MODULE 5

RIZZA A. CALUAG
Pharmaceutical Jurisprudence
 IMPORTANT STATUTES SUMMARIZED (Must know)
RA No. Common name Date Amendments/
supplemental AOS
RA 5921 Pharmacy Law June 23, 1969 EO 174
RA 10918
RA 3720 Food, Drugs and Cosmetics Act June 22, 1963 EO 175
AO 55
AO 56
RA 6675 Generics Act of 1988. September 13, 1988 AO 62
AO 63
RA 8203 Special Law on Counterfeit Drugs July 22, 1996
RA 6425 The Dangerous Drugs Act of 1972." April 4, 1972 RA 9165
RA 9165 Comprehensive Dangerous Drugs Act of 2002" June 7, 2002 None
RA 7432 Senior Citizen Act of 1992 April 23, 1992 RA 9257
RA 9257 Expanded Senior Citizens Act of 2003 February 26, 2004 RA 9994

RA 9994 Expanded Senior Citizens Act of 2010 February 15 2010

RA 7394 Consumer Act of the Philippines April 13 1994
RA 7581 Price Act May 7, 1992
RA 9502 Universally Accessible Cheaper and Quality June 6, 2008
Medicines Act of 2008
RA 9711 Food and Drug Administration (FDA) Act of 2009 August 18, 2009
RA 8423 "Traditional and Alternative Medicine Act (TAMA) of December 9, 1997
1997."
 OO no. 1, s. 1988 Implementation of Executive Order No. 119, Reorganizing the Bureau of Food and Drugs January 26, 1988
AO no. 153, s. 2004 Revised Guidelines in cGMP in manufacturing, packing, repacking or holding food May 07, 2004
September 29,
AO no. 43, s. 1999 Current Good Manufacturing Practice Guidelines For Drugs 1999
AO no. 90, s. 2002 Current Good Manufacturing Practice Guidelines For Cosmetic Products March 18, 2002
AO no. 42, s. 1982 Drug Registration of Herbal and/or Traditional Drugs, Both Local And Imported August 19, 1992
Declaring and Adopting the Philippine Pharmacopoiea as The Official Book of Standards
EO no. 302 and Reference for Pharmaceutical Products and Crude Plant Drugs in the Philippines March 29, 2004
AO no. 55, s. 1988 Requirements for Labelling Materials of Pharmaceutical Products December 07, 1988
AO no. 64, s. 1989 Amendment of AO no. 55, s. 1988 March 13, 1989
AO no. 107, s. 1991 Guidelines on Dispensing Multiactive-Ingredient Fixed-Dose Combination of Drug Products May 16, 1991
AO no. 56, s. 1989 Revised Regulations For The Licensing of Drug Establishment and Outlets January 03, 1989
AO no. 67, s. 1989 Revised Rules and Regulations on Registration of Pharmaceutical Products March 15, 1989
Policy and Requirements for Availing of Compassionate Special Permit (CSP) for
AO no. 4, s. 1992 Restricted Use of Unregistered Drug and Device Product/Preparation November 03, 1992
Rules and Regulations for Licensing Local Manufacturers of Vaccines and Biological
AO no. 27, s. 2001 Products June 19, 2001
Rules and Regulations on the Registration, including Approval and Conduct of Clinical
AO no. 47-A, s. 2001 Trials and Lot or Batch Release Certification of Vaccines and Biologic Products August 30, 2001
Rules and Regulations to Implement Prescribing Requirements under the Generics Act of
AO no. 62, s. 1989 1988 March 15, 1989
AO no. 90, s. 1990 Amendment to AO no. 62, s.1989 April 23, 1990
Rules and Regulations to Implement Dispensing Requirements under the Generics Act of
AO no. 63, s. 1989 1988 March 13, 1989
 Ethical Principles Summarized
Ethical Principle Definition

Non-maleficence To do no harm

Beneficence Duty to promote good

Respect for Respect for the individual’s right to decide on issues

autonomy that affect self
Confidentiality right to give or refuse consent relative to release of
privileged information
Veracity obligation to tell the truth, or honesty

Role fidelity Obligation

UNLAWFUL ACTS & PENALTIES
IMPRISONMENT FINE
1P LIFE 500K- 10M
IMPRISONMENT TO
DEATH
2P 12 YRS 1 DAY – 20 100K-500K
YRS
3P 6 MOS 1 DAY – 4 10K-50K
YRS
MAXIMUM PENALTY
 LIFE IMPRISONMENT TO DEATH
1P 500K- 10M

Maintenance
Importation of Manufacture of of Den, Dive
Unlawful
Dangerous Dangerous or Resort of
Drugs Prescription
Drugs Dangerous
Drugs

Sale of Possession of
Cultivation or
Dangerous Dangerous
Culture
Drugs Drugs
 POSSESSION OF
DANGEROUS DRUGS
• 10 grams or more of opium;
• 10 grams or more of morphine;
• 10 grams or more of heroin;
• 10 grams or more of Marijuana Resin/Oil
• 10 grams or more of LSD,GHB
• 50 grams or more of Shabu
• 500 grams or more of Marijuana
 12 YRS 1 DAY – 20 YRS
2P 100K-500K

Importation of Manufacture Illegal diversion

chemical of chemical of any controlled
Unnecessary
Precursor or Precursor or Prescription
precursor and
Essential Essential essential
Chemical Chemical chemical

Sale of Maintenance of
chemical Den, Dive or
Coddler/
Precursor or Resort of chemical
Protector Precursor or
Essential
Essential Chemical
Chemical
 6 MOS 1 DAY – 4 YRS
3P 10K-50K

Possession of
Equipment,
Instrument,
Apparatus and Drug User
Other Paraphernalia
for Dangerous
Drugs
 MAXIMUM PENALTY
2. Bringing any
1. Possession of D.D, C.P., E.C
Dangerous Drugs through the use
Meetings of DIPLOMATIC
PASSPORT

3. Selling, trading,
4. Financer and
distributing illegal
Drug sellers who use
substance 100
Mentally deranged
meters away from
people and minors
school
Drug Delivery Systems and
Manufacturing Pharmacy
 Organic Synthesis
New Chemical Entity
Molecular Modification

Chemistry
Pre-Clinical Studies Physical Properties
Biological

Pre-formulation

Investigational New Drug

Clinical Trials
Phase 1 Pre-Clinical Studies
Phase 2 (continued)
Phase 3
New Drug Long term animal toxicity
Application
Product Formulation
(NDA)
Manufacturing Control
Package and Label design

Postmarketing (Phase 4)
Philippine GMP regulation
-- AO43 1999 - adoption of the 1st edition of the
current GMP guidelines by FDA
-- AO2012-0008 - adoption and implementation of
the PIC/s GMP as the standard on the
manufacturer
-- FDA MC 2012- Philippine FDA mandated all
drug manufacturers to ensure strict and full
compliance to the newly adopted PICS
 Container
• device that holds a drug and is or may be in direct
contact with the drug
1. Well-Closed protects against extraneous solids and liquids, loss of drug under
Container ordinary conditions of handling, shipment, storage and distribution

2. Tight Container protects from extraneous solids, liquids or vapors, from loss of drug and
from efflorescence, deliquescence or evaporation

3. Hermetic Container impervious to air or any other gases under ordinary conditions of handling,
shipment, storage and distribution
generally sterile

4. Light Resistant protects the contents from photochemical deterioration

Container amber, opaque, blue
Materials Used for Packaging:
1. GLASS
Type General Description Uses Test

I HRBSG for parenteral PG TEST

II TSLG for parenteral WA TEST

III SLG for parenteral PG TEST

NP GPSLG other products PG TEST
except parenteral

Powdered Glass Test Water Attack Test

• performed on ground/powdered glass to • exposure of the
expose internal surface
• tests the leaching potential of the glass glass with sulfur
• alkali titrated with 0.02 N sulfuric acid dioxide at 121ºC
Plastic Materials
PE - cannot be autoclave
- Low-density – droppers & sprays
- High-density – solid oral prepns
PET - For beverages
- APETG (amorphous PET glycol)
- PETG (PET glycol)
- have transparency and luster
PP - Autoclavable
PVC - Rigid & good clarity
- blister packaging
 USP STORAGE CONDITIONS
Cold Place < 8 deg C
Freezer -25 to -10deg C
Refrigerator 2-8 deg C
Cool 8- 15 deg C
Room Temperature 20-25deg c
*Controlled Room 15-30deg C
Temperature
Warm 30-40 degC
Excessive Heat ABOVE 40deg C
 Solubility

Terms of Solubility Parts of Solvent

Very Soluble <1

Freely Soluble 1-10
Soluble 10-30
Sparingly Soluble 30-100
Slightly Soluble 100-1000
Very slightly Soluble 1000-10000
Insoluble >10000
1. Purified Water obtained by distillation, ion-exchange or reverse osmosis
pH 5-7
used in prescription and manufactured finished products except
parenteral and other sterile solutions

2. Water for Injection purified water that is FREE of pyrogens

obtained by distillation or reverse osmosis
used for the preparation of parenteral solutions
3. Sterile Water for -WFI that is sterilized & packaged in single-dose containers < 1L
Injection
4. Bacteriostatic Water -SWI that contains 1 or more antimicrobial agents
for Injection packaged in single or multiple-dose containers <30ml

5. Sterile Water for -Water purified by distillation or reverse osmosis & rendered sterile
Inhalation -Not used for the preparation of parenteral solutions or other sterile
dosage forms

6. Sterile Water for WFI that is sterilized and suitably packaged

Irrigation
 Classification of powders based on particle size:

USP Standards for Powders of Animal and Vegetable drugs

FINENESS SIEVE SIZE SIZE UNIT % of particles

All particles that passed.
pass thru
Very coarse #8 236mm nmt 20% thru #60

Coarse #20 850um nmt 40% thru #60

Moderately #40 425um nmt 40% thru #80

coarse
Fine #60 250um nmt 40% thru #100

Very fine All passed #80 180um No limit to greater

fineness
 USP Standards for Powders for Chemicals

FINENESS SIEVE SIZE UNIT % of particles passed.

SIZE
All
particles
that pass
thru
Coarse #20 850um nmt 60% thru sieve#40
Moderately #40 425um nmt 60% thru sieve #60
coarse
Fine #80 180um no limit to fineness
Very fine #120 125um no limit to greater
fineness
 Parts of a Tablet
1.Hopper - LOADS THE
GRANULE Press (HFPDC)

2. Feed shoe- DIRECTS

GRANULES FROM THE 5. Cam tracks-GUIDES THE
HOPPER TO THE SIDE MOVEMENT OF UPPER
AND LOWER PUNCHES
3. Punch- COMPRESS
GRANULES INTO TAB 4. Die- CONTROL THE
SIZE AND SHAPE OF
THE TABLET
COLORANTS:
• FD&C Red No. 2 (amaranth)
- causes cancer in rats, unproven safety
• FD&C Red No. 4
- found in maraschino cherries and ingested drugs; only
used in external drugs and cosmetics
• FD&C Yellow No. 5 (tartrazine)
- causes allergic type reaction in many people
• D & C RED No. 22 (EOSINE)
• FD and C #6 (SUNSET YELLOW)
• BRILLIANT BLUE- FD AND C BLUE NO.2
• ALLURA RED- FD AND C BLUE NO.40
Steps in sugar-coating (SSSFP)
1. Sealing / waterproofing-- FOR COMPONENTS EASILY
AFFECTED BY WATER
2. Subcoating-- IMPROVE BOND BETWEEN SUGAR COAT
AND TABLET CORE
3. Syruping / smoothing-- COMPLETE ROUNDING OFF
• Glossing - establishing color base
• Heavy syruping - build a solid color base rapidly
• Regular syruping - to attain appropriate color
4. Finishing – TO ATTAIN FINAL SMOOTHNESS
• DEBOSSED- imprinted with a mark BELOW the surface
• EMBOSED- imprinted with a mark ABOVE the surface.
5. Polishing– for sheen or gloss
FILM-COATING
1. Film Former - PRODUCES SMOOTH THIN FILM
Examples: Cellulose acetate phthalate, HPMC
2. Alloying Substance- PROVIDES WATER SOLUBILITY /
PERMEABILITY TO THE FILM TO ENSURE PENETRATION
BY BODY FLUIDS
Ex. polyethylene glycol (PEG)
3. Plasticizer - PRODUCES FLEXIBILITY + ELASTICITY
DURING APPLICATION
Ex. Castor oil, PG, Glycerin, PEG,
4. Surfactant - ENHANCE SPREADABILITY OF THE FILM
DURING APPLICATION
Ex. Spans & Tweens
5. Opaquant & Colorant- TO ENHANCE AESTHETIC
QUALITIES OF THE COAT
ex. TiO2, FD&C
6. Sweetener, Flavor and Aroma - ENHANCE ACCEPTABILITY
OF THE TABLET BY THE PX
Ex. vanillin, saccharin
7. Glossant - PRODUCES LUSTER TO TABLET
Ex. Beeswax
8. Volatile Solvent - ALLOWS THE SPREAD OF OTHER CMPD
OVER THE TABLET WHILE ALLOWING RAPID EVAP TO
PERMIT AN EFFECTIVE YET SPEEDY OPERATION
Ex. alcohol-acetone mixture
 SPANSULE: - Ends of both bodies and cap
- A capsule composed of hard gelatin shell are highly tapered/narrowed.
containing hundreds of tiny coated beads/pellets Used by Smith Kline
of drugs for sustained release. Beecham.

PULVULES
- End of the body-producing peg is
tapered but the cap-making peg is
rounded. Used by Eli Lilly.

KAPSEAL
-This is a distinctive looking capsule because
of the sealing with a colored band of gelatin.
This is used by Parke-Davis.

Coni-Snap
- The rim of the capsule body is not straight but tapered
slightly. This eliminates splitting of the joined capsule.
A pH-sensitive, non-digestible radiofelemettric device used as a
nonradioactive means of measuring gastric pH, gastric residence
time and gastric emptying time of solid dosage forms is called
HEIDELBERG CAPSULE.
• Lontabs is an example of specially coated beads
• Endurates is an embedded drug in a slowly eroding
matrix
• Durabond forms slowly dissolving complexes that is
insoluble in body fluids
• Gradumet is an example of drug in an inert plastic
matrix.
HLB Value Surfactant Application
Range
0-3 Antifoaming agents
4-6 W/O emulsifying agents
7-9 Wetting agents
8-18 O/W emulsifying agents
13-15 Detergents
10-18 Solubilizing agents
Transdermal administration

Electroporation is a TDDS enhanced by the application of short, high-voltage

electric pulses to create aqueous pores in the lipid bilayer of skin and thereby
facilitate drug diffusion.

Iontophoresis is a TDDS enhanced by the use of applied

electric current to facilitate drug diffusion through the skin.

Phonophoresis is a TDDS enhanced by the application of low-

frequency ultrasound to facilitate drug diffusion through the skin.

High velocity powder particles A transdermal drug delivery system using

supersonic shock waves of helium gas to enhance drug diffusion through the
skin
 Suppository Bases:
• Fattibase, Wecobee bases, Witepsol base, Cocoa
butter
1. Fatty / Oleaginous • Cocoa butter
• good base for rectal suppository
Bases • melting just below body temperature and yet
maintaining its solidity at usual room temperatures

2. Water-Soluble and • glycerinated gelatin, PEG

Water-Miscible Bases

• are mixtures of oleaginous and water-

3. Miscellaneous Bases soluble or water-miscible materials
 Ointment Bases
1. OLEAGINOUS

- hydrocarbon bases
- not water-washable, incorporation of water with some degree of
difficulty

PETROLATUM
WHITE PETROLATUM
YELLOW OINTMENT
WHITE OINTMENT (USP)
MINERAL OIL
 Ointment Bases
2. ABSORPTION

are not easily removed from the skin

A. Anhydrous type those that B. Hydrous type

permit the incorporation of aqueous those that are w/o emulsions that permit
solutions resulting in the formation of the incorporation of additional quantities
w/o emulsions of aqueous solutions

HYDROPHILIC PETROLATUM USP COLD CREAM

ANHYDROUS LANOLIN
HYDROCREAM
AQUAPHOR
LANOLIN
AQUABASE
POLYSORB EUCERIN
NIVEA CREAM
 Ointment Bases
3. WATER-REMOVABLE BASES

- are o/w emulsions resembling creams

- easily washed from the skin, hence called “water-washable”

DERMOVAN
HYDROPHILIC OINTMENT USP, UNIBASE
VANISHING CREAM
 Ointment Bases
4. WATER-SOLUBLE BASES

- do not contain oleaginous components

- are completely water-washable, hence called
“greaseless”

PEG OINTMENT
POLYBASE
PG
PEG
Actuator – provides a rapid and convenient means for releasing the
contents from a pressurized container; button that activates the system

Valve – expels the contents from the

container; regulate the flow of
product from container

Stem – Part of the usual aerosol valve

assembly that supports the actuator and
delivers the formulation in the proper
form

Dip tube – the tube that delivers the content

Gasket – Placed snugly with the stem, prevents
leakage of the formulation when the valve is closed.

Spring – Holds the gasket in place and is

Mounting cup – Part of the usual aerosol valve the mechanism by which the actuator
assembly that is attached to the aerosol can or retracts when pressure is released, returning
container and hold the valve in place. the valve to the closed position
1. The most commonly used class of aerosol propellant which is composed of butane,
iso-butane and propane gasses. It has excellent solvent powers;
A.Hydrocarbon propellants C. Hydrofluroalkanes
B. Chlorofluorocarbons D. Compressed Gas propellants
2. A class of aerosol propellants, which require the use of a non-volatile co solvent. It
produces only coarse droplets and is applicable only to surface and topical sprays;
A. Hydrofluroalkanes C. Hydrocarbon propellants
B. Compressed Gas propellants D. Chlorofluorocarbons
3. It is a Zwitterionic type of an aerosol propellants;
A. Oleic acid C. Cetyl pyridinium chloride
B. Phosphatidylcholine D. Sorbitan trioleate
4. An aerosol container material, which is lightweight and seamless. And is mostly
used for inhalation and topical aerosols;
A. Three-piece tin plate C. Plastic coated glass
B. Plastic D. Plastic
5. An aerosol container material, which can be pressurized from the base with
compressd gasses. Visible seams make this container visually less appealing;
A. Aluminium glass C. Plastic coated glass
B. Three-piece tin plate D. Plastic
Manufacture of sterile product
Should be carried out in clean areas, entry to which should be
through airlocks for personnel and/or for equipment and materials
Clean areas
An area with defined environmental control of particulate and
microbial contamination, constructed and used in such a way as to
reduce the introduction ,generation, and retention of contaminants
within the area
Airlock
An enclosed space with two or more doors, which is interposed
between two or more rooms
Grade A
-- Local zone for high risk operations
-- EX: Filling zone, stopper bowls, open ampoules and vials, , aseptic
connections
-- provided by a laminar air flow work station with a HEPA
Grade B
-- For aseptic prepn and filling
Grade c and d
-- clean areas for Carrying out less critical stages of the manufacture of sterile
Grade C
-- Hair and where relevant beard should be covered
-- A single or two piece suit gathered at the wrist and with high neck and appropriate
shoes or overshoes should be worn should shed virtually no fibers or particulate matter
Grade D
-- Hair and where relevant beard should be covered
-- General protective suit and appropriate shoes and overshoes should be worn
-- Appropriate measures should be taken to avoid any contamination coming from
outside and clean areas
 a. Materials support area
Production facilities- -- surfaces should be continuous
5 sections class 10,000 environment
( nmt 10,000 particles or 0.5 um or larger are present in per cubic ft.)

b. Compounding area
-- most stringent control
stainless steel cabinets and counters
-- continuous surfaces
-- class 100 environment

c. Aseptic filling area

-- “heart” of production area
laminar air flow (LAF) with HEPA filter (High Efficiency Particulate Air)
-- 99.95% efficiency
-- Used to test efficiency of hepa filter: DOP TEST

d. Quarantine area
storage while waiting for QC results
e. Finishing area
STERILIZATION METHODS
Type Principle Applications Equipment Notes
1. Moist heat/ steam Protein Solutions in sealed Autoclave (121ºc, 15-30
sterilization denaturation containers and mins, 15psi)
ampules
2. Dry heat sterilization Oxidation Oils and dry Hot air oven (160-170ºc, 2-4
powders hrs)
180 oC for 4 hrs
250 oC for 45 mn
650 oC for 1 min
3. Radiation/ cold Mutation Glasswares and UV light (240-280 nm)
sterilization equipment
4. Gas sterilization Protein Gas chamber with Thermolabile
denaturation ethylene oxide substances
5. Filtration Physical Membrane filters Thermolabile Bubble test-
removal substances used to measure
the efficiency of
membrane filter
Sterilization Biological Indicators
1. Steam: B. stearothermophilus
2. Dry Heat: B. subtilis
3. Ionizing Radiation UV: B. pumilus
4. Ethylene Oxide: B. subtilis
SOME STUFFS FOUND IN PACOP
HOMOGENIZER An equipment used to produce fine emulsion droplets, by first
compressing the liquid with a high pressure and then allowing
the liquid to escape radically past a flat disc, held by strong
spring mechanism;

CHILSONATOR A method of preparing tablet granulations, wherein the powders

are de-aerated and passes between two rollers, forming a thin
cake, which is screened to form granules;
TWIN OR V SHELL An equipment, which alternately combine and draw apart the
BLENDER tablet material, as this equipment revolves. Ideal for precise
blending of dry-to-dry or dry-to-liquid materials, with short
processing times;

GRANULATOR/FLUID An equipment, which delivers a reliable and uniformly mixed

BED DRYER dried product, without the necessity for pre-mixing. It produces a
dry granulation from a wet powder mix;
Vibratory The most efficient type of motion in
sieving
Cutting mill Type of mill used for tough, fibrous
materials
Paar Calorimeter Determination of moisture for
effervescent tablets is conducted
through:
Rotor stator Type of mill used for the reduction
of solid particle size and for
dispersion of suspensions
containing poorly wetted solids
Hammer mill Striking effect
Ball mill/pot mill/jar mill Produces pulverization with
minimal lost of drugs
Terpineol clarifying agent in the formulation of shampoos

Behemic acid Opacifying agent

Ceresin and ozokerite Stiffens the cream

Nitrogen Anti-oxidant in parenterals
Sorbitol in Al OH gel Viscosity builder
Cetyl Alcohol Minimize the foam
Ethocel Ethyl cellulose- binder
TEA Emulsifying agent
carbomer Cost effective thickener
nitrocellulose Primary film former
Butane, Isobutane, Propane HC bases: Excellent solvent power
Polyurethane/cheesecloth Used in pan polishing
Polyethylene Used for ophthalmic solution
Manihot esculenta Tapioca starch
Tragacanth Forms a heavy mucilage in water
Physical Pharmacy
 FORCES OF ATTRACTION
A. Intramolecular forces
1. Ionic Bond - Transfer of electron

2. Covalent Bond - Sharing of electron

B. Intermolecular forces
1. Van der waals - Keesom, Debye, London KODD, DIDID, LDIDID

2. Ion Dipole - polar molecules are attracted to either positive/negative

charges
3. Ion-Induced dipole - the force of attraction induced by a close proximity of a
charged ion into a non-polar molecule

4. Hydrogen Bonds - attraction of H for a strongly electronegative ion

1. BOYLE’S LAW P1V1=P2V2
2. CHARLES’ LAW T1/V1 = T2/V2

3. GAY LUSSAC’S P1/T1 = P2/T2

4. COMBINED GAS Ideal Gas Law

LAW PV = nRT
STP- Standard Temperature Pressure
5. REAL GAS Van der Waals eq. for real gases
EQUATION (P +an2/v2) (V-nb) =Nrt
6. HENRY’S LAW OF states that the amount of gas dissolved in a solution is proportional to the
GAS SOLUBILITY partial pressure of the gas in equilibrium with the solution
-- increased pressure, increased gas solubility

7. DALTON’S LAW OF -- states that the total pressure in a mixture of gases is equal to the sum
PARTIAL PRESSURE of the partial pressure of each gas
-- the partial pressure is the pressure a gas would exert if it alone
occupied the whole volume of the mixture
8. GRAHAM’S LAW --speed of diffusion of gas is inversely proportional to the density
 METHODS OF ADJUSTING ISOTONICITY

CLASS 1 CLASS 2
- Addition of a tonicity adjusting - Addition of water and dilution with
agent buffered isotonic solution

Cryoscopic Sprowl’s Method

Method

E Value White Vincent

Method Method

E value - gram of NaCl equivalent to 1 gram of substance

Isotonic NaCl Concentration - 0.9% (w/v) NaCl

Cryoscopic Method Based on the adjustment of freezing point of a
solution to -0.52degC

NaCl Equivalent method Based on the adjustment of freezing pt of a solution to

0.9% NaCl

Sprowl’s Method Based on the method of calculating values when the

weight of the drug is 0.3g
V=0.3g X E X 111.1
White Vincent Merhod Method of adjustment of tonicity where in a stock
solution which is isotonic is added to bring solution
into its volume
V= W x E X111.1
USP METHOD
 Step 1: Calculate the amount of NaCl
E-Value
represented by the ingredients in the
prescription.
Method

Step 2: Calculate the amount of NaCl that would

make the volume of solution specified in the
prescription isotonic.

Step 4: If an agent other than NaCl,

is to be used to make a solution
isotonic, divide the amount of NaCl
Step 3: Subtract the amount of NaCl represented by (obtained in Step 3) by the sodium
the ingredients in the prescription (Step 1) from the chloride equivalent (E value) of the
amount of NaCl that would make the specific volume in other substance.
the prescription isotonic (Step 2).
How many grams of NaCl should be used in
compounding the following prescription?
Rx
Pilocarpine nitrate (E=0.23) 0.3 g
NaCl qs
Purified water qs 30.0 mL
Make isotonic solution
Sig. for the eye
Step 1.
0.23 x 0.3 g = 0.069 g of sodium chloride
represented by the pilocarpine nitrate
Step 2.
30 x 0.009 = 0.270 g of sodium chloride in 30 mL
of an isotonic sodium chloride solution
Step 3.
0.270 g (from Step 2) - 0.069 g (from Step 1) =
0.201 g of sodium chloride to be used, answer.
How many grams of boric acid should be used in
compounding the prescription?
Rx
Phenacaine HCl (E=0.17) 0.6 g
Chlorobutanol (E= 0.18) 0.3 g
Boric acid (E=0.52) qs
Purified water qs 60.0 mL
Make isotonic solution.
Sig. One drop in each eye.
Step 1.
0.20 x 0.6 g = 0.120 g of sodium chloride represented by phenacaine
hydrochloride
0.24 x 0.3 g = 0.072 g of sodium chloride represented by chlorobutanol
Total: 0.192 g of sodium chloride represented by both ingredients
Step 2.
60 x 0.009 = 0.540 g of sodium chloride in 60 mL of an isotonic sodium
chloride solution
Step 3.
0.540 g (from Step 2) - 0.192 g (from Step 1) = 0.348 g of sodium chloride
required to make the solution isotonic.
But because the prescription calls for boric acid:
Step 4.
0.348 g ÷ 0.52 (sodium chloride equivalent of boric acid) = 0.669 g of
boric acid to be used, answer
How many grams of KNO3 (E=0.58) could be used
to make the following prescription isotonic?
Rx
0.2% Silver nitrate solution (E=0.34)
60 mL

Make isotonic solution.

Sig. For eye use
Step 1.
0.33 x 0.12 g = 0.04 g of sodium chloride represented by silver
nitrate
Step 2. 60 x 0.009 = 0.54 g of sodium chloride in 60 mL of an
isotonic sodium chloride solution
Step 3.
0.54 g (from step 2) - 0.04 g (from step 1) 0.50 g of sodium
chloride required to make solution isotonic
Because, in this solution, sodium chloride is incompatible with
silver nitrate, the tonic agent of choice is potassium nitrate.
Therefore,
Step 4.
0.50 g ÷ 0.58 (sodium chloride equivalent of potassium nitrate)
= 0.86 g of potassium nitrate to be used, answer.
Using the USP method for adjusting isotonicity,
compute for the required volume to make 0.5g of
Atropine Sulfate (E=0.13)

V= W x E X111.1
 Approximate Liso Values
Compound Type by Valence Liso Values
Non electrolyte 1.86
Weak electrolyte 2.0
Di-divalent electrolyte (divalent cation and 2.0
divalent anion)
Uni-univalent electrolyte (single charge on 3.4
each)
Uni-divalent electrolyte 4.3
Di-univalent electolyte 4.8

Liso of drugs- the molar concentration that will attain isotonicity based
on freezing point depression of -0.52degC
Liso = E (MW) / 17
E = (Liso x 17) / MW

E = (1.8 x 17) / 61.8 = 0.5

pH Logarithm of H ion conc
Sorensen pH scale pH >7, pH =7, pH <7
Ionization Complete separation of ions in a crystals lattice when
salt is dissolve
Dissociation Separation of ions in solution when the ions are
associated by interionic interaction
Strong Acids pH = -log (H+)
Strong Bases pOH = -log[OH]
pH = pKw -pOH
Weak Acids pH = - log √CAKa
Weak Bases pOH = - log √ CBkb
Sorensen’s Basic solution of dibasic Sodium
buffer Phosphate
- Used by Timolol eyedrops to obtain a
pH of 6.5
BORATE BUFFER SYSTEM

Feldman’s Buffer BORIC ACID, NaCl, ALKALINE SOLN CONTAINING

SODIUM BORATE
Atkins and Pantin BORIC ACID AND NaCl AND ALKALINE SOLN OF SODIUM
Buffer CARBONATE

Gifford Buffer BORIC ACID AND KCl AND ALKALINE SOLN OF SODIUM
CARBONATE
Acetate- most Biological Buffer System:
important buffer Phosphate, Oxyhemoglobin and
of blood.
Carbonates
Surface Tension Measurement
Du Nouy measures the maximum pull on the ring by the surface

Wilhelmy plate measures equilibrium surface or interfacial tension

Pendant Drop based on the shape of the drop.

Bubble Pressure based on the pressure

Volumetric Tensiometers based on the size of the drops

Measuring Surface Area

Method 1: Adsorption Method

Method 2: Air-permeability method
Quantasorb- This instrument is generally used for
surface area determination by gas adsorption and air
permeability method.
 Properties of Colloids

Optical Faraday Tyndall effect- Ability to scatter or to dispersed light.

Brownian Motion – random collisions of particles resulting to

irregular zigzag path
Kinetic Diffusion – spontaneous movement of the particles from a
region of higher concentration to one lower concentration until the
concentration of the system is uniform throughout.

1. Nernst Potential -- Difference between the potential of the

actual surface and the electroneutral region of the surface.
Electric
2. Zeta Potential -- Difference between the potential of the surface of
the tightly bound layer and the electroneutral region of the surface.
Newtonian Stress versus strain rate curve is linear.
• F is directly proportional to G
Unit for viscosity: • Constant Viscosity with increasing rate of shear
Poise • Dependent only on temperature
Cgs unit for poise: EX: water, air, gasoline, honey, glycerin, milk, oil in salad
dyne-sec/cm2 dressing, benzene
Non-Newtonian • Substances that fail to follow Newton’s equation to
flow
• Exhibit VISCOELASTICITY
1. Plastic - Substances that exhibit yield value
(Bingham body) - the yield value must overcome in order for the
system to flow
Ex: flocculated particles in suspension drilling mud,
slurries, toothpaste, blood, butter, maragarine
2. Pseudoplastic - Decrease viscosity, Increase rate of shear
(Shear thinning Ex: natural and synthetic gums, liquid dispersion of
system) tragacanth, Na alginate, methylcellulose and Na CMC
3. Dilatant - Increase Viscosity with Increasing Rate of shear
(Shear thickening - exhibited by suspension with high percentage of
system) dispersed solids (>50% of the particle )
Ex: paint, whipped cream, corn starch, clay slurries
Henderson Hasselbach Eq Buffer

Van Slyke Eq. Buffer Capacity

Fick’s Law Rate of Diffusion(Passive)

Stoke’s Law Sedimentation Rate

Michaelis Menten Kinetics Active Diffusion

Noyes Whitney Dissolution

Hess Law Proposed Heat of Summation

Poiseuille Eq. “Radius of the tube- has the greatest influence on

the rate of flow of liquid though a capillary tube”

Amagat’s Law Gives direct opportunity between shear stress

*states that the extensive volume of a gas mixture
is equal to the sum of volumes of
the K component gases, if the temperature T and
the pressure p remain the same
FARADAY’S LAW The passage of 96,500 coulombs of
electricity through a conductivity cell
produces a chemical change of 1 gram
equivalent weight of any substance.
Langmuir Proposed the monolayer theory of gas
adsorption on solid surface

Arrhenius equation An equation used to determine the contact

angle

Schulz-Hardy rule According to this rule “the higher the velocity

of the ion, the greater is the precipitating
power”.

Regnault and Meyer Used to determine the MW of easily

vaporized liquid
Young’s equation Equation used to determine the contact
angle
 BIOPHARMACEUTICS CLASSIFICATION
OF DRUGS
CLASS 1 INCREASE SOLUBILITY, DILTIAZEM,
INCREASE PERMEABILITY PROPRANOLOL,
ACETAMINOPHEN
CLASS 2 DECREASE SOLUBILITY, GLIPIZIDE, NIFEDIPINE
INCREASE PERMEABILITY

CLASS 3 INCREASE SOLUBILITY, INSULIN, ACYCLOVIR

DECREASE PERMEABILITY

CLASS 4 DECREASE SOLUBILITY, TAXOL, HCTZ

DECREASE PERMEABILITY
PRACTICE QUESTIONS
• 1. Cold Cream, USP is also known as:
A. Petrolatum Rose Water Ointment
B. Vanishing Cream
C. Wool fat Ointment
D. Rose Water Ointment
2. These type of preparation are small, cylindrical in
shape administered by implantation and are prepared
by implantation
A. Lozenges
B. Pellets
C. Chewable tablets
D. NOTA
3. This type of containers is impervious to air or any
other gas
A. Light resistant containers
B. Hermetic containers
C. Tight containers
D. Single dose containers
E. AOTA
4. This is added to Collodions to make them flexible:
A. Olive oil
B. Gelatin
C. Castor oil
D. Camphor
5. Concentration of “Diluted Alcohol” by volume is:
A. 10%
B. 50%
C. 70%
D. 20%
6. Clear, colorless, odourless, liquid, sterilized and
suitably packaged and contains no bacteriostatic
agent
A. Sterile Water for Injection
B. Bacteriostatic Water for Injection
C. Water for Injection
D. Distilled Water
7. This type of extract is suitable for use in ointments
and pastes:
A. Semiliquid
B. Pilular
C. Powdered
D. Any
8. Mineral Oil is also known as:
A. Liquid Paraffin
B. Paraffin
C. Petroleum Jelly
D. White Ointment
9. In percolation, “to percolate slowly” means the rate
of flow is:
A. 1 to 3 mL/minute
B. Not exceeding 1 mL/minute
C. 3 to 5 mL/minute
D. 5 to 10 mL/minute
10. USP defines Type I glass as
1. Treated soda lime glass
2. Intended for parenteral products
3. Resistant to leaching alkali
A. 1 and 2
B. 2 and 3
C. 2 only
D. 1, 2 and 3
11. The pressure required to push the air through a
liquid saturated filter
A. Bubble point
B. Flash point
C. Saturation point
D. AOTA
• 12. The containers used to package drugs may
consist of several components. This term best
describes the release of an ingredient from
packaging components into the actual product
• A. Sorption
• B. Leaching
• C. Permeation
• D. Porosity
• 13. The USP medicine dropper when held vertically
delivers how many drops of water?
• A. 15 drops of water
• B. 18 drops of water
• C. 25 drops of water
• D. 20 drops of water
14. Compute for the E value of Papaverine sulfate HCl
(MW 376) which is a 2 ion electrolyte dissociating
80% in a given concentration.
A) 0.1554
B) 0.1555 58.5 1. 8
C) 0.1556 E = ------------- x --------------- =
D) 0.1557 1.8 376
15. Prohibited drugs, EXCEPT
A. Morphine
B. Phenobarbital
C. Meperidine
D. Codeine
16. The following conditions ay be used to destroy
pyrogens, EXCEPT:
A. 121 oC for 15 mins
B. 180oC for 4 hours
C. 250 oC for 45 mins
D. 650 oC for 1 min
17. Kristine Kate, a 2-year old child is suffering from
fever and vomiting. As pharmacist, what would you
recommend to the doctor to be the most appropriate
dosage form to treat fever in this case?
A. Suspension
B. Suppository
C. Syrup
D. Injection
18. Which technique is typically used to mill camphor?
A) trituration
B) levigation
C) pulverization by intervention
D) geometric dilution
A.SMECTIC – SOAP LIKE/ GREASE LIKE/
ROTATES IN ONE AXIS/ MOBILE IN 2
DIRECTIONS/ MOST PHARM.IMPT
B. NEMATIC– THREAD LIKE/ ROTATES IN
ONE AXIS/ MOBILE IN THREE
DIRECTION
19. Type of liquid crystal in which the molecules are
mobile in 2 directions and can rotate about 1 axis
A. Nematic
B. Cholesteric
C. Smectic
D. Both B and C
20. Type of liquid crystal in which the molecules are
mobile in 3 directions and can rotate about 1 axis
A. Nematic
B. Cholesteric
C. Smectic
D. Both B and C
21. HLB value of o/w emulsifier
A. 3-6
B. 8-18
C. 15-20
D. 7-9
Comminution
Particle size reduction
Principal Means of Milling
1. Cutting / shearing mill (CUTTIING)
2. End runner mill- (Compression)
3. Hammer mill, vibration mill(Impact)
4. Ball mill, pin mill, Fluid energy mill (Impact
and attrition)
5. Roller mill- (attrition & compression)
22. One of the basic actions involved in comminution
which involves the operation of hammers or bars at
high speeds
A. Attrition
B. Rolling
C. Impact
D. Mixing
23. Amount of morphine subject to life imprisonment to
death penalty and a fine of 500,000 pesos to 10M
pesos:
A. 500g
B. 50g
C. 10g
D. 1g
24. Compute for the specific gravity of potassium
dichromate (K2Cr2O7) if its weight t in air =5.76g and
its weight in oil 3.08g. The sp.gr of the oil is 0.86.
A. 1.86
B. 1.85
C. 1.87
D. 1.88
Sp. Gr = [ wt. in air/ (wt. in air – wt. in oil)] x sp. Gr of oil
25. An ordinary prescription shall be preserved for a
period of_______.
A. 5 years
B. 1 year
C. 3 years
D. 2 years
26. Soda lime glass: ______
A. Type I glass
B. Type II glass
C. Type III glass
D. General purpose soda-lime glass
27. Water attack test is intended for:
A. Highly resistant borosilicate glass
B. Treated soda-lime glass
C. Soda-lime glass
D. General purpose soda-lime glass
28. The general behavior of gasses with variations of
pressure, volume and temperature can be given by
the _____
A. Boyle’s law equation
B. Charle’s law equation
C. Gay-lussac law equation
D. Ideal gas law
29. Alcohol content of elixirs:
A) 15-18%
B) 10-40%
C) >60%
D) no alcohol content
30. Type of gelatin prepared from acid hydrolysis
A) Type A
B) Type B
C) Type C
D) Type D
31. BCS Classification with high permeability and low
solubilty?
A) Class I
B) Class II
C) Class III
D) Class IV
 BIOPHARMACEUTICS CLASSIFICATION
OF DRUGS
CLASS 1 INCREASE SOLUBILITY, DILTIAZEM
INCREASE PERMEABILITY
CLASS 2 DECREASE SOLUBILITY, NIFEDIPINE
INCREASE PERMEABILITY

CLASS 3 INCREASE SOLUBILITY, INSULIN

DECREASE PERMEABILITY

CLASS 4 DECREASE SOLUBILITY, TAXOL

DECREASE PERMEABILITY
32. Most preferred container for aerosols
A) Tin plated
B) Aluminum
C) Glass
D) Stainless stell
33. Government agency who issued national
identification card and purchase slip booklet to senior
citizen
a. BFAD c. OSCA
b. DILG d. DOLE
34. __________ is a list of drug which cure the vast
majority of illness, affordable and available to all
persons
a. EDL c. USP/NF
b. NDF d. None
35. Which of the ff. systems is referred to as “shear
thickening”?
a. Plastic c. Newtonian
b. Pseudoplastic d. Dilatant