Download Calcium Carbonate

Laboratory Manual
for
Pharmaceutics II
By
Dr. Ahmed F. Asker, Professor
and Section Leader of Pharmaceutics
College of Pharmacy & Pharmaceutical Sciences
Florida A & M University, Tallahassee
Florida 32307
Revised: 01/05/05
1
Laboratory Instructions and Regulation
1.
Practice good manners in the laboratory at all times.
2.
Appropriate lab. Jackets/coats are to be worn to all laboratory sessions.
3.
Personal cleanliness and neatness are important. This includes clean lab. Jacket,
clean hands, fresh shaves (well groomed), etc.(Do Not wear shorts to the
laboratory). No open toe shoes or sandals shall be warn in the lab.
4.
All student must have a personal set of metric and apothecary weights. Mark these
weights distinctly and permanently so that if they are lost the finder can be readily
identified. Students will furnish liquid detergent, cloth or paper towels, and tissues
to cry into for their own desk.
5.
There should be a minimum of conversation with other students. Avoid
unnecessary and loud conversation during lab. time. Do Your Own Work. (save
chitchat with your fellow students for before and/or after class time).
6.
Balances and other equipment in the laboratory are delicate, and expensive to
purchase as well as maintain. Learn how to use the instruments and equipment
properly. Take care in cleaning and use to extend the life of your lab. equipment.
7.
Keep your desk orderly at all times. Clean your equipment, bottles, desk draw and
table top area daily.
8.
Keep general laboratory area neat and clean. As a reflection of yourself, and a
courtesy to your classmates. Pay special attention to sink, floor, shelves, and typing
area.
9.
Return all stock bottles to the end of your workbench, and special equipment and
books to the lab. office when you are finished with them.
10. Do Not place insoluble solids (such as some powder prescriptions), ointments, or
oils in the sink. Wrap these substances in paper towels and place them in the trash
container. If there is a question pertaining to disposal ask the instructor or lab.
personnel.
11. Never work in a laboratory section other than your own without first obtaining
permission for the Instructor in charge of the lab.
Remember - It is the primary responsibility of the instructor to assist you in learning the
proper techniques and practices that will equip you to be a good Pharmacist/Pharm. D.
They are there to help you as well as all other students in the laboratory. They have
authority to issue orders concerning work and conduct in the laboratory.
2
Laboratory Procedure
1. Laboratory questions sheets are to be completed before the laboratory period ends.
Amount of ingredients, used, doses and procedures must be entered in ink or
typewritten. All of the question for the day’s assignments should be answered. The
instructor will check these question sheets during the laboratory period.
2. A label on or under the container must identify any preparation on or in your desk.
Unidentified preparation will be confiscated and/or disposed of by the instructor.
3. After the preparations have been graded and handed back, the contents should be
properly disposed of by dumping in proper receptacle, or flushed by drain. Do Not
take any product out of the laboratory for personal use unless permission is obtained
from the instructor in charge.
3
Experiment I
Density and Porosities of Powders
The purpose of this experiment is to determine the densities and porosities of
ingredients in a bulk powder prescription.
Prescription
S.M. Smog, M.D.
264 Washington Ave.
Name:
Address:
Big City, U.S.A.
Mr. A. Fay
Date:
22 Brigs Ave.
Rx
Calc. Carbonate
Mgo, lt.
Sodium bicarbonate
Flavor oil
12.5 gm.
12.5 gm
5.0 gm.
0.5 ml
M & Ft Powder
Sig. ss in water a.c.
Refill
Signed:
Procedure:
1. Preparation.
(a) Weigh out the calcium carbonate and place it in a cylindrical graduated
Cylinder. Gently tap the cylinder three (3) times from 1” high to the counter
top.
(b)
Note the total volume and record on the data sheet. This is the bulk volume
(Vb). Carry out the calculations on the data sheet.
(c)
Do the same for the magnesium oxide (Mgo lt.).
2. Dispensing the Prescription.
(a) Mix the ingredients of the powder by geometric dilution*, adding the flavor oil
as you mix.
(b) Place the bulk powder in a prescription carton. Properly label and hand in the
prescription.
*Note Geometric dilution, is a technique involving the blending of materials in small portions to
insure that the mixture is consistent throughout. This will be demonstrated by the instructor.
4
Data and Calculation Sheet
Calcium Carbonate
True Density
2.72 g/cc
Bulk Volume of 12.5 gm. =Vb
Bulk Density =
True Volume =
wt.
Vb
wt.
= Vp
True Density
Void Volume
v = Vb - Vp
Porosity
e=
v
Vb
Specific Bulk Density
(Bulikiness)
1/Bulk Density
5
Magnesium Oxide (Light)
3.65g/cc
Experiment II
Evaluating Flow Properties of Solids
The purpose of the following exercise is to evaluate the flowability of calcium
carbonate (powder) and sucrose (granular), and to determine their bulk densities and
porosities.
Procedure:
1. Flowability: Determined by the angle of repose of each of calcium carbonate and
sucrose, using the “Fixed Funnel and Free-Standing Cone” Technique as follows:
(a) A funnel with the end of the stem cut perpendicular to the axis of symmetry is
secured with its tip at a given height (H), (e.g. 1.5 cm.) above graph paper placed
on a flat horizontal surface.
(b) Carefully pour the powder (CaCO3) through the funnel until the apex of the
conical pile formed just reaches the tip of the funnel.
(c) Determine the mean diameter* of the base of the powder cone for three different
diameter readings from three different points of reference on the circumference of
the base.
*note the diameter is equal twice the radius or (2R)
(d) Calculate the tangent of the angle of repose;
Tan  =
H
R
Where  = angle of repose
(e) Find our from the tables the corresponding value of the angle.
(f) Repeat the above three times and determine the value of the angle of repose of the
four trials.
(g) Repeat (a) through (f) for Sucrose.
2. Bulk Density and Porosity:
(a) Weigh out 25g of each CaCO3 and Sucrose. Carry out the instructions for
determining Bulk Density and Porosity as you did in the previous experiment.
(b) Note and record the totals for each chemical in chart provided.
6
Data and Calculation sheet
Flowibility:
2R
Experiment
R
(1)
(2)
(3)
Avg. (Avg.)
(1)
(2)
(3)
(4)
Mean value of 
7
Tan  =
H
R avg.

Data and Calculation Sheet
Calcium Carbonate
True Density
2.72 gm./cc
Bulk Volume of 25 gm. =Vb
Bulk Density =
True Volume =
wt.
Vb
wt.
= Vp
True Density
Void Volume
v = Vb - Vp
Porosity
e=
v
Vb
Specific Bulk Density
(Bulkiness’)
1/Bulk Density
8
Sucrose
1.587gm./cc
QUESTIONS:
1. Why should powder which are to be compress into tablets or filled in capsules have
free flowing properties?
2. Bismuth subcarbonate (heavy) has a bulk density of 1.01 g/cc., and a true density of
5.9g/cc. Therefore, bismuth subcarbonate (light) should have: (Circle one)
(a)
a bulk density that is
= ,  , or  1.0, and
(b)
a true density that is
= ,  , or  6.9.
3. Why is light MgO preferred for administration in liquids?
4. If 200 mg. of a drug is to be weighed on a balance with a sensitivity requirement of
5mg, calculate the percentage of possible error.
5. If the permissible error is 5% and the sensitivity requirement of the balance is 6mg,
calculate the smallest amount that can be weighed within this limit of error.
9
Experiment III
A Baby Powder Preparation
The purposes of these exercises are to develop a proficiency in compounding a
bulk powder. As well as study different techniques of geometric dilution, and to develop
a proficiency in calculation of possible percentage error for weighing.
Study Assignment:
1. E. Parrott, - Powder, Pharmaceutical Technology, pp. 58-63
2. E. Parrott, and W. Seain, - Matroloy, Experimental Pharm. Technology, pp. 4-9.
Rx
Amount used:
Methylbenzethonium Chloride 0.05%
Zinc Oxide
Ʒ ii
Starch

Talcum,
c.s. ad
(10% Triturated*)
ii
℥i
Dispense in a sprinkling - type box. Sig. Admin. b. i. d.
P.S. Drugs and Chemicals should be in an impalpable form before mixing.
* The process of grinding a drug in a mortar with a pestle to reduce its particle size is
termed trituration. A type of pharmaceutical preparation termed a trituration is a
powder mixture usually containing 10% W/W of a potent medicinal substance in a
vehicle of lactose or other suitable dilutent. Triturations provide a convenient
means whereby pharmacist can accurately obtain small amounts of potent drugs.
For example 50 mg. of a potent drug may be obtained by weighing 500mg. of
10%W/W trituration of that drug.
The technique of mixing a small amount of drug with a relatively large amount of
diluent is called geometric dilution. Geometric dilution may also be used in mixing
powders consisting of several ingredients. The non-potent ingredients are treated as
diluents.
Procedure:
Weigh and place the active ingredient in a glass mortar. Weigh the diluent and place
it aside. Add a volume of the diluent (by visual estimation) equal to volume of active
ingredient and mix until a uniform mixture is obtained. Add an additional volume of
diluent (by visual estimation) equal in volume to the homogeneous mixture in the mortar.
Continue to mix until uniform. Repeat this procedure, adding each time as much diluent
as there is homogeneous mixture in the mortar, until all the diluent is used (mix by the
technique demonstrated).
10
Ingredients Weighed:
maximum potential error in each
weighing (Balance sensitivity gr. 1/8)
Methylbenzethonium Chloride (Trituration)
Zinc Oxide
Starch
Talcum
Total maximum potential error:
Percentage error = Sensitivity x 100
Quantity Weighed
Medical category of Methylbenzethonium Chloride (N.F.)
QUESTIONS: Calculation of powder % error.
1. Assuming the sensitivity of your balance to be gr. 1/6 (or 10 mg.) calculate the
maximum potential error of each of the following weighings:
(a) gr. 1/6
(b) gr. ½
(c) gr. v
(d)
i
(e) 100 mg.
(f) 0.5 gm.
2. Give two advantages of solid dosage form over a liquid dosage forms.
11
Experiment IV
Divided Powder
The Purpose of this exercise is to develop proficiency in compounding the
individual dosage form of powder and to understand the composition of some o-t-c
antacids.
Rx
Amount used:
Sodium Bicarbonate (NaHCO3)
gr. iv
Precipitated Calcium Carbonate (Ca O3)
gr. vi
Peppermint Oil
gtt. ss
M. ft. chart #1
D.T.D. #XVIII
label: Antacid Powder No. 1
Procedure:
Record chronologically the procedure used:
Rx
Amount used:
Al (OH)3
1 5
Magnesium trisilicate
4 5
Menthol
0 03
M. ft. Chart #15
Label: Antacid Powder No. 2
Procedure:
Record chronologically the procedure used:
12
Preparation Of Powders As Individual Doses
The purpose of this demonstration is to show the technique of compounding and
dispensing the individual dosage from powders.
After weighing, comminuting and mixing of ingredients are completed, the
powder must be accurately divided into the prescribed number of doses. In order to
achieve accuracy consistent with the other steps in the compounding, each dose should be
weighed individually and transferred to a powder paper. The number of powder paper
should correspond to the number of doses being prepared.
The powders are dispensed in a powder box, usually in a hinge type. There are
many sizes available, identified by the number and No. 4-6 are most often used. Since
the boxes are of different heights a trail folding has to be performed first.
Fold down a long edge of the weighing paper approximately ¼” for the 5 or 6
powder box. Bring the lower edge of the paper to the creased line under the top fold.
Press down the latter. Holding down the fold with both thumbs and index fingers pull the
top creased edge toward yourself until it divides the paper approximately in half. A new
top is thus made. The correct line for this fold will depend on the style and the height of
the powder box to be used. The powder should be slightly higher (ab. 1/8”) than the edge
of the box so that they can be picked out easily.
Now fold the ends of the powder paper by pressing equal lengths of them down
while gently squeezing the sides of the box. Holding securely the folded powders in
fingers, place the paper on desk, and crease sharply the end folds with the spatula. Note,
the center of the powder paper in not creased in order to insure the even packing to the
box later. The folded paper is place vertically into the box to check for proper height. If
the height has to be adjusted repeat the folding until proper size in obtained. Use this
paper as a guide for future folding.
Using about six papers at a time make about ¼” fold and crease them with the
spatula, If too many papers are folded at one time variation in the depth may result. Place
the paper on the prescription counter (usually left of the balance) in a uniform fashion so
that the tops will be away from the compounder. For example, it 12 powders are
compounded place 3 rows of four papers or 2 rows of 6 papers each. Remove ingredients
from the mortar onto paper in front of the balance and set the balance in equilibrium with
weighing papers on the pans. Place the rider in proper position and weigh the required
amounts. Using the same powder paper during all weighings transfer each time the
weighed amount to the center of each paper.
After all powders are weighed folded each paper as described before. Crease each
powder securely placing them on the counter or in the top portion of the box.
The most common method of packaging folded powders in a box is by placing all
tops up and folds toward the operator.
The hinged powder boxes may be labeled by two methods: 1) placing the label on
top of the box or 2) on the underside.
When 2 to 5 powders are prescribed, they may be dispensed in an envelope or a
slide box.
13
Experiment V
Compounding of Capsules
The purposes of this exercise are to develop a proficiency in formulating and
compounding capsules as solid dosage forms and to perform weight variation test on the
capsule as one of the quality control measures.
Rx
Amount used: (must be calculated)
Phenobarbital
015
Ephedrine HCl
025
Aminolphylline
2
lactose* q.s.
Per 1 Capsule
Dispense 10/(20) capsules
Label: Asthma capsules
*Use lactose as diluent to adjust the content of each capsule to weigh 0.4 gm.
Procedure:
1. Record all necessary calculations for compounding 10/(20) capsules and the size
of the capsule used.
2. Weigh the amount of each ingredient and the diluent.
3. Mix by the correct procedure.
4. Weigh each capsule and dispense as directed.
Weight Variation Test:
The following test (U.S.P. XIX, p. 670) provides for the permissible variations in the
weigh of individual dosage units, expressed in terms of the allowable deviation from the
average weight of a sample.
14
Weigh 10/(20) intact capsules individually, and determine the average weight. The
requirements are met if each of the individual weights is within the limits of 90% and
110% of the average weight. (Refer to the U.S.P. XIX)
(a)
Record individual weight of each capsule:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
(b)
Total weights of 10/(20) capsules (W) =
(c)
Average weight of the capsules (w) = W
when N is number of capsules
N
(d)
Calculate 90% of the average weight (w) x
(e)
Calculate 110% of the average weight (w) x 110 =
100
Record the number of capsules whose weight
are less than 90% of the average weight
(f)
90 =
100
(g)
Record the number of capsules whose weight are
greater than 110% of the average weight
(h)
What is the % number of capsules that meet the U.S.P.
weight variation requirement.
(i)
Refer to the U.S.P. for interpretation of results.
Questions:
1. What is the reason for using lactose in your capsule formulation?
15
2. What are the various sizes of hard gelatin capsules for human use?
3. What are the differences between hard and soft gelatin capsules?
16
Experiment VI
Compounding of capsules (Continued)
A. Capsules containing potentially “Eutectic” Combination
Rx
Amount used: (must be calculated)
Aspirin
Chloral Hydrate
aa
0.1 gm.
M. ft. cap # 1
mitte x
Label Insomnia capsules
Procedure:
1. Choose a proper inert absorbent and record all necessary calculations for compound
11 capsules.
2. Mix each compound separately (1:1) with absorbent, on a one to one basis (1:1).
3. Now combine the two homogeneous mixtures and mix lightly.
4. Fill and weigh each capsule and dispense as directed.
B. Capsules containing Oil
Rx
Amount used: (must be calculated)
Castor Oil
ʒii
Mitti cap.
#XV
label Castor Oil Capsule.
Procedure:
1. Calculate the volume of caster oil need for one capsule in minims.
2. Calibrate your dropper with caster oil (for example, count the number of drops of
Caster Oil for 20 minims)
3. Calculate the number of drops to be used in each capsule.
17
4. Fill 15 proper size capsule and seal as shown in demonstration.
5. Record the size for the capsule used and check for any possible leaking of capsules.
6. Package the capsules into proper size box or prescription vial and properly label.
18
Experiment VII
Category: Tablet Triturate:
The purpose of this exercise is to compound accurately the following prescription:
Dr. O. B. REHBURG
Doctor’s Clinic
216 First St.
Waycross, GA
Rx
For
Address
Refill
Signed
Date
Method of Preparation:
Use:
Direction:
19
Questions:
1. How did you calibrate your mold?
2. Name drugs that are commonly used in the form of T.T. or H.T’s.
3. Name some diluents, which may be used in T.T. and H.T.
4. What care should be exercised in handling T.T. and H.T.
5. Differentiate between:
a. H.T.
b. T.T.
c. C.T.
d. D.T.
e. E.C.T.
f. S.C.T.
g. Soluble Tabs.
h. Pellets
i. Buccal Tabs
j. D.A. Tabs
k. Wafers
6. Give the chemical formula, use and dose of nitroglycerin.
20
Experiment VIII
Ointment Bases and Ointment Formulations
The purposes of this exercise are to learn (1) the method of preparing so official
ointment bases and (2) the procedure for incorporating some substances into ointment
bases.
Study Assignment:
1. Remington’s Pharm. Sci. XIV ed. “Ointments”, pp. 1594 - 1612.
2. Pharmac. Technology, “Ointments”, pp. 365-374
Ointments are plastic or semisolid preparations intended for external application.
Ointment base is a plastic or semisolid preparation that in itself has no
physiological activity. Ointment base is used as a vehicle for a drug, but it may also
serves as a prospective or emollient (e.g. Petrolatum) White Ointment and Polyethylene
Glycol Ointments are actually only ointment bases.
Part A. - Ointment Bases
There are five types of ointment bases:
1.
2.
3.
4.
5.
Anhydrous Fatty Base - as in Petrolatum and White Ointment,
Anhydrous Absorption Base - as in Hydrophilic Petrolatum and Amh. Lanolin,
Water-in-Oil Emulsion Type Base - as in cold cream,
Oil-in-Water Emulsion Type Base - as in Hydrophilic Ointment, and
Water-Miscible Base (or water-soluble Base) - as in PEG Ointment.
Anhydrous Fatty base or Oleaginous Bases consist of hydrocarbon and glyceride
bases (fats). In addition to being stable and inert, the hydrocarbons are bland and have a
wide range of melting points, which permits blending to form an ointment base of any
consistency. As the degree of unsaturation of the acids in glycerides increases, they are
more prone to rahoidity. From the viewpoint of the patient, oleaginous bases have the
disadvantage of being greasy and difficult to remove from the skin; from the viewpoint of
the pharmacist, they have the disadvantage of being unable to absorb aqueous liquids.
Therapeutically, oleaginous ointment bases hinder the loss of heat from the inflamed area
and prevent drainage from congested, oozing lesions.
Anhydrous Absorption Bases are those, which are anhydrous but still readily
absorb appreciable amounts of aqueous liquids. For example, Hydrophilic Petrolatum is
anhydrous, yet water may be readily incorporated by virtue of the cholesterol present
forming a W/O emulsion.
21
Emulsion Type Bases may be either W/O or O/W emulsions. Generally patients
because of its esthetic appeal, and ease of removal more readily accept the O/W or
washable ointment bases. The washable emulsion base absorbs serious discharge from a
lesion and allows the heat of inflamed area to be easily dissipated. Hydrophilic Ointment,
Weobase, Onibase, Multibase, and Dermabase are examples of O/W emulsions; Rose
Water Ointment, Cold Cream, U.S.P. and Hydrous Wool fat (Lanolin) are examples of
W/O emulsions.
Although some water-dispersible ointments bases are often listed under the
classification of water-soluble ointment bases, polyethylene glycol ointment bases (as
PEG Ointment, U.S.P.) are the only widely used truly water-soluble bases. The
polyethylene glycol’s range from liquids to wary solids, which permits blending until and
ointment of a desired consistency, is obtained. As there is the possibility of complex
formation between polyethylene glycol and certain drugs especially phenolic compounds,
care must be observed in formulations containing these compounds.
A. Anhydrous Absorption Base
Prepare 60 gm. of Hydrophilic Petrolatum U.S.P.
Rx
U.S.P. Formula
Factor
Cholesterol
30.0 gm.
0.06
Stearyl Alcohol
30.0 gm.
White Wax
80.0 gm.
White Petrolatum
860.0 gm
To make
1000.0 gm.
Working Formula
60 gm.
Procedure:
Melt the stearyl alcohol, white wax, and white petrolatum together on a steam bath.
Next add the cholesterol and stir until completely dissolved. Remove from the bath and
stir until the mixture congeals.
22
B. Oil-in-Water Emulsion Type Base
Prepare 90 gm. of hydrophilic Ointment, U.S.P.
Rx
U.S.P. Formula
Methylparaben*
0.25 gm.
Propylparaben*
0.15
Stearyl Alcohol
250.0 gm
White Petrolatum
250.0 gm.
Propylene Glycol
120.0 gm.
Sodium Lauryl Sulfate
Purified Water
To Make
Factor
Working Formula
0.09
10.0 gm.
370.0 gm
1000.0 gm.
90.0 gm.
Procedure:
Melt the Stearyl Alcohol and the white petrolatum on a steam bath warmed up to
o
about 75 C. Separately warm Purified Water, mixed with Methylparaben*, Propylene
Glycol, Propylparaben*, add the Sodium Lauryl Sulfate and stir until completely dissolve.
o
With both contents completely dissolved at 75 C mix the two together and stir until the
mixture (emulsion) is completely congealed.
* Content is dissolved in alcohol as a 1% solution.
23
Part B - Ointment Formulation
Mechanical incorporation performed by trituration in a mortar or on a glass slab
with a spatula is more frequently used by the pharmacist than other methods. The
medicaments being incorporated into a base frequently insoluble in the base and it is
necessary, therefore, to reduce them to and impalpable powder. The fineness of powder
cannot be overemphasized. Using a small portion of the base and gradually
incorporating the powder to form a very smooth nucleus, which can then be incorporated
with less effort with the remainder of the base and with the assurance of a smooth
homogeneous ointment, can obtain best results. Sulfur is incorporated into and ointment
base by wetting it first with a few drops of mineral oil or glycerin and them mix with
small amount of the base.
Using the correct procedures compound the following prescription.
Rx
Amount Used:
Ppt. Sulfur
Ʒss
Salicylic acid
4%
hydrophilic Ointment, q.s. ad
℥i
MSA Ointment and package it into an ointment tube.
Label: Apply u.d. for Acne
Procedure:
1. Calculate the amount of salicylic acid, and the base needed to complete the
prescription. Record the calculations and proceed to measure out all the necessary
components to complete the prescription.
2. Using a glass slab mix the sulfur and salicylic acid using geometric trituration
technique. Add a few drops of glycerin to the powder mixture (until properly wet or
consistency of congeal to that of the hydrophilic ointment) and mix thoroughly.
Record the number of drops of glycerin used.
3. Add approximately on dram of the ointment base and make a smooth past passing the
mixture back and forth over the rough surface of the glass plate/slab with the flat side
of a spatula.
4. Incorporate the rest of the ointment base in small portions at a time; making sure that
there is a complete incorporation of new portion of base to the mixture, until all
portions are used.
5. Package into and ointment tube and properly label.
24
Experiment IX
The purpose of this experiment is to observe the characteristics of representative
ointment bases, and to observe the drug release from the ointment.
A. Characteristics of representative ointment bases.
1. Samples of various types of bases will be available for your observation and
evaluation of some of their most pertinent characteristics. Representative class
will include hydrocarbon, absorption, water washable, and water-soluble.
You should answer the following questions about at least one specific base from each
class.
a. What are the ingredients in the base?
b. How much water or drug solution can be incorporated into the base?
c. If the base has an aqueous external phase, what is its pH?
d. What happens when a levigating agent (e.g., mineral oil) is incorporated into
the base (a reasonable amount, say 5% of the amount of base).
e. What type of drugs should not be used with this base? Give some specific
examples.
Data can be itemized for each base or a table can be constructed showing data from all
bases.
25
B. Rate of Release from Ointments
Ointments and Testing
Purpose:
To determine the effect of added substances on the release rate of active
ingredient from and ointment base.
PROCEDURE
Equipment and supplies:
Salicylic Acid
Tween 20 (Polyoxyethylene(2)
sorbitan monolaurate)
White Petrolatum
Liquid Petrolatum
2% Ferric Chloride Solution
Spatulas
6-test tubes
2-250 ml. beakers
2-10 ml. cylindrical graduates
1-1 ml. pipette
Make up the following Ointments;
Rx 1
Salicylic acid
Liquid Petrolatum aa 5%
Petrolatum, q.s. ad 30
Rx 2
Salicylic acid
Tween 20
aa 5%
Petrolatum, q.s. ad 30
Levigate salicylic acid with
liquid petrolatum and then
incorporate petrolatum.
Levigate salicylic acid with Tween 20
and then incorporate petrolatum.
Place each ointment into a separate beaker and layer with 100 ml. of distilled water. Do
both of these at the same time since this will be time zero.
After 10 minutes, 30 minutes, and 60 minutes, remove exactly 5 ml. samples, after
swirling a few seconds, and place in marked test tubes. Mix 0.02 ml. of the 2% ferric
Chloride solution with each of six samples. Note and record the color and intensity.
Prescription
10’
30’
Rx 1 Color
Intensity
Rx 2 Color
Intensity
Conclusions:
26
60’
Experiment X
Preparation of Suppositories
The purposes of this exercise are to lean the methods of preparing the
suppositories and to study their composition and properties.
Study Assignments:
1. Remington’s Pharm. Sci. XIV ed. “Suppositories”, pp. 1617- 1624.
2. Pharmac. Technology, “Suppositories”, pp. 382-393.
3. Dispensing of Medication, Martin, 1971, pp. 835-854.
Prepare the following suppositories as directed:
Rx A.
Miss Gloria Miller
Aminophylline
Cocoa Butter,
amount used:
0.5
gm.
q.s. ad supp. #1
Dispense #6
Label:
Insert 1 suppository as needed for asthma.
Procedure:
1. Prepare by the fusion method using the technique shown in the lab. demonstration.
o
The temperature should be about 34-35 C. Standardize the mold by weight.
Thoroughly clean mold!! ─ Lubricate the mold wells lightly with (glycerin/green
soap tincture)using a cotton swab. Then place in the refrigerator to reduce the
temperature. The density factor of aminophylline is 1.1.
a. Weight of 8 suppositories made of plain cocoa butter =
b. Average weight of plain cocoa butter suppository =
gm.
c. Weight of aminophylline needed for 8 suppositories =
gm.
d. Weight of cocoa butter that will be replaced by the drug in 8 suppositories =
gm.
e. Weight of cocoa butter needed for 8 suppositories of aminophylline =
gm.
27
Questions:
1. Define Theobroma Oil, U.S.P.
2. What is meant by the term “Polymorphism”.
3. Draw the chemical structure of Aminophylline.
4. Explain the mechanism of solubilization of Aminophylline in water.
5. Give the storage condition for suppositories containing cocoa butter.
Experiment:
Determination of the density of a medicinal substances (e.g. benzocaine),
in relations to cocoa butter.
1. Mix the amount of drug for one suppository with a little melted theobroma oil,
pouring it into a suppository mold and carefully filling the mold with plain cocoa
butter.
2. The cooled suppository is then weighed and the weight of the dedication is subtracted
from it. This will indicate the amount of theobroma oil used (denote it by X)
3. Make 4 suppositories made with plain cocoa butter. Calculate the average weight of
suppository (denote it by Y)
Density factor of the drug =
28
Wt. of drug
Y-X
Rx B.
Mrs. E. Mitchell
amount used:
Belladonna Extract
gr. ¼
Bi Subgallate
gr. 1 ¼
Benzocaine
Theobroma Oil,
3%
q.s. ad supp. #3
Label Hemorrhoidal Suppository’s
Procedure:
1. Prepare by the fusion method as in Rx A. The density factors of belladonna extracts
and bismuth Subgallate are 1.3 and 2.7 respectively.
2. Calculate the weight of Anesthesin and of cocoa butter used in compounding the
above Rx B.
3. Weight of six(6) suppositories prepared by fusion
gr.
4. The therapeutic purpose of each active ingredient in the above Rx:
a. Belladonna extract
,
b. Bi Subgallate
, and
c. Benzocaine
.
5. Therapeutic use of the above suppositories:
6. What is the reason for having two official Belladonna Extracts in N.F. XIII?
29
7. Name the Main Alkaloid present in Belladonna Extract:
8. a. Give the common name for benzocaine:
b. Draw the chemical structure for Benzocaine:
c. Explain why benzocaine is soluble in dilute acid.
30
Experiment XI
Chemical Kinetics
Explanation:
Esters used both medicinally an non-therapeutically are readily hydrolyzed in
water in the presence of hydrogen ions. In this experiment the rate of a methyl or ethyl
Acetate hydrolysis is measured and the reaction rate constant is calculated.
Theory:
Methyl acetate (Ch3COOCH3) or Ethyl Acetate (CH3OOC2H5) in water
hydrolyzes to give either methanol or ethanol and acetic acid.
RCOOCH3 + H2O + H+
= CH3COOH + ROH + H+
Although two molecules are involved in the reaction, the water is present in great
excess – thereby forcing the equilibrium to the right and gives a pseudo first order
reaction. Only the concentrations of the acetate and acetic acid changes. For all practical
purposes the reaction goes to completion.
Chemical Kinetics - Remington’s, 14th Edition, pp. 294-298
- Martin, pp. 354-363
- Parrott, pp. 250-265
Procedure:
Notes:



The concentration of methyl acetate degraded at any time is determined by the
titration of the released acetic acid against 0.2 N sodium hydroxide. Using
phenolthalein as an indicator.
The success of the experiment depends chiefly on the care in technique during
pipetting and titration.
The sodium Hydroxide solution used is prepared from saturated sodium Hydroxide
to reduce the amount of carbonate present, because carbonates cause a fading end
point with phenolphthalein.
1. Prepare two 4 oz. bottles containing one hundred milliliters (100 ml.) of 1 N HCl in
o
each, and placed both in a water bath at 40 C. Place about 15 ml. of methyl acetate in
a test tube and also place it in the water bath. Prepare on the side a beaker containing
ice and a small Erlenmeyer flask containing 50 ml of cold distilled water. While
allowing 10 to 15 min. for the solutions to become acclimated the to the temperature
of the water bath set up a burette and stand. Load the burette with 0.2 N NaOH. Once
acclimated to the temperature the reaction can be started (YOUR LAB
INSTRUCTOR WILL HELP YOU CARRY OUT THE PROCEDURE TO THIS
POINT). Each student group should attain a clock to keep time.
31
2. To start the reaction* pipette exactly 5 ml. of the methyl acetate directly into one of
the bottles of HCl and shake vigorously to mix, then place it back in the water bath.
Using the pipette, immediately withdraw a 5-ml. sample of the mixture just created
and add it to the 50 ml. of chilled distilled water on the side. Add approximately 5
drops of phenolphthalein to the dilution and swirl to mix. The solution should then
be titrated at once (using NaOH) to minimize the amount of errors (The dilution with
water arrests the previously stated reaction, error is further minimized by chilling the
water). Record the time and volume of NaOH used to (maintain/create) precipitate.
*Note: The time at which the first 5 ml of methyl acetate is pipette into the HCl the clock should
be started and that time is marked as zero time. This also is time zero for the sample
drawn off and added to the flask of cold distilled water.
3. Two more samples of the mixture are titrated in the same manner as the first at 5
minute intervals (a); two additional samples are taken at 10 minute intervals (b); and
then 5 more samples are taken at 20 min intervals(c); the remainder of the solution is
stopped up and allow to stand for a one week period to permit the reaction to reach
equilibrium before a final titration. Record all the information on the following chart.
3.a. For comparison purposes, about 30 min. after start of first reaction, extract 5 ml
of HCl from the second bottle, Add approximately 5 drops of phenolphthalein
to the dilution and swirl to mix. Then titrate with NaOH. Record the time and
volume of NaOH used to (maintain/create) precipitate and then the two
experiments are carried along together.
Time
in min.
0
5(a)
ml. of NaOH
Acetate Degradation
Temperature
tn
meq of NaOH
tp - tn
Log (tp – tn)
10(a)
20(b)
30(b)
50(c)
70(c)
90(c)
110(c)
130(c)
1 week
32
Plot log(tp-tn) against time and from the slope obtained calculate the specific reaction rate
constant K for the hydrolysis of methyl acetate or ethyl acetate.
33
time
in min.
Check Determination
tn
ml. of NaOH
meq of NaOH
Temperature
(tp - tn)
Log(tp - tn)
0
30
50
70
90
110
130
1 week
o
3.b. Additional determinations are carried out at 25 C in the manner just described
o
for 35 C. The reaction goes less than half as fast, and samples are taken at 15
minutes intervals for an hour and then at 30 minute intervals for 2 hours more.
The second determination may be started shortly after the first one, as titrations
are not required so frequently Again, a sample of the remaining solution is
retained for a final titrations after standing a week.
Calculations:
The difference between the titration (Meq.) at any time “tn” and the titration (Meq.) at the
end of a week “tp” when the reaction is completed is a measure of the concentration of
methyl acetate remaining unhydrolyzed at tn. Each molecule of methyl acetate that
hydrolyzes produces on molecule of acetic acid, and the increase in acidity is a direct
measure of the amount of methyl acetate that has reacted. The amount of hydrochloric
acid remains unchanged throughout the experiment.
Calculate concentrations of methyl acetate from the differences between the titration
values (tn) and the final titration (tp).
Arrange these values in tabular form.
Determine the order of the reaction showing the necessary graphs.
Determine the k values at each temperature.
34
Experiment XII
Effects of Buffers and Antioxidants on Drug Stability and Solubility
Introduction:
Both the solubility and chemical stability of drug and chemical stability of drug
solutions can depend upon pH. Because of the is the Pharmacist must often buffer a
solution to a suitable pH and /or add pharmaceutical aid (i.e. antioxidants). In this
experiment the effects of pH and antioxidants on some pharmaceutical solutions will be
demonstrated.
Required Reading(s):
1. Remington’s Pharmaceutical Sciences, 14th Edition, pp. 283-286.
Suggested Reading(s):
1. A. L. Martin, “Physical Pharmacy”, 2nd Ed., Ch. 10.
2. E. L. Parrott, “Pharmaceutical Technology”, pp. 224-237.
Procedure:
A. Students work in teams of two (2).
B. Obtain 4 ounces of each of the buffer solutions provided by the laboratory
instructor. Label these properly as buffer A. and B.
C. In three clean, dry 50 ml beakers place 25 ml. each of the following solutions and
label:
1. 25 ml. distilled water
2. 25 ml. buffer A., and
3. 25 ml. buffer B.
Using a pH meter and the stock solutions provided collect the data necessary to
complete table I.
Test Solution
pH
Table I
pH after 1ml. of
.2 N NaOH
Distilled Water
Buffer A.
Buffer B.
35
pH after 2.0 ml. of
.2 N HCl
D. Below are the formulas for three solutions. Prepare each solution twice: first with
buffer A. and then with buffer B. Label each properly and collect the data
necessary to complete table II. Store in one once prescription bottles and label to
be turned in.
1. Sulfathiazole Na
1.5
Sodium Sulfite
0.3
Buffer Soln. q.s. ad 30.0 ml.
2. Epinephrine
1.0%
Buffer Soln. q.s. ad 30.0 ml.
3. Epinephrine
1.0%
Sodium Sulfite
0.3
Buffer Soln. q.s. ad 30.0 ml.
(Note: Under description include color precipitate, clear and other descriptive data as needed.
The Spectronic-20 may be used if the student so decides.)
Table II
Solution No.
1
1
Buffer
A
B
2
2
A
B
3
3
A
B
Immediately
pH
Description
Foot notes:
ppt = precipitate
c
= clear
q
= opaque
n.p. = no precipitate
36
Day 1
Description
1 Week
Description
E. Draw the structure of the Epinephrine and Sulfathiazole molecules and explain
how pH could effect their stability and/or solubility.
F. List 5 name buffers used in pharmaceutical solutions, their pH ranges and a
reference where you could go to obtain the formula for each (Title - Volume page).
Define the following terms: Buffer Capacity, pH, pKa, and Ka.
37
Experiment XIII
Category : Ophthalmic Solution;
Purpose: To compound accurately the following prescription.
Patient
Age
Address
Date
Rx
Refill
Times
Do Not Refill
Dr.
Label
Reg. No.
Address
Method of Preparation: Adjust Solution with sodium nitrate.
Use:
Directions:
38
Questions:
1. How many grains of sodium nitrate should be used to make the prescription isotonic
using the freezing point method?
2. The isotonic Factor Method?
3. Why is sodium nitrate used as the adjusting substance? Show by a chemical equation
what would happen if sodium chloride were used.
4. Why do some states require that silver nitrate be place in the eyes of newborn infants?
39