Phbps113L PDF: Density and Specific Gravity

Module 6 Density and Specific Gravity The absolute density of a solid or liquid is the mass of a unit volume of the substance. Density=MassVolume Generally, however, in using the term density, we refer to the relative density or the density at a given temperature relative to the density of distilled...

Module 6 Density and Specific Gravity The absolute density of a solid or liquid is the mass of a unit volume of the substance. Density=MassVolume Generally, however, in using the term density, we refer to the relative density or the density at a given temperature relative to the density of distilled water, either at the same temperature, represented by d, or at 40C, represented by d4t. When, in the latter case, the density is corrected for the buoyancy of the air, the number obtained represents the true specific gravity of the substance. In common practice, however, and in all except very exact work, the specific gravity of a substance is taken as the ratio of the weight of the substance to the weight of an equal volume of distilled water at the same temperature. Specific Gravity=Weight of substance/Weight of an equal volume of distilled water In the official standards, the specific gravity of a substance has been established as the ratio of the apparent weight of the substance in air at 250C to that of an equal volume of distilled water at the same temperature, or d25/25, except when otherwise stated and for alcohol, which should be determined at 15.560C and compared with water at the same temperature. The standard temperature for measurement of the specific gravity of alcohol was established by the US Internal Revenue Service based on the fact that a 50% by volume alcoholic liquid occupies exactly 1 gallon of liquid at this temperature. An alcoholic liquid which contains exactly 50% alcohol by volume at 15.560C is said to be 100 proof. (A more detailed discussion of proof strength is in Learning Module No. 4 of the lecture.) Commonly, specific gravity is determined by two (2) methods: the pycnometer method (for liquids) and the displacement method (for both liquids and solids). Method I in the United States Pharmacopoeia Chapter Specific Gravity specifies the procedure for the pycnometer method of determining specific gravity. Method II involves an instrumental technique based on the oscillation of the liquid inside a U-shaped tube; this method will not be covered in this course. Pycnometer Method The specific gravity of liquids can be determined very accurately by means of some form of pycnometer or specific gravity bottle, such as that shown in Figure 6.1. A pycnometer is a special glass bottle used to determine specific gravity. Although a number of different kinds of pycnometers have been developed by investigators, those described in this module may be used for practically all determinations of the specific gravity of liquids required in pharmaceutical analysis. Pycnometers have fitted glass stoppers with a capillary opening to allow trapped air and excess fluid to escape. The Geissler pycnometer (Figure 6.2) is well suited for accurate determinations of specific gravity and can be procured in sizes varying from 25- to 100-mL capacity. Pycnometers of this type may be provided with a thermometer stopper and a capillary overflow tube fitted with a ground-glass cap to prevent evaporation. The cap should have a very small perforation in its top to permit the liquid to expand without forcing the cap loose. The thermometers provided with these pycnometers are not always accurate and should be tested by comparison with one of known accuracy whenever exact determinations are made. Geissler pycnometer is a specific gravity bottle that is fitted with a thermometer to simultaneously determine the temperature with the weight of the liquid in the bottle. In determining the specific gravity of a liquid with a pycnometer, the thermometer and cap are removed, the previously cleaned bottle is filled with the liquid, which has been cooled from 1 to 30C below the temperature at which the specific gravity is to be determined. Displacement or Plummet Method Calculating the specific gravity of a liquid determined by the displacement or plummet method is based on Archimedes' principle (Figure 6.3), which states that : a body immersed in a liquid displaces an amount of the liquid equal to its own volume and suffers an apparent loss in weight equal to the weight of the displaced liquid Thus, we can weigh a plummet when suspended in water and when suspended in a liquid the specific gravity of which we want to determine; and by subtracting these weights from the weight of the plummet in air, we get the weights of equal volumes of the liquids needed in our calculation. The volume of regular solids (i) can be determined by using the lengths of their sides or their radii (or diameters). On the other hand, the volume of an irregularly shaped object (ii) can be determined by displacement method, which is based on Archimedes' principle. When the irregularly shaped object is fully immersed in the liquid, its volume is the same as the volume of the displaced liquid, and the weight of the displaced liquid is the same as the apparent loss in weight of the object. In determining the specific gravity of an unknown liquid, a glass plummet with known weight is determined and its apparent loss in weight of the unknown liquid and of the distilled water are used. The specific gravity is the ratio of the apparent loss in weight of the unknown liquid to the apparent loss in weight of the distilled water. (Photo from Gupta, Yellishetty, & Singh, 2017) The displacement method for determining the specific gravity of solids require only distilled water as the standard liquid. Generally, the basic principle is to determine the apparent weight loss of the solid immersed in distilled water. This represents the weight of a volume of the liquid equal to the volume of the solid. Remember that a solid immersed in a liquid displaces its own volume of the liquid according to Archimedes' principle. The common formula is shown below: specific gravity =weight of the solid/weight of displaced water specific gravity =weight of the solid/ apparent weight loss of water The apparent weight loss of the solid in water is simply the difference between its weight in air and its weight in water. However, in order to determine the specific gravity of solids using the displacement method, its relative density to water and solubility in it must be taken into consideration. Study the following scenarios: If the solid is less dense than water, it will float, so its entire body will not be immersed in water. The volume of water displaced by a solid lighter than water will not be equal to the volume of the whole solid. To completely immerse the solid, a sinker (e.g., metal washer) can be attached to it. The weight of the sinker in water is likewise determined to be subtracted from the sum of the weight of the solid in water and the weight of the combined solid and sinker in water. This will give the apparent weight loss of the solid when "immersed" in water. If the solid is soluble in water, it cannot be immersed it, so another liquid must be used. As discussed in the lecture (Learning Module No. 3), the weights of equal volumes of any two substances are proportional to their specific gravities. Thus, the apparent weight loss of the solid in water can be estimated by proportion with its apparent weight loss in any liquid in which it is immersed. Module 7 Medications are ordered by a physician either on a written prescription for the patient to take to a pharmacy for dispensing, or as a medication order in a patient medical record. A prescription is an order of medication issued by a physician, dentist, or other properly licensed medical practitioner. It designates a specific medication and dosage to be prepared by a pharmacist and administered to a particular patient. On the other hand, a medication order contains instructions written by the physician in hospitals and other institutions. A prescription is used in the outpatient, or ambulatory setting, whereas medication orders are used in the inpatient or institutional health system setting. In whatever setting, the order must be read and interpreted exactly so the correct medication and its dosage can be provided for patient safety. Before dispensing the prescription or medication order, the pharmacist’s responsibility is to evaluate the prescription or medication order for appropriateness. This includes ensuring the correct drug, dose and dosage form, frequency, route of administration, duration of therapy, and indication. Additionally, the patient’s profile is evaluated for therapeutic duplication, drug allergies, drug–disease state interactions, and drug–drug interactions, and laboratory data are reviewed, if available. This process helps ensure that the benefits of the therapy are maximized and the potential for harm is minimized. The five major components are the superscription (the Rx or ℞ symbol), inscription (the medication prescribed), subscription (instruction/s to the pharmacist), signa (instruction/s to the patient), and the signature of the prescriber. Aside from these parts, a prescription also has to contain the preprinted name of the physician or group of physicians, the address and phone number. This should also include the patient’s name, address, date of the prescription, and the patient’s age if the patient is a child. Dating prescriptions is important because prescriptions must be filled within 12 months of writing, except with controlled substances or scheduled medications. Furthermore, the refilling of the prescription is dependent on the date. Medication orders typically contain similar information that would be included on a prescription. 1. Prescriber information and signature 2. Patient information 3. Date prescription was written 4. Rx symbol (the Superscription), meaning "take thou," "you take," or "recipe" (Figure 7.2) 5. Medication prescribed (the Inscription) 6. Dispensing instructions to the pharmacist (the Subscription) 7. Directions to the patient (the Signa) 8. Special instructions The prescription sign or the Rx symbol (left) and the Eye of Horus subscription gives specific directions for the pharmacist (right) on how to compound the medication. The ability to understand the components of the prescription, as well as the ability to interpret the order or prescription, is an essential skill for the pharmacists and other health professionals who work with medications on a daily basis. Abbreviations and symbols are common in prescriptions and medication orders. Most abbreviations and symbols in prescriptions and medication orders are derived from Latin words and phrases. For a list of Latin abbreviations, download the glossary that can be found on this link: https://bit.ly/35YbZYs. A list of common abbreviations, acronyms, and symbols used in prescriptions and medication orders can also be downloaded from this link: https://bit.ly/32P8d1M. Although they may save time for the prescriber, they are sometimes a source of confusion and can be misinterpreted, resulting in medication errors. According to the US National Coordinating Council for Medication Error Reporting and Prevention, a medication error is “any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer.” As a result, the Joint Commission (formerly the Joint Commission on Accreditation of Healthcare Organizations, or JCAHCO) requires healthcare organizations to develop an approach to standardizing abbreviations, acronyms, and symbols, as well as to create a list of those that should not be used. In addition, the Institute for Safe Medication Practices (ISMP) has published a comprehensive list of symbols, abbreviations, and dose designations that lead to harmful medication errors called ISMP’s List of Error-Prone Abbreviations, Symbols, and Dose Designations. The use of these should be avoided; however, they are still being used so their definitions need to be misunderstood. Likewise, you can also access the Official "Do Not Use" list by the Joint Commission by clicking this link: https://bit.ly/32Rxng8. A whole number should be shown without a decimal point and without a terminal zero (e.g., express 4 milligrams as 4 mg and not as 4.0 mg). A quantity smaller than one should be shown with a zero preceding the decimal point (e.g., express two tenths of a milligram as 0.2 mg and not.2 mg). Leave a space between a number and the unit (e.g., 10 mg, and not 10mg). Use whole numbers when possible and not equivalent decimal fractions (e.g., use 100 mg and not 0.1 g). Use the full names of drugs and not abbreviations (e.g., use phenobarbital and not PB). Use USP designations for units of measure (e.g., for grams, use g and not Gm or gms; for milligrams, use mg and not mgs or mgm). Spell out "units" (e.g., use 100 units and not 100 u or 100 U since an illegible U may be misread as a zero, resulting in a 10-fold error, i.e., 1000). The abbreviation I.U., which stands for "International Units" should be spelled out, so it is not interpreted as I.V., meaning "intravenous."  Certain abbreviations that could be mistaken for other abbreviations should be written out (e.g., write "right eye" or "left eye" rather than use o.d. or o.l., and spell out "right ear" and "left ear" rather than use a.d., or a.l.). Spell out "every day," rather than use q.d.; "every other day," rather than q.o.d.; "four times a day," rather than q.i.d.; and "three times a week," rather than t.i.w. to avoid misinterpretation. Avoid using d for "day" or "dose" because of the profound difference between terms, as in mg/kg/day versus mg/kg/dose. Integrate capital or "tall man" letters to distinguish between "look-alike" drug names, such as hydrOXYZINE and hydrALAZINE, and DIGoxin and DESoxyn. Amplify the prescriber's directions on the prescription label when needed for clarity (e.g., use "Swallow one (1) capsule with water in the morning" rather than "one cap in a.m."). As previously mentioned, a number of commonly used abbreviations in writing prescriptions are derived from Latin words and phrases. With the arrival of computerized prescriptions (or e-prescriptions), however, the era of prescriptions in Latin is coming to an end. To ensure medication safety by minimizing dispensing errors, prescriptions should be written in English (or the language of the country). Prescribing that is unclear or illegible is both unethical and dangerous. It is noteworthy that prescriptions and in-patient orders are legal orders that can be used for medications, devices, laboratory tests, procedures, and the like. In some instances, “local” or nonstandard abbreviations might become an area of concern for possible misinterpretation. Electronic prescribing (e-prescribing) is the computer-to-computer transfer of prescription information between authorized prescribers, pharmacies, intermediaries, and payers under nationally accepted standards. In the inpatient or outpatient setting, a medication order for a patient is entered into an automated data entry system as a personal computer or a hand-held device loaded with e-prescribing software and sent to a pharmacy as an e-prescription. When an e-prescription is received in the pharmacy, then, it is printed out. Benefits of e-Prescriptions Among the advantages cited for e-prescriptions over traditional paper prescriptions are: reduced errors due to prescription legibility; concurrent software screens for drug allergies and drug interactions; integrated information exchange between health care providers; reduced incidence of altered or forged prescriptions; efficiency for both prescriber and pharmacist; and convenience to the patient, whose prescription would likely be ready for pick-up upon arrival at the pharmacy. Module 8 According to the Republic Act No. 10918, otherwise known as the “Philippine Pharmacy Act” drugs refer to “pharmaceutical products that pertain to chemical products or biological substances, other than food, intended for use in the treatment, prevention, or diagnosis of disease in humans or animals.” In drugs, the chemical substances, which are biologically active or responsible for their claimed therapeutic effects, are designated as active constituents. They are seldom administered alone; rather, they are given as part of a formulation in combination with one or more nonmedicinal agents that serve varied and specialized pharmaceutical functions. Selective use of these nonmedicinal agents, which are referred to as pharmaceutical ingredients or excipients, produces dosage forms of various types. The pharmaceutical ingredients solubilize, suspend, thicken, dilute, emulsify, stabilize, preserve, color, flavor and fashion medicinal agents into efficacious and appealing dosage forms. Each type of dosage form is unique in its physical and pharmaceutical characteristics. These varied preparations provide the manufacturing and compounding pharmacist with the challenges of formulation and the physician with the choice of drug and delivery system to prescribe. The general area of study concerned with the formulation, manufacture, stability, and effectiveness of pharmaceutical dosage forms is termed pharmaceutics. The proper design and formulation of a dosage form require consideration of the physicochemical and biologic characteristics of all of the drug substances and pharmaceutical ingredients to be used in fabricating the product. The drug and the pharmaceutical materials must be compatible with one another to produce a drug product that is stable, efficacious, attractive, easy to administer, and safe. The product should be manufactured with appropriate measures of quality control and packaged in containers that keep the product stable. The product should be labeled to promote correct use and be stored under conditions that contribute to maximum shelf life. The Need for Dosage Forms The potent nature and low dosage of most of the drugs in use today preclude any expectation that the general public could safely obtain the appropriate dose of a drug from the bulk material. That is, most drug substances are administered in milligram quantities, much too small to be weighed on anything, but a sensitive prescription or electronic analytical balance. When the dose of the drug is minute, solid dosage forms such as tablets and capsules must be prepared with fillers or diluents so that the dosage unit is large enough to pick up with fingertips. Besides providing the mechanism for the safe and convenient delivery of accurate dosage, dosage forms are needed for additional reasons: To protect the drug substance from the destructive influences of atmospheric oxygen or humidity (e.g., coated tablets, sealed ampuls) To protect the drug substance from the destructive influence of gastric acids after oral administration (e.g., enteric-coated tablets) To conceal the bitter, salty, or offensive taste or odor of a drug substance (e.g., capsules, coated tablets, flavored syrups) To provide liquid preparations of drug substances, either as dispersions (e.g., suspensions) or as clear preparations (e.g., solutions) To provide rate-controlled drug action (e.g., various controlled-release tablets, capsules, and suspensions) To provide optimal drug action from topical administration sites (e.g., ointments, creams, transdermal patches, and ophthalmic, ear, and nasal preparations) To provide for insertion of a drug into one of the body's orifices (e.g., rectal or vaginal suppositories) To provide for placement of drugs directly in the bloodstream or body tissues (e.g., injections) To provide for optimal drug action through inhalation therapy (e.g., inhalants and inhalation aerosols) Common Pharmaceutical Dosage Forms Drugs may be formulated as solid (tablets, capsules, powders, and granules), semi-solid (ointments, creams, and gels), liquid (solutions, suspensions, and emulsions), or gaseous (inhalants) dosage forms. In dealing with the problem of formulating a drug substance into a proper dosage form, research pharmacists employ knowledge gained through experience with other chemically similar drugs and through proper use of the physical, chemical, biologic, and pharmaceutical sciences. In addition, the most effective routes of administration (e.g., oral, rectal, parenteral, topical) must be determined, and guidelines for the dosages recommended for persons of varying ages (e.g., neonates, children, adults, the elderly), weights, and states of illness have to be established. Liquid Dosage Forms Solutions Solutions are liquid preparations that contain one or more chemical substances (solute/s) dissolved in a solvent or mixture of solvents. The solutes may be active or inactive ingredients and may be solids, liquids, or gases in their natural, undissolved state. The most common solvent used in pharmaceuticals is water; however, such liquids as alcohol, glycerin, and propylene glycol are used as solvents or co-solvents depending on the product requirements for stability and use. Solutions are formulated for administration by various routes, such as oral solutions (mouth), ophthalmic solutions (eye), otic solutions (ear), nasal solutions (nose), rectal solutions, urethral solutions, epicutaneous solutions (skin), and those administered by injection. Solutions used to bathe or flush open wounds or body cavities are termed irrigations. Certain solutions have special requirements, such as sterility (e.g., injections, irrigations, and ophthalmic solutions). Specific Types of Solutions Aromatic Waters Aromatic waters are clear, saturated solutions of volatile oils or other aromatic substances in water. They are used orally, topically, or pharmaceutically for the characteristics of the aromatic material they contain. Collodions Collodions are liquid preparations composed of pyroxylin dissolved in a solvent mixture usually composed of alcohol and ether with or without added medicinal substances. They are intended for external application to the skin. The solvent rapidly evaporates, leaving a thin protective film of pyroxylin (and medication, such as salicylic acid as a corn remover) as an occlusive coating. Elixirs Elixirs are sweetened, flavored, hydroalcoholic solutions intended for oral administration. They may be nonmedicated or medicated and are used in the same manner as syrups. Compared to syrups, elixirs are usually less sweet and less viscous because they contain a lesser amount of sugar. Because of their hydroalcoholic character, elixirs are better able than syrups to maintain both water-soluble and alcohol-soluble components in solution. Additional co-solvents, such as glycerin or propylene glycol, also may be used. The proportion of alcohol present in elixirs varies widely with the formulation and the requirements for solution. Elixirs of high alcoholic content generally include artificial sweeteners rather than sucrose as the sweetener. Because of their alcoholic content, elixirs generally are not administered to infants, young children, or other persons following alcohol-restricted diets. Spirits Spirits are alcoholic or hydroalcoholic solutions of volatile substances. Depending on their contents, some spirits are used orally for medicinal purposes and others as flavoring agents. Syrups Syrups are concentrated, aqueous solutions of a sugar or sugar substitute. Nonmedicated syrups are sweet, pleasant-tasting vehicles for medicinal substances to be added later, either in the extemporaneous compounding of prescriptions or in the preparation of a standard formula for a medicated syrup. Among the nonmedicated ingredients in syrups, other than the sugar or sugar substitute, are flavoring agents, colorants, co-solvents, and antimicrobial preservatives to prevent microbial growth. Syrups are administered orally for the therapeutic value of the medicinal agent/s. Tinctures Tinctures are alcoholic or hydroalcoholic solutions of either pure chemical substances or of plant extractions. Most chemical tinctures are applied topically (e.g., Iodine Tincture). Plant extractions are used for their content of active pharmacologic agents. Some extractions are administered as standardized preparations (e.g., Belladonna Tincture), whereas other types, such as fluidextracts and extracts, are mostly used to prepare other dosage forms. Fluidextracts are liquid preparations of plant extractives, each milliliter containing the active constituents from 1 g of the standard drug that it represents. Extracts are highly concentrated powdered or pilular (ointment-like) extractives of plant constituents prepared by the reduction of fluidextracts through evaporation. Suspensions Suspensions are preparations containing finely divided, undissolved drug particles dispersed throughout a liquid vehicle. Because the drug particles are not dissolved, suspensions assume a degree of opacity depending on the concentration and size of the suspended particles. Suspensions are one type of disperse systems, common among pharmaceutical preparations. Other types of disperse systems include emulsions, lotions, magmas, and gels. In these preparations, the suspended particles are referred to as the suspensoid, or the disperse, (or dispersed) phase, and the vehicle is termed the dispersion (or dispersing) phase. The particles of the disperse phase may be colloidal (about 1 millimicron, equivalent to 1 nm, or less), fine (about 1 micrometer), or coarse (100 micrometer). Particles of greater density have a tendency to settle and form a sediment. The addition of suspending agents, which add viscosity to the vehicle, is one method of maintaining the dispersed phase in suspension. Before administration, it is essential to redistribute any settled particle to assure uniform dosing. Suspensions are formulated for administration by a number of routes, including oral, otic, ophthalmic, epidermal, parenteral (by injection), and others, each with its own requisite characteristics. For example, ophthalmic suspensions must be sterile and the suspensoid must be micronized or very finely reduced to eliminate any grittiness that might cause irritation. Emulsions An emulsion is a type of disperse system in which one liquid is dispersed throughout another liquid in the form of fine droplets. The two liquids, generally an oil and water, are immiscible and constitute two phases that tend to separate into layers unless a third agent, an emulsifier or emulsifying agent, is added to facilitate the emulsification process and to provide stability to the system. In emulsions, the disperse phase is referred to as the internal phase, and the dispersing phase is termed the external phase. When the oil is the internal phase, the emulsion is called an oil-in-water (O/W) emulsion. If the water is the internal phase, the emulsion is called a water-in-oil (W/O) emulsion. The type of emulsion produced is largely determined by the hydrophilicity or lipophilicity of the emulsifying agent. Emulsifying agents that are more hydrophilic generally produce O/W emulsions, whereas emulsifying agents that are more lipophilic generally produce W/O emulsions. Emulsifying agents may have both hydrophilic and lipophilic characteristics. The term hydrophile-lipophile balance (HLB) quantifies this characteristic and is used in formulating and preparing emulsions of the desired type. Calculations are used to determine the quantities of oil, water, and emulsifying agent to use in preparing a stable emulsion. Emulsions are most frequently prepared and administered orally for the medicinal benefit of the oil (e.g., mineral oil, oleaginous vitamins A and D). The taste and oleaginous feel of the oil is masked when administered in the form of an O/W emulsion with flavored aqueous external phase. In addition to oral emulsions, some emulsions are prepared for topical administration (such as some lotions, foams, and creams) and for intravenous injection, for the nutritional benefit of the oil (usually soybean oil). Liniments Liniments are alcoholic or oleaginous solutions, suspensions, or emulsions of medicinal agents intended for external application to the skin, generally by rubbing. Lotions Lotions 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. Their fluidity allows rapid and uniform application over a wide skin surface. Lotions are intended to soften the skin and leave a thin coat of their components on the skin's surface as they dry. Magmas and Gels Magmas and gels are examples of fine pharmaceutical suspensions in which the suspensoid have a high degree of physical attraction to the aqueous vehicle, forming a gelatinous mixture that maintains the uniformity and stability of the suspension. Magmas and gels are administered orally. Injections Injections are sterile preparations intended for parenteral administration by needle or pressure syringe. Drugs may be injected into most any vessel or tissue of the body, but the most common routes are intravenous (IV), intramuscular (IM), and subcutaneous (SC). Injections may be solutions or suspensions of a drug substance in an aqueous or nonaqueous vehicle. They may be small volume injections, packaged in ampuls for single-dose administration, or vials for multiple dose injections. Large volume parenterals, containing 100-mL to 1 L of fluid, are intended for the slow intravenous administration (or infusion) of medications and/or nutrients in the institutional or home-care setting. Calculations with regard to injections include a number of special aspects: the relation of the injection volume to drug dosage and patient factors such as weight, body surface area, or disease state; the relation of the dosing regimen to the flow rate of the parenteral; and the formulation calculations related to isotonicity, osmolarity, or milliequivalent content. Solid Dosage Forms Capsules Capsules are solid dosage forms in which one or more medicinal and/or inert substances are enclosed within small shells of gelatin. Capsule shells are produced in varying sizes, shapes, thickness, softness, and color. Hard shell capsules, which have two telescoping parts—the body and the cap—are commonly used in extemporaneous hand-filling operations as well as in small and large scale manufacture of commercial capsules. They usually are filled with powder mixtures and granules. After filling, the two capsule parts are joined for tight closure. They may also be sealed and bonded through a variety of special processes for added quality assurance and capsule integrity. Soft-shell gelatin capsules, which are unibodied, are formed, filled, and sealed in the same process. Highly specialized and large-scale equipment is required, and thus soft gelatin capsules are only prepared commercially. They are rendered soft through the addition of a plasticizer to the capsule shell formation. Soft gelatin capsules may be filled with powders, semisolids, or liquids. Capsules are intended to contain a specific quantity to fill, with the capsule size selected to accommodate that quantity most closely. In addition to their medication content, capsules usually contain inert pharmaceutical substances, such as fillers, disintegrants, solubilizers, etc. When swallowed, the gelatin shell is dissolved by the gastrointestinal fluids releasing the contents. Capsules containing only nontherapeutic materials are termed placebos and are used widely in controlled clinical studies to evaluate the activity of a drug compared to nondrug in a group of human subjects. Some capsules and tablets, or their granulated contents, may be enteric coated, i.e., coated with special materials to resist the release of the medication in the gastric fluid of the stomach to prevent either drug inactivation or gastric irritation. Drugs in enteric coated products are intended to be released after transit through the stomach into the intestines. Extended-release capsules are formulated in such a manner to provide the active release of the medication from the dosage form over an extended period of time, such as 12 hours. The purpose is to provide constant drug release and sustained blood levels of the drug for steady-state therapy and/or to enhance patient compliance by reducing the need for more frequent dosing. Implants or Pellets Implants or pellets are small, sterile, solid dosage forms containing concentrated drug for implantation in the body where they continuously release their medication over prolonged periods. Pellets generally are prepared by compression and implanted subcutaneously by means of a special injector or by surgical incision. Lozenges Lozenges are solid dosage preparations containing one or more medicinal agents in a flavored, sweetened base intended to dissolve or disintegrate slowly in the mouth, releasing medication generally for localized effects. Lozenges are prepared by molding or compression. Powders Powders are dry mixtures of finely divided medicinal and nonmedicinal agents intended for internal or external use. Powders may be dispensed to a patient and used in bulk form (such as powders measured by the spoonful to make a douche solution) or they may be divided into single dosage units and packaged in folded papers or unit-of-use envelopes (paper tabs or papelitos). Suppositories Suppositories are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert localized or systemic effects. They are commonly used rectally or vaginally, and occasionally urethrally. Suppositories are prepared in various weights, sizes, and shapes depending on their intended use. Rectal suppositories intended for adults usually weigh about 2 g, measure 1 1/2 in in length, and are cylindric or bullet-shaped. Rectal suppositories for infants and children are proportionately smaller. Vaginal suppositories commonly weigh about 5 g and are globular, oviform, or conical. Urethral suppositories are thin and pencil-shaped, weighing approximately 4 g and measuring about 140 mm when intended for males and half the weight and length when intended for females. Bases of various types are used for suppositories as vehicles for the medication, including cocoa butter (theobroma oil), glycerinated gelatin, polyethylene glycols of various molecular weights, hydrogenated vegetable oils, and fatty acid esters of polyethylene glycol. Depending on the base used, the suppository either softens, melts, or dissolves after insertion, releasing its medication for the intended local action or for absorption and systemic effects. In addition to suppositories, especially prepared and shaped tablets, capsules, aerosol foams, ointments, creams, jellies, and solutions are designed for vaginal use. Rectal ointments, creams, foams, and enema solutions are also available. Tablets Tablets are solid dosage forms containing one or more medicinal substances with or without added pharmaceutical ingredients. Among the pharmaceutical agents used are diluents, disintegrants, colorants, binders, solubilizers, and coatings. Tablets may be coated for appearance, for stability, to mask the bitter taste of the medication, or to provide controlled drug release. Most tablets are intended to be swallowed whole. Some, however, are prepared to be "chewable," and produce a pleasant taste and feel with mastication. Other tablets are intended to be dissolved in the mouth (buccal tablets) or under the tongue (sublingual tablets), whereas effervescent tablets are intended to be dissolved in water before taking. Tablets are formulated to contain a specific quantity of drug substance. To enable flexibility in dosing, manufacturers commonly make available various tablet or capsule strengths of a given medication. As required, a tablet may also be broken in half (many tablets are "scored" or grooved for this purpose), or, more than a single table may be taken as a prescribed dose. Semisolid Dosage Forms Creams Creams are semisolid preparations containing one or more drug substances dissolved or dispersed in a suitable base. Many creams are either O/W emulsions or aqueous microcrystalline dispersions of long chain fatty acids or alcohols in a water-washable base. Compared to ointments, creams are easier to spread and considered by many patients to be more aesthetically appealing in the topical delivery of medications.Creams are used primarily for administering drugs to the skin, although some are prepared for vaginal use. Ointments Ointments are semisolid preparations intended for topical application. Most ointments are applied to the skin, although they may also be administered ophthalmically, nasally, aurally, rectally, or vaginally. With a few exceptions, ointments are applied for their local effects on the tissue membrane rather than for systemic effects. It is possible for systemic effects to occur after the topical application of medications. Systemic absorption, which takes place through the skin's surface, is referred to as percutaneous absorption. Percutaneous absorption may be enhanced by many factors, including the hydration of the skin, a concentrated (rather than dilute) application of preparation over a large surface area, application to thin rather than thick skin, through the hydrophilic-lipophilic nature of the drug, and by virtue of the occlusive features of the topical preparation and/or dressing. Nonmedicated ointments serve as the vehicles, or ointment bases, for the addition of the medication. Ointment bases are usually of four general types: 1. Hydrocarbon or oleaginous bases (such as petrolatum), which do not mix well with aqueous preparations and provide an occlusive barrier to the skin; 2. Absorption bases (such as lanolin), which permit the absorption of aqueous solutions, usually resulting in W/O emulsions; 3. Water-removable bases (such as hydrophilic ointment), which are O/W emulsions; or 4. Water-soluble bases (such as polyethylene glycol ointment), both of which are water-washable In preparing a medicated ointment, the appropriate ointment base is selected to which the medication is added. The solid and semisolid materials in ointments are generally weighed in preparing a prescription or product. Liquid components may be measured volumetrically or converted by calculation to corresponding weight and then weighed. Because ointments are semisolid preparations, they are also prepared, packaged, and dispensed on a weight basis. Special care must be taken in the preparation of ophthalmic ointments to render them free from microorganisms and to assure that the powders used in the formulation are either dissolved in the ointment base or micronized to a state of powder fineness to reduce or eliminate grittiness that could cause eye irritation. Pastes Pastes are semisolid dosage forms that contain one or more drug substances intended for topical application. Generally, pastes contain a higher proportion of solid materials than ointments and thus are more stiff, less greasy, and more absorptive of serous secretions when used on the skin. Medicated dental pastes are also prepared for adhesion to the mucous membranes for local effect. Plasters Plasters are solid or semisolid adhesive masses spread across a suitable backing material and intended for external application to a part of the body for protection or for the medicinal benefit of added agents. Aerosols Pharmaceutical aerosols are products packaged under pressure that contain therapeutically active ingredients that are released as a fine mist, spray, or foam on actuation of the valve assembly. The pressure within the aerosol container that forces the product out of the valve is provided by an inert compressed or liquified gas, termed the propellant. The product formulation and the type of valve used determine the emission, i.e., fine mist, coarse spray, foam, etc. Some aerosol emissions are intended to be inhaled deep into the lungs (inhalation aerosol) and must be of finer particles (less than 10 µm) than those intended for topical application to the skin or the mucous membranes of the nose, mouth, vagina, or rectum. Some aerosols have metered valve assemblies that permit a specific quantity of emission on valve actuation for dosage regulation. Inhalations Inhalations are finely powdered drug substances, solutions, or suspensions of drug substances administered by the nasal or oral respiratory route for local or systemic effects. Special devices are used to facilitate administration. Module 9 A solution is a chemically and physically homogeneous mixture of two or more substances. Homogeneous systems may be characterized as those having a uniform composition throughout the entire system; in contrast, heterogeneous systems are made up of matter in different states of aggregation (or phases), which are separable from one another by definite physical boundaries. The term solution generally denotes a homogeneous mixture that is liquid even though it is possible to have homogeneous mixtures that are solid or gaseous. Thus, it is possible to have solutions of solids in liquids, liquids in liquids, gases in liquids, gases in gases, and solids in solids. The first three of these are the most important in pharmacy, but the focus of this exercise will be on solutions of solids in liquids as these are the most common. The components of a solution are the dispersed substance (solute) and the dispersing medium (solvent). By common usage, the component that establishes the phase of a solution may be termed the solvent―this usually being the one in largest concentration. However, in considering an alcohol-water solution, such as Diluted Alcohol, either one could be considered the solvent. In fact, there is no theoretical basis for distinguishing one component as the solute and the other as the solvent. Broadly, solutions can be classified as one of two types. In the first type, although there may be lesser or greater interaction between the solute and the solvent, the solution phase contains the same chemical entity as found in the solid phase; thus, upon removal of the solvent, the solute is recovered unchanged. An example would be sugar dissolved in water where, in the presence of sugar in excess of its solubility, there is an equilibrium between sugar molecules in the solid phase with the sugar molecules in the solution phase. In the second type, the solvent contains a compound that is different from the one in the solid phase. The difference between the compound in the solid phase and solution is due generally to some chemical reaction that has occurred in the solvent. An example would be dissolving aspirin in an aqueous solvent containing some basic material capable of reacting with the acidic aspirin. Now, the species in solution would not only be undissociated aspirin but aspirin also as its anion, whereas the solid phase is aspirin in only its undissociated acid form. In this situation, if the solvent were removed, part of the substance obtained (the salt of aspirin) would be different from what was present initially in the solid. Solubility A saturated solution is one which has dissolved all of the solute it is capable of holding at a given temperature, this temperature being 250C, unless otherwise specified. As implied by the fact that a solution can be saturated with a chemical, the constituents of a solution are not always miscible in all proportions to form a homogeneous mixture. The solubility is the extent to which the solute dissolves resulting in a saturated solution at a specified temperature. For any given solute, the solubility has a constant value at a given constant temperature. The solubility of a chemical substance is expressed in many ways. The official compendia have adopted a system of stating the amount of solvent necessary to dissolve 1 g of the substance at 250C. Whenever the exact solubility of a chemical substance is not known or designated, the following descriptive terms are helpful to the pharmacist: Descriptive Terminologies Denoting Solubility Descriptive Term Parts of Solvents for 1 Part of Solute Very Soluble Less than 1 Freely Soluble From 1 to 10 Soluble From 10 to 30 Sparingly Soluble From 30 to 100 Slightly Soluble From 100 to 1,000 Very Slightly Soluble From 1,000 to 10,000 Practically Insoluble (or Insoluble) More than 10,000 The solubility of a substance in a given solvent may be determined by preparing a saturated solution of it at a specific temperature and by determining by chemical analysis the amount of chemical dissolved in a given weight of solution. The amount of solvent required to dissolve the amount of solute can be determined by a simple calculation. This method of determining the solubility will be discussed in more detail in a later course, in particular, in the Physical Pharmacy course. As mentioned in the previous section, the solubility of a chemical agent in a particular solvent relates to the maximum concentration to which a solution may be prepared with that agent and that solvent. When a solvent at a given temperature has dissolved all of the solute possible, it is said to be saturated. Intermolecular Forces of Attraction The most important factor that affects solubility of a chemical agent in a particular solvent involves the intermolecular forces of interaction (attraction/repulsion) between solute molecules, solvent molecules, and solute-solvent molecules. Attractive forces between atoms lead to the formation of molecules and ions. The intermolecular forces, which are developed between like molecules, are responsible for the physical state (solid, liquid, or gas) of the substance under given conditions, such as temperature and pressure. When molecules interact, attractive and repulsive forces are in effect. The attractive forces cause the molecules to cohere, whereas the repulsive forces prevent molecular interpenetration and destruction. When the attractive and repulsive forces are equal, the potential energy between two molecules is minimal and the system is most stable. Some of important intermolecular forces of attraction involve the following: 1. Ionic interactions 2. Hydrogen bonding 3. Van der Waals forces 4. Hydrophobic interaction When a solute dissolves, the substance's intermolecular forces of attraction must be overcome by forces of attraction between the solute and the solvent molecules. This entails breaking the solute-solute forces and the solvent-solvent forces to achieve the solute-solvent attraction. The Effect of pH Many of the important organic medicinal agents are either weak acids or weak bases, and their solubility depends on a large measure on the pH of the solvent. These drugs react either with strong acids or strong bases to form water-soluble salts. For instance, the weak bases, including many of the alkaloids (e.g., atropine, codeine, and morphine), antihistamine (e.g., diphenhydramine and promethazine), local anesthetics (e.g., cocaine, procaine, and tetracaine), and other important drugs, are not very soluble in water, but they are soluble in dilute solutions of acids. Pharmaceutical manufacturers have prepared many acid salts of these organic bases to enable the preparation of aqueous solutions. However, if the pH of the aqueous solution of these salts is changed by the addition of alkali, the free base may separate from solution unless it has adequate solubility in water. Organic medicinals that are weak acids include the barbiturate drugs (e.g., phenobarbital) and sulfonamides (e.g., sulfadiazine and sulfacetamide). These and other weak acids form water-soluble salts in basic solution and may separate from solution by a lowering of the pH. Energetics of Solution (Dissolution) Temperature is an important factor in determining the solubility of a drug and in preparing its solution. Most chemicals absorb heat when they are dissolved and are said to have a positive heat of solution (ΔHsolution > 0: endothermic), resulting in increased solubility with an increase in temperature. A few chemicals have a negative heat of solution (ΔHsolution < 0: exothermic) and exhibit a decrease in solubility with a rise in temperature. It is noteworthy that the solubility of a pure chemical substance at a given temperature and pressure is constant. That is, applying heat to the solute-solvent mixture or cooling down the system simply affects the rate of solution, that is, the speed at which the solute dissolves in the solvent, but not its solubility. Solubility and Rate of Solution Some chemical agents in a given solvent require an extended time to dissolve. To hasten dissolution, a pharmacist may employ one of several techniques, such as applying heat (i.e., for substances whose dissolution is endothermic), reducing the particle size of the solute, subjecting the ingredients to vigorous agitation, and/or using a solubilizing agent. Most chemical agents are more soluble at elevated temperatures than at room temperature or below because an endothermic reaction between the solute and the solvent uses the energy of the heat to enhance dissolution. However, elevated temperatures cannot be maintained for pharmaceuticals, and the net effect of heat is simply an increase in the rate of solution rather than an increase in solubility. An increased rate is satisfactory to the pharmacist because most solutions are unsaturated anyway and do not require a concentration of solute above the normal capacity of the solvent at room temperature. Pharmacists are reluctant to use heat to facilitate solution, and when they do, they are no to exceed the minimally required temperature, for many medicinal agents are destroyed at elevated temperatures and the advantage of rapid solution may be completely offset by drug deterioration. If volatile solutes are to be dissolved or if the solvent is volatile (as is alcohol), the heat would encourage the loss of these agents to the atmosphere and must therefore be avoided. Pharmacists are aware that certain chemical agents, particularly calcium salts, undergo exothermic reactions as they dissolve and give off heat. For such materials, the use of heat would actually discourage the formation of a solution. Methods of Expressing Concentration The concentration of a solution may be expressed in a number of different ways depending on the convenience of the person or persons concerned with its use. Those commonly used are as follows:  Molarity. The molarity of a solution expresses the number of gram-molecular weights (moles) of solute in 1 L of the solution. This is synonymous with formality (gram-formula weights per liter). Normality. The normality of a solution expresses the number of gram-equivalent weights of the solute in 1 L of the solution. Usually, we are concerned with aqueous solutions of acids, bases, and salts. The equivalent weight is defined as the weight of compound containing one equivalent of the element or radical in which we are interested. With respect to acids, the equivalent weight is the amount of the acid which can furnish 1.008 g of hydrogen ion and with respect to bases, it is the amount of base that can furnish 17.008 g of hydroxide ion. In salts it is necessary to determine which ion is to be considered. For example, a gram-molecular weight of sodium chloride (NaCl) contains one equivalent of each ion and one-half of the gram-molecular weight of sodium sulfate (Na2SO4) contains one equivalent of each ion. However, with a compound such as sodium bisulfate (NaHSO4), one gram-molecular weight contains one equivalent each of sodium or hydrogen ion and two equivalents of sulfate ion. Thus, if it is to be used for its sodium or for its hydrogen (as an acid) a gram-molecular weight is equal to the equivalent weight, but when used for its sulfate ion, the equivalent weight is one-half the molecular weight. Molality. The molality of a solution expresses the number of moles of the solute in 1 kg of the solvent. Mole fraction. Mole fraction is the number of moles of a component divided by the number of moles in that solution. Mole percent may be obtained by multiplying mole fraction by 100. Percent. Percent (also, per cent) means “parts per hundred parts.” Aside from the analytical aspects of pharmacy, the percent designation is the most important to pharmacists. Percentage concentrations are expressed as follows: Percent Definition Percent Weight-in-Weight (%w/w) Expresses the number of grams of a constituent in 100 g of solution Percent Weight-in-Volume (%w/v) Expresses the number of grams of a constituent in 100 mL of solution and is used in prescription practice regardless of whether water or another liquid is the solvent Percent Volume-in-Volume (%v/v) Expresses the number of milliliters of a constituent in 100 mL of solution The USP indicates that the term percent, when used in prescriptions without qualification, means percent weight in weight for mixtures of solids and semisolids; percent weight in volume for solutions or suspensions of solids in liquids; and percent volume in volume for solutions of liquids in liquids. Preparation of Syrup, NF Syrups are prepared in various ways, the choice of the proper method depends on the physicochemical characteristics of the substances entering into the preparation. Among the various methods are (a) solution with heat; (b) agitation without heat; (c) addition of a medicating liquid to syrup; (d) percolation; and (e) reconstitution. Percolation is the preferred method for the preparation of Syrup NF. In this procedure, purified water, or an aqueous solution, is permitted to pass slowly through a bed of crystalline sucrose, thus dissolving it and forming a syrup. A cotton pledget is placed in the neck of the percolator and the water or aqueous solution added. By means of a suitable stopcock the flow is regulated so that drops appear in rapid succession. If necessary, a portion of the liquid is recycled through the percolator to dissolve all the sucrose. Finally, sufficient purified water is passed through the cotton to make the required volume. Preparation of Calcium Hydroxide Topical Solution, USP Certain chemical agents, particularly calcium salts, undergo exothermic reactions as they dissolve and give off heat. For such materials, the use of heat would actually discourage the formation of a solution. Calcium hydroxide is soluble in water to the extent of 140 mg/100 mL of solution at 250C and 170 mg/100 mL of solution at 150C. The official concentration is based upon a temperature of 250C. Preparation of Diluted Alcohol NF When equal volumes of alcohol and water are mixed together a rise in temperature and a contraction of about 3% in volume take place. In small operations, the contraction generally is disregarded; in larger operations, it is very important. Preparation of Zinc Oxide Ointment USP Ointments are prepared by: (a) incorporation, or (b) fusion depending on the nature of the ingredients. The oleaginous base of Zinc Oxide Ointment USP is White Ointment USP, which is prepared by melting the components white wax and white petrolatum. Module 10 Constitution of Dry Powders for Oral Solution or Suspension Some drugs, most notably antibiotics, lose their potency in a relatively short period when prepared in a liquid dosage form. To enhance the shelf-life of these drugs, manufacturers provide products to the pharmacy in a dry powder form for constitution (or reconstitution) with purified water or special diluent at the time a prescription or medication order is received Depending on the product, the dry power may be stable for about 24 months. After constitution, the resultant solution or suspension is stable in the quantities usually dispensed, for up to 10 days at room temperature or 14 days if maintained under refrigeration. Dry powders for constitution are packaged in self-contained bottles of sufficient size to accommodate the addition of the required volume of diluent. In addition to the quantitative amount of therapeutic agent, the powder contains such pharmaceutical agents as solubilizing, or suspending agents, stabilizers, colorants, sweeteners, and flavorants. On receipt of a prescription order, the pharmacist follows the label instructions for constitution, adding the proper amount of purified water or other diluent to prepare the liquid form. Depending on the product's formulation, constitution results in the preparation of a clear solution (often called a syrup for many commercially available oral dosage forms), or a suspension. The final volume of product is the sum of the volume of solvent or diluent added and the volume occupied by the dissolved or suspended powder mixture. These products generally are intended for infants and children but also can be used by adults who have difficulty swallowing the counterpart solid dosage form products, such as tablets and capsules. Constitute or Reconstitute? Some labeling instructions use the term "reconstitute" rather than "constitute" in describing the general process. Technically, if a dry powder is prepared from its original solution by removing the solvent (as through freeze drying), and then the solution is restored by the pharmacist, the term "reconstituted" would correctly apply. Some injectible products are prepared in this fashion. Like the medical substances intended for oral administration, some drugs (particularly antibiotics) intended for injection are provided as dry powder in vials to be constituted with sterile water for injection, or other designated solvent or diluent immediately before use. Generally, these medications are small-volume products intended for use by injection or as additives to large-volume parenterals. In contrast to the dry powders intended for oral use after constitution, injectable products may contain only limited amounts of specified added ingredients (e.g., antimicrobial preservatives particularly in multiple-dose sterile preparations) to increase the stability and effectiveness of the drug. These powders for injection do not contain colorants, flavorants, or sweeteners. Therefore, the bulk volume of the dry powder is largely entirely the medication. If the quantity of the drug powder is small and does not contribute significantly to the final volume of the constituted solution, the volume of solvent used will approximate the final volume of solution. If the dry powder, however, because of its bulk, contributes to the final volume of the constituted solution, the increase in volume produced by the drug must be considered, and this factor must be used in calculating the amount of solvent needed to prepare the solution of a desired concentration. Procedure In order to understand the basis of the volume of Purified Water used to constitute (or reconstitute) a dry powder for solution or suspension, bulk density and tapped density of powders will be introduced. The following procedures are specified in the United States Pharmacopoeia and National Formulary General Chapter. Bulk Density The bulk density of a powder is the ratio of the mass of untapped powder sample and its volume including the contribution of the interparticulate void volume. It is expressed in grams per milliliter (g/mL) although the international unit is kilograms per cubic meter (1 g/mL = 10000 kg/m3) because the measurements are made using cylinders. Below is the procedure for Method I (Measurement in a Graduated Cylinder): 1. Pass a quantity of material sufficient to complete the test through a sieve with apertures greater than or equal to 1.0 mm, if necessary, to break up agglomerates that may have formed during storage; this must be done gently to avoid changing the nature of the material. 2. Into a dry graduated 250-mL cylinder (readable to 2 mL) introduce, without compacting, approximately 100 g of test sample, M, weighed with 0.1% accuracy. 3. Carefully level the powder without compacting, if necessary, and read the unsettled apparent volume (V0) to the nearest graduated unit. 4. Calculate the bulk density in g/mL by the formula: M/V0 Generally, replicate determinations are desirable for the determination of this property. If the powder density is too low or too high, such that the test sample has an untapped apparent volume of either more than 250 mL or less than 150 mL, it is not possible to use 100 g of powder sample. Therefore, a different amount of powder has to be selected as the test sample, such that its untapped apparent volume is 150–250 mL (apparent volume greater than or equal to 60% of the total volume of the cylinder); the weight of the test sample is specified in the expression of results. For test samples having an apparent volume between 50 mL and 100 mL, a 100-mL cylinder readable to 1 mL can be used; the volume of the cylinder is specified in the expression of results. Tapped Density The tapped density is an increased bulk density attained after mechanically tapping a container containing the powder sample. Tapped density is obtained by mechanically tapping a graduated measuring cylinder or vessel containing a powder sample. After observing the initial powder volume or weight, the measuring cylinder or vessel is mechanically taped, and volume or weight readings are taken until little further volume or weight change is observed. The mechanical tapping is achieved by raising the cylinder or vessel and allowing it to drop under its own weight a specified distance by any of the methods outlined in USP General Chapter. Below is the procedure for Method I: 1. Proceed as directed above for the determination of the bulk volume (V0). 2. Secure the cylinder in the holder of the “tapping” apparatus. 3. Carry out 10, 500, and 1250 taps on the same powder sample and read the corresponding volumes V10, V500, and V1250 to the nearest graduated unit. If the difference between V500 and V1250 is less than or equal to 2 mL, V1250 is the tapped volume. If the difference between V500 and V1250 exceeds 2 mL, repeat in increments such as 1250 taps, until the difference between succeeding measurements is less than or equal to 2 mL. Fewer taps may be appropriate for some powders, when validated. Calculate the tapped density (g/mL) using the formula: M/VF where VF is the final tapped volume. Generally, replicate determinations are desirable for the determination of this property. Specify the drop height with the results. If it is not possible to use a 100-g test sample, use a reduced amount and a suitable 100-mL graduated cylinder (readable to 1 mL) weighing 130 ± 16 g and mounted on a holder weighing 240 ± 12 g. If the difference between V500 and V1250 is less than or equal to 1 mL, V1250 is the tapped volume. If the difference between V500 and V1250 exceeds 1 mL, repeat the increments such as 1250 taps, until the difference between succeeding measurements is less than or equal to 1 mL. The modified test conditions are specified in the expression of the results. Volume Occupied by Dry Powder 1. Weigh 5 g of the dry powder (lactose) in a suitable beaker. 2. Accurately transfer about 15 mL of distilled water to the beaker using a burette. 3. Allow the powder to dissolve. Ensure that no spillage of the solution occurs. If the powder does not dissolve, transfer more volumes of distilled water from a burette. 4. Gently shake the mixture to dissolve the powder. 5. Transfer the resulting solution to a clean and dry 50-mL volumetric flask. As much as possible, avoid droplets of liquid to adhere to the upper portion of the neck of the volumetric flask. 6. Swirl the flask. 7. Slowly add distilled water from the burette to fill the volumetric flask to the mark. 8. Note the total volume of distilled water delivered to fill the volumetric flask. 9. Determine the volume (in milliliters) occupied by the dry powder (lactose).