SYRUPS & ELIXERS

Presented by: M Nauman Siddique 23-E-14 M Arsalan Chishti 85-E-14 Presented to: Ma’am Bushra

SYRUPS

Contents

What are syrups?Types of SyrupsComponents of syrupsPreparation of SyrupsAid of preparation of syrup

“Syrups are concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances.”

Syrups:

Simple syrup Medicated syrups Non-medicated syrups

Types of Syrups:

A simple syrup contains only sucrose and purified water (e.g. Syrup USP). Saturated sugar solution without flavor or medicine.

Concentration of Syrup:According to B.P: 67.7% W/WAccording to USP: 85% W/V

Simple Syrups:

“Syrups containing flavoring agents but not medicinal substances are called non-medicated or flavored syrups”Use: These syrups are to serve as pleasant

tasting vehicle for medicinal substances to be added in the preparation of a standard formula for a medicated syrup.

Non-Medicated Syrups

Cocoa syrup Suspension of cocoa powder in aqueous vehicle sweetened and thickened with sucrose, liquid glucose, glycerin; flavored with vanilla, sodium chloride. Particularly effective in administering bitter-tasting drugs to children Orange syrup Sucrose-based syrup uses sweet orange peel tincture, citric acid as the source of flavor and tartness. Resembles orange juice in taste; good vehicle for drugs stable in acidic medium. Raspberry syrup Sucrose-based syrup with raspberry juice about 48% by volume. Pleasant-flavored vehicle to disguise salty or sour taste of saline medicaments

Examples of non medicated syrup:

Syrups containing therapeutic agent are called medicated Syrups.

Medicated Syrups:

Examples of medicated syrup: Syrup Commercial

ProductUses product

Analgesic

Mepridine HCL

Progesic paracetamol

(FT metiska Farma)

paracetamol, is commonly used for its analgesic and antipyretic effects.

Anticholinergics

Diclomine HCL

Bentyl

(Axcam Scandipharm)

Adjunctive therapy in treatment of peptic ulcer.

Syrup Commercial product

Use Product

Anticonvulsant

(Sodium valproate)

Depkene syrup

(Abbott)

Sole or adjunctive therapy in simple,complex absence seizure disorder

Antiviral

(Amantadine HCL)

Symmetral syrup

(ALLAINCE)

• Prevention of respiratory infections caused byA2 viral strains.

• Treatment of iodopethic parkinson disease

Functions of sucrose or its derivatives:i. Viscosityii. Sweetnessiii. Flavoring agentiv. Masking bitter taste.

i) SugarSucrose and non-sucrose based syrup

Most syrups contain a high proportion of sucrose, usually 60% to 80% not only because of desirable sweetness and viscosity of such solutions but also because of their inherent stability in contrast to the un stable character of dilute sucrose solutions.

Aqueous sugar medium dilute sucrose has efficient nutrient medium for growth of microorganisms.

While concentrated sugar solutions are quite resistant to microbial growth because of unavailability of water required for growth of microorganisms.

So, concentrated sugar solutions generally no require additional preservatives if it is to be used soon; preservative are added if syrup is to be stored.

The amount of a preservative required to protect a syrup against microbial growth varies with the proportion of water available for microbial growth and capability of preservative itself.Most commonly used preservative:

Compositioni. Benzoic acid (0.1 to 0.2%)ii. Sodium benzoate (0.1 to 0.2%)iii. Methyl-, propyl-, and butylparabens (0.1%)iv. Alcohol (15 to 20%) [if alcohol soluble components are present in syrup]

ii. Antimicrobial preservatives:

Syrups can be preserved by:-

i) Storage at low temperatureii) Adding preservatives in the formulationiii) By the maintenance of a high concentration of sucrose as a part of the formulation.

Preservation:

Most syrups are flavored with:-1. Naturally occurring materials: Volatile oils i.e. Orange oil.2. Synthetic flavorants: Vanillin and others.

Purpose:To render the syrup pleasant taste.

Note:Sometime small amount of alcohol is added to ensure

continued solution of poorly water soluble flavorants.

iii. Flavorants:

To enhance the appeal of the syrup , a coloring agent that correlate with the flavorant employed is used:

Characteristics:The colorant is generally:

water soluble, nonreactive with the other syrup components, color stable at the pH range and under the intensity of light.

Colorants:

Preparation of Syrups

Syrups are frequently prepared by one of four general methods.

1) solution of the ingredients with the aid of heat,2) solution of the ingredients by agitation without the

use of heat, or the simple admixture of liquid components,

3) addition of sucrose to a prepared medicated liquid or to a flavored liquid,

4) 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.

Syrups are prepared by this method when it is desired to prepare the syrup as quickly as possible,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,

1. Solution With the Aid of Heat:

the mixture is allowed to cool, 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 then solution is rapidly cooled to room temperature.

P.T.O

Use of heat facilitates rapid solution of sugar and certain other components but caution must be exercised using excessive heat . Sucrose may be hydrolyzed to Dextrose and Fructose . Than combination of these mono saccharides product will be invert sugar. So, syrup containing mixture of glucose and fructose is termed as invert syrup.

MERITS: More sweet than simple syrup.

DEMERITS: Susceptible to fermentation and microbial growth. Normally colorless darkens because of effect of heat on

levulose portion of invert sugar

Invert Surup:

Precautions

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.

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 vessel larger then the volume of syrup permitting thorough agitation of mixture.

This process is more time consuming than 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.

2. Solution by Agitation Without the Aid of Heat

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.

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 desired medicinal agents, then this method is not applicable

3. Addition of Sucrose to a Medicated Liquid or to a Flavored Liquid

However if the alcohol soluble components are undesirable they are generally removed by mixing the tincture or fluidextract with water , allowing the mixture to stand untill separation of water insoluble components is complete and filter them from mixture,

The filtrate is the medicated liquid to which the sucrose is added in prep, of syrup.

If tincture or fluidextract is miscible with aqueous preparations it may be directly added to simple syrup or to flavored syrup.

ADDITION OF SUCROSE(cont)

In the percolation method, there are two possibilities:-

1. sucrose may be percolated to prepare the syrup.Method:

A sucrose bed is prepared and then water or vehicle containing therapeutic agent is passed.

2. the source of the medicinal component may be percolated to form an extractive to which sucrose or syrup may be added.Method: This latter method really is two separate procedures: 1. Preparation of the extractive of the drug.2. Preparation of the syrup.

Percolation

This syrup is categorized as an emetic with a usual dose of 15ml.This amount is commonly used in the management of poisoning in children when evacuation of stomach content is required.

80% of children given that dose will vomit within half an hour.

Disadvantage: Excessive use of IPECAC

syrup increase toxicity level in body tissues which cause irreversible damage of heart muscles (heart attack)

Medicinal use of IPECAC

Symptoms:

• Shortness of breath• Low blood pressure•Irregularities of heart

beat

Syrup, as a pharmaceutical product requires safe, secure and tamper-proof handling while packaging. Packaging of syrups needs to ensure complete protection from contamination and microbial growth. Our inevitable packaging support assures the safe and secure packaging of syrups so as to ensure their extended shelf life.

The general process: Filling Sealing Capping Coding & labeling Wrapping

Packaging of Syrup

Process Involved in Syrup Packaging –

Empty Bottles are rinsed though Air-jet cleaning After complete cleaning, bottles are tested & transferred

ahead for filling Filling machines with their automatic piston fills the bottles

with accurate volume of syrup Capping is done on bottle through capping machines Plastic or aluminum capsules are bound over the neck of the

bottle for secure sealing Important details regarding packaging date & expiry date are

printed on bottles

LabelingEvery pharmaceutical preparation requires a label

to be produced before the product can be dispensed or sold to patient. The accuracy of the label is of paramount importance as it conveys essential information to the patient on the use of preparation. Storage

All the products dispense extemporaneously require some form of additional storage instructions to be detailed on the label. This information can be the addition of just a product expiry date through to a number of important additional label

Appropriate for any patient, whatever the age is.

ADVANTAGES OF SYRUP

The most natural and easiest route of administration Economical and safe to the patient No nursing is required, which means the patient can

take it with no help The liquid dosage form is expected for certain types of

products like cough medicines.

Delayed onset of action because absorption takes time. Not suitable in emergency and for unconscious patients. Not convenient for a patient with a certain disorders such

as diarrhea, ulceration, and nausea. Can’t avoid first pass metabolism.

DISADVANTAGES OF SYRUP:

Elixirs

What are Elixirs?Aid of preparation of ElixirsComponents of ElixirsTypes of ElixirsPreparation of Elixirs

Contents

“Elixirs are , clear, sweetened, flavored, hydro-alcoholic solutions intended for oral Use and are usually flavored to enhance their palatability.”

Elixirs:Alcoholic content vary from 10% to 12% and up to 40%.

Some drug are insoluble in water so in this case we can’t use syrups & suspension.

So we have to make a dosage form which could dissolve non polar compounds

Aid in masking the unpleasant taste of the active ingredients.

Need of elixir

Components of elixirs:

Alcohol Sweetening agents Water Propylene glycol flavorants

The proportion of alcohol in elixir varies widely because the individual components of the elixir have different water and alcohol solubility characteristics.

Each elixir requires a specific blend of alcohol and water to maintain all of the components in solution.

Naturally, proportion of requirement of alcohol is greater for those elixirs having components with poor water solubility than those elixirs having components with good water solubility.

Water to Alcohol ratio:

Although many elixrs are sweetened with sucrose or with sucrose syrup,some use sorbitol,glycerine or artificial sweetner

Elixirs having a high alcoholic content usually usea an artificial sweetner such as saccharine,which is required in very small amount rather than sucrose which is slightly soluble in alcohol and require in greater quantity for equalent sweetness.

Propyline glycol: A colorless viscous liquid used as a solvent in the preparation of certain medications. It also inhibits the growth of fungi and microorganisms

Sweetning agents

Elixirs containing more than 10 to 12% of alcohol are usually self-preserving and do not require the addition of an antimicrobial agent.

Preservatives used for Elixirs:Parabenes: Parabens are a class of widely used preservatives in pharmaceuticals products.

Benzoates:(salts of Benzoic acid) can refer to:

Potassium benzoate Sodium benzoates

Elixirs are usually prepared by simple solution with agitation and/or by admixture of two or more liquid ingredients.

Alcohol-soluble and water-soluble components are generally dissolved separately in alcohol and in purified water, respectively.

Then the aqueous solution is added to the alcoholic solution to maintain the highest possible alcoholic strength at all times so that minimal separation of the alcohol-soluble components occurs.

When the two solutions are completely mixed, the mixture is made to volume with the specified solvent or vehicle.

Preparation of Elixirs

Frequently the final mixture will be cloudy because of separation of some of the flavoring oils by the reduced alcoholic concentration.

Talc filter is use to absorb excessive amount of oils and therefore assists in their removal from the solution.

Types of elixir:

Non medicate

d

Medicated

These are simple elixirs that do not contain medicated agents.

Non medicated elixirs may be useful to the pharmacist in following ways:-

i. The addition of a therapeutic agent to pleasant tasting vehicleii. Dilution of an existing medicated elixir.

These only containi. Water ii. alcoholiii. sweetening agentiv. coloring agent v.

Non medicated elixir

If hydroalcoholic vehicle is selected the proportion of alcohol should be only slightly above the amount needed to effect and maintain the drug's solution. If dilution of existing medicated elixer is required than non medicated elixir choose for dilution should have same concentration of alcohol as the elixir being diluted.EXAMPLE:

Most common non medicated elixir are following:i. Aromatic elixir . perfumeii. Compound benzaldehyde elixiriii. Isoalcoholic elixir

Medicated elixirs are a solution of the active ingredient dissolved in water and an alcohol often along with other excipients such as preservatives.

Medicated elixirs

Most official and commercial elixirs contain single therapeutic agent . The main advantage of having only single therapeutic agent is that the dosage of that single drug may be decreased or increased simply by taking more or less elixir,

Examples of medicated elixirs:i. Antihistamine Elixir: Diphenhydramine HCl

ii. Analgesic Elixir: acetaminophen

iii. Cardio tonic Elixir: digoxin

iv. Antispasmodic Elixir: hyoscyamine sulfate

v. Sedative Elixir: phenobarbital

Antihistamines elixirs are useful primarily in the symptomatic relief of certain allergic disorders.

They supress symptoms caused by histamine(one of the chemical agents released during antigen -antibody reactions of allergic response.

Only minor differences exist in properties of most antihistamines

A perscriber's preference may be based on the incidence of adverse effects that maybe expected to occur.

The most common adverse effect is sedation and patient taking antihistamines should be warn against engaging in activities requiring mental alertness such as driving or operating machinery.

Other common adverse effects include dryness of the nose, throat, and mouth; dizziness; and disturbed concentration.

Antihistamines elixirs

Barbiturates are sedative and hypnotic agent that use to produce various degree of CNS depression.

Large dose increased the effect go from sedation to hypnosis to respiratory depression , the last being the cause of death in fatal barbiturate over dosage.

Barbiturates are administered in small doses in the daytime hours as sedatives to reduce restlessness and emotional tension.

Greater doses may be given before bed time as hypnotics to release insomnia.

Barbiturate sedative/hypnotic elixirs

Barbiturates are classified according to the duration of their hypnotic effect .i.e.

i. Long acting i.e. Phenobarbitalii. Intermediate acting i.e. Amobabitaliii. Short acting i.e. Secobarbitaliv. Ultra short acting i.e. Thiopental

Untoward effect: . Drowsiness and lethargy. . In heavy chronic users abrupt withdrawl may lead to convulsions,delirium, and occasionally to coma and death.

Phenobarbital elixir is formulated to contain phenobarbital 0.4%,which provides about 20 mg of drug per teaspoonful (5mL)of elixir.

This elixir is commonly flavored with orange oil , colored red and sweetened with syrup.

Official elixir contain 14% alcohol which is use to dissolve phenobarbital

Phenobarbital is a long lasting barbiturate with a duration of action of 4-6 hours

A usual dose as a sedative of about 30mg and hypnotic dose of about 100mg .

i) Phenobarbital Elixir

Phenobarbital 4.0g Orange oil 0.25ml Propylene glycol 100ml Alcohol 200ml Sorbitol solution 600ml Color q.s Purified water 1000ml

Phenobarbital Elixir

Digoxin is a cardiotonic glycoside obtained from the leaves of Digitalis lanata. It is white crystalline powder that is insoluble in water but soluble in dilute alcohol solutions.

There is no official method of preparation is indicated for digoxin Elixir . however it is required to contain 4.5 to 5.25 mg of digoxin per 100 ml of elixir or about 0.25 mg per 5 ml teaspoon.

Digoxin is poisonous and its dose must be carefully determined and administered to each individual patient.

Commercial products available for this purpose is packaged with calibrated dropper to facilitate accurate dosing.

Digoxin Elixir:

Digoxin is one of many drugs available in more than single dosage firm.

Drug administered in different dosage forms may exhibit different bioavailability characteristics, with varying pattern of drug release ,rates and extent of absorption..

DIGOXIN ELIXER (cont)

Keep below 30°C (at room temperature). Container should be tightly closed. Keep in light resistant ambered color

container; Protect from direct sunlight.

storage

Examples of medicated ElixirsELIXIR Commercial

productUse Product

Adrenocortical steroid

(dexamethsone)

Dexamethasone elixir

(Qualitest)

Synthetic analogue of hydrocortisone. Used for skin diseases , allergies and inflammatory conditions.

Analgesic

(acetamanophen)Children’ Tylenol Elixir

(McNeil)

Reduction of pain and lowering of fever in patients sensitive to or unable to take aspirin

ELIXIRS Commercial product

USES Product

Cardio tonic

(Digoxin)

Lanoxin pediatric elixir

(Glaxowellcome)

Increase the force of myocardial contraction . Used in CCF , atrial fibrillation and other cardiac conditions.

Sedative , hypnotics

(phenobarbital)

Phenobarbital elixir

(Qualitest)

Use as sedative and hypnotic.Contain 14% alcohol.

Elixirs containing 10-12% alcohol are self-preservative.

Better able to maintain both water-soluble and alcohol-soluble components in solution.

Has stable characteristics. Easily prepared by simple solution. Easily administered in patients having problem of

swallowing solid dosage form. Used as a vehicle. Used for dilution of medicated elixirs.

Merits of elixir

Less effective than syrups in masking taste of medicated substances.

Contains alcohol, can be vicious to children and adults who avoid alcohol.

Because they contain volatile materials, it must be stored in a air-tight screw-top jar to avoid their escape.

Needed to keep away from sources of ignition.

Demerits of elixir

Difference between Syrups And Elixirs:

Syrups Elixirs1.Alcohol is not necessary component2.more sweet than elixir3.more viscous than elixirs4.High concentration of sugar5.Less Stable6.Difficult to formulate than elixirs7.More effecting in masking the taste of medicinal agents8.May not be clear formulations9.Sucrose Syrup can not be used for diabetic patient but if used exercise care.

1.Alcohol is necessary component

2.Less sweet than syrup3.Less viscous than syrup4.Less proportion of sugar5.More stable6.Easy to formulate than syrups7.Less effecting in masking the taste of medicinal agents8.These are clear formulations9.Can be used for Diabetic patients easily