet.
 Direct compressible vehicle is an inert substance that may be compressed

directly without difficulty and which may be compressed even when small quantities of drug are mixed with it.  Direct compression vehicles should have: • • •  Advantages: 1. 2. 3.
2.

High fluidity, High compressibility, and Should be inert and compatible with all of the active

ingredients. Economy (less areas, reduced processing time, reduced labor costs, Elimination of heat and moisture. Stability. Dry granulation (slugging) method:

and fewer manufacturing steps).

• This method involves the compaction of the components of tablet

formulations by means of tablet press or specially designed machinery followed by milling and screening prior to final compression into a tablet, i.e., the granulation of powder mixture is carried out by compression and without the use of heat and solvent. • On a relative basis, it is the least desirable of all of the methods of preparing tablet granulation. However, when direct compression is not possible due to the properties and dose of the drug, and wet granulation can

38

not be used because the drug is sensitive to moisture and heat, then dry granulation remains the only method available. • Advantages: 1. 2. Suitable for moisture and heat sensitive materials. Results in an improved disintegration, since powder particles are

not bonded together by a binder. • Disadvantages: Requires a specialized heavy duty tablet press to form slugs. Creates more dust than wet granulation. Does not permit uniform color distribution. 3. Wet granulation:

The preparation of granulation for tabletting by wet granulation is the oldest .method and still the most widely used :Steps of wet granulation 1. 2. 3. 4. 5. 6. 7. 8. 9. :Advantages Improved cohesiveness & compressibility of powders due to added binders. Suitable for high-dosage drugs having poor flow or compressibility properties. Good distribution for low dosage drugs and color additives. :Disadvantages
39

Milling of drug and excipients. Mixing of the milled powders. Preparation of binder solution. Mixing of binder solution with powder mixture to form wet mass. Course screening of wet mass using 6-12 mesh screen. Drying of moist granules. Screening of dry granules through 20/35 mesh screen. Mixing of screened granules with lubricant and the remaining Tablet compression.

disintegrant.

1. 2.

High cost (because of the time, equipments and space Not suitable for moisture and heat sensitive drugs.

requirements).

PREPARATION OF ACETAMINOPHEN TABLETS (150 mg) BY WET GRANULATION METHID Prepare 500 acetaminophen tablets each containing 150 mg of the drug and the :total tablet weight is 225 mg Rx Acetaminophen (binder)Polyvinylpyrrolidone (diluent)Lactose Alcohol Starch (glidant) Talc 150 mg 11.25 mg 28.625 mg Q.S. 21.625 mg 4.5 mg (9.61%) (3%) (2%) 6.75 mg (66.67%) (5%) (12.72%) *F

(lubricant)Magnesium stearate Calculations: 1. 2.

add 20 % excess to compensate for the mechanical loss: F=

No. of tablets =

Method of preparation (wet granulation): 1. Mix acetaminophen with PVP, lactose, and half the amount of starch. (Mixing is to be made geometrically in a large dish or in a jar by tumbling for 15 minutes).
2.

Add alcohol slowly to form a wet mass which retain its shape on

handling.

40

3.
4.

Screen the wet mass through a mesh-12 sieve to get the granules. Dry the granules at 50 oC overnight (in an oven). Make size reduction for the dried granules through a mesh-20 Weigh the granules (W), then add the remaining half of starch, talc Remaining starch Talc Mg stearate = (4.81/100) x W = (3/100) x W = (2/100) x W

5.
6.

sieve (0.8 mm). and Mg stearate:

7. 8.

Mix the ingredients in a jar by tumbling for 15 min. Compress.

Lab # 3 TABLET EVALUATION

41

Compressed tablets may be characterized or described by a number of specifications. These include: shape, diameter, thickness, weight, hardness, friability, disintegration time and dissolution characteristics. Diameter and shape: • The diameter and shape depend on the die and punches selected for the compression of the tablet.


Generally, tablets are discoid in shape, although they may be oval, oblong, round, cylindrical, or triangular. Their upper and lower surfaces may be flat, round, concave or convex to various degrees. The tablets may be scored in halves or quadrants to facilitate breaking if smaller dose is desired. The top or lower surface may be embossed or engraved with a symbol or letters which serve as an additional mean of identifying the source of the tablets. These characteristics along with the color of the tablets tend to make them distinctive and identifiable with the active ingredient which they contain.

Tablet thickness: The thickness of the tablet is the only dimensional variable related to the compression process. The thickness of individual tablets may be measured with a micrometer.
 

Thickness should be controlled within ± 5% variation of a standard value. Thickness must be controlled for consumer acceptance of the product, and to facilitate packaging.

QUALITY CONTROL TESTS OF TABLETS

42

UNOFFICIAL TESTS 1. HARDNESS (CRUSHING STRENGTH): Tablets require a certain amount of strength, or hardness to



withstand mechanical shocks of handling in manufacture, packaging and shipping. 
• • •

Recently, the relationship of hardness to tablet disintegration and

the drug dissolution (release) rate has become apparent. Tablet hardness can be defined as the force required to break a tablet in a Several devices operating in this manner have been used to test tablet Hardness determinations are made throughout the tablet runs to diametric compression test. hardness, e.g., the Erweka hardness tester. determine the need for pressure adjustments on the tabletting machine. If the tablet is too hard, it may not disintegrate in the require period of time to meet the dissolution specifications, and if it is too soft, it will not withstand the handling, packaging and shipping operations.

Method: Carry out the test on the batch of tablets provided using Erweka hardness tester. Calculate the mean crushing strength of 10 tablets (taken randomly). N.B., a crushing strength of 4-8 Kg for uncoated tablets is acceptable. 2. FRIABILITY TEST:

Tablets that tend to powder, chip, and fragment when handled lack elegance and consumer acceptance, and can create excessively dirty processes in

43

such areas of manufacturing as coating and packaging. They can also add to tablet’s weight variation or content uniformity problems. The measurement of friability is made by Roche friabilator. Method:
1. Select 20 tablets randomly, and weigh (WO).

2. Place the tablets in the Roche friabilator drum; switch on the apparatus adjusting the timer at 4 min. and the speed at 25 rpm. 3. At the end of this operation, remove the tablets from the friabilator, dedust and reweigh (W). (Any tablet that breaks up should be rejected before reweighing). 4. friability is expressed as a percentage loss in weight: i.e., % loss =
WO − W x 100 WO

N.B., if the value of friability (% loss) is less than or equal to 1%, the batch is accepted. RESULTS 1. Thickness:

Tab. No. 1. 2. 3. 4. 5.

Average Thickness thickness (cm) (cm)

Upper limit

Lower limit

Comment

2. Diameter:

44

Tab. No. 1. 2. 3. 4. 5.

Diameter (cm)

Average diameter (cm)

Upper limit

Lower limit

Comment

3. Hardness: Average hardness (Kg)

Tab. No

Hardness (Kg)

Comment

4. Friability: Weight of 20 tablets = Weight of the tablets ( after 4 min in the friabilator) = % loss in weight = comment: Lab # 4 EVALUATION OF TABLETS (CONT.) OFFICIAL TESTS 1. DISINTEGRATION TEST:

45



Disintegration test is a measure of the time required for a group

of tablets to break up into particles under a given set of conditions. The USP disintegration apparatus:
 This apparatus consists of a basket rack containing 6-open-ended glass

tubes held in a vertical position. A number 10-mesh stainless steel wire screen is attached to the bottom.
 To be in compliance with the USP standards, the tablets must disintegrate,

and all of the particles must pass through the 10-mesh screen in the time specified. If any residue remains, it must have a soft mass with no palpably firm core.  Limit:
 Uncoated USP tablets have disintegration time standards as low as 5

minutes (aspirin tablets), but the majority of tablets have maximum disintegration time of 30 minutes.
 N.B., if one tablet fails to disintegrate within 30 minutes, the

disintegration test is repeated on 12 additional tablets. Not less than 16 out oh the total 18 tablets tested disintegrate completely within 30 minutes. Method: 1. Place one tablet in each of the six tubes of the basket (tablets are selected randomly).
2. Position the basket rack in 1- L beaker containing distilled water (as the

disintegration medium) maintained at 37 oC. 3. Start the apparatus (to move the basket assembly containing the tablets), and record the time required for all of the six tablets to break into particles and to pass to the disintegration medium.

2.WEIGHT VARIATION (UNIFORMITY OF WEIGHT) TEST:

46

 The weight of the tablets being made should be routinely measured to help ensure that the tablet contains the proper amount of drug.


The USP weight variation test is run by weighing 20 tablets individually, calculating the average weight, and comparing the individual tablet weights to the average. The weight variation tolerances for uncoated tablets differ depending on average tablet weight. (See the next table)



Table : Weight variation tolerances for uncoated tablets: Average weight of tablets (mg) Less than 130 130 – 324 More than 324 Method: 1. Select 20 tablets randomly from the batch provided, and then weigh the tablets individually. 2. Weigh the 20 tablets together and calculate the average weight (W). 3. Compare the average weight calculated to the previous table to determine the maximum % difference allowed. 4. calculate the upper and lower limits at the % difference allowed: Upper limit = W + [(%/100) (W)] Lower limit = W – [(%/100) (W)] 5. Furthermore, calculate the upper and lower limits at double the % difference allowed: Upper limit = W + [(2x %/100) (W)] Lower limit = W – [(2x % /100) (W)] 6. Compare the individual weights of tablets to the upper and lower limits calculated at the % difference allowed and at double that percentage. 7. Comment on the results. Maximum % difference allowed ± 10 ± 7.5 ± 5

47

Limit: For the batch to be accepted: 2. Not more than 2 tablets (out of the 20 tablets) differ from the average weight by the % difference listed, and 3. No tablet differs from the average weight by double that percentage.

RESULTS 1. Disintegration test:  Time recorded for the tablets to break into particles and pass to the liquid medium = ----------------- minutes.  Comment: 2. Weight variation test:  Total weight of tablets
 Average weight of tablets (W)

= = total wt. / 20 = = W + [(%/100) (W)] = = W - [(%/100) (W)] =

 Upper limit (at the % diff. Allowed)  Lower limit (at the % diff. Allowed)

 Upper limit (at double the % diff. Allowed) = W + [(double%/100) (W)] =  Lower limit (at double the % diff. Allowed) = W - [(double%/100) (W)] = Tab. No. 1 2 3 Weight (g) Comparison at % difference allowed Comparison at double % difference allowed

48

4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Comment: Lab # 5 3. DRUG CONTENT: Range: Official compendia or other standards provide an acceptable potency range around the label potency.


For highly potent, low-dose drugs such as digitoxin, this range is usually not less than 90% and not more than 110% of the labeled amount. For most other larger – dose drugs in tablet form, the official potency range that is permitted is not less than 95% and not more than 105% of the labeled amount. For less potent, low-dose drugs such as indomethacin, the official potency range that is permitted is not less than 85% and not more than 115% of the labeled amount.





Three factors that can directly contribute to content uniformity problems in tablets:

49

1. Non-uniform distribution of the drug throughout the powder mixture or granulation. 2. Segregation (demixing) of powder mixture or granulation during the various manufacturing processes. 3. Tablet weight variation. DETERMINATION OF DRUG CONTENT OF ASPIRIN TABLETS (B.P.) 1. Weigh and powder 20 tablets. (Powder in a dry mortar). 2. Weigh an amount of the powder equivalent to 0.5 g of aspirin. 3. Place the calculated amount in a conical flask, and add 30 ml of 0.5 M NaOH solution (by burette). Boil gently on a hot plate, for 10 minutes; (cover the flask). 4. Cool, and then make back titration of the excess NaOH with 0.5 M HCl, using phenol red indicator. (E.P.: red to yellow color). 5. Repeat the above operation without the drug. (Blank). 6. Calculate the content of aspirin. N.B., each ml of 0.5 M NaOH is equivalent to 0.04504 g of aspirin. (F). Content: tablets should contain 95 – 105 % of the prescribed or stated amount. Results for drug content of aspirin tablets: % aspirin = =
( B − Exp) xFxfx100 0 .5

Comment:

50

Lab # 6 4. DISSOLUTION TEST The dissolution test: is an in vitro test for measuring the time required for a given percentage of the drug substance in a tablet to go into solution under a specified set of conditions. USP / NF have provided procedures for dissolution testing: Apparatus I (USP basket method): in general, a single tablet is placed in a small wire mesh basket fastened to the bottom of the shaft connected to a variable speed motor. The basket is immersed in the dissolution medium contained in 1000 ml flask. The flask is maintained at 37 ± 0.5 oC by a constant temperature water bath. Samples of the fluid are withdrawn at specified time intervals to determine the amount of the drug in solution. Apparatus II (USP paddle method): the same equipment as in apparatus I is used, except that the basket is replaced by a paddle, formed from a

51

blade and a shaft, as the stirring element. The dosage form is allowed to sink to the bottom of the flask before stirring. Description of a dissolution test in USP/NF monograph specifies: The dissolution test medium, and volume, Which apparatus is to be used, The speed at which the test is to be performed (rpm), The time limit for the test, and The assay procedure. The test tolerance is expressed as: The percentage of the labeled amount of the drug dissolved in the time limit. The results are plotted as concentration vs. time. Values for t 50% , t 90%, and the percentage dissolved in 30 minutes are used as guides. The value for t
50%

is the length of time required for 50% of the drug to go into solution. DISSOLUTION TEST FOR ASPIRIN TABLETS (U.S.P. 1995)

Conditions: o apparatus : o medium :
o Temp.

I (basket) 500 ml of 0.05 M acetate buffer pH 4.5

: :

37 ± 0.5 oC 50 rpm

o speed o Time Procedure:

: 30 min.

1. Place one tablet in the basket, immerse in the vessel, and then start the apparatus at the above conditions. 2. At specified time intervals (5, 10, 15, 20, 25, 30, and 45 min) withdraw 5 ml sample from the dissolution medium, through a Millipore filtration unit (polyethylene tube with a cotton), and place the sample in a test tube.
3. Replace the withdrawn sample with 5 ml fresh acetate buffer kept at 37 ±

0.5o C.

52

4. Dilute 1 ml of the collected sample to 5, 10, 20 or 25 ml (dilution factor =

1:5, 11:10, 1:20 or 1:25) with fresh acetate buffer (in a volumetric flask), mix well. (Dilution is made if necessary.) 5. Read the absorbance for the diluted samples at 265 nm against a blank of acetate buffer.
6. Calculate the concentration of aspirin released (taking 0.036 as the value

of E1mg%), and express this conc. As a percentage of the labeled amount. 7. Plot the dissolution curve of aspirin (% released vs. time).
8. From the dissolution curve, determine the time required for 80% of the

labeled amount of the drug to be released (go into solution), i.e., t 80%. Tolerance: the tablet should release not less than 80% of its content within 30 minutes. Results of the dissolution of aspirin tablets: (Bayer tablets, 300 mg) Dilution factor = ( total vol / vol taken from the sample)

Time (min ) 5 10 15 20 25 30 45

Abs. at 265 nm

Conc. = E x dil 1mg % factor x 5 (mg/500ml)

abs.

% released =
conc. x 100 strength

Plot of the Dissolution curve (on a graph paper):

53

Comment:

54

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