PH 107: Pharmaceutical Dosage Forms, Drug Delivery Systems and Medical Devices, Laboratory

MIDTERM

TABLETS
 Are solid dosage forms prepared by compression with the aid of suitable pharmaceutical excipients
 Characteristics of ideal tablets:
 Free of defects- chips, cracks, discoloration & contamination
 Strength to withstand mechanical stresses production
 Stable
 Release medicinal agents in a predictable & reproducible manner

Methods of manufacturing tablets:

 WET GRANULATION
 Widely employed method for manufacturing compressed tablet

 All-in-One granulation methods

 FLUID BED GRANULATOR
 Continuous operation:
Pre-blending the formulation powder
Granulating the mixture by spraying onto the fluidized powder bed
Drying the granulated product to the desired moisture content
 MICROWAVE VACUUM PROCESS
 Using a microwave
 Powder is mixed, wetted, agglomerated and dried

 DRY GRANULATION
 Powder mixture is compacted in large pieces/ slugging and broken down or sized into granules
 Active ingredient/ diluent must have cohesive properties
 Advantages: for materials degraded by moisture- elevated temperature during drying
 Conditions at which materials are applicable for drying granulation:
 Possess free-flowing & cohesive properties
 Be compressed directly in a tablet machine without need for granulations

Property of Granulation important in making tablets:

 Provides the powders free-flowing
 Increases material density and improving powder compressibility
 Slugging- after weighing and mixing the ingredients, the powder mixture is slugged or compressed into
large flat tablets or pellets
 Roller compaction- powder compactors used to increase the density of powder by pressing it between
roller at 8000-1200 pounds of pressure
 DIRECT COMPRESSION
 Compressed directly in a tablet machine without a need for granulation
 Granular chemicals possess free-flowing and cohesive properties (e.q. potassium chloride)

Tablet Excipients:
 Diluents
 Fillers to make up the bulk of the tablet; improve cohesion, permit use of direct compression or promote flow
 Common diluents: kaolin, lactose, mannitol, starch, powdered sugar & Ca 3(PO4)2
 Binders & Adhesives
 Either dry or liquid form to promote granulation process or cohesive compacts during direct compression process
 Common binders: 10-20% Aq. Cornstarch; 25-50% glucose; molasses; natural gums (acacia); cellulose derivatives
(methylcellulose, CMC, microcryst cellulose, gelatins & povidone)
 Disintegrants- facilitates tablet disintegration
 Lubricants, antiadherents & glidants
  Lubricants- reduce friction during tablet ejection between the walls of tablet & die cavity (e.q. talc, Mg stearate &
Ca stearate)
 Color & dyes – disguise off-color drugs to provide product ID & to produce a more elegant product
 FD& C, D&C dyes and lakes
 Flavoring agents- limited to chewable tablets, or tablets intended to dissolve in the mouth (flavor oils or dry powders)
 Artificial sweeteners
 Only for chewable tablets or tablets intended to dissolve in the mouth
 Sweetness from diluents (mannitol, lactose), saccharin (unpleasant after taste), aspartame (unsuitable in the
presence of moisture)
 Adsorbents
 Hold quantities of fluid in an apparently dry state
 MgO, MgCO3, bentonite, SiO2

Tablet Compression Machine Tablets are made by compressing a formulation containing a drug or drugs with excipients on
stamping machine called presses.
Tablet presses are designed with following basic components:
1) Hopper for holding and feeding granulation
2) Dies that define the size and shape of the tablet.
3) Punches for compressing the granulation within the dies
4) Cam tracks for guiding the movement of the punches
5) A feeding mechanism for moving granulation from hopper into the dies

PROBLEMS ENCOUNTERED DURING PRODUCTION:

Results from air entrapment & high speed production:
a. Capping- partial or complete separation of the top or bottom crowns of a tablet from the main body of the tablet
Cause: unclean punches and imperfectly smooth or by granulation with too much fine
b. Splitting/ Lamination (horizontal striations)- separation of a tablet into 2 or more distinct layers
Cause: aging tablets, improper storage

Results from excessive moisture or substance with low melting temperature in the formulation:
a. Sticking- adhesion of tablet material to a die wall
b. Picking- removal of tablet’s surface by a punch

Results from use of a drug with a color different from that of tablet excipients or from a drug with colored degradation products :
a. Mottling- unequal distribution on a tablet with light or dark areas standing out on an otherwise uniform surface

 Three ways of imprinting logos/ ID on tablets:

 Debossed
 Imprinted with a mark below the surface
 Embossed
 Imprinted with a mark raised above the surface
 Engraved
 Imprinted with a code that is cut into the surface during production

 FLUID BED or AIR SUSPENSION COATING

 Spray coating of powders, granules, beads, pellets or tablets held in suspension by a column of air
 Fluid bed equipment is multifunctional and may also be used in preparing tablet granulation
 WURSTER PROCESS
 Items to be coated are fed into a vertical cylinder and supported by a column of air that enters from the bottom of
the cylinder

Types of Fluid Bed System:

 Top Sprays
 Provides greater capacity up to 1500kg than the other air suspension coating method
 For taste masking, enteric release and barrier films on particles or tablets
 Most effective when coatings are applied from aqueous solutions, latexes, or hot melts
 Tangential spray technique
 Used in rotary fluid bed coater
 Used for layering coating, for sustained-release & enteric coated
 Bottom spray
 For sustained release & enteric release products
 Employed using a modified apparatus used for bed coaters
Tablet Evaluation & Control:
 General Appearance
 Visual identity & overall appearance
 Hardness & Resistance
 Withstand mechanical shocks of manufacture, packaging & shipping
 TABLET HARDNESS TESTER
Measures the degree of force required to break a tablet
 FRIABILATORS
Determines friability (tablets tendency to crumble)
 Weight
 To ensure tablet contains proper amount of drugs
 Content Uniformity
 Tablet contains 50mg or less of drug substance
 Dissolution & bioavailability
 Disintegration- ensures that the tablet drug substance is available for dissolution & absorption from the GIT
 Uncoated USP tablets- disintegration time of 2mins (NTG) to 5 min (ASA); majority less than 30 mins
 Buccal tablets- 4 hrs

LOZENGES
◼ Solid dosage forms intended to slowly dissolve in the mouth
◼ Deliver drugs systemically by releasing the drug either bucally or sublingually for absorption

Types of Lozenges:
1. Hard Lozenges- From syrups of sucrose & other sugars and/or carbohydrates that are boiled so that the moisture content
in the product is 0.5%-1.5%. Preparation is similar to candy making

2. Soft Lozenges- From flavored fatty base such as chocolate, PEG base & sugar-acacia base

3. Chewable Lozenges- Glycerinated gelatin-base chewable oral drug preparation which was made after a candy “gummy
worms” or “gummy bears” for children was launched

Method of preparation:
❑ Hand Rolling- does not require special calculation and equipment

❑ Fusion or Molding- method used for hard candy, chocolate, gummy gel chewable
- requires heat, special mold, skills and calculation
- Dose unit may be determined either by weight or volume or (both)

Advantages/Disadvantages of Handrolled and Fusion method:

Preparation: Chocolate Based Calcium Lozenges

❑ Synonyms: Calx Chocolate Lausiae

❑ Description of final product: The lozenges are chocolate-brown in color with a smooth surface. The lozenges are round disks
with a diameter of 2.5 cm, and each appears uniform in size with a depth of 0.5 cm.
Uses of Calcium:
✓ Calcium – as a reducing agent in order to extract metals such as uranium, zirconium and thorium.
✓ Cheese - made using calcium ions to promote the coagulation of milk.
✓ Cement and mortar, important when constructing buildings and other things, are made using calcium.
✓ Calcium hydroxide - to determine whether carbon dioxide is present.
- commonly used in science laboratories
✓ Calcium tungstate - in bright paints, X-ray studies and fluorescent lights.
✓ Calcium carbonate - to make lime and limestone which are important in the glass industry.
✓ Calcium gluconate - food additive; also added to vitamin pills.
✓ Calcium sulfate - Blackboard chalk
✓ Calcium hypochlorite - to disinfect pools (remove bacteria) and is also a bleach.
- added to deodorants and fungicide.
✓ Calcium - in liquid rocket fuel, textile production, dental products (including toothpaste), fertilizer and the making of dough
and yeast products.
- required for the growth and development of the bones
- responsible for the rigidity in human bones
✓ Calcium carbonate works as an antacid to relieve heartburn
- helps treating and preventing rickets
- most likely that calcium could be effective for treating and preventing osteoporosis

Use/s of Lozenges:
✓ Cepacol – sore throat
✓ anaesthetics
✓ demulcent
✓ antibacterial
✓ Nicorette – smoking cessation
✓ Fentanyl (actiq) (buccal) - cancer

Recommended Dietary Allowance (RDA) for calcium:

**19- 50 years old MALE- 1,000 mg FEMALE- 1,000 mg

CREAM
- Solid dosage preparation containing one or more medicinal agents dissolved or dispersed in either an o/w emulsion or in another
type of water washable base
- Easier to spread and remove than ointment
- Lighter, less viscous than ointment, imparts pseudoplastic flow when applied

TYPES OF CREAM:

A. Oil in Water (o/w)- Vanishing cream, tends to vanish on skin

- contains large percentages of water and stearic acid/other oleaginous components
Examples: Shaving cream, Hand cream, Foundation Cream

B. Water in Oil (w/o)- Cold cream, imparts oily feeling on skin

Examples: Emollient cream (Cold cream –Galen’s cream)

Preparation: Cold Cream

✓ Synonyms: Petrolatum rose water ointment

Galen’s cerate unguentum aquae

✓ Description of the final product: It is white semisolid preparation

✓ USES: used in topical skin, rectally, and vaginally products

emollient
cleansing cream
ointment base

✓ Remarks: This is w/o emulsion

The method of preparation used is FUSION method
Spermaceti is a viscosity modifier
OINTMENT- Semi solid preparation intended for external application to skin and mucous membrane

✓ Also known as: Ointment/Salve/Charisma

✓ Category: Hydrocarbon or oleaginous

Characteristics:
✓ Homogenous, smooth & free from grittiness
✓ Easily spreadable
✓ Becomes rancid with time (not dispensed with slight evidence of rancidity or mold)

Types of Ointment:

A. Medicated
- for treatments of cutaneous (skin diseases).
- for both local and systemic effects
- systemic drug absorption considered
Examples: Sulfur Ointment, Zinc Oxide Ointment and Compound Resorcinol

B. Non-medicated
- referred to as “ointment bases”
- used for their physical effects: protectant, emollient or lubricating effect or use as vehicles in medicated ointments.
- Example: White Ointment

Method of Preparation:

1. Mechanical Incorporation/Levigation- reducing to impalpable powder to reduce grittiness and to form a very smooth nucleus
2. Fusion- heat first the substance with high melting point like wax and spermaceti using water bath before adding soft, oleaginous
material

Ointment Bases
- used for medicated ointments: *physical effects *vehicles

4 general groups of ointment bases:

(a) Oleaginous bases/ Hydrocarbon bases
Uses: emollient effect
effective as occlusive dressings
remain on the skin for long periods without drying out (occlusive dressing)
immiscibility with water (difficult to wash off)

*levigating agent : liquid petrolatum when powdered substance is incorporated into HC bases

1. Petrolatum, USP (yellow petrolatum & petroleum jelly)

- purified mixture of semisolid HCs obtained from petroleum
- Product: Vaseline (Chesebrough-Ponds)

2. White Petrolatum, USP (white petrolatum jelly)

- wholly or nearly decolorized purified mixture of semisolid HCs from petrolatum
- Used: diaper rash, dry skin
- Commercial product : White Vaseline (Chesebrough-Ponds)

3. Yellow Ointment, USP (simple ointment)

- purified wax obtained from the honeycomb of the bee Apis mellifera
- has slightly greater viscosity than plain petrolatum

4. White Ointment
- consists of white wax & white petrolatum

(b) Absorption bases

2 Types - Those that:
(1) permit the incorporation of aqueous solutions resulting in the formation of W/O emulsions (e.g., hydrophilic petrolatum
and Anhydrous Lanolin)
(2) W/O emulsions that permit the incorporation of additional quantities of aqueous solutions (e.g., lanolin – as emollient
and Cold cream )
 ◼ Characteristics
1. Not easily removed from skin with water washing,
2. possess some power of penetration into the deepest layers of the skin - therefore are used for “endodermic” ointment.

◼ USES
1. As emollient but do not provide the degree of occlusion
2. Incorporates aqueous solutions into oleaginous bases

1. Hydrophilic Petrolatum
- Composed of: stearyl alcohol, white wax, cholesterol & white petrolatum
- Characteristics: ability to absorb water with the formation of W/O emulsion
- Commercial product - Aquaphor (variation of hydrophillic petrolatum).

2. Anhydrous Lanolin, USP

- may contain NMT 0.25% water.
- Characteristics:
* insoluble in water but mixes without separation with about 2x its weight in water.
* incorporation of water results in the formation of a W/O emulsion
- Synonym: Refined Wool Fat

3. Lanolin, USP
- Obtained from wool of sheep (Ovis aries)
- purified waxlike substance - cleaned, deodorized, and decolorized.
- processed to reduce contents of free lanolin alcohols, any detergent & pesticide residues.
- Characteristics:
*W/O emulsion that contains between 25 to 30% water.
*Additional water may be incorporated by mixing
- Synonym: Hydrous Wool Fat

4. Cold Cream, USP

- semi solid white W/O emulsion prepared with cetyl esters wax, white wax, mineral oil, sodium borate, and purified water
- Uses: emollient and base.
- Example: Eucerin cream - is a W/O emulsion of petrolatum, mineral oil, mineral wax, wool wax, alcohol and bronopol.

(c) water-removable bases

- O/W emulsions resembling creams.
- Aqueous external phase easily washed from skin
- can absorb serous discharges
- Characteristics
- Resemble creams in their appearance
- May be diluted with water or with aqueous solution
- can absorb serous discharges
- Certain medicinal agents may be better absorbed in the skin
1. Hydrophilic Ointment
*Sodium lauryl sulfate (emulsifying agent),
*stearyl alcohol and white petrolatum (oleaginous phase of the emulsion).
*Methylparaben & propylparaben (antimicrobial preservatives).
USE: employed as water removable vehicle for medicinal substances
*Hydrophilic ointment and vanishing cream (o/w); hydrous woolfat and cold cream (w/o)

(d) water-soluble bases

- do not contain oleaginous components.
- water washable, referred to as greaseless.
- soften greatly with water, large amount of aqueous solutions not effectively incorporated
- used for incorporation of solid substances.

* Polyethylene Glycol Ointment - polymer of ethylene oxide and water

- Combining PEG 3350 (solid) with PEG 400 (liquid), results in a very pliable semisolid ointment.

Ointment container
◼ Ointment jars- Clear, opal, amber & green glass or white or green plastic ointment jars
◼ Collapsible tubes

Preparation: White Ointment

Synonym: Salve/charisma/Simple Ointment/Unguentum Simplex
Description of the final product: It is a white, semisolid preparation that is insoluble in water

Use/s: For its physical effect – emollient effect

Protection against the escape of moisture and effectiveness as occlusive dressing
Used as a vehicle in the preparation of medicated ointment

Preparation: Zinc Oxide Ointment

Synonym: Unguentum zinci oxide

Zinc ointment

Description of the final product: It is a white, semisolid preparation

Uses/s : it has a mild, astringent, protective and antiseptic action

employed widely in the treatment of dry skin and skin disorder like eczema, pruritis and psoriasis

Remarks: The method of preparation is mechanical incorporation. It should be preserved in a well closed container.
White ointment is the base.
Avoid prolong exposure to temperature exceeding 300C

Preparation: Sulfur Ointment

Synonym: Unguentum Sulfuris

Description of the final product: It is a yellow, semisolid preparation

Use/s: parasiticide
treat ringworm and scabies

Remarks: The method of preparation was mechanical incorporation.

Precipitated sulfur is the active ingredient
White ointment is the hydrocarbon base
Mineral oil is the levigating agent

SOLUTIONS
❑ Homogenous mixture of solid, liquid or gas in a liquid vehicle

A. Aqueous solution- uses water as vehicle

B. Non-aqueous solution
a. Hydroalcoholic – alcohol
b. Oleaginous – oil
c. Ethereal - ether

A. Aromatic Water
- Clear saturated aqueous solution of volatile oil or other aromatic or volatile substance
- Odors or taste are the same as those of the drug or volatile substance from which they are prepared
- Free from empyreumatic (smoke-like) and other foreign odor
- Generally used as flavored and perfumed vehicle

Stability of Aromatic water:

✓ are not permanently stable preparations
✓ protect from excessive light and heat
✓ deterioration may be due to volatilization
✓ decomposition/mold growth producing cloudy preparation/ disagreeable odor

Preparation of Aromatic water:

1. DISTILLATION- slowest, most expensive method but the most satisfactory method of preparation (e.g. is Strong Rose Water).
❑ COHOBATION – distillate is repeatedly used with fresh portions of flowers/plant materials to minimize loss of water
soluble components. (e.g. Orange / Rose flowers)
2. SOLUTION
A. Direct Solution Method
❑ 2 g or 2mL of liquid + 1000mL purified water → shake several times for a period of 15 minutes
❑ Set aside for 12 hours or longer
❑ Filter through wetted filter paper
❑ q.s ad water to 1000mL
 ❑ Advantage :Save time and equipment

❑ Disadvantage: Do not agitate when drawing of aromatic water if the excess volatile oil is allowed to remain

B. ALTERNATE SOLUTION METHOD

❑ Most frequently involved volatile oil/solid + 15 g talc/purified siliceous earth/pulped filter paper + 1000 mL purified water
→ shake for several times for 10 minutes → filter → clear filtrate → q.s ad water to 1L
❑ Remarks: The dispersing agent increases the surface of volatile substance ensuring more rapid saturation of water and
forms an efficient filter bed thus producing a clear solution

Preparation: Cinnamon Water

(Non-medicated Aromatic water)
Synonyms: Aqua Cinnamon
Saigon cassia
Casio Nare
Cassia oil

Description of the final product: It is a clear, colorless, saturated aqueous solution with characteristic odor and taste of cinnamon

Use: Flavoring vehicle

Remarks: The method used was direct method

It should be stored in a tight and light resistant container to prevent the preparation from light and excessive volatilization

Preparation: Concentrated Peppermint Water

(Medicated Aromatic water)
Synonyms: Aqua Menthos Piperitas
Brandy water
Aqua Mint

Description of the final product: It is a clear, saturated solution of peppermint oil in purified
A colorless aqueous solution with a characteristic odor and taste of peppermint

Use: Carminative; Flavoring vehicle

Remarks: The method of preparation is alternate solution method

Ethyl alcohol is used to dissolve peppermint oil
Talc is used as dispersing agent
Talc increases the surface of volatile substance ensuring:
- more rapid saturation of water &
- forms an efficient filter bed thus producing a clear solution.

Preparation: Camphor Water

(Medicated Aromatic water)
Synonyms: Aqua camphorae
Laurel camphor
Gum camphor

Description of the final product: It is a clear, colorless, saturated aqueous solution with characteristic odor of camphor

Use: Rubefacient

Remarks: The method of preparation used was alternate solution method

Ethyl alcohol was used to dissolve camphor crystals and talc is used as dispersing

B. Solution
❑ Liquid preparation that contains one or several soluble chemical substance dissolved in suitable solvent or mixture of
mutual miscible liquid
❑ Homogenous mixture of 2 or more substances.

2 components:
1. Solute- one that is being dissolved
2. Solvent- one that dissolves
 Relative terms of solubility

Method/s of preparation:
1. Simple Solution- prepared by dissolving the solute in a suitable solvent
Examples: NaCl solution, Strong Iodine Solution
2. Chemical Reaction- prepared by reacting two or more solute with each other in a suitable solvent
Examples: Aluminum subacetate solution, Magnesium citrate solution, Sulfurated lime solution
3. Solution by Distillation- if the solute is a volatile oil
4. Solution by Extraction- drug or pharmaceutical necessities of vegetable or animal origin
- Also called extractives
Different Methods of Extraction:
a. Maceration- submerging the solute
b. Percolation- submerging the solute using percolator
c. Digestion- with the aid of gentle heat.
d. Infusion- “blanching”, addition of hot water
e. Decoction- boiling for 15 minutes

Preparation: Calcium hydroxide topical solution

(Topical solution)
◼ stored in well-filled, tightly stoppered containers to deter the absorption of CO 2
◼ kept in a cool place to maintain an adequate concentration of dissolved solute.
◼ categorized as an astringent.
◼ employed in combination with other ingredients in dermatologic solutions and lotions to be applied topically

Synonym: Lime water

Description of the final product: Clear, colorless solution with an alkaline taste

Use/s: employed with other ingredients in dermatological solution and lotion

as protector in lotion preparation and an emulsifying agent

Remarks: The method preparation was simple method

Undissolved portion is not suitable for preparation of additional quantity of Ca(OH)2
Bottle should be filled up to the brim

Preparation: Strong Iodine solution

(Topical solution)
◼ contains, in each 100 mL, 4.5 – 5.5 g of iodine, and 9.5 – 10.5 g of potassium iodide.
◼ One g of iodine dissolves in 2950 mL of water.
◼ solutions of iodides dissolve large quantities of iodine.
◼ therefore, a solution of polyiodides in excess iodide.

Synonyms: Lugol’s solution

Iodine Potassium Iodide
Liquor iodi
Aqueous Iodine Solution

Description of the final product: A liquid with a deep brown color and odor of iodine

Use/s: treatment of thyrotoxicosis

antigoiterogenic
Germicidal and fungicidal
antiseptic
keratolytic
Remarks: The method of preparation used was simple solution
In weighing the iodine crystals, use porcelain spatula instead of stainless because it reacts with metal
KI is used as solubilizing agent

Preparation: Magnesium Citrate Oral Solution

(Oral solution)
Synonyms: Citrate
Citrate of magnesia
Magnessi citralis
Lemonada purgante

Description of the final product: It is a to slightly yellow, clear effervescent liquid having a sweet acidulous taste and a lemon flavor

Use: Saline cathartic

Remarks: The method of preparation used was chemical reaction

Sterilizing the bottle is done to prevent the growth of microorganism

◼ Troublesome solution – has tendency to deposit a crystalline solid upon standing due to the formation of some almost
insoluble normal Mg citrate.
◼ Cause of the problem has largely been attributed to the indefinite composition of the official MgCO 3, which by definition is
a “basic hydrated MgCO3 or a normal hydrated MgCO3

Preparation: Dakins solution

(Solution)
Synonyms: Sodium Hypochlorite Solution

Description of the final product: It is clear, light yellow solution with the characteristic odor of chlorine

Use: Disinfectant; Antiseptic

Remarks: The expiry date of the solution is 30 days after it has been compounded
The solution must be discarded 48 hours after it has been opened
It must be stored at room temperature

C. Syrup- concentrated solution of a sugar usually sucrose in water

3 Kinds of Syrup:
1. Simple Syrup
✓ Clear concentrated, sweet aqueous hypertonic solution with striations of sucrose in purified water
2. Medicated Syrup
✓ Aqueous solution of sucrose that contains pharmaceutically active ingredient and has a therapeutic effect
3. Flavored Syrup
✓ Contains aromatic and pleasantly flavored substance and is intended as a vehicle of flavor for prescription
✓ It does not contain an active ingredient

Methods of preparation:
1. Agitation with Heat
- Sucrose is added to water and heated until solution is effected
Advantage: FAST
Disadvantage: Excessive heating will cause inversion of sucrose → glucose + fructose (sweeter, with an increase tendency to
ferment) * Caramelize, yellowish to brownish in color

2. Agitation without Heat

Advantage: For substance that are heat sensitive
Disadvantage: Slower

3. Percolation - Permits the purified water to pass slowly through a bed of crystalline sucrose to dissolve it
4. Addition of sucrose to medicated liquid

Simple syrup
❑ A good syrup has a specific gravity of not less than 1.33 and the concentration should be 85% w/v or 65% w/w
❑ 60 -80% concentration makes the syrup self preserving
❑ 60% concentration prone to microbial growth
❑ 85% concentration can crystallize the sucrose present
Preparation: Simple syrup
Synonym: Syrupus
Sirup, syrup

Description of the final product: It is clear solution of sucrose in purified water

Use/s: Sweetening agent

Sweet vehicle and as basis for many flavored and medicated syrup

Remarks: The method of preparation was percolation

Tight cotton inhibits the flow of liquid
Loose cotton will permit the sucrose light flow freely
Filter paper is used to prevent holing of sugar

Preparation: Chocolate syrup

Synonym: Cacao Syrup
Chocolate Flavored Syrup

Description of the final product: A viscous, dark brown syrup with the odor and taste of cocoa

Use/s: Flavored vehicle

Remarks: Cocoa containing NMT 12% non-volatile ether soluble extractives or fats yields syrup having a minimum tendency
to separate

Sodium benzoate and glycerin are preservatives added to prevent bacterial and mold growth when sucrose
concentration is low.

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