Pharmaceutical Technology: Syrups PDF

# PHARMACEUTICAL TECHNOLOGY ## **Syrups** Syrups are concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances. Syrups containing flavoring agents but not medicinal substances are called **nonmedicated syrups** (flavored vehicles)....

# PHARMACEUTICAL TECHNOLOGY ## **Syrups** Syrups are concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances. Syrups containing flavoring agents but not medicinal substances are called **nonmedicated syrups** (flavored vehicles). Some official and commercially available non medicated syrups are: - **Cherry syrup**: Sucrose-based syrup with cherry juice about 47% by volume. - **Cocoa syrup**: Suspension of cocoa powder in aqueous vehicle. Particularly it is effective in administering bitter-tasting drugs to children. - **Orange syrup**: Sucrose-based syrup uses sweet orange peel tincture, citric acid as sources of flavor and tartness. - **Raspberry syrup**: Sucrose-based syrup with raspberry juice about 48% by volume. - **Syrup**: 85% sucrose in purified water. Simple syrup may be used as basis for flavored or medicated syrups. These syrups are intended to serve as pleasant tasting vehicles for medicinal substances to be added in the compounding of prescriptions or in the preparation of a standard formula for a medicated syrup, which is a syrup containing a therapeutic agent. Due to the inability of some children and elderly people to swallow solid dosage forms, it is common today for a pharmacist to prepare an oral liquid dosage form tablets or capsules. The liquid dosage form selected for compounding may be a solution or a suspension, depending on the chemical and physical properties of the drug and its solid dosage form. Vehicles are commercially available for this purpose. **Medicated syrups** are prepared from the starting materials the syrup, such as sucrose, purified water, flavoring agents, coloring agents, the therapeutic agent, and other necessary and desirable ingredients. Naturally, medicated syrups are employed in therapeutics for the value of the medicinal agent present in the syrup. - Syrups provide a pleasant means of administrating a liquid form of a disagreeable-tasting drug. They are effective in the administration of drugs to youngsters, since their pleasant taste usually dissipates any reluctance. - Any water-soluble drug that is stable in aqueous solution may be added to a flavored syrup. ## **Components of Syrups** Most syrups contain the following components in addition to the purified water and any medicinal agents present: - **the sugar**, usually sucrose, or sugar substitute used to provide sweetness and viscosity; - **antimicrobial preservatives**; - **flavorants**; and - **colorants**. Also, many syrup, especially those prepared commercially, contain special solvents, solubilizing agents, thickeners, or stabilizers. ## **Sucrose- and non-Sucrose-Based Syrups** Sucrose is the most sugar frequently used in syrups, although in special circumstances it may be replaced in whole or in part by other sugars or substances such as sorbitol, glycerin, and propylene glycol. In some instances, glycogenetic substances (materials converted to glucose in the body), including the agents mentioned earlier, are replaced by nonglycogenetic substances, such as methylcellulose or hydroxy ethylcellulose. These two materials are not hydrolyzed and absorbed into the blood stream, and their use results in an excellent syrup-like vehicle for medications intended for use by diabetic patients and others whose diet must be controlled and restricted to nonglycogenetic substances. The viscosity resulting from the use of these cellulose derivatives is much like that of a sucrose syrup. This quality, together with the sweetness and flavorants, results in a type of pharmaceutical preparation that masks the taste of added medicinal agents. When the syrup is swallowed, only a portion of dissolved drug actually makes contact with the taste buds, the remainder of the drug being carried and past down the throat in the viscous syrup. This type of physical concealment of the taste is not possible for a solution of a drug in an unthickened aqueous preparation. In the case of antitussive syrups, the thick, sweet syrup has also a soothing effect on the irritated tissues of the throat as it passes over them. Most syrups contain a high proportion of sucrose, usually 60 to 80%, not only because of the desirable sweetness and viscosity of such solutions but also because of their stability in contrast to the unstable character of dilute sucrose solutions. The aqueous sugar medium of dilute sucrose solutions is an efficient nutrient medium for the growth of microorganisms, particularly yeasts and molds. On the other hand, concentrated sugar solutions are quite resistant to microbial growth because of the unavailability of the water required for the growth of microorganisms. This aspect of syrups is best demonstrated by the simplest syrup, **Syrup, NF**, also called simple syrup. It is prepared by dissolving 85 g of sucrose in enough purified water to make 100 mL of syrup. The resulting preparation generally requires no additional preservation if it is to be used soon; in the official syrup, preservatives are added if the syrup is to be stored. When properly prepared and maintained, the syrup is stable and resistant to the growth of microorganisms. An examination of this syrup reveals its concentrated nature and the relative absence of water for microbial growth. Syrup has a specific gravity of about 1.313, which means that each 100 mL of syrup weighs 131.3 g. Because 85 g of sucrose is present, the difference between 85 g and 131.3 g, or 46.3 g, represents the weight of the purified water. Thus, 46.3 g, or mL, of purified water is used to dissolve 85 g of sucrose. The solubility of sucrose is 1 in 0.5 mL of water; therefore, to dissolve 85 g of sucrose, about 42.5 mL of water is required. Thus, only a very slight excess of water about 3.8 mL per 100 mL (46.3 42.5) of syrup is employed in the preparation of syrup. The slight excess of water is not enough to be particularly amenable to the growth of microorganisms, but it permits the syrup to remain physically stable in varying temperatures. If the syrup were completely saturated with sucrose, in cool storage some sucrose might crystallize from solution and initiate a type of chain reaction that would result in separation of an amount of sucrose disproportionate to its solubility at the storage temperature. The syrup would then be very much unsaturated and probably suitable for microbial growth. As formulated, the official syrup is both stable and resistant to crystallization and microbial growth. However, many of the other official syrups and a host of commercial syrups are not intended to be as nearly saturated as Syrup, NF, and therefore must add preservative agents to prevent microbial growth and to ensure their stability during their period of use and storage. ## **Preparation of Syrups** Syrups are most frequently prepared by one of four general methods, depending on the physical and chemical characteristics of the ingredients. These methods are: - **solution of the ingredients with the aid of heat**, - **solution of the ingredients by agitation without the use of heat, or the simple admixture of liquid components**, - **addition of sucrose to a prepared medicated liquid or to a flavored liquid**, and - **percolation of either the source of the medicating substance or of the sucrose.** Sometimes a syrup is prepared by more than one of these methods, and the selection may simply be a matter of preference on the part of the pharmacist. ### **Solution With the Aid of Heat** Syrups are prepared by this method when it is desired to prepare the syrup as quickly as possible and when the syrup’s components are not damaged or volatilized by heat. In this method the sugar is generally added to the purified water, and heat is applied until the sugar is dissolved. Then other heat-stable components are added to the hot syrup, the mixture is allowed to cool, and its volume is adjusted to the proper level by addition of purified water. If heat-labile agents or volatile substances, such as volatile flavoring oils and alcohol, are to be added, they are generally added to the syrup after the sugar is dissolved by heat, and the solution is rapidly cooled to room temperature. The use of heat facilitates rapid solution of the sugar and some other components of syrups; however, caution must be exercised against becoming impatient and using excessive heat. Sucrose, a disaccharide, may be hydrolyzed into monosaccharides, dextrose (glucose), and fructose (levulose). This hydrolytic reaction is inversion, and the combination of the two monosaccharide products is invert sugar. When heat is applied in the preparation of a sucrose syrup, some inversion of the sucrose is almost certain. The speed of inversion is greatly increased by the presence of acids, the hydrogen ion is acting as a catalyst to the reaction. If inversion occurs, the sweetness of the syrup is altered, because invert sugar is sweeter than sucrose; and the normally colorless syrup darkens because of the effect of heat on the levulose portion of the invert sugar. When the syrup is greatly overheated, it becomes amber-colored as the sucrose caramelizes. This decomposed syrup is more susceptible to fermentation and to microbial growth than the stable, undecomposed syrup. Because of the prospect of decomposition by heat, syrups cannot be sterilized by autoclaving. The use of boiled purified water in the preparation of a syrup can enhance its permanency, and the addition of preservative agents, when permitted, can protect it during its shelf life. Storage in a tight container is a requirement for all syrups. ### **Solution by Agitation Without the Aid of Heat** To avoid heat-induced inversion of sucrose, a syrup may be prepared without heat but by agitation. On a small scale, sucrose and other formula live agents may be dissolved in purified water by placing the ingredients in a vessel larger than the volume of syrup to be prepared, permitting thorough agitation of the mixture. This process is more time consuming than use of heat, but the product has maximum stability. Sometimes simple syrup or some other non-medicated syrup, rather than sucrose, is employed as the sweetening agent and vehicle. In that case, other liquids that are soluble in the syrup or miscible with it may be added and thoroughly mixed to form a uniform product. When solid agents are to be added to a syrup, it is best to dissolve them in a minimal amount of purified water and incorporate the resulting solution into the syrup. When solid substances are added directly to a syrup, they dissolve slowly because the viscous nature of the syrup does not permit the solid substance to distribute readily throughout the syrup and also because of limited amount of available water. ### **Addition of Sucrose to a Medicated Liquid or to a Flavored Liquid** Occasionally a medicated liquid, such as a tincture or fluidextract, is employed as the source of medication in the preparation of a syrup. Many such tinctures and fluidextracts contain alcohol-soluble constituents and are prepared with alcoholic or hydroalcoholic vehicles. If the alcohol-soluble components are the desired medicinal agents, use means that rendering them water soluble. However, if the alcohol-soluble components are undesirable or unnecessary components of the corresponding syrup, they are generally removed by mixing the tincture or fluidextract with water, allowing the mixture to stand until separation of the water-insoluble agents is complete, and filtering them from the mixture. The filtrate is the medicated liquid to which the sucrose is added in preparation of the syrup. ### **Percolation** In the percolation method, either sucrose may be percolated to prepare the syrup, or the source of the medicinal component may be percolated to form an extractive to which sucrose or syrup may be added. This method is two separate procedures: first the preparation of the extractive of the drug and then the preparation of the syrup. An example of a syrup prepared by percolation is **ipecac syrup**, which is prepared by adding glycerin and syrup to an extractive of ipecac obtained by percolation. The drug ipecac comes from Cephaelis ipecacuanha that contains the medicinally active alkaloids like emetine. These alkaloids are extracted from ipecac by percolation. The syrup is categorized as an emetic with a usual dose of **15 mL**. This amount of syrup is commonly used in the management of poisoning in children for evacuation of the stomach contents. Most of children given this dose will vomit within half hour. Pharmacists must be aware of misuse of syrup of ipecac. An attempt to lose weight by vomiting because one of the active ingredients in the syrup is emetine. With continual use of the syrup, emetine builds up toxic levels within body tissues and in 3 to 4 months can do irreversible damage to heart muscles. Shortness of breath is the most common symptom in patients who misuse syrup of ipecac. ### **Some examples of syrup preparations that are commonly available:** - **Bromhexine** is a mucolytic agent, used to treat respiratory disorders linked with excessive mucus. - **Salbutamol** is a bronchodilator, works by relaxing the muscles and air passages in the lungs, making breathing easier. - Other cough preparations such as **Samilin, Tussilet** are also formulated as syrups containing different ingredients to treat cough....