Pharmaceutical Calculation Techniques and Terminologies PDF

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EncouragingClematis

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Addis Ababa Science and Technology University

2024

Yibekal. M

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pharmacokinetics pharmaceutical calculations emulsions pharmaceutics

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This document discusses pharmaceutical calculation techniques and terminologies, including emulsions and semisolid dosage forms. The content seems to be lecture notes or study materials focused on the topic.

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PHARMACEUTICAL CALCULATION TECHNIQUES AND TERMINOLOGIES By :-Yibekal. M( PHA,PH & SPECIALTY IN EPIDEMIOLOGY) 12/8/2024 1 Emulsion  is a dispersion in which the dispersed phase is composed of small...

PHARMACEUTICAL CALCULATION TECHNIQUES AND TERMINOLOGIES By :-Yibekal. M( PHA,PH & SPECIALTY IN EPIDEMIOLOGY) 12/8/2024 1 Emulsion  is a dispersion in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible  An emulsion consists of at least two immiscible liquid phases  In emulsion terminology, the dispersed phase is the internal phase, and the dispersion medium is the external or continuous phase  12/8/2024 2 Emulsion…  The main advantages of emulsions:  Increased drug bioavailability(administration of a hydrophobic drug in a soluble/dissolved state)  coadministration of lipid increases bile secretion  Increased drug stability  Prolonged drug action  12/8/2024 3 Emulsion…  Types of emulsions: a. Oil-in-water emulsion(o/w): When the oil phase is dispersed as globules throughout an aqueous continuous phase  aqueous phase constitutes more than 45% of the total weight and a hydrophilic emulsifier is used b. Water-in-oil emulsion(w/o): When the aqueous phase is dispersed, and the oil phase is the continuous phase  used mainly for external applications 12/8/2024 4 Emulsion…  The use of a lipophilic emulsifier enables the formation of w/o c. Multiple emulsions: are emulsions whose dispersed phase contains droplets of another emulsion  Both water-in-oil-in-water (w/o/w) and oil-in-water-in-oil Water (o/w/o) are of interest as delayed- and/or sustained-action drug delivery systems d. Microemulsions are: visually homogeneous, transparent/isotropic systems of low viscosity 12/8/2024 5 2. Semisolid dosage forms  Dosage forms that can change shape upon application of force, malleable and semisolid state at room temperature e.g. ointments, creams, gels, pastes, lotions  semisolid formulations can be used for topical or systemic drug action  Topical applications can be designed for either local effects or systemic absorption 12/8/2024 6 Semisolid dosage forms… A. Ointments:  are semisolid preparations intended for external application to the skin or mucous membranes (medicated or non medicated)  are typically used as: a. emollients to make the skin more pliable, b. protective barriers to prevent harmful substances from coming in contact with the skin, and c. vehicles in which to incorporate medication. 12/8/2024 7 Semisolid dosage forms…  Ointment Bases: are generally classified into four groups a. Oleaginous bases (hydrocarbon bases):  they have an emollient effect  protect against the escape of moisture  Greasy and difficult to wash off  Incorporation of hydrophobic drug  E.g. Petrolatum, Wax 12/8/2024 8 Semisolid dosage forms… b. Absorption bases:  are of two types:  those that permit the incorporation of aqueous solutions resulting in the formation W/O e.g., hydrophilic petrolatum 12/8/2024 9 Semisolid dosage forms…  used as emollients  not easily removed from the skin with water washing(oil ex. Phase) c. Water-Removable Bases are( oil-in-water emulsions):  Water-removable bases (commonly called creams)  easily washed from skin (water-washable bases)  Drug carriers  Foundation for makeup  E.g. Hydrophilic Ointment, vanishing cream 12/8/2024 10 Semisolid dosage forms d. Water-Soluble Bases:  do not contain oleaginous components  may be anhydrous or may contain some water  They are washable in water and absorb water to the point of solubility  E.G. Polyethylene glycol (PEG) ointment  12/8/2024 11 Semisolid dosage forms… B. Cream:  are semisolid dosage forms containing one or more drug substances dissolved or dispersed in a suitable o/w or w/o emulsion base.  Are generally described as either non washable or washable  Compared to ointments, creams are easier to spread and remove 12/8/2024 12 Semisolid dosage forms… c. Gels: consisting of either a suspension of small inorganic particles or large organic molecules interpenetrated by a liquid  are semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle rendered jellylike by the addition of a gelling agent 12/8/2024 13 Semisolid dosage forms… d. lotion:  is a low- to medium-viscosity medicated or non medicated topical preparation, intended for application to unbroken skin  are liquid preparations intended for external application to the skin. They are generally suspensions or emulsions of dispersed solid or liquid materials in an aqueous vehicle.  Most lotions are o/w emulsions, but w/o lotions are also formulated 12/8/2024 14 Semisolid dosage forms… e. Pastes:  are semisolid dosage forms that contain a large proportion of solid component  Contain larger amounts of solids and consequently are thicker and stiffer.  Semisolid dispersion system, where a solid particles (> 25%) are dispersed in ointments – mostly oleaginous (Petrolatum) 12/8/2024 15 Semisolid dosage forms… e. Suppository:  solid or semisolid mass intended to be inserted into a body orifice (i.e., rectum, urethra)  intended for insertion into body orifices where they melt, soften, or dissolve and exert local or systemic effects.  Types of suppositories:  Rectal suppositories : usually cylindrical and tapered to a point, forming a bullet-like shape. 12/8/2024 16 Semisolid dosage forms…  Vaginal suppositories are oval and typically weigh approximately 5 g  Urethral suppositories (bougies)  Suppository bases:  should remain solid at room temperature but soften, melt, or dissolve readily at body temperature  A suppository base should be physically and chemically stable 12/8/2024 17 Semisolid dosage forms…  nonirritating, nontoxic, no sensitizing, chemically and physiologically inert,  compatible with a variety of drugs, stable during storage, and esthetically acceptable  The types include: a. Fatty or Oleaginous Bases:  E.g. cocoa butter melts at 30°C to 36°C, it is an ideal suppository base, melting just below body temperature and yet maintaining 12/8/2024 its solidity at usual room temperatures 18 Semisolid dosage forms… b. Water-Soluble and Water-Miscible Bases:  slower to soften and mix with the physiologic fluids than is cocoa butter and therefore provides a slower  E.g. by glycerinated gelatin and polyethylene glycols (PEGs) f. foam: is a coarse dispersion of a gas in a liquid which is present as thin films 12/8/2024 19 4. Gaseous dosage forms 1. Aerosols :  are colloidal dispersions of liquids or solids in gases  Some aerosol emissions are intended to be inhaled deep into the lungs (inhalation aerosol), whereas others are intended for topical application to the skin or to mucous membranes 2. volatile anaesthetics 12/8/2024 20 2. MEASURING PHARMACEUTICAL QUANTITIES A. Mathematical Review:  Fraction: indicates a portion of whole number  It contain two numbers bottom number (Denominator ) and the upper number (Numerator)  A proper fraction: should always be less than one ; the numerator is smaller than denominator. A/B, where, A < B  Improper fractions: is a fraction in which the numerator is greater than or equal to the denominator A/B, Where, A ≥ B 12/8/2024 21 cont…  Accuracy:  represents the degree of closeness of a measurement to the desired, target, or actual quantity  is a measure of distance from the target.  E.g. quantity to be weighed is 125 mg but the actual weighed quantities are 121 and 123 mg hence 123 is more accurate  Precision:  represents the reproducibility or repeatability of a measurement  In pharmacy practice, both accuracy and precision are needed. 12/8/2024 22 cont… Digits other than zero are significant. A zero between digits is significant. Final zeros after a decimal point are significant. Zeros used only to show the location of the decimal point are not significant. E.g.  0.0125 = 3 significant figures (two leading zeros)  1.032 = 4 significant figures (zero within digits)  18,543 = 5 significant figures  4.34 = 3 significant figures  0.9 = 1 significant figure (leading zero) 12/8/2024 23 cont… Ratio & ratio strength:  Ratio:  T he relative amount of two quantities (one to the other)  A colon( : ) generally separates the two numbers in a ratio  Where as a fraction is presented as, A/B i.e 1/2 , a ratio is presented as 1:2 and read as “ one is to two”  In pharmacy practice, ratios are often used to express the concentration of a drug in a solution or the weight or dose of a drug in a delivery unit or volume 12/8/2024 24 cont… Exercise: a. Dispense cimetidine 400 mg per dose; on hand is 200 mg tablets b. Dispense 10 mg metoclopramide per dose; on hand is 5 mg/mL 28. c. Dispense 250 mg dicloxacillin per dose; on hand is 500 mg/5 mL e. 12/8/2024 25 cont…  proportion:  represents the equality of two ratios is defined as an expression of two equal ratios It may be written in any one of three standard forms:  a:b=c:d or a:b::c:d or a/b=c/d  expressions is read as : a is to b as c is to d  a and d are called the extremes (meaning “outer members”) and b and c the means (“middle members”) 12/8/2024 26 cont… Exercise: a. An antilipidemic agent contains 5 mg of the medication per tablet. How many tablets would be necessary to supply 35 mg per dose? b. A cough medication contains 50 mg of active ingredient per mL. The physician desires 100 mg per dose. How many mL would each dose contain? c. A physician orders a 250 mg dose of an antibiotic for a child. The pediatric liquid medication contains 125 mg per 5 mL. How many ml should the child take with each dose? 12/8/2024 27 cont… percent: is a type of ratio. Percent comes from the Latin phrase per centum, translated per hundred( i.e. per hundred parts or hundredth part) To change a percent to a fraction, drop the % sign and place the remaining number as the numerator over the denominator 100. Reduce the fraction to lowest terms To change a percent to a decimal, drop the % sign and divide by 100 12/8/2024 28 cont…  To change a decimal to a percent, multiply by 100 and add the % sign.  To change a ratio to a percent, first convert the ratio to a fraction. Convert the resulting fraction to a decimal and then to a percent.  E.g. 1) 15 is what percentage of 45?  Solution: 15/45=1/3×100=33%  2) What is 3% of 42?  Solution: First change the % to a decimal by dividing by 100 or moving the decimal point 2 places to the left or 0.03. Then multiply 42 × 0.03 = 1.26. So 1.26 (what) is 3% of 42. 12/8/2024 29 cont…  The fraction may be found in three ways: I. Finding the percentage, as in “What is 50% of 15?”  Percentage or whole quantity (x ) = percent number ( 50% ) × whole number ( 15) II. Find the whole quantity, as in “15 is 60% of what number?”  Percentage or whole quantity (15) = percent number ( 60 %) × whole number (x ) III. Finding the percent number, as in “5 is what percent of 15?”  Percentage or whole quantity (5) =percent number (x ) × whole number (15 ) 12/8/2024 30 cont… System of Measurement Used in Pharmacy Practice  quantitative accuracy is essential in the preparation of safe and effective medications  E.g.  the compounding and dispensing of prescriptions  large-scale industrial manufacture of pharmaceuticals  clinical dose calculations and adjustments for individual patient needs 12/8/2024 31 cont…  Pharmaceutical measurement of weight and volume is an important part of pharmacy practice  The measurement systems include: A. Metric System B. Apothecary systems C. Household system D. Avoirdupois 12/8/2024 32 cont… A. Metric System (International System of Units)  The system was formulated in France in the late 1799.  the most widely used and accepted system of measurement in the world  based on the principle of multiples of 10 to define different ranges of quantities  Parts of basic units are named by adding a prefix. Each prefix has a numerical value  T he base units of the SI are the meter (for length), the kilogram (for weight), and the liter (for volume). 12/8/2024 33 cont… 12/8/2024 34 cont… Guidelines for the Correct Use of the SI  Unit names and symbols are not capitalized except when used at the beginning of a sentence or in headings. however, the symbol for liter (L, l) may be capitalized or not. E.g. 4 g not 4G  Periods are not used following SI symbols except at the end o a sentence  A compound unit that is a ratio or quotient of two units is indicated by a solidus (/) or a negative exponent, for example, 5 mL/h or 5 mL·h−1.  Symbols should not be combined with spelled-out terms in the same expression e.g. 3 mg/mL, not 3 mg/milliliter. 12/8/2024 35 cont…  Plurals of unit names, when spelled out, have an added “s.” Symbols or units, however, are the same in singular and plural, for example, 5 milliliters or 5 mL, not 5 mLs.  Decimal fractions are used, not common fractions, for example, 5.25 g, not 5¼ g  A zero always should be placed in front of a leading decimal point to prevent medication errors caused by uncertain decimal points, for example, 0.5 g, not.5 g  To prevent misreadings and medication errors, “trailing” zeros should not be placed following a whole number. E.g. 5 mg, not 5.0 mg 12/8/2024 36 cont…  In selecting symbols of unit dimensions, the choice generally is based on selecting the unit that will result in a numeric value between 1 and 1000.  E.g. , 500 g, rather than 0.5 kg; 1.96 kg, rather than 1960 g; and 750 mL, rather than 0.75 L Exercise 1:A container of IV fluids contains 1/2 liter. How many milliliters is this? Exercise2: Amoxicillin is available as 250 mg/capsule. How many grams of amoxicillin does each capsule contain? Exercise3: A 5 L bag of fluid contains how many microliters? 12/8/2024 37 cont…  Measure of Length: meter is the basic unit of length used to measure distances in the metric system.  1 kilometer (km) = 1000 meters  1 hectometer (hm) = 100 meters  1 decameter (dam) = 10 meters  1 decimeter (dm) = 0.100 meter  1 centimeter (cm) = 0.010 meter  1 millimeter (mm) = 0.001 meter  1 micrometer (mm) = 0.000,001 meter 12/8/2024 1 nanometer (nm) = 0.000,000,001 meter 38 cont…  Measure of Volume: The liter is the metric unit of volume Example: How many liters are there in 350 mL?  Common instruments for the pharmaceutical measurement of volume range from micropipets and burettes used in analytic procedures to large, industrial-size calibrated vessels.  Examples of common containers for measuring volume are:  Graduated Measuring Cylinders  Conical measures  Beakers 12/8/2024 39 cont…  Conical Graduate :  The Conical graduate has a wide mouth and wide base to allow the stirring of liquids with a glass stirring rod. The conical graduate varies in size from 10ml to 4000ml  Cylindrical Graduates :  The Cylindrical graduate is uniform from top to bottom and is the most accurate graduate for the measurement of liquids 12/8/2024 40 cont..  As a general rule:  carefully observe the meniscus at eye level to achieve the desired measurement.  select the graduate with a capacity equal to or just exceeding the volume to be measured.  Measurement of small volumes in large graduates tends to increase the size of the error  the narrower the bore or chamber, the lesser the error in reading the meniscus and the more accurate the measurement 12/8/2024 41 Read the amount of liquid at the level of the bottom of meniscus 12/8/2024 42 cont..  According to the United States Pharmacopeia, a deviation of 1 mm in the meniscus reading causes an error of approximately 0.5 milliliter when a 100- milliliter cylindric graduate is used and an error of 1.8 milliliters at the 100- milliliter mark in a comparable conical graduate 12/8/2024 43 Conical and cylindrical graduates 12/8/2024 44 cont..  Measure of Weight:  The unit of weight in the metric system is the gram(g).  A gram equals approximately the weight of 1 cubic centimeter (cc) or 1 milliliter (mL) of water at 4°C  1 kilogram (kg) = 1,000 grams 1 hectogram (hg) = 100,000 grams 1 dekagram (dag) = 10,000 grams 1 decigram (dg) = 0.100 gram 1 centigram (cg) = 0.010 gram 1 milligram (mg) = 0.001 gram 1 microgram ( mcg) = 0.000,001 gram 12/8/2024 45 cont..  Example 1: If a chlorpheniramines maleate tablet weights 0.26g, one fourth of the same tablet weighs how many milligrams?  Example 2: If a vial of gentamycin contains 80mg of a drug in 2ml, how many micrograms of the drug are present in 0.025ml?  The selection of balance and scale for weight measurements depends on the task at hand, from highly sensitive electronic analytic balances and prescription balances in extemporaneous compounding procedures to large-capacity scales in the industrial manufacturing and production of pharmaceutical products 12/8/2024 46 cont..  There are two main types of prescription balances: Class A and B  Sensitivity: Is the smallest weight that makes a perceptible change in the pointer of a balance which indicates the equilibrium position  Sensitivity Requirements(SR):  the minimum weight required to move the pointer by one division on the scale.  SR for class A prescription Balance is 6mg while that of class B prescription balance is 30mg.  Capacity : Is the maximum weight, which a balance can weigh.  The capacity of most class A and class B prescription balance is 120g 12/8/2024 47 cont..  Percentage of error : defined as the maximum potential error multiplied by 100 and divided by the quantity desired  When a pharmacist measures a volume of liquid or weighs a material, two quantities become important:  the apparent weight or volume measured, and  the possible excess or deficiency in the actual quantity obtain Percentage of Error = (Error/quantity desired)×100% = SR×100%/Quantity desired= (approximate- exact/exact)× 100% 12/8/2024 48 cont..  Example: Using a graduated cylinder, a pharmacist measured 30 mL of a liquid. On subsequent examination, it was determined that the pharmacist had actually measured 32 mL. What was the percentage of error in the original measurement?  Solution: The volume of error = 32 ml – 30 ml = 2ml  2×100%/30= 6.7% Exercise: A pharmacist weighed 475 mg of a substance on a balance of dubious accuracy. W hen checked on a balance of high accuracy, the weight was found to be 445 mg. Calculate the percentage of error in the first weighing. 12/8/2024 49 The apothecary system of measurement  was the traditional system used in the practice of pharmacy  an early English system of weights and liquid measure.  The ancient apothecary system was the first system of medication measurement used by apothecaries (precursor pharmacists) and physicians  The basic unit for weight is the grain(gr).  Dram(dr is also a unit of weight); 1 dr =60 gr.  An ounce(abbreviated as oz) is larger than a dram; 1 oz =8 dr. 12/8/2024 50 The apothecary system of measurement 12/8/2024 51 The household system of measurement  is the most commonly used system in outpatient settings, where a patient at home without accurate measuring equipment  1 teaspoonful(tsp) = 5ml  1 dessertspoonful(dssp) =8ml  1 tablespoonful(tbsp) = 15ml  1 ounce = 2tbsp or 30 ml  1 wine-glass = 1ounce  1 coffee cup = 6 fluidounce  1 glass = 8 fluidounce  1 quart(qt) = 1 liter 12/8/2024 53 The avoirdupois system of measurement  is a French system of mass that includes ounces and pounds and used in commerce to supply bulk chemicals and other items by weight  The grain is the same weight in the apothecary and avoirdupois systems  the ounce and the pound in the two systems differ in the number of grains per unit  The apothecary ounce contains 480 grains, whereas the avoirdupois ounce contains 437.5 grains  The apothecary pound contains 5,760 grains, whereas the avoirdupois pound contains 7,000 grains 12/8/2024 54 The avoirdupois system of measurement  The interconversions between these units and their relationship to the metric system are as follows: 1 kg = 2.2 lb 1 lb = 16 oz 1 oz = 437.5 gr = 28.4 g 1 gr = 65 mg 12/8/2024 55 The avoirdupois system of measurement  Example:  Suprax ® suspension contain 100mg/5ml of the drug cefixime. If the patient takes one teaspoonful of the suspensions twice daily for ten days. How many grams of the drug does the patient consume? 12/8/2024 56 6. Density, specific gravity and specific volume Density(d):  is mass per unit volume of a substance  usually expressed as grams per cubic centimeter (g/cc)  Because the gram is defined as the mass of 1 cc of water at 4⁰C, the density of water is 1 g/cc.  the United States Pharmacopeia states that 1 mL may be used as the equivalent of 1 cc, the density of water may be expressed as 1 g/mL. Density= mass/volume 12/8/2024 57 Density, specific gravity and specific volume…  Example :  What is the density of hydrochloric acid weighing 10 mL and 20g?  Specific gravity (sp gr):  is a ratio, expressed decimally, of the weight of a substance to the weight of an equal volume of a substance chosen as a standard, both substances at the same temperature or the temperature of each being known.  Water is used as the standard for the specific gravities of liquids and 12/8/2024 solids; the most useful standard for gases is hydrogen 58 Density, specific gravity and specific volume… Specific gravity(spgr)= weight of substance/weight of equal volume of water  In the United States Pharmacopeia, the standard temperature for SPGR is 25°C, except for that of alcohol, which is 15.56°C  The specific gravity of water is always 1  Substances that have a SPGR less than 1 are lighter than water.  Substances that have a SPGR greater than 1 are heavier than water 59 Density, specific gravity and specific volume…  Example: if 10ml of sulfuric acid weighs 18g, and 10ml of water, under similar condition weigh 10g, determine the specific gravity of acid?  Spgr= 18g/10g= 1.8  Example 2: If 32.5 mL of oil weighs 28.8 g, what is the specific gravity of the oil?  Weight of the oil = 28.8g , volume of oil = 32.5ml  Volume of water = volume of oil = 32.5ml  32.5 mL of water weighs 32.5gm therefore, spgr= 28.8g/32.5g= 0.88 12/8/2024 60 Density, specific gravity and specific volume…  A pycnometer:  is a special glass bottle used to determine specific gravity.  To calculate the specific gravity of a liquid by means of a specific gravity bottle, the container is filled and weighed first with water and then with the liquid  By subtracting the weight of the empty container from the two weights, we have the weights of equal volumes  Since 1 g of water equals 1 mL, the exact volume of the pycnometer 12/8/2024 becomes known. 61 Density, specific gravity and specific volume… Example1: A specific gravity bottle weighs 23.66 g. When filled with water, it weighs 72.95 g; when filled with another liquid, it weighs 73.56 g. What is the specific gravity of the liquid?  Weight of liquid = 73.56 g - 23.66 g = 49.90 g of liquid  Weight of water= 72.95 g - 23.66 g = 49.29 g of water  Specific gravity of liquid = 49 90 (g)/ 49.29 (g) = 1.012 Example2: A 50ml pycnometer is found to weigh 120g when empty, 171g when filled with water and 160g when filled with unknown liquid. Calculate the specific gravity of the unknown liquid. 12/8/2024 62 Density, specific gravity and specific volume…  Specific volume:  in pharmaceutical practice, is usually defined as an abstract number representing the ratio, expressed decimally, of the volume of an equal weight of another substance taken as a standard, both having the same temperature.  Water is the standard for liquids and solids  It may be calculated by dividing the volume of a given mass by the volume of an equal weight of water. 12/8/2024 63 Density, specific gravity and specific volume… Example :If 25g of glycerin measure 20ml and 25 g of water measure 25 ml under the same conditions, the specific volume of the glycerin is: Vol. of 25 g of glycerin/ Vol. of 25 g of water = 20ml/25ml = 0.8  sp gr and sp vol are reciprocals  a substance that is heavier than water will have a higher specific gravity and a lower specific volume  a substance that is lighter than water will have a lower specific gravity and a higher specific volume. 12/8/2024 64 Density, specific gravity and specific volume… Example: What is the specific volume of phosphoric acid having a specific gravity of 1.521?  1/1.521 = 0.66 Calculating the specific gravity of Solid spgr of Solid determined using displacement methods Solid heavier than water and insoluble in water Measure the weight of solid in air Calculate the weight of displaced water when the solid immersed in it. 12/8/2024 65 Density, specific gravity and specific volume… Weight of displaced water = weight of the solid in air - weight of the solid in water Spgr= weight of solid/weight of displaced water Example: A piece of glass weighs 38.525 g in air and 23.525 g when immersed in water. What is its specific gravity? 38.525 g – 23.525 g = 15 g of displaced water (weight of an equal volume of water) 12/8/2024 66 Density, specific gravity and specific volume… Weight of substance = volume x specific gravity The weights of equal volumes and the volumes of equal weights of liquids are proportional to their specific gravities Although it’s both obvious and true that one can’t multiply milliters by specific gravity and have product in grams, the equation” works’’ because the volume of the liquid in questions is assumed to be the same volume as water for which milliters equal grams 12/8/2024 67 Percentage preparations  The amounts of therapeutically active and/or inactive ingredients in certain types of pharmaceutical preparations are expressed in terms of their percent concentrations.  Concentration is the quantity of a substance in relation to a definite volume or weight of other substance( e.g. 2g/5g, 4ml/5ml, 5mg/1ml)  The relative amount of a substance in a multicomponent system represents its concentration 12/8/2024 68 Percentage preparations…  T he percent concentrations of active and inactive constituents in various types of pharmaceutical preparations are defined as follows: a. Percent weight-in-volume (w/v)  Expresses the number of grams of a constituent in 100 mL of solution or liquid preparation,  is used regardless of whether water or another liquid is the solvent or vehicle.  Expressed as: ____% w/v. 12/8/2024 69 Percentage preparations… b. Percent volume-in-volume (%v/v):  Expresses the number of milliliters of a constituent in 100 mL of solution or liquid preparation.  Expressed as: % v/v. c. Percent weight-in-weight (%w/w):  expresses the number of grams of a constituent in 100 g of solution or preparation.  Expressed as: % w/w. 12/8/2024 70 Percentage preparations…  The term percent, or the symbol %, when used without qualification means:  for solutions or suspensions of solids in liquids, %W/V  for solutions of liquids in liquids, % V/V  for mixtures of solids or semisolids, %W/W and  for solutions of gases in liquids, %W/V 12/8/2024 71 Percentage preparations…  Special Considerations in Percentage Calculations  In general, the nature of the ingredients in a pharmaceutical preparation determines the basis of the calculation.  A powdered substance dissolved or suspended in a liquid vehicle would generally be calculated on a weight-in-volume basis;  A powdered substance mixed with a solid or semisolid would generally be calculated on a weight in weight basis.  a liquid component in a liquid preparation would be calculated on a volume-in-volume basis. 12/8/2024 72 Percentage preparations…  In most instances, use of percentage concentrations in the manufacture and labeling of pharmaceutical preparations is restricted to instances in which the dose of the active therapeutic agent (ATI) is not specific  In most dosage forms, such as tablets, capsules, injections, oral solutions, and syrups, among others, the amounts of ATIs are expressed in definitive units of measure, such as milligrams per capsule, milligrams per milliliter, or other terms. 12/8/2024 73 Percentage preparations… Examples: 1. How many grams of dextrose are required to prepare 4000ml of a 5% solution?  5g/100ml=x/4000ml x=( 5gx4000ml)100ml= 200g 2. How many grams of potassium permanganate should be used in compounding the following prescription?  Rx Potassium permanganate …………….0.02%  purified water ad…………………………….. 250ml  sig. As directed.  Solution:  250ml represent 250g of solution, 0.02% = 0.0002  250 g x 0.0002 = 0.05g, answer 12/8/2024 74 Percentage preparations… 3. What is the percentage strength (w/v) of a solution of urea, if 80ml contain 12g? 80ml of water weigh 80g  80g/12g= 100%/x% x= 15% or (12g/80ml)×100 4. An ear drop preparation contains 54 mg of antipyrines and 14 mg of Benzocaine in each ml of solution. Calculate the percentage strength(W/V) of each ingredient in the formula. Ans. Antipyrine 5.4% , Benzocaine 1.4% 12/8/2024 75 Percentage preparations… Exercises: 1. A hydrocortisone cream contains 1% hydrocortisone. Calculate the grams of hydrocortisone used to prepare each 15-g tube of product. 2. 1500 g o a solution contains 75 g of a drug substance, what is the percent strength (w/w) of the solution? 3. 5 g of boric acid are added to 100 mL of water, what is the percent strength (w/w) of the solution?(hint: 100ml of water= 100g) 12/8/2024 76 Ratio strength  Ratio Strength Solutions:  Concentration expressions for weak solutions (or solids)  is another way of expressing percentage strength.  Because percentage strength is essentially a ratio of parts per hundred, conversion between ratio strength and percentage strength is easily accomplished by proportion  E.g. Express 0.1% w/v as a ratio strength  0.1g/100ml= 1part/x = calculating the proportion results, 1000 parts, for ratio strength of 1:1000 12/8/2024 77 Ratio strength…  Example2:  Express 1:2500 as a percentage strength  1 part/ 2500= x part/100 calculating the proportion results, x= 0.04% 12/8/2024 78 Percentage preparations…  Parts per Million (PPM) and Parts per Billion (PPB)  The strengths of very dilute solutions are commonly expressed in terms of parts per million (ppm)  Parts per million (ppm) represents 1 part of a substance in 1 million parts of the total mixture  E.g. fluoridated drinking water in which fluoride has been added at levels of between 1 to 4 parts per million (1:1,000,000 to 4:1,000,000) ) for the purpose of reducing dental caries 12/8/2024 79 Percentage preparations…  Parts per billion (ppb):  represents 1 part of a substance in 1 billion parts of the total mixture  is dimensionless and does not represent a state (solid or liquid) of the substance  E.g. The concentration of a drug additive in an animal feed is 12.5 ppm. How many milligrams of the drug should be used in preparing 5.2 kg of feed? Answer: 65mg 12/8/2024 80 concentrations based on moles and equivalents  Molecular weights or moles of a compound are more useful for calculations when two or more chemical compounds are to be compared for a given attribute  The molecular weight of a compound represents the weight of one mole (abbreviation: mol) of a compound, in grams  An equivalent weight of a compound represents its molecular weight divided by the number of valence or ionic charges in solution  It takes into account the chemical activity of an electrolyte 12/8/2024 81 concentrations based on moles and equivalents…  One equivalent (abbreviation: Eq): in grams, of a compound represents 1 mole of compound in grams divided by its valence  E.g. molecular weight of Mg2+ ions is 24.3 g , On the other hand, the equivalent weight of Mg2+ ions is 24.3/2 = 12.15 g  A milliequivalent(mEq): represents the amount, in milligrams, of a solute equal to 1 1000 / of its gram equivalent weight, taking into account the valence of the ions  The valence of an element is a number that represents its capacity to combine to form a molecule of a stable compound 12/8/2024 82 concentrations based on moles and equivalents…  Example: What is the concentration, in percent w/v, of a solution containing 2 mEq of potassium chloride per milliliter? a. Find the molecular weight (mol wt) Atomic wt K = 39 Atomic wt Cl =35.5 39 + 35.5 =74.5 g mol wt of KCl b. Calculate the equivalent weight (Eq wt) of KCl. Eq wt = mol wt/ valence = 74.5 /1 = 74.5 g hence, mEq wt = 74.5 g/1000 = 0.0745 g or 74.5 mg c. 0.0745 g/mEq ×2 mEq = 0.149 g of drug, therefore, 0.149 g drug/1 mL = xof g drug /100ml= 14.9 g/100 mL= 14.9% 12/8/2024 83 values for some important ions 12/8/2024 84 Cont… 12/8/2024 85 concentrations based on moles and equivalents…  Molarity (abbreviation: M): is defined as the moles of solute per liter of solution.  E.g. 1 M of sulfuric acid solution represents 98 g (molecular weight) of H2SO4 dissolved in 1 L of solution  Normality (abbreviation: N): represents gram equivalent weight of solute (atomic weight or molecular weight)/valence) per liter of solution  Molality (abbreviation: m): is a less frequently used term that represents the number of moles of solute per kilogram of solvent 12/8/2024 86 calculations involving units  International Units(IU):  A unit is the amount of medication required to produce a certain effect and the size of a unit varies for each drug  they are standardized by international agreement  E.g. Some medications, such as vitamins, Insulin, heparin, and penicillin are measured in USP units.  Most types of insulins are manufactured in concentrations of 100 units/mL or 500 insulin units per milliliter o solution or 12/8/2024 suspension 87 calculations involving units  E.g. How many milliliters of U-100 insulin should be used to obtain 40 units of insulin? U-100 insulin contains 100 units/mL  Ans. 100 units/40 units = 1ml/xml X= 0.4 ml  Exercise: T he content of a vial of penicillin G potassium weighs 600 mg and represents 1 million units. How many milligrams are needed to prepare 15 g of an ointment that is to contain 15,000 units of penicillin G potassium per gram?(ans. 135 mg; hint first determine the total units out of 15g the use proportion with 600mg/ 1 mill. units) 12/8/2024 88 Dilution and concentration  Stock Solutions:  are solutions of known concentration that are prepared by the pharmacy professionals for convenience in dispensing  are frequently used in pharmacy dispensing to increase the efficiency, ease, and accuracy of dispensing, as well as the space and cost advantages with the transportation and storage of lower-volume concentrated solutions.  They are usually strong solutions from which weaker ones may be made conveniently. 12/8/2024 89 Dilution and Concentration  Pharmaceutical preparation are diluted by :  By adding diluent  Admixture with solutions or mixtures of lower strength  Pharmaceutical preparation are concentrated by:  By addition of active ingredient  Evaporation of diluent  Admixture with solution or mixture of higher strength. 12/8/2024 90 Dilution and Concentration…  If the amount of drug remains constant in a dilution or concentration,  any change in the mass or volume of a mixture is inversely proportional to the concentration  Dilution and concentration problems can be solved by the equation: a. quantity1 × concentration1 = quantity2 × concentration2 Q1 X C1 = Q2 X C2 12/8/2024 91 Dilution and Concentration  Examples: 1. dilute a 50% w/v stock solution to make 200 mL of a 5% w/v solution,  ans: c1 = 50, c2 = 5, and v2 = 200 v1= c2 × v2/c1 = 5 × 200/50= 20ml  Hence, the amount of stock solution needed = 20 mL and the amount of solvent needed = 200 − 20 = 180 mL to make a total of 200 mL of the diluted solution. 12/8/2024 92 Dilution and Concentration 2. If 500ml of a 15% (v/v) solution of methyl salicylate in alcohol are diluted to 1500 ml, what will be the percentage strength (v/v)? 1500 ml = 15 % = X=5% 500 ml X% Or, Q1(quantity) x C1(concentration) = Q2(quantity) x C2( Concentration) 500 x 15 % = 1500 ml x X X = 5% 3. How many mL of 5 percent acetic acid solution must be used to make 125 mL of 2 percent acetic acid solution? 12/8/2024 93 Dilution and Concentration… b. Alligation: is an arithmetical method of solving problems that involves the mixing of solutions or mixtures of solids of different percentage strengths. I. Alligation medial: A method for calculating the average concentration of a mixture of two or more substances  E.g. W hat is the percentage of zinc oxide in an ointment prepared by mixing 200 g o 10% ointment, 50 g o 20% ointment, and 100 g of 5% ointment? 12/8/2024 94 Dilution and Concentration…  Answer: 0.1 × 200= 20, 0.2 × 50g=10, 0.05 × 100g=5  20+10+5=35 and 200g+50g+100g=350 hence, (35/350) × 100= 10% II. Alligation alternate. A method for calculating the number of parts of two or more components of known concentration to be mixed when the final desired concentration is known  It involves matching pairs of ingredients, one higher in strength and one lower in strength than the desired strength, which lies somewhere in between 12/8/2024 95 Dilution and Concentration…  The alligation alternate method can be used for more than two ingredients by pairing off the values of:  one higher (than the desired) strength ingredient with two lower (than the desired) strength ingredients, or vice versa 12/8/2024 96 Dilution and Concentration 12/8/2024 97 Dilution and Concentration…  E.g.1 In what proportion should alcohols of 95% and 50% strengths be mixed to make 70% alcohol? 12/8/2024 98 Dilution and Concentration…  E.g.2 A hospital pharmacist wants to use three lots of zinc oxide ointment containing, respectively, 50%, 20%, and 5% of zinc oxide. In what proportion should they be mixed to prepare a 10% zinc oxide ointment?(ans. See on the next slide)  E.G.3 How many milliliters each of a 50% w/v dextrose solution and a 5% w/v dextrose solution is required to prepare 4500 mL of a 10% w/v solution?( ans. See the answer on slide 163) 12/8/2024 99 Dilution and Concentration…  Note that pairs must be used in each determination, one lower and one greater in strength than the desired strength. 12/8/2024 100 Dilution and Concentration…  T here is a total of 45 parts to prepare the 4500 mL mixture, or 100 mL per part (4500 mL/45 parts)  5 (parts) × 100 mL = 500 mL of the 50% w/v dextrose solution 40 (parts) × 100 mL = 4000 mL of 5% w/v dextrose solution 12/8/2024 101 Enlarging and Reducing formula  T he need to prepare different quantities of a pharmaceutical product depends on nature of the practice:  only small quantities may be required in a community pharmacy  modest quantities in a hospital pharmacy  larger quantities in outsourcing facilities  very large quantities are prepared in the pharmaceutical manufacturing industry 12/8/2024 102 Enlarging and Reducing formula  methods of ratio and proportion, dimensional analysis, and the factor method (the simplest way) may be used to reduce or enlarge a pharmaceutical formula  E.g. 1. From the following formula(next slide) for a dexamethasone ophthalmic ointment, calculate the quantity of each ingredient needed to prepare 7.5 g of ointment 12/8/2024 103 Enlarging and Reducing formula…  E.g.1. Dexamethasone sodium phosphate …..55 mg Lanolin, anhydrous …………………………….5 g Mineral oil ………………………………………….10 g White petrolatum, ad …………………………100 g  Step1 : finding factor  7.5g/100g= 0.075 12/8/2024 104 Enlarging and Reducing formula…  Step2:  Dexamethasone sodium phosphate = 55 mg × 0.075 = 4.125 mg Lanolin, anhydrous = 5 g × 0.075 = 0.375 g Mineral oil = 10 g × 0.075 = 0.75 g White petrolatum, ad …………………..…..7.5 g 12/8/2024 105 Enlarging and Reducing formula…  Eg.2.From the following standard formula for Calamine Compounded Topical Suspension, calculate the quantity of each ingredient required to prepare 240 mL of product  Calamine …………………………….80 g Zinc oxide ……………………………80 g Glycerin ……………………………..20 mL Bentonite magma ……………..250 mL Calcium hydroxide Topical solution, qs ad …………1000 mL  12/8/2024 See the Answer from the next slide( proportion method) 106 Enlarging and Reducing formula… 12/8/2024 107 calculating doses  Exercise: A prescription is written to prepare a mouthwash containing tetracycline 1 g, nystatin suspension 60 mL, Benadryl 60 mL and qs to 240 mL with dexamethasone.  What is the percentage of tetracycline in the final compound  What is the percentage (v/v) of nystatin suspension in the final mixture?  What volume of dexamethasone is needed to prepare the desired volume? 12/8/2024 108 calculating doses  Dosage is optimally calculated by using the child’s body weight or mass and the appropriate dose in milligrams per kilogram (mg/kg). Without these data, the following formulas based on an adult dose can be used:  Clark’s rule : based on the weight of the child  Pediatric dose = (Child s weight in pounds/ 150 pounds) × Adult dose  Young’s rule: Young’s rule is used for children older than 1 year  Pediatric dose= (Child’s age in years/ Child’s age in years 12/8/2024 +12) ×adult dose 109 calculating doses  Note: that Young’s rule is not valid after 12 years of age  Fried’s rule: is a method of estimating the dose of medication for infants younger than 1 year of age. (Age in months/150) × average adult dose  The formula for determining a dose for a child based on the BSA and adult dosage is: Pediatric dose = (Body surface area (BSA) of child /1.7) × Adult dose 12/8/2024 110 Pharmaceutical equipments 1. Mortar &pestle:  are two tools used with each other to mill (grind) and mix substances  The mortar is bowl-shaped, and used to hold the substance to be grounded.  The pestle is a stick used for pounding and grinding  Might be glass or porcelain 12/8/2024 111 Cont… porcelain mortars and pestles are used to decrease particle size of solids to aid in dissolution in liquids and also to ensure comparable mixtures of semisolids and semisoft dosage forms Glass mortars and pestles are preferred for mixing liquids and semisoft dosage forms Advantages of glass mortars and pestles are that they are nonporous and non staining 12/8/2024 112 Cont… 2. A water bath:  It is used to incubate samples in water at a constant temperature over a long period of time.  All water baths have a digital or an analogue interface to allow users to set a desired temperature 12/8/2024 113 cont… 3. Beam/digital balance : is the most accurate and precise instrument that uses force sensors to measure the load of an object E.g. Triple beam balance:  The maximum mass it can measure is 610 grams (500 grams + 100 grams + 10 grams).  the smallest mass 0.1g  Has Weighing pan , base, Beams, Adjusting knob, riders and pointers 12/8/2024 114 cont… Digital (electronic)Class A balances:  have a weighing capacity that ranges from 1 mg to a maximum of 300 g 12/8/2024 115 Pharmaceutical equipments… 4. Spatula: is a hand-held tool that is used for lifting, flipping, or spreading of ingredient 12/8/2024 116 Cont.. 5. Watch glass:  It is a general utility item, used to hold small samples, to evaporate liquids, to cover a beaker, and etc... 12/8/2024 117 Cont.. 6. Measuring cylinder:  A graduated cylinder, measuring cylinder or mixing cylinder is a common piece of laboratory equipment used to measure the volume of a liquid  It has a narrow cylindrical shape  designed with a narrow diameter that is the same from top to base 12/8/2024 118 Cont… 7. Conical flasks( Erlenmeyer flask or titration flask)  is a type of laboratory flask which features a flat bottom, a conical body, and a cylindrical neck  for holding liquids and mixing them by swirling 12/8/2024 119 Cont… 8. Beakers:  are simple liquid containers that are usually cylindrical in shape, with a flat bottom.  they commonly range in size from 25 mL to 600 mL  should be used to mix and melt substances. 12/8/2024 120 Cont… 9. Pipettes (pipets):  are small glass or plastic tubes used to transfer measurable amounts of liquid from one container to another.  are used to measure small amounts of solution very accurately using a bulb (a pipette filler) to draw solution into the pipette 12/8/2024 121 Cont… 10. Droppers:  A short glass tube with a rubber bulb at one end and a tiny hole at the other, for measuring out drops of medicine or other liquids. 12/8/2024 122 Cont… 11. Electronic Mortar and Pestle:  is an advanced piece of machinery that uses the latest technology and high speeds to mix ingredients in a fast and uniform manner. It is used to prepare liquids, creams, lotions, and gels. 12/8/2024 123 cont… 11. Greasy proof paper:  is paper that is impermeable to oil or grease and is normally used in cooking or food packaging 12/8/2024 124 Cont… 13. Amber colored dispensing bottle  These environmentally sensitive bottles help eliminate waste and help to insure product integrity for long term storage  protect sample from UV rays and are ideal for light sensitive products. 12/8/2024 125 Cont… 14. Ointment slab:  is either ground glass plates or porcelain and provide a hard, non absorbable surface for mixing 12/8/2024 126 Cont… 15. Ointment jars:  A container which is used to pack, hold and transport ointment preparation 12/8/2024 127 Cont… 16. Suppository moulds:  Are a materials come in a variety of cavity sizes and with a variety of number of cavities per mold which used to design shape of suppository preparation. 12/8/2024 128 Cont… 17. Ointment Mill:  is used to decrease particle size of creams, lotions, gels, pastes, and liquids  Ceramic rollers compress the material and reduce the particles to minute sizes( ensures a product that is smooth and free of large particles) 12/8/2024 129 Cont… 18. Hot plates:  are used for fast heating of substances and are available with ceramic or aluminum tops, which heat to different temperature levels (the ceramic tops heat to higher temperatures). 12/8/2024 130 Cont… 19. Tongs:  include crucible tongs with or without ridges, beaker tongs, flask tongs, and test tube holders  They are used for the sterile grasping and maneuvering of a variety of different types of laboratory equipments 12/8/2024 131 Cont… 20. Ultrasonic cleaners(ultrasonic baths):  can clean metal and plastic equipment  They effectively remove blood, proteins, contaminants, grease, waxes, and oils  work by moving sound waves through a heated solution to create cavitations 12/8/2024 132 Cont… 21. Stirring rods:  may be made of glass, rubber, polypropylene, or bendable  are used to stir a variety of solutions or mixtures in the laboratory 12/8/2024 133 Cont… 22. Funnels:  are tubes that have a wide mouth and a narrow bottom  are used when pouring liquids from one container into another, commonly in conjunction with filter papers in order to remove insoluble particles or contaminants 12/8/2024 134 Cont… 23.Safety glasses, gloves, and masks:  are all used in the compounding pharmacy setting to enhance disease control and to prevent the transfer of pathogens to and from the staff  They also protect technicians from exposure to hazardous or potentially hazardous materials. 12/8/2024 135 Thank You 12/8/2024 136

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