Pharmaceutical Calculations Density: Def.: It is a mass per unit volume of substance (1.8 g/ml). Calculated by dividing mass by volume. Example: If 10 ml of sulfuric acid weight 18 g, Density = 18 (g) = 1.8 g per ml (g/ml) 10 (ml) Specific gravity: Def.: Weight of substance / weight of equal volume of standard substances have the same temperature. For specific gravity of liquids and solids, water used as standard. It is a ratio between like quantities (no dimension). Example: 10 ml of H2O (with same conditions) = 10 g (weight) Specific gravity of acid: wt of 10 ml of acid 18 (g) 1.8 wt of 10 ml of water 10 (g) It is a constant value for each substance. Pharmaceutical calculations: I- Specific gravity of liquids II- Specific gravity of solids I- Specific Gravity of Liquids Calculate specific gravity by three methods (liquids): 1- Weight and volume known. 2- Specific gravity bottle (pycnometer). 3- Displacement or plummet method. -1- 1- Specific gravity by known weight and volume of liquids: Ex: If 54.96 ml of oil weight 52.8 g Specific gravity of oil = wt of 54.96 ml of oil 52.78 0.9603 = wt of 54.96 ml of water 54.96 N.B.: 54.96 ml of water weight 54.96 gm (under similar conditions). 2- Specific gravity of liquids by pycnometer (specific gravity bottle): 1- Wt of container (specific gravity bottle) (empty) (1). 2- Filled the container with water and weight (2). 3- Filled the container with liquid and weight (3). 4- Wt of water = (2) – (1) (4) 5- Wt of liquid = (3) – (1) (5) Specific gravity = wt of liquid (5) wt of water (4) Example Specific gravity bottle weights = 23.66 g (1) Filled with water weights = 72.95 g (2) Filled with liquid weights = 73.56 g (3) Specific gravity ? Wt of water = 72.95 – 23.66 = (2) – (1) = 49.29 gm Wt of liquid = 73.56 – 23.66 = (3) – (1) = 49.90 gm Specific gravity = 49.90 1.012 49.29 -2- II- Specific Gravity of Solids A- Heavier than water. 1- Insoluble 2- Soluble B- Lighter than water and insoluble C- Granulated solids (heavier and insoluble in water). A1) Specific gravity of solids heavier than and insoluble in water: Specific gravity = wt of solid in air wt of displaced in water N.B.: Wt of displaced water = apparent loss of wt in water. Examples: Wt of glass in air = 38.525 gm Wt of glass when immersed in water = 23.525 g Specific gravity of glass Wt of displaced water ? = apparent loss of wt in water = 38.525 – 23.525 = 15.000 g Specific gravity of glass = 38.525 2.268 15.000 A2) Specific gravity of solids heavier than and soluble in water: Example: Wt of equal volumes of two substances and their specific gravities. Crystal of chemical salt weight = 6.423 g (air) When immersed in oil weight = 2.873 g (oil) Oil specific gravity = 0.858 Specific gravity of salt ? Wt of displaced oil = 6.423 – 2.873 = 3.550 g -3- 3.550 (g. oil) 0.858 (sp. gr. oil) 6.423 (g. salt in air) x (sp. gr. salt) ? x (specific gravity of salt) = 1.55 B) Specific gravity of solid lighter than and insoluble in water: - Use sinker to prevent solid from floating. Wt of sinker when immersed in water alone. Wt of solid in air. Combined wt of sinker (water) and solid in air (before immersion). Wt of water displaced by solid = combined wt (sinker + solid) before immersion – combined wt (sinker + solid) after immersion. Specific gravity solid = wt of solid in air wt of displaced water Example: Wt of empty bottle = 80.0 g Wt of filled water bottle = 96.8 g Wt of granulated metal = 28.8 g Wt of bottle (total weight) (metal filled water) = 118.4 g Specific gravity of metal ?? 1- Wt of water filling bottle = 96.8 – 80.0 = 46.8 g 2- Combined wt of water and metal = 46.8 + 28.8 = 75.6 g 3- Combined wt of water and metal in bottle = 118.4 – 80.0 = 68.4 g 4- Wt of water displaced by metal = 75.6 – 68.4 = 7.2 g (wt of equal volume of water) Specific gravity of metal = wt of solid 28.8 4.0 wt of an equal volume of water 7.2 -4- Specific Volume Specific volume of substance = volume of substance volume of equal wt of water (liquids and solids) standard under the same conditions Specific gravity: comparison Wts of equal volumes Specific volume: comparison Vs of equal weights Are reciprocals of each other If multiplied together = 1 Specific volume calculation (liquid): 1- Given volume of specified Wt. 2- Given its specific gravity 3- Calculate specific gravity by having specific volume. Example: 1- Determine specific volume of syrup, 91.0 ml (its wt = 107.16 g) Specific volume = 91.0 91.0 0.850 volume of standard (water) 107.16 107.16 g of water = 107.16 g ml (volume) 2- What is specific volume of phosphoric acid having sp. gr. 1.71 ? 1 0.585 sp. volume = 1.71 3- What is sp. gr. of liquid has sp. volume 1.396 1 0.716 sp. gr. = 1.396 Calculations of weight (liquid): Calculation the weight of liquid when given - Volume - specific gravity -5- sp. gr. water wt of equal volume of water sp. gr. liquid x x = weight of liquid N.B: sp. gr. of water = 1 Wt of liquid = wt of equal volume of water x sp. gr. liquid Example: What is the wt of 3620 ml of alcohol having sp. gr. of 0.820 ? Sp. gr. of liquid x wt of equal volume of water = wt of liquid 3620 ml of water = wt of 3620 g Wt of liquid = 3620 (g) of water x 0.820 = 2968 g. Calculations of volume (liquid): Calculate the volume of liquid: - Wt - sp. gr. sp. gr. liquid volume of equal wt water sp. gr. water x x = volume of liquid V liquid = volume of equal wt water sp. gr. liquid Example: What is the volume of 492 g nitric acid with sp. gr. 1.40 ? 492 g of water measure 492 ml volume = 492 351 ml 1.4 Percentages Def.: Rate for hundred, no. and percent (%). Ex: 25% = 25 parts of 100 parts = 25 / 100 = 0.25 Uses in Pharmaceutics: 1- Express the conc. of solute in solution. 2- Amount of active ingredient (drug or preparation). -6- 3- Amount of active ingredient in dosage form. Percentage calculation (concentration): I- Percent (w/v) % No. grams of substance in 100 ml (solution liquid). Ex: water or another. II- Percent (v/v) % No. of milliliters of substances in 100 ml of solution III- Percent (w/w) % No. of grams in 100 gm of solution or liquid. N.B.: mg. % - Number of milligrams of substances in 100 ml of liquid - Used to determine conc. of drug or natural substances in biological fluid (blood). ppm (part per million): - Used for very dilute solutions (determine conc.) - For test limits. I) Percentage weight-in-volume (w/v) %: 1- Calculate (wt) of substance of known % (w/v) in specific volume. 2- Calculate the % (w/v) of solution by knowing: wt. solute or volume of solution. 3- Calculate the volume of solution by knowing: (w/v) % or (wt) of solute gr. solute = vol. in ml x % = (w/v) % Examples: -7- 1- How many grams of dextrose required to prepare 4000 ml of 8% solution ? g. solute = 4000 x S = 200 g 100 S g. 100 ml X= , X 4000 ml 4000 x S 200 g 100 2- What is the % strength (w/v) of solution of urea, if 80 ml contain 12 g. ? %= g. solute or constituen t W x100 volume in ml V %= 12 x100 15% 80 3- How many milliliters of 3% solution can be made from 27 g. ephedrine sulfate ? Volume in ml = g. solute 27 900 ml % 0.03 II) Percentage volume-in-volume (v/v) %: 1- Calculate (v) of active ingredient by knowing: (V) liquid % (v/v) or 2- Calculate % (v/v) by knowing: (V) active ingredient volume of solution or 3- Calculate (V) of solution by knowing: % (v/v) (V) active ingredient. or Examples: 1- How many ml. liquefied phenol should be used in: R/ Liquefied phenol Calamine lotion ad 2.5% 240.0 ml -8- (V) active ingredient = (V) in ml. x % …….. ml 240 ml x 0.025 = 6 ml. 2.5 – 100 ml or x= x – 240.0 ml 240 x 2.5 6 ml 100 2- Calculate the % (v/v) of solution given the volume of active ingredient and volume of solution ? %= Ex: ml. of active ingredient V x100 volume in ml. V - 250 ml of lotion - used 4 ml liquefied phenol Calculate the % (v/v) liquefied phenol in lotion ? %= 4 x 100 1.6% (V/V) 250 3- Calculate volume of solution given the volume of active ingredient and its % (v). Volume in ml = ml of active ingredient % Example: Peppermint spirit contains 10% (v/v) of peppermint oil. What volume of spirit contain 75 ml of active ingredient ? Volume in ml = 75 750 ml 0.1 III) Percentage weight-in-weight (w/w) %: 1- Calculate the (wt) g drug by knowing: % or (wt) solution. 2- Calculate the (wt) of solution by knowing: % or (wt) of active ingredient -9- 3- Calculate % by knowing: (wt) of solution or (wt) of solution Examples: 1- How many grams of phenol should be used to prepare 240 g. of 5% (w/w) solute in water ? g. of solute = wt solution (g.) x % Weight of phenol = 240 x 0.05 = 12 g How many g. of drug to make 120 ml of 20% (w/w) solute in having sp. gr. of 1.15 ? 1- wt of solution (120 ml) = 120 x 1.15 = 138 g. 2- wt of solute = 138 x 0.2 = 27.6 g. 2- If 1500 g. of solution contain 75 g. of drug substance, what is the % (w/w) of solution ? %= g. of solute x 100 wt. solution g. %= 75 x100 5% 1500 3- Calculate wt. of solution either by knowing % or wt. of active ingredient. Ex: What wt. of 5% (w/w) solution can be prepared from 2 g. active ingredient ? Wt. of solution (g.) = g. of solute 2 40 g. % 0.05 -10- Ratio Strength For expression the conc. of weak solution. 5% = 5 parts per 100 parts 5 : 100 1 : 20 (ratio strength). Example: 1- Express 0.02% as ratio strength ? 0.02 100 1 : 5000 2 100 100 1/50 100 Ratio strength = 1 : 5000 2- Express 1 : 4000 as percentage strength ? 1 4000 x 100 x= 100 0.025% 4000 Dilution and Concentration of Liquids A- Calculate the % or ratio strength of solution made by diluting or concentrating a solute, giving strength or quantity (solution) Example: 1- If 500 ml of 15% (v/v) solution of methyl salicylate in alcohol are diluted to 1500 ml. What % (v/v) ? 1500 15% 500 x x = 5% 2- Quantity x conc. = quantity x conc. 500 x 15% = 1500 x (x%) x = 5% -11- B- Calculate the amount of solution with known strength by either diluting or concentrating a specific quantity of solution of given strength Example: - How many grams (g.) 10% (w/w) ammonia water can be made from 1800 g. of 28% (w/w) ammonia water ? 10% 1800 28% x x = 5040 g. or 1800 (g.) x 28% = x (g.) x 10% x = 5040 g. Stock Solutions Definition: Are solution of known concentration. Are strong solution from which weaker ones are made. Are prepared in (w/v). Their concentration expressed by ratio strength (--- : ---). Example: - How many milliliters of 1:400 (w/v) stock solution should be used to make 4 liters of a 1:2000 (w/v) solution ? 1) 4 liter = 4000 ml 1:400 (ratio strength) = 100 = 0.25% 400 1:2000 = 0.05% 0.25(%) 4000 (ml) 0.05(%) x (ml) 1 4000 (ml) 2) 1 400 x (ml) x = 800 ml x = 800 ml 2000 -12- (quantity x conc. = quantity x conc. ) Dilution of Alcohol Examples: 1- How much water should be mixed with 5000 ml of 85% (v/v) alcohol to make 50% (v/v) alcohol ? 50 (%) 5000 (ml) 85 (%) x (ml) x = 8500 ml i.e. 5000 ml (85%) alcohol add water to 8500 ml. 2- How much water should be added to 4000 g. of 90% (w/w) alcohol to make 40% (w/w) alcohol ? 40 (%) 4000 (g.) 90 (%) x (g.) x = 9000 g. Triturations Powders as dosage forms Definition: Are dilutions of potent medicinal substances. Are prepared by mixing them with suitable diluent (lactose) in a definite proportions by wt. Dilute one part by (wt) of drug + g. parts (wt) of finely powdered lactose. - Calculate the quantity of trituration required to obtain a given amount of medicinal substance. Example: -13- - How many grams of 1:10 trituration atropine sulfate are required to obtain 25 mg of atropine sulfate ? 10 g. of trituration contain 1 g. atropine sulfate 1 g. 10 g. 25 mg x 0.025 g x 25 mg. = 0.025 g. x= 10 (g.) x 0.025 (g.) 1 (g.) x = 0.25 g trituration 0.25 g. trituration contain 25 mg atropine 25 mg : 0.25 g 0.025 g. : 0.25 g. 1:10 -14- Alligation 1- Alligation medial 2- Alligation alternate 1- Alligation Medial: Def.: A method by which the weighted average percentage strength of mixture of two or more substances whose quantities and concentrations known quickly calculated. Determine percentage strength of a mixture. Example: Calculate the (%) of mixture of two or more components of known (%). Examples: 1- What is the percentage (v/v) of alcohol in a mixture of 3000 ml of 40% (v/v) alcohol, 1000 ml of 60% (v/v) alcohol and 1000 ml of 70% (v/v) of alcohol. 40 x 3000 = 120,000 60 x 1000 = 60,000 70 x 1000 = 70,000 Total 5000 = 250,000 % of alcohol in mixture = 250000 50% 5000 2- What is the % of zinc oxide in ointment prepared by mixing 200 g. of 10% ointment, 50 g. of 20% ointment, and 100 g. of 5% ointment? 10 x 200 = 2000 % of zinc oxide = 20 x 50 = 1000 5 x 100 = 800 Total 350 = 3500 -15- 3500 10% 380 2- Alligation Alternate: 1- Calculate the relative amounts of solutions or substances of different strengths that used to make a mixture of required strength. Example: In what proportion should 20% benzocaine ointment be mixed with ointment base (without drug) to produce 2.5% benzocaine ointment ? Ointment ? 20% 2.8 parts of 20% (drug + base) 2.5% 0% (base + drug) 17.5 parts of oint. base Relative amounts = 2.5 : 17.5 or 1:7 Check: 20 x 1 = 20 0x7=0 Total 8 = 20 Percentage of mixture 20 / 8 = 2.5% 2- Calculate the quantity of a solution or mixture of given strength that should be mixed with a specified quantity of another solution or mixture of given strength to make a solution or mixture of desired strength. Example: How many grams of 2.5% hydrocortisone cream should be mixed with 360.0 g. of 0.25% cream to make a 1% hydrocortisone cream ? 2.5% 0.75 parts of 2.5% cream 1% 0.25% 1.5 parts of 0.25% Relative amounts = 0.75 (2.5%) : 1.5 (0.85%) or 1:2 -16- 2 (parts) 360.0 (g.) 1 (part) x (g.) x= 360 180 g 2 180 : 360 = 1:2 180 (g.) of 8.5% hydrocortisone cream + 360 (g.) of 0.25% cream 1% hydrocortisone cream. 3- Calculate amount of active ingredient that must be added to increase the strength of a mixture of given amount and strength. Example: How many grams of coal tar should be added to 8200 g. of 5% coal tar ointment to prepare an ointment containing 20% of coal tar ? Coal tar (active ingredient) = 100% 100% 15 parts of 100% coal tar 20% 5% 80 parts of 5% ointment Relative amounts = 15:80 or 3:16 16 (parts) 3200 (g.) 2 (parts) x (g.) x= 600 g. from 100% coal tar Specific Gravity of Mixtures I- To calculate specific gravity of a mixture given the specific gravity of its ingredients. Examples: What is sp. gr. of mixture of 1- 1000 ml of syrup sp. gr. = 1.3 2- 400 ml glycerin sp. gr. = 1.25 3- 1000 ml alixir sp. gr. = 0.950 1.3 x 1000 = 1300 1.25 x 400 = 500 0.95 x 1000 = 950 -17- Total 2400 = 2750 Sp. gr. of mixture = 2750 1.146 2400 II- Calculate the relative or specific amounts of ingredients of given sp. gr. required to make mixture of desired sp. gr. ? Examples: 1- In what proportion must glycerin with sp. gr. of 1.25 and water be mixed to give a liquid having sp. gr. 1.10 ? Gly. 1.25 0.10 parts of glycerin 1.10 water 1.00 0.15 parts of water Relative amounts = 0.10 : 0.15 or 2:3 (gly. : water) 2- How many milliliters of each of two liquids with sp. gr. 0.950 and 0.875 should be used to prepare 1500 ml of liquid having sp. gr. of 0.925%. (1) 0.950 0.050 parts of liquid (1) 0.025 parts (2) 0.925 (2) 0.875 Relative amounts = 0.050 : 0.025 = 2 : 1 Total = 3 parts 3 parts 1500 ml 2 parts x ml x = 1000 ml of liquid with sp. gr. 0.950 3 parts 1500 ml 1 part y ml y = 500 ml of liquid with sp. gr. 0.875 1000 + 500 = 1500 -18-