BREX Pharmacy Review Center Phils., Co.

BREX Pharmacy Review Center Phils. Co. Manufacturing Pharmacy

Module V: Pharmaceutics (17.5%): • Manufacture, production, preparation,

Manufacturing Pharmacy propagation of drugs on a LARGE SCALE
BASIS (vs.) _______________________
Prepared, revised and updated by:
• Packing, repacking, or changing the
Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM
container, wrapper, or label of any drug
BREX Pharmacist-Review Lecturer in prep’n. for distribution

References for the Lecture: • The complete set of activities to produce

a drug that comprise production and
Ansel, Howard C, et. al., ed. Pharmaceutical quality control from dispensing of
Dosage Forms and Drug Delivery Systems. 7th ed. materials to the release for distribution
USA: Lippincott Williams & Wilkins. 1999. of the finished product
BREX Pharmacy Review Center Phils, Co. BREX (AO 43 s 1999)
Lecture Manual, power point presentations and Recall: Definition of Terms
lecture notes, compiled previous BREX modular
exams, pre-board exams and final coaching 1) API-
materials.

Gennaro, Alfonso, ed. Remington: The Science

Example of an API:
and Practice of Pharmacy. 20th ed. Philadelphia.
Mack Publishing Co. 2000

Katzung, Bertram G., ed. Basic and Clinical

Pharmacology. 9th ed. Philadelphia. 2004.

Limuaco, Olivia M. and Emma G. Pena.

Pharmaceutical Jurisprudence. 1988.
Philippines: Centro Escolar Univeristy.

Shargel, Leon. et al. Comprehensive Pharmacy

Review. 5th ed. USA: Lippincott Williams &
Wilkins.
Generic and Brand names:
I) Introductory Topics in Pharmaceutics
Pharmacologic Category and MOA:
Pharmaceutics is the general area of study that
Drug of Choice for:
is concerned with:
Premedication:
F
2) Excipients-
S
3) DDS-
M
4) Pharmaceuticals-
E
5) Drug Product-
of pharmaceutical dosage forms

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

Different Manufacturing Activities III-B) Drug Exporter –export products to

1) Primary manufacturing – manuf. of API (drug)
and Excipients (aka: __________ ex:
Polyethylene Glycol)
2) Secondary manufacturing – manuf. of
_________ (from APIs and excipients)
be distributed to other countries
III-C) Drug Wholesaler –acquires
products from local establishment distributed on
a wholesale basis
Departments of a Drug Establishment

3) Tertiary manufacturing – packaging, labeling, 1) RESEARCH Department

repackaging of BULK FP
2 important major functions:

A)
Drug Establishment
B)
-Involved in manuf, importation, repacking, &/or
Other functions:
distribution
• Handles research activities (market,
Types of Drug Establishment
pharmaceutical, chemical,
I) Manufacturer - refers to any establishment pharmacological, biological, clinical)
engaged in the operations involved in the
3 required Facilities:
production of a drug with the end view of
storage, distribution, or sale of the product L
I-A) Ethical manufacturers (ex: Jantoven, A
Inderal)
P
I-B) Proprietary
2) PRODUCTION Department
I-C) Biologicals Manufacturers (ex: Dengvaxia)
• receives materials and supplies
I-D) Veterinary Product Manufacturers
• oversees warehousing and storage and
I-E) Medical/Chemical shipping of the final product to
customers
I-F) ________________ – an arrangement
whereby a competent company processes raw • manufactures and packages products
materials or semi-finished goods, or packages
products for another company • exercises production, personnel,
labeling and packaging control.
Examples: __________ and __________
• ________________________________
II) Drug trader –__________________ of the
drug product (may subcontract to a toll) 3) QUALITY CONTROL Department

III) Drug Distributor • Heart and soul of drug manufacturer

III-A) Drug Importer –import products to • reasons for setting up the QC

other countries for distribution to local outlets department:

1)___________ 2)___________

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

Functions of the QC Dept 5) ENGINEERING Department

S • Locates, installs, maintains and repairs

equipment
A
6) PURCHASING Department
R
7) MEDICAL Department
S
• conducts physical and medical
4) QA Department
examination of new employees
• assures all operations meet the require
• oversees the medical treatment of
stds of safety and efficacy
employees
• -responsible for the preparation of SOPs
• performs clinical studies and prepares
• -quality–audit and monitoring literature and package inserts

• cGMP Overview: Drug Product Development

Operational Definition of Terms 1. Drug Discovery and Design

a) QA: Quality Assurance

The sum total of the organized
Lead Compound:__________________
arrangements made with the object of
ensuring that products will be 2. Pre-Clinical Studies
consistently produced of the quality
a) Animal Testing
required by their intended use
Drug Test Animal
Glucagon and
b) QMS : _____________ is a set of
Atropine
policies, processes and procedures
Digitalis
required for planning and execution
Insulin,
(production / development / service) in Tubocurarine
the core business area of a and Meticurine
pharmaceutical manufacturing company injections
Oxytocin
c) cGMP: ____________________ Heparin
Part of quality assurance which ensures Protamine
that products are consistently Sulfate
produced and controlled to the quality PTH
standards appropriate to their intended
use (WHO, 2007) b) Pre-formulation studies

d) QC: Quality Control c) Pilot Production

Part of cGMP concerned with sampling,
3. INDA
specifications and testing and with the
organization of document and release
procedures

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

4. Clinical Trials 9) _____________ Department – ensures

compliance of the company and its products
Phase1: Safety in _________ healthy human
with all pertinent regulations and laws about
volunteers
drugs and their marketing
• ideal dosage range
“safety of the company’s products”
• Pharmacokinetics
Other operational definition of terms:
• Pharmacodynamics
Batch – specific qty. of drug/other mat’l.
• Pharmacogenetics intended to be homogenous in character and
quality, produced during the same single cycle of
[N-acetyltransferase (NAT): manufacture → bulk product
Isoniazid]
Lot – a specific identified portion of a batch
Phase 2: To check for ________ of new drugs
Batch/lot number –
• broader range of toxicities
Importance: a) identifies a single batch/lot
• ________________ Px with disease
b)
Phase 3: safety and efficacy
A) Ex of drug withdrawn in the market by the
• side-effects especially with long-term FDA:
use

• clinical pharmacology

• 2000 – 3000 patients with the disease

5. NDA

Purpose of NDA is to gain permission to

market the new drug Generic and Brand names:

6. Post-Marketing Surveillance Pharmacologic Category:

Therapeutic Indication:

Why was it withdrawn in the market?

B) A) Ex of a batch of food withdrawn in the

market by the FDA: Nagaraya.
8) MARKETING Department
Documents
-promotes the maximum volume of sales of
products – Establishes what to do

-provides professional service through – Provide audit trail

intelligent presentation
-handles advertising through
professional journals
Master formula record
direct mail
-contains the formulation, specifications, and
manufacturing processes

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM


Type of Documents
• Standard Operating Procedures (SOPs)
–______________________ for
performing operational tasks/activities
• Manufacturing Order –is a document
which just gives instructions to the
production dept to produce a products
• ______________________ –addition of
an active in an unstable preparation to
compensate for the loss during
manufacture
Quarantine –an area that is designated or set
aside for the holding of an incoming
components prior to accept testing and
qualifications for used (Yellow)
Validation is a documented evidence that a
system does what it is supposed to do
1) Accuracy
2) Precision
3) _________– ability of assay to
discriminate between small differences
in analyte concentration
4) Specificity – ability of assay to
differentiate and quantify the intended
analyte in the presence of other
components expected to be present in
the sample
5) Linearity – measured test results are
directly proportional to the
concentration of the analyte in the
sample within a range of the analyte
concentration
6) ________ – measurement of an assay’s
tolerance to small perturbations in one
or more components in the assay
systems
Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM
BREX Pharmacy Review Center Phils., Co.
________ ________ for Finished Products
A) One year after the expiration date of
the product
OR
B) 3 years after the distribution of the
product
PACKAGING –economic way of protecting,
preparing, identifying and containing the drug
product
Containers
Primary
• immediate contact; direct effect on
stability of product
• may provide means of administration
• (Inhalers, Bottles, Strip packs, Blister
packs)
Secondary
• additional protection, avenue for
________ (Boxes, Pallets)
Classification of Containers
I) According to Protection Ability
1. Well-Closed Container
• protects against extraneous solids
and loss of drug under 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 and
loss of drug under ordinary
conditions of handling, shipment,
storage and distribution
3. Hermetic Container
• impervious to air or any other gases
under ordinary conditions of
 BREX Pharmacy Review Center Phils., Co.

handling, shipment, storage and IV) According to Material it is Made

distribution
• generally sterile 1. Glass
4. Light Resistant Container – Most widely used
• protects the contents from – Major component: _____________
photochemical deterioration
• amber, opaque, blue Advantages
II) According to Safety Packaging
– Strong
1) Child Resistant Containers
– Rigid
-difficult for children under 5 years old to open
– Adequate moisture protection
within a reasonable amount of time
– Ease of reclosure
Principle involved:
_______________________________________ – Economical
_______________________________________
Disadvantages:
Designs:
– LEACHING vs SORPTION
i) Push/Press and then turn
– Fragility
ii) Squeeze and turn
Types of Glasses:
2) Tamper Resistant Container
Type General Uses Test
Principle involved: Uses an indicator which if Description
breached or missing provides visible evidence to
consumers that tampering has occurred I for
buffered
Examples: and non-
buffered
• Blister packs
parenteral
• Tape seal: do not accept if seal is
broken II

• Aerosol container: the only III

______________ tamper resistant NP other
packaging products
III) According to Quantity Held except
parenteral
1. Single-Unit
A) Powdered glass test

-performed on powdered glass

2. Multiple-Unit -challenges the leaching potential of the interior

of glass

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

-possibly leached alkali titrated with 0.02 N Polypropylene (Pwedeng Painitan )

H2SO4 (indicator: ___________) after autoclaving
- Autoclavable
the glass with high purity H2O
Polyvinyl Chloride
B) Water attack test @ _________ deg C
- Rigid & good clarity
-type II only
- blister packaging
-challenges only the intact surface of the glass
3. Metal
C) Surface glass Test

-all types
4. Rubber
-tests leaching of glass if filled to its filling vol. ,
titrant: 0.01 M HCl

2. Plastic 5. Paper & Board

• does not apply to a single material but Other container materials:
rather to a vast number of materials each
developed to have desired features Liner
• adv.: lightweight, flexibility, resistance to
impact
• disdv: permeability, leaching, sorption, Inner Seal
transmission of light, alteration of container
upon storage
• two types: Rubber Stopper
Thermoplastic – squeezy

Thermoset – firm & rigid

Coil
Examples:

Polyethylene (PE)
Desiccant
- cannot be autoclaved

- Low-density – droppers & sprays

Package Insert
- High-density – solid oral prepns
Types of Paper:
Polyethylene Terephthalate (PET)
• Bond paper
- For beverages
– No moisture resistance
- APETG (amorphous PET glycol)
– opaque
- PETG (PET glycol)
• Vegetable parchment
- have transparency and luster
– Limited moisture resistance
- Gamma radiation sterilization
– Thin, semi-transparent

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

• Glassine Dapsone

– With moisture resistance DOC for:

– For volatile drugs CA:

• Waxed paper AEs:

– Waterproof Storage Temperatures of Pharmaceutical

Products
– For volatile, _____, _____,
_____ drugs Term Condition
AO no. ______: Labeling Requirements Cold Place
1) Name of the product a. Freezer
2) Dosage form
3) Pharmacologic category
b. Refrigerator
4) Rx symbol for prescription drugs
5) Name and address of the
Manufacturer, Packer, or Distributor
6) Net content Cool

– PRINCIPAL DISPLAY PANEL Room

Temperature
7) Formulation

8) Indications *Controlled
Room
9) CI(s), Precation(s), Warning(s) Temperature
10) Direction(s) for use Warm
11) Batch / Lot No(s) Excessive Heat
12) Expiation date

13) Registration No (DR# _________) II-A) Unit Processes Involved in the

14) Proper storage conditions Manufacture of Solid Dosage Forms

A) Dispensing

B) Milling

C) Mixing

D) Granulation

E) Tableting

F) Coating

G) Encapsulation

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

A) Dispensing 2) COMPRESSION

• Like mortar and pestle  reduction of

particle size

2a) END RUNNER MILL

B) Milling
• weighed pestle is turned by friction of
Classification of Size Reduction Equipment
material passing beneath it as the
I) Crusher mortar rotates

– Edge runner mill, end runner 2b) EDGE RUNNER MILL

mill.
• -pestle equivalent (muller) mounted
II) Grinder horizontally

– (1)Impact mill: Hammer mill. • -the size reduction is done by ________

due to heavy weight of the mechanical
– (2)Rolling-compression: Roller wheel
mill.

– (3)Attrition mills: Attrition mill.

– (4)Tumbling mills: Ball mill.

III) Ultrafine grinder

– Fluid energy mill.

IV) Cutting machine 3) IMPACTS

– Cutter mill. • Involves __________ of materials
Methods of Milling 3a) HAMMER MILL
1) ROTARY CUTTER MILL • consist of four or more hammer placed
• Size reduction occurs by fracture of on a central shaft and enclosed within a
particles between 2 set of knives rigid metal

• used for ___________ active

pharmaceutical ingredients and
medicinal plants

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

3b) FLUID ENERGY / JET MILLING aka C) Mixing

M______________
• Process of putting together ingredients
• Drug particles are swept and reduce into in one mass
violent turbulence by supersonic
• Objective: to obtain uniform dosage
velocity of air steams
units
• Application: R_____________________
2 Types of Mixing
4) ATTRITION
a) BATCH TYPE (V-Blender, Double Cone Blender,
• ____________ action between 2 Sigma Blade Mixer, Ribbon blender)
surfaces
• -all ingredients are loaded and mixed
4a) ROLLER MILL together

• 2 cylindrical rolls mounted /horizontally • -output: kg/batch

and rotated
Exs:
• Used to reduced the particle size of
a1) Sigma Blade Mixer for __________________
powders in ______ mats.
a2) V-Blender for_________________________

b) CONTINUOUS TYPE

• -ingredients are continuously charged

into the mixer

• -for _________ volume products

• -output: kg/hour

D) Granulation

Granulation – any process of powder size

enlargement to granules, rendering them into a
freely flowing state

• Granules – aggregates of
4b) VIBRATION MILL
powders adhered to each other
• -filled to 80% with balls and then the forming larger unit particles
mills is vibrated
• Granules improve: flowability
5) Combined Impact and Attrition and compressibility

• ____________– Narrow cylinder Types of Granules

rotated on its horizontal axis w/c
• Good granules”
contains balls that occupy 30-50 % of
volume – pass through sieve#20 but not
through sieve#40

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

• “Fines” Steps:

– pass through sieve#40

– used to fill interparticulate

space

– limit to ______% of the

granulation

Reasons for granulation

• Improve flowability and compression of

solid mixtures 2) DRY Granulation
• Prevents segregation of components • “aka: ____________________”
• Allows good uniformity of dose • Eliminates wetting and drying step
• Allows accurate dispensing • Powder is mixture is compacted large
pieces (slugs) and subsequently broken
• Reduce dust in manufacturing
down into granules
• Easier wetted than powders
• For moisture- and heat-sensitive
Methods of Granulation ingredients (ex. _________ and Vitamin
B family complex)
1) WET (:P) Granulation
• Disadvantages
• Most commonly used method because it
produce tablets of best quality – suitable only if tablet
ingredients have some inherent
• Wetting powders allow for good chances
flowability and compressibility
of making granules with good flowability
already
& compressibility
– dusty
Disadvantage:
2 Methods under Dry Granulation
• costly and involves too many no.
of separate steps

• more time and labor required

• NOT for heat and moisture

sensitive

NOTE:

• Granulating liquid aka Binder:

solution is added to turn the
powders to a single wet mass

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

3) Direct Compression Types of Tablet Press

I) Single punch/eccentric tablet press

• -200 tablet per minute

II) Rotary, multi station tablet press

4) Fluid Bed Granulation • -____________ tablets per minute

Requirements for Tableting

1)

3 Major Qualities of Good Granulation 2)

a)

b) Problems Encountered During Tablet Formation

c) • _______________–discharge takes
place only above the hopper outlet

• Bridging/arching –arch shaped

E) Tableting
structure above the hopper outlet
Principle involved: _______________ of the
• Flooding – continuous, unstoppable
formulation within a steel die cavity to the
flow
pressure exerted by the movement of 2 steel
punches TABLET EXCIPIENTS

Parts of Tablet Press

1) Hopper

2) Punches

Upper punch

Lower punch

3) Cam tracks
1) Diluents/Fillers
4) Dies

5) Feed shoe/frame

6) Receiver

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

Low Moisture Content Diluents 4) Anti-Frictional Agents (GAL)

1) Dicalcium Phosphate G- enhances Flow of Granules

2) Lactose principal bulking agent
3) Anhydrous Lactose
Intermediate Moisture Content Diluents
1) Mannitol diluents for _________
sensitive drugs
2) Dextrose
Ex. talc, corn starch, colloidal silica, calcium
silicate, calcium phosphate, Zn, Mg, and Ca
stearates
A- Prevents the adherence of granules to the
Punches
Ex. colloidal silica, corn starch, sodium lauryl
sulfate, stearates

3) Monocalcium Phosphate L- Decrease friction of tablet’s surface with the

die wall; avoids wear and tear.
High Moisture Content Diluents
Ex. talc, magnesium stearate, and calcium
1) __________________ stearate
2) __________________ Generalizations on Tablet Excipeints

a)
2) Binders/Adhesives b)

c)

d)
3) Disintegrants Important Brand Names in the Manufacturing
Practice

a) NUTAB

b) AVICEL

c) CAB-O-SIL

d) VEGETEL

5) Adsorbents

adsorb fluids and moisture, keep products

dry

ex. magnesium oxide, magnesium carbonate,

bentonite, silicon dioxide

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

6) Colorants 8) Sweetening Agents

Colorants FD&C Number Color and Natural:
to
other notes • sucrose (sugar cane, sugar beet,
remember
sugar maple)
• honey (Apis mellifera)
Tartrazine #5 Yellow
• stevia (Stevia rebaudiana)

Amaranth #2 _________
Artificial:
Sunset #6 Yellow • saccharin – has bitter aftertaste
Yellow • aspartame – methylester
dipeptide of phenylalanine and
Yellow N/A A pigment used aspartic acid; contraindicated to
Ferric as a component phenylketonurics
Oxide for external • acesulfame K – used more in
applications confectionary

Functions:
F) Tablet Coating
a) For product identification
b) For aesthetic purposes A. Sugar-coating

• successive addition of sucrose-

2 Major Types:
based solutions to a tablet core
a) Dyes
b) Lakes
3 Processes
Classification according to use:
1. Pan Coating – most widely-used
FD&C
D&C 2. Pan Spraying
external D&C
3. Pan Suspension
7) Flavorants

Steps in Sugar-coating

1. Sealing / Waterproofing

2. Subcoating

3. Syruping / Smoothing

4. Finishing

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

6. Sweetener, Flavor and Aroma

Ex. vanillin, saccharin

5. Polishing

7. Glossant

Ex. beeswax
B. Film-coating

The process of placing a thin, skin-tight coating

8. Volatile Solvent
of a plastic-like material over a tablet core
Ex. alcohol-acetone mixture
adv.: no significant increase in tablet size and
weight unlike sugar-coating

About 2-5% increase in thickness only C. Enteric-coating

Materials for Film Coating Ex. shellac, HPMC

1. Film Former

Examples: Spansule
Cellulose acetate phthalate Major Tablet Processing Problems
Hydroxypropyl methylcellulose (HPMC) 1. Capping

2. Chipping
2. Alloying Substance
3. Lamination
Ex. polyethylene glycol (PEG)
4. Picking

3. Plasticizer 5. Sticking

Ex. castor oil 6. Mottling

7. Weight Variation
4. Surfactant
8. Hardness Variation
Ex. Spans & Tweens
9. Blistering

5. Opaquant & Colorant 10. Wrinkling

ex. TiO2, FD&C 11. Bridging

12. Sweating

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

13. Orange-peel • formed and sealed in a single

manufacture process
14. Flaking • plate process
• rotary or reciprocating die process
15. Blooming Materials for Capsule Shell Making

16. Spotting 1. Gelatin

• partial hydrolysis of collagen from animals

VII) Encapsulation
• types: Gelatin A & B
CAPSULES

Capsule
2. Plasticizer
• solid dosage form in which one or more
medicinal and/or inert substances are • for elasticity & flexibility
enclosed within a small edible shell usually • glycerin, sorbitol
made of gelatin

3. Colorants
Types of Capsules
• FD&C
1. Hard Gelatin Capsule (HCG)

• aka: Dry Filled Capsule 4. Preservatives

• has 12-15% or 13-16% moisture
• gelatin shells are manufactured in a • 0.15% sulfur dioxide
separate process (dipping pegs made of
manganese bronze in a melted gelatin
5. Opacifying Agent
mixture)
• shell composed of: • titanium dioxide
1. gelatin
2. water
3. sugar *For large scale, glidants, lubricants and
4. colorants surfactants may also be employed.
5. 0.15% sulfur dioxide
6. titanium dioxide Capsule filling steps
• has 2 parts: body and cap/head 1. Supply
• has 8 sizes (5 to 000)
2. Soft Gelatin Capsule (SCG) 2. Rectification

• has 6-10% moisture 3. Separation

• rendered plastic-like with the addition
4. Filling
of plasticizers (glycerin or sorbitol)
• oblong, oval, spherical, tube, pearl, 5. Joining
suppository-type
• filled with pumpable solutions, 6. Finishing ( Dedusting/Polishing)
suspensions, pasty material or powders

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

III) Manufacture of Semi-Solid Dosage Forms Methods of Manufacture:

A) OINMENTS A) Incorporation – mixing/levigating until

uniform
• From the Latin word “Unguentum”
(ung.) Equipment: Ointment roller mills

• Semisolid dosage forms for external

application to skin or mucous
B) ____________ – involves melting of some
membranes, either medicated or
components, mixing,then cooled with constant
nonmedicated
stirring until congealed
Types of Oinment Bases
Equipment: Large steam-jacketed kettles
1) Oleaginous/HC bases – greasy, difficult to
Preservation:
remove, most stable
(-) from Staphylococcus aureus, Bacillus subtilis,
– Petrolatum
and Pseudomonas aeruginosa
– Yellow ointment
B) GELS
– _______ (aka liquid petrolatum)
Dispersion system composed of small or large
2) Absorption bases molecules dispersed in a liquid vehicle rendered
jelly-like by the addition of a gelling agent
– Either anhydrous or hydrous
bases capable of absorbing • Contain gelling agents – polymers
water
– Proteins – gelatin
– W/O emulsion
– Complex carbs – celluloses,
– Hydrophilic petrolatum, anh. starches, gums
Lanolin, cold cream (cetyl esters
– Synthetic – ex. Carbomer
wax)
Carbomer swells in water in the presence of
3) Water-removable
alkaline substance (Ex: _____________)
– O/W emulsion
Quality-Control Tests for Semi-Solid Dosage
– Allows absorption of serous Forms
discharges
• Spreadability
– Most common ointment base
• Texture and feel
– Ex: Hydrophilic ointment
• Melting range
4) Water-soluble
• Irritancy testing
– Completely water washable
• Metal particles (ophthalmic)
– Ex: _________
• FPQC: __________________ – applied
to containers with contents nmt 150 g or
150 mL

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

IV) Manufacture of Liquid Dosage Forms 7) Flavors, sweeteners (syrups, etc.), colors,
odorants
Advantages:

• Easier to administer

• More economical

• More bioavailable

Disadvantages

• Less stable

• More prone to microbial growth

• Greater inaccuracy in dosing

A) SOLUTIONS

Common Components of Solutions

Methods of Preparing Solutions
1) Active/s
1. Simple solution
2) Solvent/vehicle – water or hydroalcoholic
usually -

3) Buffers/pH adjusters Ex: _______________________

– WAs/WBs, their salts; 2. Solution by Chemical Reaction

– most common pH range for oral -prepared by reacting 2 or more solutes w/

prepn’s: _______________ each other in a suitable solvents.

4) Viscosity enhancers – generally polymers: Ex: Aluminum Sub-acetate Topical Soln.

gums, celluloses, sugars, gelling agents 3. Solution by Extraction
5) Stability enhancers -vegetable or animal origin extracted by
Preservatives water or w/ water containing other substances.

Parabens, benzoates, alcohols, phenols, General Method of Manufacture for Liquids:

benzalkonium Cl (quats), thimerosal (mercurial) Mixing Tank Equipment
Antioxidants

Vit. C & E, BHA, BHT, Na and K sulfites

Chelating agents

EDTA, citric acid, tartaric acid

6) Humectants – prevent __________

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

B) EMULSIONS

2 Phase L-L System

Surfactants – organic cpds. with surface-active

polar grp.

Types:

1) Anionic
Advantages:
– Polar part (-) charge
• Improved disso and BA of poorly
soluble drugs – Good foamers

• Effective masking of tastes within the – Sensitive to water hardness

dispersed phase – Ex. Soaps, SLS
• Control of absorption rate 2) Cationic
Types: – Poor foamers, no washing
• O/W or W/O ability

• Mixed emulsion (ex. O/W/O, W/O/W) – Polar part (+) charge

• Microemulsion – Ex. ________ Cl

Equipment for manufacturing emulsions: 3) Nonionic

colloid mills, homogenizers, ultrasonic devices – Uncharged polar part
Method of Manufacture for Emulsions: – Not sensitive to water hardness

– Ex. Cetyl alcohol, cocamide DEA

4) Amphoteric

– Both anionic and cationic

– Ex. _________________

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

Instabilities of an Emulsion General QC tests for Liquids

• Sedimentation • Viscosity

• Creaming • Bulk volume

• Breaking/Cracking • pH

• Phase Inversion –o/w to w/o or vice • organoleptic

versa
• microbial tests
C) SUSPENSIONS
• FPQC: ________
2 Phase: S-L system
– Tests if oral liquids can deliver
Added formulations: the amount stated on the label

Suspending agents – viscosity enhancers – For containers nmt 250 mL

-Oral – NaCMC, tragacanth, acacia, guar gum, V) Manufacture of Sterile Dosage Forms
xanthan gum
STERILE DOSAGE FORMS
-Topical – carbomer (Carbopol®)
a) “Parenteral”
Wetting agents (usually 0.05-0.5%) – allow
-injectable routes of admin. (ex. IV, IM, SC)
displacement of air from hydrophobic material
-IV: 100% BA because _____(?) _____
-HLB value of: _____
-__: most vaccines such as Dengvaxia
-Glycerin, PEG, Syrup
-__: insulin
Flocculating agents (usually <1%) – electrolytes
(ex. NaCl, KCl) b) Ophthalmic preparations
General Manufacturing Steps for Suspension: C) Irrigation solutions

2 Major Requirements

1)

2)

Pyrogens –fever-causing agents

Sources of pyrogens:
Instabilities of a suspension: – Water
• Caking – Containers
• Settling too rapidly – Equipment
• Solubilization of dispersed phase – Solutes (processed with water
not depyrogenated)
• Polymorphism

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

Destruction/Conditions of pyrogens: General Formulation for Sterile Dosage Forms:

– 180°C for 4 hrs A) SOLVENT

– 250°C for 45 mins AQUEOUS SOLVENT

– 650°C for ______ – WFI

• not required to be
sterile but required to
be pyrogen-free

• no added substances

• used in products that

are sterilized after
preparation

– SWFI – sterile and pyrogen free

– BWFI – contains 1 or more

antimicrobials

– NaCl injection USP

– Ringer’s injection (NaCl, KCl

and ______)

Advantages of parenterals: – Lactated Ringer’s USP

(+Sodium ______)
a) 100% absorption
NON-AQUEOUS SOLVENT
b) Can be given to unconscious px
A) Fixed Oils
c) The only way to correct blood vol
Se
d) Capable of most immediate action
Co
Disadvantages of parenterals:
Co
a) Painful
Pea
b) Requires skill and aseptic technique
B) Solvents
c) Risk of acute tissue toxicity
Benzylbenzoate
d) Difficulty to correct error
Ethylolate

Isopropyl myristate

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

B) SOLUTES Additional notes:

At least __________ grade with acceptable

solubility

A) Antioxidants

To minimize or prevent degradation of

parenterals

Categories

Lipid Soluble: Tocopherols, BHA

Water Soluble: Vit C, Citric acid, Tartaric acid,

Phosphoric acid and Sodium metabisulfite

B) Chelating agents

C) Buffers

Acetic acid or Citric acid and their respective

salts

D) _____________________

Minimize pain in areas with NERVE ENDINGS

-Sodium Chloride

-Sodium Sulfate
Methods of Sterilization
-Dextrose
• Moist heat (autoclave)
E) Antimicrobials
• Dry heat (Oven)
-Benzalkonium chloride
• Tyndalization (Intermittent steam
-Benzyl alcohol sterilization)
-Parabens • Gas sterilization (EO)
Propyl paraben • Filtration (Membrane filter)
Methyl paraben • Ionizing radiation (Gamma and
Cathode rays)

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM

 BREX Pharmacy Review Center Phils., Co.

I) Moist heating / Steam Sterilization VI) Tyndalization

(Autoclave)
MOA: Intermittent steam
Conditions: _______________ sterilization exposing the materials to 100 deg C
for 30 mins or at 80 deg C for 1 hour for 3
MOA: _______________
consecutive days
II) Dry heating (Oven)

Conditions: 160-170 deg C for 2-4 hours

MOA: _______________

Application:

-useful for: heat stable subs

- useful for: glasswares

III) Filtration (Membrane Filter)

MOA: _______________

Application:

-useful for: parenterals sensitive to heat

IV) Ionizing Radiation (Gamma and Cathode

Rays)

MOA: Mutation

Application:

-useful for: AQ and Non-AQ injection

with heat sensitive substances (Hormone
Vitamins and Steroids)

V) Gas Sterilization (Ethylene oxide,Propylene

oxide)

MOA: _______ of essential metabolites

Application:

-useful for: dry materials. Hospital and

medical supplies, equipments, hospital rooms
and packaged products

Prepared by: Mr. Jerico Isaiah S. Dumbrique, RPh, MCEM