Preps

4-6
Pamela Berilyn So, RPh, MSc
 Schedule
2 Discussion
6 Quiz 1, prep 4
9 Prep 6 & 5
13-16 pharmaweek
20 Submission, discussion
23 Prep 7/8, quiz on ointments
27-30 Easter Break
3 Prep 9
6 Quiz: Tablets
2nd SHIFTING EXAM
 Powders
•  Mixture of finely divided drugs and/or chemicals
in a drug form
•  Maybe finely subdivided, coarsely comminuted
product or product of intermediate particle size.
 Advantages
•  Flexibility of compounding
•  Good chemical stability
•  Rapid dispersion of ingredients
 Disadvantages
•  Time-consuming prep.
•  Inaccuracy of dose
•  Unsuitability for many unpleasant-tasting
hygroscopic & deliquescent drugs.
 Classification
1.  According to size
–  Coarse comminuted – very coarse, coarse
–  Finely subdivided – very fine, fine
–  Intermediate particle size
2.  According to use or manner of administration
–  Internal – ORS
–  External – dusting powder
 Classification
3.  According to manner of dispensing
–  Bulk powder
•  Dispensed in bulk quantities
•  Perforated/ sifter can external dusting
•  Aerosol container spraying into skin
•  Wide mouth glass easy removal of a spoonful of powder
–  Divided powder
•  Dispensed in single dose quantities
•  Usually folded in papers (i.e. Chartulae)
•  Dispensed in metal foil or small heat sealed or reusable
plastic bag or container
 Requirements in manufacturing of
powder
•  homogenous blending
•  must be of the most advantageous particle size
 Blending Techniques
•  Spatulation
–  Method by which small amount of powder
may be blended by the use of a spatula with
the powders on a sheet of paper or tile
–  Useful for solid substances that liquefy or
forms eutectic mixture (very little
compression or compaction)
–  Not for large quantities & potent products
 Blending Techniques
•  Trituration
–  Provides intimate blending of powders
–  Porcelain or ceramic mortar
–  Glass mortar
–  Wedgewood mortar
 Blending Techniques
•  Geometric Dilution
–  For mixing potent substances with a large
amount of diluents
–  Diluents added portion by portion
–  Ensures uniform distribution of the potent
drug
–  Recommended for potent products
 Blending Techniques
•  Sifting
–  Powders are mixed by passing them through
sifters like the type used in the kitchen to sift
the flour
–  Results in a light fluffy product
–  Not acceptable for incorporating potent
drugs into a diluents base

 Blending Techniques
•  Tumbling
–  For large scale
–  2/3 max volume
–  Method of mixing powder in a large enclosed
container rotated by a motorized process
–  Instruments: V-blender; Twin shell blender
 Comminution Techniques
•  Comminution – process of reducing particle size
with a finer state of subdivision

•  Micromeritics – study of particle size

 Comminution Techniques
•  Trituration
–  The substance is reduced to small particle by
rubbing it on a mortar with a pestle

•  Levigation
–  Particle size of a substance is reduced by
adding a suitable nonsolvent (levigating
agent) to form a paste. The paste is then
rubbed in a mortar and pestle
 Comminution Techniques
•  Pulverization with Intervention

–  With the aid of an additional volatile material
which can be removed easily after the
pulverization has been completed
 Comminution Techniques
•  Milling
–  Employed in large scale production
–  Mechanical process of reducing particle size of
solids before mixing with other components,
further processing or incorporation into final
product
–  Example of equipment used: a) Rotary cutter
b) Roller mill c)Fluid energy mill d) hammer mill

 Considerations in Comminution and
Blending of powders
•  Quantity or amount to be processed
•  Equipment available
USP standards for powders of animals
and vegetable drugs
Type of Powder Sieve size all Sieve size %
particles pass particle pass
through through
Very coarse (#8) #20 20% through
#60 sieve
Coarse (#20) #20 40% through
#60 sieve
Moderately coarse #40 40% through
(#40) #80 sieve
Fine (#60) #60 40% through
#100 sieve
Very Fine (#80) #80 No Limit
USP standards for powders for
chemicals
Type of Powder Sieve size all Sieve size %
particles pass particle pass
through through
Coarse (#20) #20 60% through
#40 sieve
Moderately coarse #40 60% through
(#40) #60 sieve
Fine (#60) #80 No Limit
Very Fine (#120) #120 No Limit
 Manufacturing procedure
1.  Triturate
2.  Weigh
3.  Blend
4.  Sieve
5.  Blend
6.  Tumble
7.  Pack
8.  Weigh
 Preparation #4 Oral Rehydration Salt
•  Oral rehydration therapy
– administration of fluid & electrolyte by mouth to prevent/
treat dehydration due to acute diarrheal disease
•  Diarrhea
– Normal physiologic body response to aid itself of a
noxious or toxic substance
– Increased frequency of loose watery stool
– Dehydration can be an outcome
•  ORS – effective in the treatment of patients with mild
volume depletion of 5-10% of body weight
 Advantages
•  OTC
•  Inexpensive
•  Diminished the incidence of complications
associated with parenterally administered
electrolyte solution

 Availability
•  Liquid
•  Powder in sachet form for reconstitution
•  Tablet to be dissolved

 Ingredients
•  Sodium chloride/ Potassium chloride – source
of sodium, potassium and chloride
•  Bicarbonate – Helps correct the subsequent
metabolic acidosis which is caused by diarrhea
& dehydration
•  Glucose – glucose transport is coupled with
sodium absorption
 ORS
Ingredient Amount Used Purpose
NaCl 1.6g Source of Na+, Cl-
KCl 1.5g Source of K+, Cl--
NaHCO3 1.5g For metabolic
acidosis
Anhydrous Glucose 36.4g Transport system
to increase Na+
absorption
 Guidelines for labeling
•  Electrolytes for ORS must be prepared in mEq.
•  Quantities of electrolytes admixture to patients
are usually expressed by the term mEq.
 Guidelines for labeling
•  Preparation of Label

Oral Rehydration Salts

Provides in 200mL solution
Sodium………………………mEq
Potassium……………………mEq
Chloride……………………..mEq
Bicarbonate………………….mEq
Anhydrous Glucose………g
 Guidelines for labeling
•  Direction for reconstitution must be indicated in
the labeling materials.
•  Each dose should be dissolved in sufficient,
freshly boiled, &cooled water to make 200mL
solution taking hygiene and precaution.
 Guidelines for labeling
•  Storage: Powder - tightly closed container
•  After reconstitution: Unused solution must be
discarded after 1hr.
•  Refrigerated: Maybe kept for 12-24hrs

 Computations
mEq= wt(g)
MW
hx1000
•  Example
NaCl = 1.6g
58.45
1x1000
= 27.37mEq
 Procedure
1.  Triturate the powders individually. Weigh the
powder
2.  Blend the powder for 15mins using trituration
method
3.  Pass the blended powder in sieve 40
4.  Reblend the powder using tumbling method
5.  Weigh and pack the powder
 Granules
•  Prepared agglomerates of smaller particles
•  Irregularly shaped & behave as single larger
particles
•  Make use of sieve #4-12
 Granulation
•  Pharmaceutical process that attempts to
convert powdered materials into aggregates
called granules
•  Large Scale: granulating machines – allows
granulation with or without moisture
•  Small Scale: Wet granulation
•  Powder + H2O à moist mass à sieve #4-12 à
wet granules à Drying (Oven/ Air) à Dry
granules
 Advantages over powders
•  Better flow property
•  More stable physically & chemically than
powders.
•  More easily “wetted” by a solvent than
powders. (faster to dissolve)
•  Seldom caking
 Special labeling information
•  Should indicate direction for reconstitution
•  Shelf life: 7-14days under refrigeration. Discard
whatever remains.
•  Shake well label
 Preparation #5 Phenoxymethyl Pen K
•  Granules for oral suspension
•  Penicillin G – Benzyl penicillin
•  Penicillin V – Phenoxymethyl
•  Oral Pen V K – Provides faster & higher blood
level than phenoxymethyl penicillin
•  A modified penicillin having C6H5OCH2 as radical
•  Relatively stable in the presence of gastric
acidity, soluble in duodenal fluids and orally
effective without buffer
 Pharmacologic Category
•  Antibacterial - Anti-infective agents derived
from natural source
•  Antimicrobial – From synthetic source
•  Anti-infective – Suppress/ destroy
microorganism (bacterial, fungi, virus)
•  Adverse effect
–  Hypersensitivity
–  Super infection
•  MOA
–  Inhibits the cell wall
 CGMP Requirement
•  Must be manufactured in a separate area from
non-penicillin
–  To prevent contamination
–  Maybe hazardous to personnel who are
hypersensitive to penicillin

 Formula
Ingredient Amount Used
Phenoxymethyl Penicillin K 25g
CMC 25g
Sucrose 12.5g
Sodium Benzoate 1g
Citric Acid 5g
Conc. Strawberry powder 1g
Lactose, qs. ad. 300g
Color qs.
•  For 1L suspension
 Procedure
1.  Mix the powders and blend for 15mins using trituration.
2.  Prepare a 20mL colorant solution & spray onto the
powder mixture w/ continuous trituration until moist
mass is formed.
3.  Pass the moist mass through sieve #12 & receive wet
granules in a tray.
4.  Oven dry granules at a temp not exceeding 40°C
5.  Dry the granules until nmt 2% moist is present. Check
the moisture content every 30mins.
6.  Weigh & pack the dried granules.
 Computation
•  Moisture Content
 Liquid Preparations
•  Homogenous and Heterogenous
•  GELOMAMI
–  Gel, Lotion, Magmas and Mil, Mixture
–  Lotion - External suspension
•  Dispersed system - dispersed phase and
dispersion medium
 Suspension
•  Preparation containing finely divided drug
particles distributed uniformly throughout a
vehicle
•  2 phase system
•  Vehicle – oily or aqueous (glycerin, water)
•  Suspensoid – 10-15 micrometers in size
 Characteristics of ideal suspension
•  Uniform particle size
•  No particle-particle interaction
•  Settles slowly/ No sedimentation
•  Redispersable
•  Pourable
•  Chemically stable
•  Acceptable to consumer
 Purpose
•  Sustaining effect
•  Stability
•  Taste
•  Basic solubility
 Forms
•  Ready to use
•  Oral suspension
•  Dry granules or dry powders for oral suspension
•  Reconstitute prior to use
•  “…. For Oral Suspension”
 Components
1.  Active Ingredient – Insoluble to vehicle
2.  Wetting agents
–  Displaces the air from hydrophobic material
–  Allows liquid to surround the particles and
provide proper dispersion
–  Surfactants in nature0.05–0.5%
–  HLB value 7 -9 (ex. Polysorbate – tween)
–  Example: Glycerin, Sorbitol
 Components
3.  Flocculating agents – Added if desired
–  Low concentration of electrolyte that is less
than 1%
–  NaCl, KCl induce flocculation


 Components
4.  Viscosity Agent – Suspending agent/ thickner
–  Natural – acacia, tragacanth
–  Synthetic – derivative of methylcellulose
Example: CMC, Avicel, Carbopol
–  For internal preparations – tragacanth &
acacia – 1.25%; CMC – 2.5%; Carbopol 934 –
0.3%
 Components
5.  Buffer – Drug has ionizable group to maintain
low solubility of drugs
6.  Preservative,
7.  Colorant,
8.  Flavorant
9.  Solvent
Preparation #6: Aluminum hydroxide
Magnesium hydroxide Oral Suspension
•  Antacid – Weak base react with gastric acid
–  Alkali adsorbent that neutralizes or
counteracts acidity
–  Aluminum - constipation
–  Magnesium – diarrhea

•  Drug-drug interaction – Tetracycline (Prevents
its absorption) Binds with tri/ bivalent cations
 Formula

Ingredients Amount used Purpose

Al(OH)3- Gel 7% Active Ingredient
Mg(OH)2 3%
CMCNa 2.5% Viscosity agent
Peppermint Oil 0.1% Flavorant
Na Saccharin 0.1% Sweetener
Na Benzoate 0.1% Preservative
Sorbitol Solution 20% Wetting Agent
Purified H2O, qs. ad. 100% Solvent
 Procedure
1.  Place Mg(OH)2 in a blender
2.  Add sorbitol solution
3.  Add purified H2O
4.  Blend the mixture for 5mins
5.  Add Al(OH)3 gel. Blend for 5mins.
6.  Place CMCNa in a mortar and pestle and triturate w/ 50mL H2O- until
paste is formed. Add CMC paste to blender.
7.  In a separate container, heat 200mL purified H2O to 50°C & dissolve
Na Saccharin & Na Benzoate. Cool the solution to 40°C.
8.  Add peppermint oil
9.  Homogenize the suspension for 5mins.
10.  qs. ad. Purified H2O
 Emulsion and Suspension

•  Similarities
–  2 phase system
–  Auxiliary label “Shake Well”
•  Differences
–  Dispersed phase
–  Emulsion 2 liquid phases.
–  Suspension 1 liquid, 1 solid phase.
 Next Meeting
•  QUIZ (prep 4-6)
•  Prep #4