lecture Solutions

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Liquid Dosage Forms

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1. Pharmaceutical Solutions

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Solutions are: Dosage forms prepared by dissolving the active ingredient(s) in an aqueous or non aqueous solvent.

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Solutions can be formulated for different routes of administration Orally : Syrups, elixirs, drops In mouth and throat : Mouth washes, gargles, throat sprays. In body cavities : Douches, enemas, ear drops, nasal sprays. On body Surfaces : Collodions, lotions.

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Advantages of SoIutions (1) Easier to swallow therefore easier for: children - old age - unconscious people. (2) More quickly effective than tablets and capsules. (3) Homogenous therefore give uniform dose than suspension or emulsion which need shaking. (4) Dilute irritant action of some drugs (aspirin, Kl, KBr) minimize adverse effects in the GIT like KCl.

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Disadvantages of SoIutions Bulky therefore difficult to transport and store. (2) Unpleasant taste or odours are difficult to mask. (3) Needs an accurate spoon to measure the dose. (4) Less stable than solid dosage forms. major signs of instability: colour change, precipitation microbial growth chemical gas formation

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Additives Buffers To resist any change in pH Isotonicity modifiers Solutions for injection Application to mucous membrane Large-volume solutions for ophthalmic application Most widely used isotonicity modifiers are: dextrose and NaCl Viscosity enhancement It is difficult for aqueous-based topical solutions to remain on the skin or in the eye (why?) therefore low concentrations of jelling agents are added to increase the viscosity of the product.

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Preservatives Solution may become contaminated for a number of reasons: Raw materials used in the manufacture of solutions are excellent growth media for bacterial substances such as gums, dispersing agents, sugars and flavors Equipment, environment and personnel contribute to product contamination. Consumer use may result in the introduction of microorganism.  a preservative should be added to the product Preservative used should be: effective against a wide spectrum of microorganisms stable for its shelf life non toxic, non sensitizing compatible with the ingredients in the dosage form free of taste and odour

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Preservatives may be used alone or in combination to prevent the growth of microorganisms. Alcohols Ethanol is useful as a preservative when it is used as a solvent. It needs a relatively high concentration (> 10%) to be effective. Propylene glycol also used as a solvent in oral solutions and topical preparations. It can function as a preservative in the range of 15 to 30%. It is not volatile like ethanol. Acids Benzoic acid and sorbic acid have low solubility in water. They are used in a concentration range from 0.1 % to 0.5%. Only the non-ionized form is effective and therefore its use is restricted to preparations with a pH below 4.5 (WHY?).

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Esters Parabens are esters (methyl, ethyl, propyl and butyl) of p-hydroxybenzoic acid. They are used widely in pharmaceutical products and are effective and stable over a pH range of 4 to 8. They are employed at concentrations up to about 0.2%. Frequently 2 esters are used in combination in the same preparation WHY? To achieve a higher total concentration To be active against a wider range of microorganisms. Quaternary Ammonium Compounds Benzalkonium chloride is used at a relatively low concentration 0.002 to 0.02%. This class of compounds has an optimal activity over the pH range of 4 to 10 and is quite stable at most temperatures. Because of the cationic nature of this type of preservative it is incompatible with many anionic compounds.

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Antioxidants Vitamins, essential oils & almost all fats and oils can be oxidized. Oxidation reaction can be initiated by: 1. heat : maintain oxidizable drugs in a cool place 2. light : use of light- resistant container 3. heavy metals (e.g. Fe, Cu): effect of trace metals can be minimized by using citric acid or ethylenediamine tetra­acetic acid (EDTA) i.e. sequestering agent . Antioxidants as propyl & octyl esters of gallic acid, tocopherols or vitamin E, sodium sulfite, ascorbic acid (vit. C) can be used. Sweetening agents Sucrose is the most widely used sweetening agent. Advantages: Colourless, highly water soluble, stable over a wide pH range (4-8), increase the viscosity, masks both salty and bitter taste, has soothing effect on throat. Polyhydric alcohols (sorbitol, mannitol and glycerol) possess sweetening power and can be used for diabetic preparations.

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Flavours and perfumes Mask unpleasant taste or odour Enable the easy identification of the product. Natural products: fruit juices, aromatic oil (peppermint, lemon) Artificial perfumes are cheaper, more readily available and more stable than natural products.

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Stability of solutions Both physical and chemical stability of solutions in their containers is very important A solution must retain its clarity, colour, odour, taste and viscosity over its shelf life.

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Classification of Solutions According to Vehicle (a) Aqueous solutions (b) Non-aqueous solutions Aqueous Solutions Aqueous solutions are homogeneous mixtures that are prepared by dissolving a solid, liquid or gas in an aqueous medium (vehicle). Vehicle : This may be water , aromatic water or extracts .

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WATER Water is used both as vehicle and as a solvent for the desired flavoring or medicinal ingredients. Advantages: Tasteless, odourless, lack of pharmacological activity, neutral and very cheap Tap Water It is not permitted to use tap water for the dispensing of pharmaceutical dosage forms due to its possible bacterial contamination and the presence of dissolved salts that destroy the active ingredients or enhance their decomposition. Freshly Boiled and Cooled Water Boiling is seldom used to destroy vegetative bacteria. But, on storage for long time spores may yield vegetative microorganism.

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Purified Water Must be used for most pharmaceutical operations and in all the tests and assays. Such water is prepared by distillation, deionization or reverse osmosis. "Hard" waters are those that contain the Ca and Mg cations. “Alkaline" waters are those that contain bicarbonates as the major impurity. Ultraviolet energy, heat or filtration (Millipore filtration) can be used to remove or kill the microorganisms present in the water. Water for injection Must be used for the formulation of parental solutions. It is obtained by sterilizing pyrogen-free distilled water.

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Aromatic Waters Aromatic waters (medicated waters) are clear, saturated aqueous solution of volatile oils or other aromatic or volatile substances. They are used principally as flavored or perfumed vehicles. Volatile oils solutions represent an incompatibility problem of salting out. This occurs after the incorporation of a very soluble salt in their solution. Aromatic water will deteriorate with time therefore : - should be made in small quantities - protected from intense light and excessive heat by storing in air tight, light resistant containers. If they become cloudy or otherwise deteriorate; they should be discarded. Deterioration may be due to volatilization, decomposition or mould growth. There are 2 official methods of preparation:

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(a) Distillation process (Stronger Rose Water NF) Adv .: most satisfactory method Dis .: slow and expensive The drug should be coarsely ground and mixed with sufficient quantity of purified water in the distillation unit. After distillation any excess oil in the distillate is removed by filtration. Drug should not be exposed to the action of direct heat during distillation; otherwise, the odour of the carbonized substance will be noticeable in the distilled aromatic water. If the volatile principle in the water are present in small quantities the distillate is returned several times to the still with fresh portions of drug. (b) Solution process (Peppermint water) Aromatic water may be prepared by shaking volatile substance with purified water. The mixture is set aside for 12 hours & filtered. Talc (inert) may be used to increase the surface of the volatile substance, insure more rapid saturation of the water and act as a filter aid.

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Methods of Preparation of Solutions (a) Simple Solution (b) Solution by Chemical Reaction (c) Solution by Extraction (a) Simple Solution Solutions of this type are prepared by dissolving the solute in a suitable solvent (by stirring or heating). The solvent may contain other ingredients which stabilize or solubilize the active ingredient e.g. solubility of Iodine is 1: 2950 in water however, it dissolves in presence of KI due the formation of more soluble polyiodides (KI.I 2 KI.2I 2 KI3.I 3 KI.4I 4 ) .[ Strong Iodine Solution USP (Lugol's SoIution)].

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(b) Solution by Chemical Reaction These solutions are prepared by reacting two or more solutes with each other in a suitable solvent e.g. Calcium carbonate and lactic acid used to prepare Calcium lactate mixture. WHY? (c) Solution by Extraction Plant or animal products are prepared by suitable extraction process. Preparations of this type may be classified as solutions but more often, are classified as extractives. Extractives will be discussed separately.

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Pharmaceutical Solutions Aqueous Douches Enemas Gargles Mouthwashes Nasal washes Juices Sprays Otic solutions Inhalations Sweet &/or Viscid Syrups Honeys Mucilages Jellies Nonaqueous Elixirs Spirits Collodions Glycerins Liniments Oleo Vitamin

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Aqueous Pharmaceutical Solutions

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Douches Douche is an aqueous solution, which is directed against a part or into a cavity of the body. It functions as a cleansing or antiseptic agent. Eye douches are used to remove foreign particles and discharges from the eyes. It is directed gently at an oblique angle and is allowed to run from the inner to the outer corner of the eye. Pharyngeal douches are used to prepare the interior of the throat for an operation and to cleanse it in supportive conditions. Similarly, there are nasal and vaginal douches. Douches most frequently dispensed in the form of a powder with directions for dissolving in a specified quantity of water.

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Enemas These preparations are rectal injections employed to: evacuate the bowel (evacuation enemas), influence the general system by absorption (retention enemas) e.g. nutritive, sedative or stimulating properties affect locally the site of disease (e.g. anthelmintic property) they may contain radiopaque substances for roentgenographic examination of the lower bowel. Retention enemas are used in small quantities (about 30ml) and are thus called retention microenema. Starch enema may be used either by itself or as a vehicle for other forms of medication

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Gargles Gargles are aqueous solutions frequently containing antiseptics, antibiotics and/or anesthetics used for treating the pharynx (throat) and nasopharynx by forcing air from the lungs through the gargle, which is held in the throat; subsequently, the gargle is expectorated. Many gargles must be diluted with water prior to use. Although mouthwashes are considered as a separate class of pharmaceuticals many are used as gargles, either as is, or diluted with water. The product should be labeled so that it cannot be mistaken for preparations intended for internal administration.

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Mouthwashes Mouthwashes can be used for therapeutic & cosmetic purposes Therapeutic mouthwashes can be formulated to reduce plaque , gingivitis , dental caries and stomatitis . Cosmetic mouthwashes may be formulated to reduce bad breath through the use of antimicrobial and/or flavoring agents. Mouthwashes are used as a dosage form for a number of specific problems in the oraI cavity; e.g. mouthwashes containing: combination of antihistamines, hydrocortisone, nystatin and tetracycline have been prepared for the treatment of stomatitis, a painful side effect of cancer therapy. Allopurinol used for the treatment of stomatitis, pilocarpine for xerostoma (dry mouth) tranexamic acid for the prevention of bleeding after oral surgery. carbenoxolone for the treatment of orofacial herpes simplex infections

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Mouthwashes generally contain four groups of excipients AIcohols: (10-20% in MW)  may function as a preservative. aids in masking the unpleasant taste of active ingredients, functions as a solubilizing agent for some flavoring agents Humectants: such as glycerin and sorbitol (5-20% in MW) increase the viscosity of the preparation enhance the sweetness of the product improve the preservative qualities of the product. Surfactants: Non ionic and anionic surfactants aid in the solubilization of flavors and in the removal of debris by providing foaming action. Cationic surfactants such as cetylpyridinium chloride are used for their antimicrobial properties, but these tend to impart a bitter taste. Flavours: are used in conjunction with alcohol and humectants to overcome disagreeable tastes. The principle flavoring agents are peppermint, cinnamon, menthol or methyl salicylate. CoIouring agents: also are used in these products.

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Nasal Solutions Nasal solutions are usually aqueous solutions designed to be administered to the nasal passages in drops or sprays. Ephedrine Sulfate or Naphaxoline Hydrochloride Nasal Solution USP are administered for their local effect to reduce nasal congestion Lypressin Nasal Solution USP for its systemic effect for the treatment of diabetes insipidus The current route of administration of peptides and proteins is limited to parental injection because of inactivation within the GIT. As a result there is considerable research on intranasal delivery of these drugs such as insulin. Intranasal drug administration offers rapid absorption to the systemic circulation . This route is safe and acceptable alternative to the parental administration

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There is a direct route of transport from the olfactory region to the central nervous system (CNS) without prior absorption to the circulating blood. The olfactory receptor cells are in contact with the nasal cavity and the CNS and they provide a rout of entry to the brain that circumvents the blood brain barrier

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Commercial nasal preparations include antibiotics, antihistamines and drugs for asthma prophylaxis. Current studies indicate that nasal sprays are deposited in the pharynx with the patient in an upright position . Drops spread more extensively than the spray and three drops cover most of the walls of the nasal cavity, with the patient in a supine position and head tilted back and turned left and right. Pharynx

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Nasal decongestant solutions are employed in the treatment of rhinitis of the common cold and for allergic rhinitis (hay fever) and for sinusitis . Sinuses are air-containing cavities in certain bones of the skull

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Their frequent use or their use for prolonged periods may lead to chronic edema of the nasal mucosa, i.e. rhinitis medicainentosa , aggravating the symptom that they are intended to relieve. Thus, they are best used for short periods of time used for short periods of time (no longer than 3 to 5 days). Nasal solutions are prepared so that they are similar in many respects to nasal secretions, so that normal ciliary action is maintained thus aqueous nasal solutions usually are isotonic and slightly buffered to maintain a pH of 5.5 to 6.5.

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Sprays Sprays are solutions of drugs in aqueous vehicles and are applied to the mucous membrane of the nose and throat by means of an atomizer nebulizer. The spray device should produce relatively coarse droplets if the action of the drug is to be restricted to the upper respiratory tract . Fine droplets tend to penetrate further into the respiratory tract than is desirable.

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Many of the older sprays were prepared by dissolving drug in light liquid petrolatum . This vehicle may retard the normal ciliary action of the nasal mucosa and if drops of oil enter the trachea, can cause lipoid pneumonia. Therefore aqueous sprays, which are isotonic with nasal secretions and of approximately the same pH are to be preferred (WHY?). Such sprays may contain antibiotics, antihistamines, vasoconstrictors, alcohol, and suitable solubilizing and wetting agents. They are used for the treatment of allergy and/or vasodilatation (congestion) that occur with common cold.

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Otic Solutions The main classes of drugs used for topical administration to the ear include local anesthetics, e.g.: benzocaine; antibiotics e.g.; neomycin; and anti-inflammatory agents, e.g.; cortisone. These preparations include the main types of solvents used, namely glycerin or water. The viscous glycerin vehicle permits the drug to remain in the ear for a long time. Anhydrous glycerin , being hygroscopic, tends to remove moisture from surrounding tissues, thus reducing swelling. Viscous liquids like glycerin or propylene glycol either are used alone or in combination with a surfactant to aid in the removal of cerumen (ear wax). In order to provide sufficient time for aqueous preparations to act, it is necessary for the patient to remain on his side for a few minutes so the drops do not run out of the ear.

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For a Middle Ear Infection : While the person receiving Otic solution lies on his/her side, the person giving the drops should gently press the ( TRAGUS ( 4 times in a pumping motion . This will allow the drops to pass through the hole or tube in the eardrum and into the middle ear . For an Ear Canal Infection While the person receiving the medication lies on his/her side, the person giving the drops should gently pull the outer ear upward and backward . This will allow the ear drops to flow down into the ear canal .

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Sweet &/or Viscid Pharmaceutical Solutions

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These include Syrups , Honeys , Mucilages , and Jellies . All of these preparations are viscous liquids or semisolids. The sweetness and viscid appearance are given by sugars, polyols, or polysaccharides (gums). SYRUPS Syrups are concentrated solutions of sugar such as sucrose in water or other aqueous liquid. simple syrup : when water is used alone for making syrup. medicated syrup : when the aqueous preparation contains some added medicinal substance flavored syrup : which contains aromatic or pleasantly flavored substances and is intended to be used as a vehicle or flavor for prescriptions

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Polyols (e.g. glycerin or sorbitol) may be added to - retard crystallization of sucrose or - increase the solubility of added ingredients. Alcohol often is included as - preservative - solvent for volatile oils. Syrups possess remarkable masking properties for bitter and saline drugs. It is important that the concentration of sucrose approaches but not quite reach the saturation point, WHY? In dilute solutions sucrose provides an excellent nutrient for molds, yeasts, and other microorganisms. In concentration of 65 % by weight or more the solution will retard the growth of such microorganisms (WHY?). A saturated solution may lead to crystallization of a part of the sucrose under conditions of changing temperature.

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When heat is used in the preparation of syrups, there is almost certain to be an inversion of a slight portion of the sucrose. C 12 H 22 O 11 2 C 6 H 12 O 6 Sucrose heat & acid Invert sugar (dextrose and levulose) The speed of inversion is greatly increased by acids (why ?); the hydrogen ion acts as a catalyst in this hydrolytic reaction. Invert sugar  is more readily fermentable than sucrose  tend to darken in color  retard the oxidation of other substances. The levulose formed during inversion is sweeter than sucrose; therefore the resulting syrup is sweeter than the original syrup. When syrup is overheated it caramelizes.

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Invert Syrup: It is prepared by hydrolyzing sucrose with hydrochloric acid and neutralizing the solution with Ca or Na carbonate. The sucrose in the 66.7% w/w solution must be at least 95% inverted. The invert syrup, when mixed in suitable proportions with syrup, prevents the deposition of crystals of sucrose under most conditions of storage.

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Preparation of Simple Syrup (a) Solution with heat This is the usual method of making syrups : in the absence of volatile agents or those injured by heat when it is desirable to make the syrup rapidly. The sucrose is added to the purified water or aqueous solution and heated until dissolved, then strained and sufficient purified water added to make the desired weight or volume. Excessive heating in the preparation of syrups must be avoided to prevent inversion of sucrose, with increased tendency to fermentation. Syrups cannot be sterilized by autoclaving without caramelization (yellow color). The specific gravity of syrup is an important property to identify its concentration. Syrup has a specific gravity of about 1.313, which means that each 100 ml of syrup weighs 1313 g.

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(b) Agitation without Heat This process is used in those cases where heat would cause loss of valuable volatile constituents . The syrup is prepared by adding sucrose to the aqueous solution in a bottle of about twice the size required for the syrup. This permits active agitation and rapid solution. The stoppering of the bottle is important, as it prevents contamination and loss during the process.

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(c) Addition of a Medicating Liquid to syrup This method is resorted to in those cases in which fluid extracts, tinctures, or other liquids are added to syrup to medicate it. Syrups made in this way usually develop precipitates since alcohol is often an ingredient of the liquids thus used and the resinous and oily substances dissolved by the alcohol precipitate when mixed with syrup. A modification of this process consists of mixing the fluid extract or tincture with the water, allowing the mixture to stand to permit the separation of insoluble constituents, filtering & and then dissolving the sucrose in the filtrate.  This procedure is not permissible when the precipitated ingredients are the valuable medicinal agents .

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(d) Percolation 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 pledget of cotton is placed in the neck of the percolator If necessary, a portion of the liquid is repassed through the percolator to dissolve all of the sucrose. This method is used for the preparation of Syrup USP .

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Preservation of Syrups The USP suggests that syrups be kept at a temperature not above 25°C. Preservatives such as glycerin, methyl paraben, benzoic acid and sodium benzoate may be added to prevent bacterial and mold growth, particularly when the concentration of sucrose in the syrup is low. The concentration of preservative is proportional to the free water. The official syrups should be preserved in well dried bottles and stored in a cool dark place.

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Dextrose-Based Syrups Dextrose may be used as a substitute for sucrose (WHEN?) in syrups containing strong acids in order to eliminate the discoloration associated with inversion. Dextrose forms a saturated solution in water at 70% w/v, which is less viscous than simple syrup. It dissolves more slowly than sucrose and is less sweet Preservatives are required to improve the keeping qualities of such syrups. Glycerin is added in 30% to 45% v/v as preservative.

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Artificial Syrups (Non-Nutritive Syrups) intended as substitutes for syrups and are to be administered to persons who must regulate their sugar and/or calorie intake accurately. e.g. persons suffering from diabetes mellitus. Some early formulae included glycerin, however, glycerin and propylene glycol are glycogenetic substances, i.e. they are materials which are converted into glucose in the body. An example of non–nutritive syrup is “Diabetic Simple Syrup”. It contains compound sodium cyclamate (6% cyclamate sodium and 0.6% saccharin sodium) However, the cyclamate studies showed that the sweetener could produce cancer in animals and, as a result, this substance was removed from a wide variety of products. Similar studies have been carried out on saccharin. Much research has been done to find a safe synthetic substitute for sucrose. As a result, aspartame which is about 200 times sweeter than sucrose, is being used now in many commercial preparations as the sweetening agent.

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Sorbitol-Based Syrups Sorbitol which is hexahydric alcohol made by hydrogenation of glucose has been used in the preparation of syrup. It is used mostly in the form of a 70% w/w aqueous solution. Sorbitol solution is not irritating to the membrane of the mouth and throat and does not contribute to the formation of dental carries. Sorbitol is metabolized and converted to glucose; however, it is not rapidly absorbed from the GlT as sugars. No significant hyperglycemia has been found (WHY?); it may be used as component of non-nutritive vehicles. Sorbitol solution does not support mold growth. Preservative should be used in solution containing less than 60% w/w sorbitol. It is chemically stable and inert with respect to drugs and other ingredients used in pharmaceutical perpetration.

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Sorbitol Glucose

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HONEYS Are thick liquid preparations. At one time, before sugar was available, honey was used as a base, instead of syrup. There are few official preparations containing honey. e.g. Oxymel, or" acid honey "'is a mixture of acetic acid, water and honey MUCILAGES The official mucilages are thick viscid, adhesive liquids, produced by dispersing gum (acacia or tragacanth) in water . Mucilages are used as suspending agents for insoluble substances in liquids; their colloidal character and viscosity prevent immediate sedimentation. Synthetic agents e.g. carboxymethylcellulose (CMC) or polyvinyl alcohol are nonglycogenetic and may be used for diabetic patients.

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Jellys Preparations having a jelly-like consistency. They are prepared also from gums. Are used as lubricants for surgical gloves and catheters Lidocaine HCl Jelly USP is used as a topical anaethetic.

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Non-Aqueous Pharmaceutical Solutions

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Advantages If the drug is not completely soluble or unstable in aqueous medium it may be necessary to use an alternative non-aqueous solvent. Oily solutions of drugs are often used for depot therapy e.g. in muscles It is essential to test: toxicity – irritancy – flammability – cost – stability and compatibility of solvents to avoid problems Solvents such as acetone, benzene and petroleum ether are not used for internal products. Internal products may contain ethanol, glycerol, propylene glycol certain oils. For parental products the choice is very limited

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This section is devoted to four groups of non-aqueous solutions: 1. alcoholic or hydroalcoholic solutions, e.g. elixirs and spirits, 2. ethereal solutions, e.g. the collodions 3. glycerin solutions, e.g. the glycerites, 4. oleaginous soIutions e.g. the liniments, medicated oils, oleo- vitamins, sprays, and toothache drops.

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ELIXIRS Are clear, pleasantly flavored, sweetened hydroalcoholic liquids intended for oral use. They are used as flavors and vehicles e.g. Dexamethasone Elixir USP and Phenobarbital Elixir USP. The main ingredients in elixirs are ethanol and water but glycerin, sorbitol, propylene glycol, flavoring agents, preservatives, and syrups are often used in the preparation of the final product. EIixirs contain ethyl alcohol, however, the alcoholic content will vary greatly, from elixir containing only a small quantity to those that contain a considerable portion as a necessary aid to solubility An elixir may contain water and alcohol soluble ingredients .

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Incompatibility of elixir: Alcohol precipitates water soluble substances e.g. tragacanth, acacia agar and many inorganic salts from aqueous solutions. If an aqueous solution is added to an elixir, a partial precipitation of ingredients may occur. This is due to the reduced alcoholic content of the final preparation.

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SPIRITS Alcoholic or hydroalcoholic solutions of volatile substances. The active ingredient may be gas, liquid or solid. Spirits may be used internally for their medicinal value, by inhalation but is mostly used as flavouring agents. Spirits should be stored in tight, light-resistant containers and in a cool place, WHY? Spirits are preparation of high alcoholic strength and when diluted with aqueous solutions or liquids of low alcoholic content turbidity may occur, WHY?

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COLLODIONS Are liquid preparations containing pyroxylin (a nitrocellulose) in a mixture of ethyl ether and ethanol. They are applied to the skin by means of a soft brush or other suitable applicator and, when the ether and ethanol have evaporated, leave a film of pyroxylin on the surface. The official medicated collodion, Salicylic Acid Collodion USP, contains 10 % w/v of Salicylic Acid in Flexible Collodion USP and is used as a keratolytic agent in the treatment of corns and warts. Collodion is made flexible by the addition of castor oil and camphor.

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GLYCERINS Glycerins or glycerites are solutions or mixtures of medicinal substances in not less than 50% by weight of glycerin. Most of the glycerins are extremely viscous. Glycerin is a valuable pharmaceutical solvent forming permanent and concentrated solutions not otherwise obtainable. Glycerin is used as the sole solvent for the preparation of Antipyrine and Benzocaine Otic Solution USP. As noted under Otic Solutions, glycerin alone is used to aid in the removal of cerumen. Glycerins are hygroscopic and should be: stored in tightly closed containers.

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LINIMENTS Are solutions or mixtures of various substances in oil, alcoholic solutions of soaps, or emulsions. They are intended for external application and should be so labeled. They are applied with rubbing to the affected area, the oil or soap base providing for ease of application and massage. Alcoholic liniments are used generally for their rubefaciant and counterirritant effects. Such liniments penetrate the skin more readily than do those with an oil base. The oily liniments are milder in their action and may function solely as protective coatings. Liniments should not be applied to skin that are bruised or broken.

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Rubefacient a substance for external application that produces redness of the skin e.g. by causing dilation of the capillaries and an increase in blood circulation . Counterirritant a medicine applied locally to produce superficial inflammation in order to reduce deeper inflammation

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OLEO VITAMINS Oleo vitamins are fish liver oils diluted with edible vegetable oil or solutions of the indicated vitamins (usually vitamins A and D). The indicated vitamins are unstable in the presence of rancid oils and, therefore, those preparations, should be stored in small, tight containers, preferably under vacuum or under an atmosphere of an inert gas, protected from light.

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