DRUG DOSAGE FORMS & DELIVERY SYSTEMS


Syrup

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 non medicated or flavored vehicles (syrups)

These syrups are intended to serve as pleasant tasting vehicles for medicinal substances to be added in the extemporaneous 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 fairly common today for a pharmacist to be asked to prepare an oral liquid dosage form of a medication available in the pharmacy only as tablets or capsules. In these instances, drug solubility, stability, and bioavailability must be considered case by case.

Medicated syrups are commercially prepared from the starting materials, i.e., by combining each of the individual components of 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 administering a liquid form of a disagreeable-tasting drug. They are particularly effective in the administration of drugs to youngsters, since their pleasant taste usually dissipates any reluctance on the part of the child to take the medicine. The fact that syrups contain little or no alcohol adds to their favor among parents

Components of Syrups

Most syrups contain the following components in addition to the purifi ed water and any medicinal agents present: (a) the sugar, usually sucrose, or sugar substitute used to provide sweetness and viscosity; (b) antimicrobial preservatives; (c) fl avorants; and (d) colorants. Also, many types of syrups, especially those prepared commercially, contain special solvents, solubilizing agents, thickeners, or stabilizers.

Sucrose- and Nonsucrose-based Syrups

Sucrose is the sugar most frequently employed 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, all glycogenetic substances (materials converted to glucose in the body), including the agents mentioned earlier, are replaced by nonglycogenetic substances, such as methylcellulose or hydroxyethylcellulose. 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. The addition of one or more artifi cial sweeteners usually produces an excellent facsimile of a true syrup.

Preparation of Syrup

Syrups are most frequently prepared by one of four general methods, depending on the physical and chemical characteristics of the ingredients. Broadly stated, these methods are (a) solution of the ingredients with the aid of heat, (b) solution of the ingredients by agitation without the use of heat, or the simple admixture of liquid components, (c) addition of sucrose to a prepared medicated liquid or to a flavored liquid, and (d) percolation of either the source of the medicating substance or the sucrose.

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 the 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 certain 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 acting as a catalyst to the reaction. Should inversion occur, 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. Syrups so decomposed are more susceptible to fermentation and to microbial growth than the stable, undecomposed syrups. 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 by agitation. On a small scale, sucrose and other formulative 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 the use of heat, but the product has maximum stability. Huge glass lined or stainless steel tanks with mechanical stirrers or agitators are employed in large-scale preparation of syrups.

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 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 to the available solvent and also because a limited amount of available water is present in concentrated syrups.

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 hydro alcoholic vehicles. If the alcohol-soluble components are desired medicinal agents, some means of rendering them water soluble is employed. 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. If the tincture or fluidextract is miscible with aqueous preparations, it may be added directly to simple syrup or to a flavored 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 latter method really 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 powdered ipecac obtained by percolation. The drug ipecac, which consists of the dried rhizome and roots of Cephaëlis ipecacuanha, contains the medicinally active alkaloids emetine, cephaeline, and psychotrine. These alkaloids are extracted from the powdered ipecac by percolation with a hydroalcoholic solvent.

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 when evacuation of the stomach contents is desirable. About 80% of children given this dose will vomit within half an hour. For a household emetic in the event of poisoning, 1-oz. bottles of the syrup are sold without a prescription. Ipecac syrup also has some application as a nauseant expectorant in doses smaller than the emetic dose.

Evidence indicates that many bulimics— most commonly young women in their late teens to early 30s—use the syrup of ipecac to bring on attacks of vomiting in an attempt to lose weight . Pharmacists must be aware of this misuse of the syrup of ipecac and warn these individuals because one of the active ingredients in the syrup is emetine. With continual use of the syrup, emetine builds up toxic levels within the body tissues and can do irreversible damage to the heart muscles in 3 to 4 months, resulting in symptoms mimicking a heart attack. Shortness of breath is the most common symptom in patients who misuse the syrup of ipecac, but some persons describe low blood pressure– related symptoms and irregularities of heartbeat.