Pharmaceutics 356C

Chapter 13
Solutions

Dr. Bill Williams

williro@mail.utexas.edu
PHR 4.214 471-4681

1
 Recalls and Safety Alerts
• Recalls are actions taken by a firm to remove a product from the
market.
• Recalls may be conducted on a firm's own initiative, by FDA
request, or by FDA order under statutory authority.
• Class I Recall
– A Class I recall is a situation in which there is a reasonable probability
that the use of or exposure to a violative product will cause serious
adverse health consequences or death.
• Class II Recall
– A Class II recall is a situation in which use of or exposure to a violative
product may cause temporary or medically reversible adverse health
consequences or where the probability of serious adverse health
consequences is remote.
• Class III Recall
– A Class III recall is a situation in which use of or exposure to a violative
product is not likely to cause adverse health consequences.

2
 Recalls and Safety Alerts
• A market withdrawal occurs when a product has a minor
violation that would not be subject to FDA legal action.
The firm removes the product from the market or
corrects the violation. For example, a product removed
from the market due to tampering, without evidence of
manufacturing or distribution problems, would be a
market withdrawal.
• A medical device safety alert is issued in situations
where a medical device may present an unreasonable
risk of substantial harm. In some case, these situations
also are considered recalls.

3
 Recent Recalls
• RECALLS AND FIELD CORRECTIONS: DRUGS -- CLASS III
• _____________________________
PRODUCT
a) Children's Tylenol (Acetaminophen) Oral Suspension,
160 mg, 4 Fl oz (120mL) bottles, Bubblegum Flavor,
NDC #50580-407-04. Recall # D-096-3.
b) Children's Tylenol (Acetaminophen) Oral Suspension,
160mg, 4 Fl oz (120mL), Grape Flavor, NDC #50580-296-04.
Recall # Recall D-097-3.
CODE
a) Lot #EFM041 exp 7/04;
b) Lot #EFM040 exp 7/04.
RECALLING FIRM/MANUFACTURER
McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA, by letter on
November 20, 2002. Firm initiated recall is ongoing.
REASON
Defective container; product packaged with incorrect dosing cups marked with metric
measurements rather than with U.S. standard measurements
VOLUME OF PRODUCT IN COMMERCE
116172 bottles.
DISTRIBUTION
Nationwide.

4
 Recent Recalls
• RECALLS AND FIELD CORRECTIONS: DRUGS -- CLASS III
• _____________________________ PRODUCT
a) R-Tanna S Pediatric Suspension (Chlorpheniramine
Tannate 4.5mg and Phenylephrine tannate 5 mg) 4 fl oz (118mL) bottles, Rx only. Recall # D-
055-3;
b) CP-Tannic Suspension (Chlorpheniramine tannate 4.5mg
and Phenylephrine tannate 75mg) 4fl oz (118mL) and 16fl oz (473mL) bottles, Rx only. Recall #
D-056-3.
CODE
a) Lot# GB024;
b) Lot# GA984, GA986, GB005, GB033 and GB036.
RECALLING FIRM/MANUFACTURER
Recalling Firm: Kiel Laboratories, Inc., Gainesville, GA, by fax on/about September 12, 2002.
Firm initiated recall is ongoing.
REASON
SUBPOTENT; R-Tanna S Pediatric Suspension for phenylephrine tannate (3 month stability);
CP-Tannic Suspension for chlorpheniramine tannate ( 1 month stability).
VOLUME OF PRODUCT IN COMMERCE
a) 5463 bottles;
b) 12817 bottles.
DISTRIBUTION
OH and MS.

5
 Recent Recalls
• RECALLS AND FIELD CORRECTIONS: DRUGS -- CLASS II
• _____________________________ PRODUCT
Robinul Forte Tablets (glycopyrrolate tablets USP) 2mg, physician sample
cartons of 8 tablets (2 cards @4 tablets per card), Rx only. Recall # D-058-
3.
CODE
Lot Number H020572.
RECALLING FIRM/MANUFACTURER
Recalling Firm: First Horizon Pharmaceutical Corp., Alpharetta, GA, by
letters dated September 6, 2002.
Manufacturer: Mikart, Inc., Pharmaceutical Manufacturers, Atlanta, GA. Firm
initiated recall is ongoing.
REASON
Product contains glass particles.
VOLUME OF PRODUCT IN COMMERCE
386 cartons (8 tablets each/2 blister cards of 4 tablets per card).
DISTRIBUTION
Nationwide.

6
 PHR 356C
• Moving to lecture notes

7
 Solubility
(Chapter 13)

8
 Introduction
• You, as the Pharmacist, must be aware of the
solubility characteristics of the solutes and
the features of the common pharmaceutical
solvents
• Each chemical agent has its own solubility in
a given solvent
• For many medicinal agents, their solubilities
are stated in the USP, Merck Index, other
reference books

9
 Solubility
• Solubility: Concentration of a solute in a saturated
solution at a given temperature
• Saturated Solution: When a solvent at a certain
temperature has dissolved all of the solute that it
can
• Supersaturated Solution--Crystallization
• The solubility of a pure chemical substance at a
given temperature and pressure is constant (USP,
Merck)--However, its RATE of Solution depends on
the particle size of the substance and the extent of
agitation
• Solubility given usually as “1 gram in X ml” of water,
alcohol, etc.
10
 General Rules of Solubility

• Inorganic (examples)
1. If both the cation and anion of an ionic compound are monovalent,
the solute-solute attractive forces are usually easily overcome, and
therefore these compounds are generally water soluble (NaCl, LiBr, KI)
2. If both the cation and anion are multivalent, the solute-solute
interaction may be too great to be overcome by the solute-solvent
interaction and the compound may have poor water solubility (CaSO4,
BaSO4)
3. Salts of alkali metals (Na, K, Li) – usually water soluble

11
Solubility
12
Dissolution Profile

13
 General Rules of Solubility
4. Ammonium and quaternary ammonium salts – water
soluble
5. Nitrates, nitrites, acetates, chlorates, lactates –
generally water soluble
6. Sulfates, sulfites, thiosulfates – generally water
soluble
7. Acid salts of corresponding insoluble salt – tend to be
more water soluble than original salt

14
 Solubility
• Inorganic (examples)
8. Hydroxides and oxides – generally water insoluble
9. Sulfides – generally water insoluble
10. Phosphates, carbonates, silicates, borates,
hypochlorites – generally water insoluble

15
 Solubility
• Organic (examples)
1. Molecules with one polar functional group--Usually
soluble to total chain lengths of five carbons
2. Branched chains--More soluble than straight chained
3. Decrease in water solubility with an increase in
molecular weight
4. Increased structural similarity between solute and
solvent is accompanied by an increased solubility

16
 Important Terms
• Definitions:
– Solution
– Solute
– Solvent
• Examples:
– Alcohol USP
– Diluted Alcohol NF
– Glycerin USP
– Propylene Glycol USP
– Purified Water USP

17
 Expression of Solubility

• Percent solubilities:
--%w/v g/100 ml solution
--%v/v ml/100 ml solution
--%w/w g/100 g solution
• Ratio strength
--volume-in-volume (ml solute/ml solution)
--weight-in-volume (g solute/ml solution)
--weight-in-weight (g solute/g solution)
18
 Polarity
• Solubility due in large part to polarity of solvent
• Three categories:
1. Polar (water)
--High dielectric constant
--Break covalent bonds of strong electrolytes by
acid/base rxns.
--Dipole interaction forces (hydrogen bonding)
2. Semi-Polar (Ketones, alcohols)
--Induces polarity in nonpolar solvents
--Co-Solvents

19
 Co-Solvents

• Used to increase aqueous solubility of weak

electrolytes and non-polar molecules
• Solute more soluble in mixture of solvents
(alcohol/water mixture)
• Examples:
--Propylene glycol
--Polyethylene glycol
--Glycerin
--Alcohol

20
 Co-Solvent Example
• Valium (Diazepam) Injection 5mg/mL
– 40% Propylene Glycol
– 10% Alcohol
– 5% Na Benzoate/Benzoic Acid
– 1.5% Benzyl Alcohol
– QS Purified Water
• Diazepam – crystalline, insoluble in water
• Inject NGT 1mL/min to avoid venous thrombosis, phlebitis,
irritation
• Do not mix with other solution or drug in IV or infusion

21
 Polarity
• 3. Non-Polar Solvents (Carbon tetrachloride,
Benzene, Mineral Oil)
--Low dielectric constant
--Cannot reduce attraction, break covalent bonds, nor
ionize weak electrolytes
• Dielectric Constant:
--Measure of polarizability of a molecule
--Polarizability (Increase DC--Increase Polarizability)
--”like dissolves like”

22
 Solubility and Rate of Dissolution
• Solid drug must pass into solution to be
absorbed
• Rate of dissolution may influence
therapeutic response and blood levels
• Decreasing particle size and increasing
surface area will increase rate of
dissolution at a given temperature
– (Sw = 6/ρd)

23
 In Vitro Dissolution Curve

Amount Dissolved

Time

24
25
 Dissolution Process
• Influenced by:
– Free surface energy (surfactant)
– Shape of particles (surface area)
– Temperature
– Agitation (type and degree; diffusion layer)
– Amount already in solution (near saturation)
– Viscosity, volume of solvent

26
 Effect of PSD of Phenobarbital on Dissolution

M50 = 150 micron

M50 = 710 micron

(with 0.2% Tween 80 in media)
Amount Dissolved

M50 = 710 micron

Time

27
 Noyes-Whitney Equation
• dC/dt = KS (Cs – Ct)
– where
• K=D/h
• dC/dt – dissolution rate
• K – dissolution rate constant
• S – surface area of exposed solid
• Cs – concentration of saturated solution
• Ct – concentration at time t
• D – diffusion coefficient of solute in solution
• h – thickness of diffusion layer
• Sink conditions – if Ct << Cs, then omit Ct
• So dC/dt = KSCs
28
Stagnant Diffusion Layer

29
Concentration Gradient

30
 Isomers
• Definition:

Fumaric Acid Maleic Acid

Sublimes at 200oC 130oC
0.72g/100mL 78g/100mL
More Stable

31
 Polymorphs
• Polymorphs
– Definition
– Properties
• Amorphous Solids
– Definition
– Examples (cefuroxime axetil)

32
 pH and Solubility
• Many drugs are weak acids or weak bases
• Many insoluble in water
• Water soluble salts formed by reaction
with strong acid or strong base
• Examples
– Phenobarbital (1:1000) + NaOH Phenobarbital Na (1:1) + HOH
– Codeine (1:120) + Sulfuric Acid Codeine Sulfate (1:30) + HOH

• Solubility depends on pH
– What if adjust pH in wrong direction??

33
 pH and Solubility
• To enhance stability, it may be necessary
to form poorly water soluble salts:
– Examples
• Erythromycin stearate
• Erythromycin estolate
• Chloramphenicol palmitate
• Hydroxyzine pamoate

34
 USP Terms of Solubility
Descriptive Term Parts Solvent for 1 Part Solute

Very soluble Less than 1

Freely soluble From 1 to 10
Soluble From 10 to 30
Sparingly soluble From 30 to 100
Slightly soluble From 100 to 1000
Very slightly soluble From 1000 to 10,000
Practically insoluble or Insoluble More than 10,000
35
Pharmaceutical Liquids

36
Advantages and Disadvantages
of Liquids
• Advantages
1. Inability to swallow capsules and tablets
2. Only suitable dosage form--Often the case with deliquescent or
hygroscopic powders
3. Irritation--Some drugs may be less of an irritant when dissolved in a
soothing liquid
4. Dosing Flexibility--Can have a greater variation of drug combinations
and dosages in liquid formulations
• Disadvantages
1. Leakage
2. Costly to ship
3. Patient compliance
4. Taste
5. Preservative(s)--Bacteriostatic Agents (WATER*)
37
 Waters

• Six USP Monographs:

• Purified Water, USP
--Less than 0.001% total solids—
--Intended for oral and topical dosage forms
--Prepared by distillation or reverse osmosis

1. Distillation
2. Ion-exchange
3. Reverse Osmosis

38
 Pressure

or
water saline

water saline water saline

Osmosis Reverse
Osmosis

39
 Waters
• Water for Injection, USP
--Prepared by distillation or RO
--Total Solids not more than 1mg/100 ml
--Use within 24 hours
--Free from pyrogens (bacterial byproduct)
--Intended for injections which are to be
sterilized after manufacture

40
 Waters
• Sterile Waters—Four grades
1. Sterile Water for Injection, USP
--Package less than or equal to 1 liter
--Single use only
2. Sterile Water for Irrigation, USP
--Package in larger containers
--Single use
--Type I—Highly resistant borosilicate glass
--Type II—Treated soda-lime glass

41
 Sterility Tests
• Fluid Thioglycate Medium
– Range of microbes
– 30 – 35C for 7 days
• Soybean-Casein Digest Medium
– Molds and fungi
– 20-25C for 7 days
• Test Results: NO GROWTH

42
 Waters
• Sterile Waters—Four grades, cont.
3. Bacteriostatic Water for Injection, USP
--Sterile
--Contains antimicrobial agents which must be stated on
label—toxicity issues
--Preserve in single-dose or multi-dose vials NGT 30 ml
--Not for seniors or newborns

43
 Bacteriostatic Agents

• Methyl paraben 0.1%

• Propyl paraben 0.01%
• Benzyl alcohol 0.9-2.0%
• Benzalkonium chloride 0.01%
• Phenol 0.25-0.5%
• Thimerosal 0.01%
• Chlorobutanol 0.25-0.5%
• Phenylmercuric nitrate 0.01%

44
 Waters
4. Sterile Water for Inhalation, USP
--Distillation or RO
--No antimicrobial agent
--Labeling

45
Waters Schematic

46
 Other Solvents
• Alcohol, USP
• Glycerin, USP
• Propylene Glycol, USP
• Polyethylene glycols, USP
• Oils
--Vegetable Oils
--Synthetic fatty acid esters (ethyl oleate; propylene glycol
dicaprylate caprate)
--Liquid paraffin (MO)
• Note: All EXCEPT the OILS may be used in internal,
external and parenteral products either alone or in
conjunction with water
47
 Oils

• Used as solvents in External products

--i.e. Liniments and ear-drops
--Nose drops—danger of lipid pneumonia
• Used alone or as co-solvent
• Most substances are more soluble in vegetable oils
or synthetic fatty acid esters than in liquid paraffin
• Heavy liquid petroleum or MO is used as a laxative
• Always use the Oil Soluble or Free Base of the drug
to form an oil solution

48
 Aromatic Waters

• Clear aqueous solutions saturated with volatile

oils or other aromatic or volatile substances
• Peppermint Water, USP—Flavoring Agent
• Strong Rose Water, USP—Fragrance
• Hamamelis Water—”Witch Hazel”—An
Astringent
• Stability Issues
--Store in tight, light resistant glass containers
--Prone to oxidation
49
Syrups

50
 Syrups

• Concentrated aqueous solutions of a sugar or

sugar substitute with or without flavoring agent
• Vehicle--Better taste, increased palatability
• Components of Syrups
--Sugar or sugar substitute
--Preservative(s)
--Flavors
--Color(s)
• Some contain medicament and are a complete
preparation in themselves--Medicated syrups
Example: Chloral Hydrate Syrup

51
 Syrups
• Syrup, NF (Simple Syrup)
--Contains 85g sucrose in 100 ml syrup
--High concentration of sucrose
1. Give desired sweetness
2. Prevent microbial growth
--Specific gravity: 1.313
--May crystallize in warmer weather – “cap lock”
--Diluted--need preservatives--subject to mold and
fungi growth (i.e. Parabens)—WHY?

52
 Non-Sucrose Syrups

• Alternative components of syrups

--Dextrose
--Glycerin
--Sorbitol (64%w/w—60% sweetness of sucrose—produces
gas and GI motility)
--Also Sorbitol used to prevent crystallization
around cap of bottles
--Xylitol (Expensive)
--Aspartame (Expensive—Some problems)

53
 Non-Sucrose Syrups
• Syrups for Diabetics
--Methyl cellulose—Non-caloric, good
suspending agent also, masks bitter
tasting drugs—Increases viscosity
--Other celluloses—
Hydroxyethylcellulose, etc.

54
 Preparation of Syrups

• Preparation of Syrups:
1. Solution with the aid of heat
2. Solution by admixture in the cold
3. Dissolution of sucrose in a medicated or
flavored liquid
4. By percolation

55
 Preparation of Syrups
• Solution with Heat:
--Quick
--Can hydrolyze sucrose (a di-saccharide)—Dextrose and
Fructose
(Inversion and result is Invert Sugar—Darker color—Too
much heat and is said to be caramelized)
--Caramelized sugars are more subject to fermentation and
microbial contamination
--Example using heat:
--Acacia Syrup
--Benzoic Acid 0.1%--WHY?

56
 Preparation of Syrups

• Preparation by Admixture:
--Prepared without heat to avoid
inversion or damage to actives
--Mix with vigorous agitation
--Example: Ferrous Sulfate Syrup—
Turns green

57
 Ferrous Sulfate Syrup USP
• Composition – function of each?
– Ferrous sulfate
– Citric Acid (weak chelating agent)
– Peppermint Spirit
– Sucrose (reducing agent)
– Purified Water

• Ferrous Sulfate Fe+2SO4-2 7 H2O (soluble)

• Ferric Hydroxide Fe+3(OH)3-1 (insoluble)
• Ferric Ion Fe+3
• Ferrous Ion Fe+2 (oxidizes to Fe+3 )
58
Oral Solutions

59
 Oral Solutions
• Two categories:
1. Colored and flavored aqueous solutions of
medicaments
2. Dry powder mixtures for reconstitution
--Usually antibiotics which are unstable in
aqueous solution
--Usually refrigerate—Use within 7-14 days
--Dry granules—Contain flavors and other
additives

60
 Preparation of Oral Solutions
• By Simple Admixture
--Method depends on the nature of the solute and solvent
• By Chemical Interaction
--For water insoluble salt in an aqueous vehicle
--Options:
1. Change the solvent (alcohol, etc.)
2. Use a soluble form of the drug
--Example:
Strong Iodine Solution (Lugol’s Solution)
I2 + KI KI3
--Water insoluble Iodine in a salt solution of
Potassium Iodide (soluble salt complex)

61
Preparation of Oral Solutions

• Isotonic Solutions:
--Same osmotic pressure as biological fluids with which they are
being compared (Tears, blood, etc.)
--Body fluids have an osmotic pressure corresponding to that of a
0.9% solution of Sodium Chloride
--Primarily Ophthalmic solutions
• Hypotonic Solutions:
--Osmotic Pressure < 0.9% NaCl solution
--Hemolysis--Why?
• Hypertonic Solutions:
--Osmotic Pressure > 0.9% NaCl solution
--Crenation or cell shrinking—Why?

62
 Preparation of Oral Solutions
• Sodium Chloride Equivalents:
--Dextrose, etc.

Example: For Atropine Sulfate

SCE = 0.12, so 1 g Atropine Sulfate
equals the tonic effect of 0.12 g NaCl

See text
63
 Osmolality (mOsmol/Kg)
• Classifications:
 > 350 Hypertonic
 329 – 350 Slightly Hypertonic
 270 – 328 Isotonic
 250 – 269 Slightly Hypotonic
 0 – 249 Hypotonic

64
 Example – FDA aware of 4 deaths
due to hemolysis – (since 1994)
• Albumin (Human) 25% (plasma exchange)
Dilute 1 part to 4 parts SWFI

Albumin (Human) 5%

Trissel’s Handbook on Injectable Drugs (1994) – states “…prepare a 5%

From a 25% with 1 part of the 25% and 4 parts of SWFI, NS, or D5W.
Hospital pharmacists relied on this information!
Plasmapheresis – replacement mixture accounts for significant
fraction of the patient’s calculated blood volume

Revised in 1996 – NO SWFI

Hypotonic albumin solutions prepared with SWFI; large volumes with plasma-
pheresis accounting for significant fraction of patient’s blood 65
 Examples of Oral Solutions

• Powders for Reconstitution to Oral Solutions

1. Cloxacillin sodium for Oral Solution, USP
(antibiotic)
2. Nafcillin sodium for Oral Solution, USP (antibiotic)
3. Oxacillin sodium for Oral Solution, USP (antibiotic)
4. Penicillin V Potassium for Oral Solution, USP
(antibiotic)
5. Potassium Chloride for Oral Solution, USP
(Potassium Supplement)

66
 Examples of Oral Solutions
• Oral Solutions
1. Furosemide Oral Solution (Lasix)—for edema and
hypertension
2. Cimetidine HCl Liquid (Tagamet)—Peptic ulcer
disease & hypersecretory disorders
3. Ergocalciferol Solution—Vitamin D2 in propylene
glycol

67
 Oral Liquid Vehicles
• Used for their solvent, suspending and/or
emulsifying properties
• Used to dilute drugs to suitable volume for
dosing
• Used to enhance flavor and palatability
• Used to provide stable and elegant
preparations

68
 Oral Liquid Vehicles (Official)
• Aromatic Elixir NF (Simple Elixir)
• Compound Benzaldehyde Elixir NF
• Peppermint Water NF
• Sorbitol Solution USP
• Suspension Structured Vehicle NF
• Sugar-Free Suspension Structured Vehicle NF
• Syrup NF (Simple Syrup)
• Xanthan Gum Solution NF

69
 Oral Liquid Vehicles (Nonofficial)
• Acacia Syrup
• Cherry Syrup
• Citric Acid Syrup (Syrup of Lemon)
• Cocoa Syrup (Cacao Syrup, Chocolate Syrup)
• Raspberry Syrup
• Tolu Syrup (Tolu Balsum Syrup, Syrup of Tolu)
• Wild Cherry Syrup
• Coca-Cola Syrup
• Ora-Sweet Syrup Vehicle
• Ora-Sweet SF Sugar-Free Syrup Vehicle
• Syrpalta

• See reference: L. Allen, Int. J. Pharm. Compounding,

70
5(1)2001,65-67.
Non-Aqueous Solutions

71
 Non-Aqueous Solutions

• Hydrocarbons
--Aliphatic hydrocarbons (Mineral Oil)
--Chlorinated hydrocarbons (Trichloroethane)
• Oils
--Used for liniments, sunscreens, lotions (i.e.
Topicals) – reduces irritation
1. Fixed Oil—Almond, Peanut, Sesame
2. Volatile Oil—Wintergreen Oil, Turpentine
Oil, Peppermint
72
 Alcohols

• Ethanol for Internal Preparations

--Glycerin is a high molecular weight alcohol
• Rubbing Alcohol, USP
--70% v/v ethanol with water, denaturants, perfume oils, and
color additives
--must contain: 355mg sucrose octaacetate or 1.40mg
denatonium benzoate
--Regulated by ATF
-- Denaturants:

73
 Alcohols
• Isopropyl Rubbing Alcohol,
USP
--70% v/v IPA with water, stabilizers,
perfume oils and color additives
--Used as a Disinfectant (skin,
equipment)

74
 Collodions
• Formed from reaction of:
Cotton Pyroxylin (cellulose tetranitrate)
HNO3
H2SO4
--Forms protective layer on skin
• Three USP Collodion products
1. Collodion USP—To protect cuts, lacerations
2. Flexible Collodion, USP—Camphor and Castor oil
3. Salicylic Acid Collodion, USP—Keratolytic agent (warts)

75
Spirits and Elixirs

76
 Spirits
• Spirits
--Alcoholic or hydro-alcoholic solutions of volatile or aromatic
substances
--Alcohol > 60%
--”Salting Out”—Too much water added, aromatic substance will
salt out
--Methods of Preparation:
1. Simple solution
2. Maceration
3. Distillation
4. Chemical reaction
Official USP Spirits:
1. Aromatic Ammonia Spirit, USP (For fainting, syncope)
2. Camphor Spirit, USP
3. Peppermint Spirit, USP
77
 Elixirs
• Elixirs:
--Clear, sweetened hydro-alcoholic solution
intended for oral use
--Palatability
--Range of 4 to 40% alcohol
--Often contain co-solvents
--Alcohol as preservative

78
 Elixirs
--Classes of Elixirs:
1. Non-medicated
--Vehicle and Diluent
2. Medicated (pg. 321 in text for other examples)
--Examples:
1. Antihistamine (Benadryl—
Diphenhydramine
HCl Elixir
2. Sedative and Hypnotic Elixirs—
Phenobarbital Elixir
3. Expectorants—Terpin Hydrate Elixir
4. Cardiotonic Elixirs--Digoxin

79
Tinctures and Fluid Extracts
(Liniments & Liquefied Phenol)

80
 Tinctures and Fluid Extracts
• Prepared by extraction
• Protect from air, light, heat—tightly sealed bottles
• Inactive plant compounds extracted from actives
• Pectin, celluloses, extraneous material removed
• Methods of extraction:
1. Maceration (“soak”)
Example: Cascara Sagrada Fluid Extract
2. Percolation
Uses column containing drug

81
 Tinctures

• Alcoholic or hydro-alcoholic solutions from

vegetable substances or chemical substances
• Contain extracts or chemical agents
• Alcohol Content: 15-80%
• Stability and Storage
• Preparation of tinctures:
1. Maceration—Compound Benzoin Tincture
2. Percolation—Opium Tincture, Belladonna
Tincture
3. Solution—Iodine Tincture (I2 + KI KI3)

82
 Tinctures
• Official Tinctures:
--Belladonna Tincture
--Iodine Tincture
--Strong Iodine Tincture
--Compound Benzoin Tincture

83
 Fluid Extracts
• Liquid preparations of vegetable drugs (plant
extracts) containing alcohol
• Adjusted (standardized) so 1 ml tincture
contains 1g of drug
• Preparation—Percolation
• Official Fluid Extracts—Laxatives
--Aromatic Cascara Fluidextract
--Cascara Sagrada Fluidextract
--Senna Fluidextract

84
 Liniments

• Oily or alcoholic liquids or semi-solids for External

Use (Ben-Gay, Theragesic)
• Counter-irritant
• Oils less irritating to skin than alcohols in base
• Actives ingredients:
--Methyl salicylate
--Camphor
--Menthol
--Thymol
--Various Oils
• There is no Official Liniment

85
 Pyrogens and Pyrogen Testing
• Pyrogens: Fever-producing organic substances arising
from microbial contamination and are responsible for
many of the febrile reactions which occur in patients
following injection
• Material is thought to be a lipopolysaccharide (endotoxin)
from the outer cell wall of the bacteria; and endotoxins are
soluble
• Is thermostable and may remain in water even after
sterilization by autoclaving or by bacterial filtration
• Are oxidized (Potassium permanganate—oxidizing agent)
• USP Pyrogen Test:
--Uses healthy rabbits— inject, check rabbit temperature for norms
--Replaced now by Limulus amebocyte lysate (LAL test)
(test solution + cell lysate from amebocytes of horseshoe crab)
Protein fraction of amebocyte coagulates if endotoxin present
--USP Bacterial Endotoxins Test utilizes LAL
86
 Pyrogens and Pyrogen Testing
• Gram (–) bacilli are most potent
• Pyrogens come from:
– Water used as solvent
– Container used in preparation
– Chemicals used in preparation
• Remove pyrogens by:
– Dry heat (250C for 30 min; 180 C for 3-4 hours)
– Washing with pyrogen free Water For Injection USP to remove
water soluble pyrogens
– Too small to filter out; SO PREVENT
• Pyrogens cause chills, fever, headache, pain in legs and
limbs

87