CAPSULES

-solid dosage forms enclosed in gelatin shells (Hard gelatin capsules)

-Soft Gelatin Capsules: Glycerin: Softening agent

3. Subtract the amount of the empty capsule from the

amount of the capsule with diluent.
*Weight Variation: 85-115%

Contents of Capsules
1.
2.
3.

Sample Prescriptions

Powders
Extracts
Semi-solid materials

1.

Rx
Theophylline
0.188 g
Ephedrine sulfate 0.024 g
Phenobarbital
0.008 g

Capsule Capacity and Size

Size
000 (for animals)
00
0
1
2
3
4
5

Weight
1000 mg
600 mg
500 mg
300 mg
250 mg
200 mg
125 mg
60 mg

M. Ft. Cap #8
Sig: 1-2 caps PRN SOB

Volume
1.36 mL
0.45 mL
0.67 mL
0.48 mL
0.37 mL
0.27 mL
0.20 mL
0.13 mL

Compounding of Capsules
1.

Interpret the prescription

-To determine if it will be divided or not

2.

Know the contents of the capsule

-It will dictate the capsule size
-Can be with diluent or without diluent
-Contents cant be seen
-If the powder is light, add diluent
-DTD (Give of such doses): Prescription is only for 1
capsule

3.

Compute for total numbers to be weighed

-Compute an excess of the powders (Overage: To make up
loses on compounding): Good for 2 capsules, but still
divide the prescribed amount.

4.
5.

Weigh powders
Mix powders
-Geometric Dilution: Only good for solids
1. Most potent= least in amount
2. Followed by the 2nd most potent or equal
amount of the diluent
3. Mix intimately
4. Add an equal amount of diluent equal to the
amount in the mortar.

6.
7.

Divide powders
Block and Divide: For 10-12 capsules only
Or Weigh individually

8.

Fill the capsules

*Unknown capsule size

-Determine the capacity of the capsule
1. Weigh empty capsule
2. Fill the capsule with diluent. Weigh the capsule

2.

1.

Add the ingredients

0.188 g + 0.024 g + 0.008 g = 0.220 g

2.

Multiply ingredients by 10
0.188 g x 10 = 1.88 g
0.024 g x 10 = 0.24 g
0.008 g x 10 = 0.08 g

3.

i. Place phenobarbital in mortar with an equal amount

of ephedrine. Triturate.
ii. Add an equal amount of ephedrine sulfate to that
amount of the powders in the mortar. Triturate.
iii. Add an equal amount of theophylline to that amount
of the powders in the mortar. Triturate.
iv. Continue adding and triturating theophylline until all
has been added.
v. Block and divide into 8 equal parts and fill the
capsules.

Rx
Acetaminophen
Diphenhydramine
Atropine sulfate
Caffeine

1.950 g
0.150 g
0.00072 g
0.180 g

M. Ft. Cap & Div. #8

Sig: 1 cap q8H PRN pain
1.
2.
3.

1.950 g + 0.150 g + 0.00072 g + 0.180 g = 2.28072 g

Divide by 8 = 0.28509 g
Divide the ingredients by 8 then multiply by 10.
1.950 / 8 = 0.24375 g x 10 = 2.44 g
0.150 / 8 = 0.01875 x 10 = 0.1875 g
0.00072 / 8 = 0.00009 x 10 = 0.0009 g
0.180 / 8 = 0.0225 g x 10 = 0.225 g

4.

i. Put atropine sulfate in the mortar with an equal

amount of diphenhydramine. Triturate.
ii. Add an equal amount of diphenhydramine to that
amount of the powders in the mortar. Triturate.
iii. Add caffeine in an equal amount to that of the
powders in the mortar and triturate.
iv. Add acetaminophen by geometric dilution.
v. Block and divide into 8 equal parts.

volatile substance. Potassium bromide will salt-out

cinnamon oil. How? Formation of bubbles

DRUG INTERACTIONS AND ADVERSE DRUG REACTIONS

Drug Interaction- change in the magnitude of drug effects due to the
combination of 2 or more drugs
Drug Incompatibility- happens when 2 or more drugs combine, it
can cause antagonistic properties
*Drug interaction is a product of drug incompatibility.
Take into action:
a.

Physical Incompatibility: Physical antagonism

Ex. Change in smell and odor, solubility

b.

Chemical Incompatibility: Due to chemical reactions

Ex. Acid and base reactions

c.

Therapeutic Incompatibility: Drug interactions

*Mouthwash
-Whitish solution
-The substances that are soluble on alcohol are
salted-out
Requirements for salting-out
a.
b.

Saturated solution
Lesser soluble substance

3.

Liquefaction of Sold Ingredients

Causes:
a. Eutexia
-most common cause
-a phenomenon where 2 solids when combined will
liquefy due to a lowering of the melting point

A. Physical Incompatibility
-A type of disagreement between ingredients causing failure of
the ingredient to combine and make a satisfactory product

Ex. Resorcinol
Acetanilide
Phenol
Phenacetin
Menthol
Camphor
Aspirin
Phenyl salicylate
Thymol
Choral hydrate

Types of Evidences:
1. Insolubility or Incomplete Solution
Causes:
a. Used the wrong solute or solvent
Ex. Solute is non-polar while solvent is polar
b.
c.

2.

Insufficient volume of solvent

Did not use heat
Ex. Preparation of Syrup: Sucrose
Preparation of Triturated Boric Acid Solution

Characteristics of solids that form eutectic mixtures:

1. Compounds having similar melting points
2. The components must be miscible in liquid state
and mostly immiscible in solid state.
3. Intimate contact between eutectic forming
materials is necessary for contact induced
melting point depression.
4. The components should have chemical groups
that can interact to form physical bonds such has
intermolecular hydrogen bonding etc.
5. The molecules which are in accordance to
modified VantHoffs equation can form eutectic
mixtures.

Salting-out
-Phenomenon where a more soluble ingredient displaces a
lesser soluble ingredient from a solution, hence, the
ingredient is salted out
-Involves a saturated solution, where in all water molecules
are used in the solution
Ex. Aromatic Waters- saturated solution of volatile solutions
Simple Syrup- saturated solution of sucrose
1.

Rx

b.

Sodium bromide
Simple Syrup
-Simple syrup is a concentrated solution (8.5% = 8.5 g
sucrose in 100 mL of water). Sodium bromide is a
polar solute. Sodium bromide is more soluble in water
than simple syrup. Sodium bromide will take water
molecules from sucrose. Sucrose will be salted-out.
How? There will be crystallization of sucrose.
2.

Ex. Zinc chloride

Epsom salt (Magnesium sulfate)
Sodium carbonate
Sodium chloride
c.

Rx
Potassium bromide
Cinnamon Water
-Cinnamon water is a kind of aromatic water, a
saturated solution of cinnamon oil. Cinnamon oil is the

Deliquescence
-absorption of moisture from the atmosphere causing
melting of liquefaction due to the presence of water of
hydration

4.

Efflorescence
-loss of water of hydration leading to a dry or
anhydrous salt

Separation of Immiscible Liquids or Separation into

Layers
Ex. Oil and Water

Alcohol and Water: Layers are not visible when

separated
5.

Gelatinization
-Formation of gelatin
-Usually seen in Acacia in combination with Ferric salts
-Not a chemical reaction but the acacia hardens
-Iron will interact with the hydrolysis of acacia

3.

Phenacetin
Acetanilide
Pyrocathechin

4.

gr i
gr ii
gr vi
i

M. Ft. Sol
Sig: For the eyes
Incompatibility: Sodium borate is alkaline. It precipitates
cocaine resulting to turbid mixture.
Correction: Change sodium borate to boric acid.

3.

Use co-solvents
Ex. Alcohol + Water: Use glycerin

4.
5.
6.

Omit the unimportant ingredient

Change the order of mixing
Make a suspension or emulsion
Ex. Calcium carbonate
Magnesium oxide

7.

Use a different form of the insoluble ingredient

Ex. Water + Phenobarbital: Phenobarbital is insoluble in water.
Use Sodium phenobarbital

5.

Dispense separately
Ex. Alcohol + Morphine sulfate: Morphine sulfate is insoluble in
alcohol

Sample Prescriptions:
1. Rx
Codeine sulfate
Aromatic syrup of Eriodicty, qs

0.13 g
30 mL

M. Ft. Sol
Incompatibility: Codeine sulfate is polar.
Salting-out due to the water from
aromatic syrups.
Correction: Use co-solvency. Dissolve codeine sulfate first
in small amount of water (1-2 mL)
(1 drachm)
gr XL
gr L

aa i
gr xii
iv
vi

M. Ft. Sol
Incompatibility: Salting-out of peppermint water since all
ingredients are salts.
Correction: Use co-solvents. Dissolve each salt in a few mL
of water first.
B. Chemical Incompatibility
-occurs when the ingredients interact with each other, hence,
altering the composition of the ingredient
Evidences:
1. Formation of a precipitate
Ex. NaCl + AgNO3
AgCl
NaCl is the isotonicity agent.
AgNO3 is used in the treatment of ophthalmia neonatorum.
When combined, they form AgCl.
Correction: Change NaCl to Boric acid
2.

M. Ft. Cap #10

Sig: One cap hs
Incompatibility: Liquefaction of solid ingredients: Formation
of eutectic mixture, choral hydrate and phenacetin.
Correction:
Use adsorbents (Magnesium oxide: Heavy adsorbent;
Magnesium carbonate)
Mix adsorbents with ingredients that undergo eutexia via
geometric dilution

Rx
Sodium carbonate
Sodium borate
Cocaine HCl
Glycerin
Peppermint water

Rx
Choral hydrate
Phenacetin
Quinine sulfate

gr V
gr X

Rx
Atropine sulfate
Cocaine HCl
Sodium borate
Dist. Water, qs

Aspirin + Water: Add an alkaline solution

2.

gr X

Incompatibility: Liquefaction of solid ingredients, eutexia

Correction of Physical Incompatibilities

1. Addition of solvent
2. Use of solubilizing agent
Ex. Iodine + Water: Iodine is insoluble in water. Add Sodium
iodide of potassium iodide

8.

Rx

Evolution of a gas
-CO2 is the most common gas evolved, commonly used to
increase the palatability of the same preparation.
2H2O2

3.

2H2O + O2

Color changes
Ex. Ferrous sulfate may be converted to Ferric oxide upon
the presence of oxygen
Fe+2
Fe+3
Ferrous (Green: Green vitriol) converted to rust
which is not absorbed in the body

4.

Production of explosive / violent reaction

-Release of oxygen

-H2SO4 is omitted to produce a fine suspension of quinine

SO4.

Ex. Glycerin + KMnO4

-both are strong oxidizing agents
-KMnO4 will become MnO2 (Black color)
5.

6.

Change in pH
-Acid becomes neutral or base
-Base becomes neutral or acid
-Neutral becomes acid or base

*Object drug- the drug affected by the interaction (effect)

*Precipitant drug- the drug causing the interaction (cause)

Development of heat or cold

-Exothermic or endothermic reactions
Ex. H2SO4 + Glucose
-Glucose will become CO2 (heat) + water

7.

Hydrolytic changes / Hydrolysis

-Not visible
Ex. ZnCl2

C. Therapeutic Incompatibility
-called drug interactions
-these are modifications of effects of one drug (object drug) by
the prior or concomitant administration of another drug
(precipitant drug)

Types of Therapeutic Incompatibilities

1. Pharmacokinetic Drug Interactions
-Drug interaction that takes place during kinetics of drug
interaction which will also explain the mechanisms of the
drug interactions.
2.

Zn(OH)2

Prevention of Chemical Incompatibility

1. Prevent precipitation by addition of glycerin, honey, or
syrup
Rx
Codeine SO4
0.13g
Eriodyctyon Syrup, qs
30 mL
(Aromatic syrup of eriodyctyon- contains volatile
oils)

Pharmacologic or Pharmacodynamic Drug Interactions

-Changes in the response of the patient to the drugs
administration
-Summation, Synergism, Potentiation, Antagonism
Mechanisms of Drug Interactions (Pharmacokinetic)
1. Absorption
-A non-ionized drug should be dissolved in a pH that is
similar to the drug. It should be absorbed.
-Drug interaction will happen if the pH of the
environment is different to the pH of the drug
a.

-Mixing codeine SO4 with glycerin first will

prevent reaction with resinous materials from the syrup.
There will be no precipitation that will occur.
2.

3.

Drugs that will change the pH of the environment

Antacids: makes environment basic
Maalox: Mg & Al(OH)2
TUMS: CaCO3
Gaviscon: NaHCO3, Na alginate

Add shake well label

-If precipitation is harmless or intentional
Ex. Preparation of White Lotion
Sulfurated Potash + ZnSO4

ZnS
(White
ppt)

Dilute before mixing

Rx
Glycerin
KMnO4
-Dilute or dissolve KMnO4 before adding directly
to glycerin to prevent explosion.

4.

Alteration of the Gastric pH

-If the drug is acidic and the environment is
basic, the drug will be ionized or will not be
absorbed.

Consult physician regarding changes in the ingredients

Ex. Rx
Quinine SO4
Dil. H2SO4
Sodium acetate
Syrup
Dist. H2O, qs
-Quinine SO4 + H2SO4, with NaAc will produce quinine
acetate, which is insoluble.

NSAIDS: acidic drugs

:Mefenamic acid + Alnix: Cetirizine
=decreased absorption of mef. acid
b.

i. Alteration in Peristaltic Movement

-Normally, the gastric emptying time is 2 hours
-If GET is delayed, foods will stay longer in the
stomach, delay of food in the intestine =
increased absorption, increased toxicity.
-Drugs that slow GET will cause constipation
Ex. Antidiarrheals: Loperamide
Anticholinergic agents: Atropine
Hyoscyamine
Propantheline + Digoxin
= might cause toxicity of Digoxin
ii. Hasten GET (Increase GET)
-Contents of the stomach goes directly to the
intestines = decreased absorption, underdose

Ex. Diarrheals
Cholinergics
Laxatives
Cathartics

-The concentration of free warfarin is increased,

increased toxicity of warfarin
Tolbutamide: Oral hypoglycemic + Phenylbutazone:
NSAID
-Tolbutamide will be displaced, increased risk for
hypoglycemia

Lactulose + Antibiotics
=decreased absorption of antibiotics,
delayed treatment of infection
3.
c.

Complexation Reactions in the

Gastrointestinal Tract
Ex. Chelation
Tetracycline + Milk
+Antacids
+Zn containing drugs
(Conzace)
Adsorption
Cholestyramine resin + other drugs
Colestipol
Colesevelam

Sulphonylureas
Carbamezapine / Cyclosporin
Rifampin
Alcohol (chronic intake)
Phenytoin
Griseofulvin
Phenobarbital / Barbiturates

-bile acid sequesterants (used to bind

to other components) used to lower
blood cholesterol
-No drug will be absorbed because
they are insoluble
d.

B. Enzyme Inhibition
-Inhibitor (precipitant) will inhibit the liver to
produce enzymes for the object drug (decreased
metabolism of the drug in the liver)
-The concentration of the drug is increased
-The action of the drug is increased

Alteration of the Gastrointestinal flora

-Some microorganisms in the GIT will aid in the
absorption and metabolism of drugs
-Antimicrobials / antibiotics can alter the GI flora
-If microorganisms are absent, there will be no
absorption, drug will have a decreased
concentration

Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol (drinking)
Chloramphenicol
Erythromycin
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole

Ex. Vit K: Anticoagulant+ Neomycin = Decreased

absorption of Vit K, Increased bleeding
*-cillin- PCN
Ceph- CPN
-mycin- Aminoglycosides
-all IV routes except Neomycin and
Paromomycin which are oral route
Erythromycin- Macrophages
Antibiotics + Oral Contraceptive Pills
-Decreased activity of OCP, Increased risk of
pregnancy
-OCPs need microorganisms to work
2.

Distribution
-Protein binding displacement
-Only occur:
i. Both drugs are acidic
ii. Both are bound to albumin
iii. One should have a higher affinity for albumin
Ex. Warfarin: Anticoagulant + Aspirin: Antiplatelet,
NSAID
-ASA will displace Warfarin since ASA has a
higher affinity for albumin than warfarin

Metabolism / Biotransformation
A. Enzyme Induction
-Inducer (precipitant) will stimulate the liver to
release enzymes to metabolize the object drug
(increases the metabolism of the object drug)
-The concentration of the object drug will be
decreased
-The action of the object drug will be decreased

*Disulfiram- treatment of chronic alcoholism

4.

Excretion
a.Alteration of pH
-Normally, for excretion, there should be an
opposite pH to promote excretion. Urinary tract is
basic, urine is acidic.
Ex. ASA toxicity + NaHCO3
=NaHCO3 will cause ASA to promote
excretion

b.Interference in Active Transport

-When there is excretion via urine, it takes place in 3

processes:
1. Glomerular filtration
2. Passive diffusion
3. Active transport

2.

The drug will go to the glomerulus and filter drugs that are
large in size, and allows passage of water and products to
be excreted. These will go to the tubules. The substances
that are to be excreted will pass through the tubules via
passive diffusion (higher concentration to lower
concentration). Urine will pass through the collecting
tubules via active transport.

Ex. ACE inhibitor + Diuretic

B-blocker + Diuretic
Antibiotics: Sulfamethoxazole + Trimethoprim
Co-amoclav
Metformin + Sitagliptin (Janumet)
3.

-In drug interaction, substances arent excreted.

Ex. PCN + Probenecid: Uricosuric
-PCN is a large molecule. It cant be excreted via
passive diffusion. It needs a carrier to be excreted.
Probenecid will compete for the carrier protein that has a
higher affinity. Probenecid will be excreted. PCN will
remain, increased treatment of UTI in the body.
-If the person is allergic to PCN, Probenecid can
also interact with CPN.
Rationalize the ff. drug interactions:
1. Phenytoin: Anticonvulsant + Isoniazid
Mechanism: Metabolism, Enzyme Inhibition
: Prolong phenytoin activity in the body

Synergism: 1+1 >2

-The combined effect of the drug is greater than the sum of
the individual effects of drugs
-Drugs involved have different target sites
-Fixed combination drugs: to increase the effect of drugs
:to decrease ADRs

Potentiation: 0+1 >1

-one drug enhances the action of the other drug due to
interference in the kinetics of the object drug
Ex. Enzyme Inhibition
-Potentiating the ADR of the object drug
Cimetidine + Theophylline
=Increased theophylline toxicity
PCN + Probenecid
=Increased PCN activity

4.

Antagonism: 1+1 =0
-drugs will cancel each others effects / action

2.

Kremil-S + Digoxin: Tx of cardiac arrhythmia

-Metabolism, Enzyme Inhibition
-Increased effect of Digoxin

3.

Alcohol + Disulfiram
-Metabolism, Enzyme Inhibition
-Decreased concentration of alcohol

ii.Chemical Interaction
-decreases the activity of the drugs
Ex. Neutralization: Acid-base reactions
Complexation / Chelation: Tetracycline + Milk

4.

Tagamet: Cimetidine + Theophylline: Tx of COPD

-Metabolism, Enzyme Inhibition
-Increased Theophylline activity

iii. Physiologic Interaction

-opposite action on the system
Ex. Ephedrine: Bronchodilator + B-blocker: B.constrictor

5.

Digoxin + Phenobarbital
-Metabolism, Enzyme Induction
-Decreased Digoxin activity

Laxative + Antidiarrheal

2 Pharmacodynamic of Pharmacologic Drug Interaction

-due to the extent of response to the drug action, either beneficial or
adverse
4 Responses to Drug Interaction
1. Summation: 1+1 = 2
-The combined effect of the drugs is equal to the sum of
the individual drugs
-The drugs involved will have the same target site
Ex. Analgesic: Ibuprofen + Paracetamol (Alaxan)
-inhibits prostaglandins
Antibiotics
Diuretics
Thiazide + K-sparring diuretics: Dyazide

i. Physical Interaction
Ex. Adsorption: Cholestyramine resin

iv. Pharmacologic Interaction

-administer an agonist + antagonist
Ex. Ephedrine: Adrenergic agonist + B-blocker: Antagonist
Alteration of Electrolyte Levels
Ex. Hypokalemia: make a person prone to the toxic effects of digitalis
Thiazide or Loop diuretics: Can cause hypokalemia
Hyponatremia
Lithium diuretics: The body will retain the lithium ion which
when accumulated in the body can be toxic
Interaction of Adrenergic Neurons
Ex. Tyrosine, a precursor of neurotransmitters (epinephrine,
norepinephrine, dopamine). MAO (Monoamine oxidase) is important
in metabolizing tyramine. It prevents the conversion of tyrosine to
tyramine, for tyrosine to be metabolites. If MAO is inhibited, tyrosine
will be converted to tyramine to octopamine, which is a false
neurotransmitter. It increases blood pressure and heart rate.

2 Instances that tyramine can accumulate in the body

1. Inhibition of MAO by taking drugs with TCA (Trichloroacetic
acid)

2. Taking foods with high tyramine: Fermented products