LOSS ON IGNITION This procedure is provided for the purpose of determining the percentage of test material that is volatilized and driven off under the conditions specified. Perform the test on finely powdered material, and break up lumps, if necessary, with the aid of a mortar and pestle before weighing the specimen. Weigh the specimen to be tested without further treatment unless a preliminary drying at a lower temperature or other special pretreatment is specified in the individual monograph. Unless other equipment is designated in the individual monograph, conduct the ignition in a suitable muffle furnace or oven that is capable of maintaining a temperature within 25° of that required for the test, and use a suitable crucible, complete with cover, previously ignited for 1 hour at the temperature specified for the test, cooled in a desiccator, and accurately weighed. Unless otherwise directed in the individual monograph, transfer to the tared crucible an accurately weighed quantity, in grams (g), of the substance to be tested, about equal to that calculated by the formula: 10/L in which L is the limit (or the mean value of the limits) for Loss on Ignition, in percentage. Ignite the loaded uncovered crucible, and cover at the temperature (±25°) and for the period of time designated in the individual monograph. When "ignition to constant weight" is specified in a monograph, ignite for successive 1-hour periods until two consecutive weighings do not differ by more than 0.50 mg/g of the specimen. Upon completion of each ignition, cover the crucible, and allow it to cool in a desiccator to room temperature before weighing accurately

DEAERATED WATER Deaerated Water or “degassed water” is Purified Water that has been treated to reduce the content of dissolved air by “suitable means” such as boiling, sonication, and/or stirring during the application of a partial vacuum, followed by immediate use or protection from air reabsorption

High-Purity Water High-Purity Water may be prepared by deionizing previously distilled water and then filtering it through a 0.45-μm rated membrane. This water must have an in-line conductivity of NMT 0.15 μS/cm (NLT 6.67 megohm-cm) at 25°C. If the water of this purity contacts the atmosphere even briefly as it is being used or drawn from its purification system, its conductivity will immediately increase by as much as about 1.0 μS/cm at 25°C as atmospheric carbon dioxide dissolves in the water and equilibrates to hydrogen and bicarbonate ions. Therefore, if the analytical use requires that water conductivity remains as low as possible or the bicarbonate/carbon dioxide levels be as low as possible, the water should be protected from atmospheric exposure. High-Purity Water is used as a reagent, as a solvent for reagent preparation, and for test apparatus cleaning where less stringent water specifications would not be considered acceptable. However, if a user’s routinely available Purified Water is filtered and meets or exceeds the conductivity specifications of High-Purity Water, it could be used in lieu of High-Purity Water.

FILTERED WATER Filtered Water is Purified Water that has been filtered to remove particles that could interfere with the analysis where this water is specified. It is sometimes used synonymously with Particle-Free Water and Ultra-Filtered Water and is cited in some monographs and general chapters as well as in Reagents, Indicators, and Solutions. Depending on its referenced location in USP– NF, it is variously defined as water that has been passed through filters rated as 1.2, 0.2, or 0.22 μm, or unspecified porosity rating. Even though the water names and the filter ratings used to produce these waters are defined inconsistently, the use of 0.2-μm or 0.22-μm filtered Purified Water should be universally acceptable for all applications where Particle-Free Water, Filtered Water, or Ultra-Filtered Water are specified.

LOSS ON DRYING PRINCIPLE Loss on drying is the loss of mass after drying under specified conditions, calculated as a percentage (m/m). Drying to constant mass means that 2 consecutive weighings do not differ by more than 0.5 mg, the 2nd weighing following an additional period of at least 30 minutes of drying under the conditions prescribed for the substance to be examined. EQUIPMENT The equipment typically consists of: – weighing bottles that are made of suitable inert material and can easily be dried to constant mass; their diameter is large enough so that the layer of the substance to be examined does not exceed about 5 mm; – an analytical balance by which it is possible to determine a change in mass of 0.1 mg; – depending on the procedure to be applied, a desiccator, a vacuum cabinet, a vacuum oven or an ordinary laboratory oven; in any case, the temperature of ovens is adjustable to the specified temperature ± 2 °C; vacuum ovens in which the pressure can at least be reduced to about 2 kPa are suitable; ovens are qualified according to established quality system procedures, for example by using a suitable certified reference material (sodium aminosalicylate dihydrate for equipment qualification may be used). Equipment using other means of drying such as microwaves, halogen lamps, infrared lamps or mixed technologies may be used provided they are demonstrated to be fit for purpose. PROCEDURE It is recommended to perform the test in an environment that has minimal impact on sample measurement (e.g. humidity). Weigh an empty weighing bottle that has been previously dried under the conditions prescribed for the substance to be examined for at least 30 minutes, then weigh the weighing bottle filled with the prescribed quantity of the substance to be examined. Dry to constant mass or for the prescribed time. Where the drying temperature is indicated by a single value rather than a range, drying is carried out at the prescribed temperature ± 2 °C. Use one of the following procedures, unless otherwise prescribed in the monograph. – In a desiccator: the drying is carried out over about 100 g of molecular sieve R at atmospheric pressure and at room temperature. – In vacuo: the drying is carried out over about 100 g of molecular sieve R at a pressure not exceeding 2.5 kPa, at room temperature or at the temperature prescribed in the monograph. – In an oven at a specified temperature: the drying is carried out at atmospheric pressure in an oven at the temperature prescribed in the monograph. After drying in an oven, allow the weighing bottle and the sample to cool to room temperature in a desiccator and weigh the weighing bottle containing the dried sample. The mass of the sample is the difference between the mass of the filled weighing bottle and the mass of the dried empty weighing bottle. The loss on drying is the difference in the mass of the sample before and after drying, expressed as a percentage, m/m being implicit.

DEIONIZED DISTILLED WATER Deionized Distilled Water is produced by deionizing Distilled Water. This water is used as a reagent in a liquid chromatography test that requires a low ionic or organic impurity level. Because of the importance of this high purity, water that meets the requirements for Purified Water may not be acceptable. High-Purity Water could be a reasonable alternative to this water. It is the user’s responsibility to verify the suitability of the alternative water used.

DEIONIZED WATER Deionized Water can be produced by starting with either Drinking Water or Purified Water, depending upon the monograph or testing procedures defined in the compendia. Deionized Water is produced by an ion-exchange process in which the cations and anions are replaced with H+ and OH− ions by use of ion-exchange resins. Similar to Distilled Water, Deionized Water is used primarily as a solvent for reagent preparation, but it is also specified in the execution of other aspects of tests, such as for transferring an analyte within a test procedure, as a calibration standard or analytical blank, and for test apparatus cleaning. Also, none of the cited uses of this water imply any needed purity attribute that can only be achieved by deionization. Therefore, water meeting the requirements for Purified Water that is derived by other means of purification could be equally suitable where Deionized Water is specified. It is the user’s responsibility to verify the suitability of Purified Water.

FRESHLY DISTILLED WATER Freshly Distilled Water or “recently distilled water” is produced in the same manner as Distilled Water and should be used soon after its generation. This implies the need to avoid endotoxin contamination, as well as any other forms of contamination from the air or containers, that could arise with prolonged storage. Freshly Distilled Water is used for preparing solutions for subcutaneous test-animal injections and for a reagent solvent in tests for which there appears to be no particularly high water purity needed that could be ascribable to being “freshly distilled”. In the test-animal application, the term “freshly distilled” and its testing use imply a chemical, endotoxin, and microbiological purity that could be equally satisfied by Water for Injection (although no reference is made to these chemical, endotoxin, or microbial attributes or specific protection from recontamination). For non-animal uses, water meeting the requirements for Purified Water derived by other means of purification and/or storage periods could be equally suitable where “recently distilled water” or Freshly Distilled Water is specified. It is the user’s responsibility to verify the suitability of Purified Water or Water for Injection.

Distilled Water is produced by vaporizing Drinking Water or a higher quality of water and condensing it into a purer state. It is used primarily as a solvent for reagent preparation, and it is also specified in the execution of other aspects of tests, such as for rinsing an analyte, transferring a test material as a slurry, as a calibration standard or analytical blank, and for test apparatus cleaning. Distilled Water is also cited as the starting water to be used for making High-Purity Water (see High-Purity Water). Because none of the cited uses of this water imply a need for a particular purity attribute that can only be derived by distillation, water meeting the requirements for Purified Water derived by other means of purification or Water for Injection could be equally suitable where Distilled Water is specified. It is the user’s responsibility to verify the suitability of Purified Water or Water for Injection

Carbon dioxide-free water is defined in the Reagents, Indicators, and Solutions section of USP–NF as Purified Water that has been vigorously boiled for NLT 5 min, then cooled and protected from absorption of atmospheric carbon dioxide. Alternatively, this could be Purified Water that has a resistivity of NLT 18 megohm-cm at 25°. Because the absorption of atmospheric carbon dioxide lowers the pH of high-purity waters, most of the uses of Carbon Dioxide-Free Water are either associated as a solvent in pH-related or pH-sensitive determinations or as a solvent in bicarbonate-sensitive reagents or determinations. The term “Carbon Dioxide-Free Water” is sometimes used improperly. Besides its use for pH or acidity/alkalinity tests, the purpose for using this water is not always clear. The intention could be to use water that was deaerated (free of dissolved air) or deionized (free of extraneous ions), or even Purified Water with an additional boiling step. Although boiling is highly effective for removing carbon dioxide as well as all other dissolved gasses, these gases are readily re-absorbed unless the water is protected. Even with protection, such as use of a stoppered container, re-absorption will occur over time as air will readily transmit through seals and diffuse through most materials. Deionization is also an efficient process for removing dissolved carbon dioxide. Carbon dioxide forms ionic bicarbonate in water, and will be subsequently removed by ion-exchange resins. However, the same problem of carbon dioxide re-absorption will occur after the deionized water is exposed to air. Also, the deionization approach for creating Carbon Dioxide-Free Water does not deaerate the water or remove other dissolved gases such as oxygen (O2); it only removes carbon dioxide and other ions. Depending on the application, Purified Water may meet the requirements where Carbon Dioxide-Free Water is called for. This could also include pH or acidity or alkalinity tests. The pH of a sample of pure Deionized Water is, by definition, 7.0. When that same sample is exposed to typical environmental atmospheric conditions, the water sample will absorb carbon dioxide and result in a pH range of approximately 5.4–6.2 ([H+] is in the range of 4.0 × 10^–6 M to 6.3 × 10^–7 M). The added acidity caused by carbon dioxide absorption may be insignificant compared to the material being analyzed.

LOTIONS Lotions are an emulsified liquid dosage form intended for external application to the skin. Historically, some topical suspensions such as calamine lotion have been called lotions but that nomenclature is not currently preferred. Lotions share many characteristics with creams. The distinguishing factor is that they are more fluid than semisolid and thus pourable. Due to their fluid character, lotions are more easily applied to large skin surfaces than semisolid preparations. Lotions may contain antimicrobial agents as preservatives. PREPARATION Lotions: Lotions are usually prepared by dissolving or dispersing the drug substance into the more appropriate phase (oil or water), adding the appropriate emulsifying or suspending agents, and mixing the oil and water phases to form a uniform fluid emulsion.

CREAMS Creams are semisolid emulsion dosage forms. They often contain more than 20% water and volatiles, and/or typically contain less than 50% hydrocarbons, waxes, or polyols as the vehicle for the drug substance. Creams are generally intended for external application to the skin or to the mucous membranes. Creams have a relatively soft, spreadable consistency and can be formulated as either a W/O emulsion (e.g., Cold Cream or Fatty Cream as in the European Pharmacopoeia) or as an O/W emulsion (e.g., Betamethasone Valerate Cream). Creams are generally described as either nonwashable or washable, reflecting the fact that an emulsion with an aqueous external continuous phase is more easily removed than one with a nonaqueous external phase (W/O emulsion). Refer Emulsions