Table 1.

1 llisage forms available for different

administration routes

Administration Ibsage forms

route
Q-al Solutions, syrups, suspensions,
emulsions,geIB,powders,
granules, capsules, tablets
Rectal Supposrtories, ointments, creams,
powders, solutions
Topical Ontments, creams, pastes, lotions,
geIB, solutions, topical aerosoIB,
foams, transdennal patches
Parenteral Injections (solution, suspension,
emulsion forms), implants,
irrigation and dialysis solutions
Respiratory krosoIB (solution, suspension,
emUIBion, powder forms),
inhalations, sprays, gases
l'bsal Solutions, inhalations
Eye Solutions, ointments, creams
Far Solutions, suspensions, ointments,
creams
Table 1.2 Variation in time of ons et of action for
different dos age forms

Tune of ons et llis age forms

of action

Seconds Intravenous injections

Mnutes Intramuscular and subcutaneous

injections, buccal tablets, aerosols ,
gases
Mnutes to Short-term depot injections ,
hours solutions, suspensions, powders,
granules, capsules, tablets,
modified-release tablets
Several hours Fnteric-coated formulations
Thys to weeks Thpot injections, implants
\aries Topical preparations
 Ga s troi nte stin a I
Skin
trac t

Ora l Bu cca l ~
Top ica l
---.. Mo uth -
pre par atio ns -::;; ~
Sub cut ane ous injection
Dir ect
or " Intramuscular injection
Sto ma ch ~ ~

hep ato - Cir cul ato ry

ent eric sys tem Res pira tory
Sm all (drug or trac t
-:::;:: ~
inte stin e me ta bot ites )
Aer oso ls
-:;;: ~
Lar ge -:::;:: ~ -
Ga s es
inte stin e
-- --- -- -- --- -
Rec tal
- Intr ave nou s injection
Re cta l ---.. Rec tum - f---. p

pre par a tions Dru g or

met abo lite
in tiss ues ,
ext rac ellu lar
Dru g in fluids and
lym pha tics
fae ces I Kidneys
I
Dru g or me tab olit es Dru g or me tab olit es in
rn unn e air, etc .
,, s aliva , ex.haled

I Exc reti on

i
I Elimination I
'
Table 1.3 Properties of drug subs tanc es important
in dosage form design and potential stres ses
occurring during proc esse s, with range of
manufacturing procedures

Properties Processing rvhnufacturing

stresses procedures
Particle siz.e, Pressure Precipitation
surface area
~cha nica l Filtration
Particle surface
Radiation Emulsification
chemistry
Exposure to Mlling
Solubility
liquids
llssolution Mxing
Exposure to
nying
Partition gases and
coeff icient liquid vapours 0-anulation
Ionization constant Temperature Compaction
Gy,stal properties, Aitoclaving
polymorphism
Gy,stallization
Stability
Hlndling
0-ganoleptic
Storage
~lec ular weight
Thlnsport
Table 2.1 Factors affecting in-vitro dissolution rates of solids in liquids

Term in N)yes-\\hitney equation (Eqn 2.4) Affected by

A surface area of undissolved solid Size of solid particles (A increases with particle size reduction)
(Rate of dissolution increases proportionally with Ilspersibility of powdered solid in dissolution medium
increasing~ Porosity of solid particles
Cs: saturated solubility of solid in dissolution 1nedium Temperature
(Rate of dissolution increases proportionally with Ntture of dissolution medium
increasing difference between Cs and C Thus high lvblecular structure of solute
C, speeds up dissolution rate) Oystalline form of solid
Presence of other compounds
C: concentration of solute in solution at time t \blume of dissolution medium (mcreased volume
(Rate of dissolution increases proportionally with decreases C)
increasing difference between Cs and C Thus low C lny process that removes dissolved solute from the
speeds up dissolution rate) dissolution medium (hence decreasing C)
k: dissolution rate constant nflusion coefficient D of solute in the dissolution medium
\is cos ity of medium

h: thickness ofboundary layer Thgree of agitation of dissolution medium (mcreased agitation

(Rate of dissolution decreases proportionally with decreases boundary layer thickness).
increasing boundary layer thickness)
Table 2.2 Thscriptive solubility: IBP and PhEur terms for describing solubility

Ths criptive term Parts solvent to 1 part solute (approximate weight Solubility range
of solvent (g) necessary to dissolve 1 g of solute) (mg mL- 1)

\ery soluble less than 1 > 1000

Freely soluble 1-10 100-1000

Soluble 10-30 33-100
Sparingly soluble 30-100 10-33
Slightly soluble 100-1000 1-10
\ery slightly soluble 1000-10000 0.1-1
Practically insoluble* rvbre than 10 000 <0.1

)f(Jhis term is absent from the Phllir.

Table 2.3 The effects of additives on critical solution temperature (CS1)

Type of CST Solubility of additive in each component Bfect on CST Fffect on miscibility

l.pper Ppprox. equally soluble in both components lowered Increased

l.pper Readily soluble in one component but not in other Raised Thcreased
lower Ppprox. equally soluble in both components Raised Increased
lower Readily soluble in one component but not in other lowered Thcreased
Table 5.1 Types of disperse systems

D.s pers ed phase D.s pers ion medium l'hme Examples

liquid Gis liquid aerosol Fogs, mists, aerosols

Solid Gis Solid aerosol Smoke, powder aerosols

Gis liquid Foam Foam on surfactant solutions

liquid liquid Emulsion Mlk, pharmaceutical emulsions

Solid liquid SoL suspension Silver iodide soL aluminium hydroxide suspension

Gis Solid Solid foam Expanded polystyrene

liquid Solid Solid emulsion liquids dispersed in soft paraffin, opals, pearls
Solid Solid Solid suspension Pigmented plastics, colloidal gold in glass, ruby glas
Table 5.2 Comparison of properties of lyophobic and lyophilic sols
Property Lyophobic
Bfect of \ery sensitive to added electrolyte, leading to
electrolytes aggregation in an irreversible manner. Thpends on:
(a) type and valency of counter ion of electrolyte,
e.g. with a negatively charged sol la3+ > :ai2+ > Ni+
(b) Concentration ofelectrolyte. It a particular
concentration sol passes from disperse to aggregated
state. For the electrolyte types in (a) the concentrations
are about 10-4, 10-3, 10- 1 moldm-3 respectively.
These generalizations, (a) and (b), form what is
known as the Schulz.e-I--hrdy rule
Stability Controlled by charge on particles
Formation of Ilspersions usually of metals, inorganic crystals,
dispersion etc., with a high interfacial surface-free energy due
to large increase in surface area on fonnation. A
positive ~Gof formation, dispersion will never form
spontaneously and is thermodynamically unstable.
Particles of sol remain dispersed due to electrical
repulsion
\1scosity Sols of low viscosity, particles unsolvated and
usually symmetrical
Lyophilic
aspersions are stable generally in the
presence of electrolytes. tvhy be salted out by
high concentrations of very soluble
electrolytes. Bfect is due to desolvation of the
lyophilic molecules and depends on the
tendency of the electrolyte ions to become
hydrated. Proteins more sensitive to
electrolytes at their isoelectric points.
Lyophilic colloids when salted out may appear
as amorphous droplets known as a coacervate
Controlled by charge and solvation of particles
~nerally proteins, macromolecules, etc.,
which disperse spontaneously in a solvent.
lnterfacial free energy is low. There is a large
increase in entropy when rigidly held chains
of a polymer in the dry state unfold in
solution. The free energy of formation is
negative, a stable thermodynamic system
Uually high. It sufficiently high concentration
of disperse phase a gel may be formed.
Particles solvated and usually asymmetric
Table 5.J Oassifica tion of surface-a ctive agents
Anionic

OSO j Na+ S0 3 Na +

Alkyl s uUate t-Jkyl>enzene sullonate

Cationic

ftJlc)'itrimethylammooiun broon1e !&~u m chloride

Zwitteri onic

CH3
I
N+ - CH COO-
I i
CH3 0

-k~ r O- P- 0
II
J 0

Alkyl betaine Phosphatidylcbolile (lecidm)

Nonioni c

Alcohol ethoxylate Pol)oX)ethy.ene-pol)UXwropy.ene-pol)OX)ethy.ene block

copolymer
Table 5.4 Emulsifying waxes

Product al-soluble Water-soluble

component component

Fmulsifying Cetostearyl Sodium lauryl

wax (anionic) alcohol (dodecyl) sulfate

Cetrimide Cetosteacyl Cetrimide (hexadecyl

emulsifying alcohol trimethyl ammonium
wax (cationic) bromide)

Cetomacrogol Cetos tearyl Cetomacrogol

emulsifying alcohol (polyoxyethylene
wax (non-ionic) monohexadecyl ether~
Table 5.5 Go up contributions to HIB values

G-oup Contribution
SQ Nt +38.7
+21.1
+19.1
SQNt +11.0
N (tertiary amine) +9.4
Ester (sorbitan ring) +6.8
Ester (free) +2.4
+2.1
a-I(free) +1.9
-0- (ether) +1.3
rn (sorbitan) +0.5
m m etc 0
cn\Clli +0.33
~m p- ii -0.15
(alkyl) -0.475
CF2, CF3 -0.8 70
Table 6.1 \isco sities of some f uids of
pharm aceut ical intere st

Fluid ~am ic viscosity

at 20 °C(m Pas)

Chloroform 0.58
\\ater 1.002
Rhanol 1.20
Fractionated coconut oil 30.0
Gyceryl trinitrate 36.0
Propylene glycol 58.1
Soya bean oil 69.3
Rape oil 163
Gycerol 1490
 1 2 3
Development Production
Drug
synthesis
~--- ➔
of formulated ~ --- ➔
of formulated
medicine medicine
'I
I
I

t
Drug
Drug Administration
removed ~ --- · ~ --- ·
in body of medicine
from body
6 5 4

Fig. 9.1 • Schema tic representation of the lifetime of

a drug .
Table 9.1 lijuivalcnt diameters of irregular particles

Equivalent diameter Symbol ll:fnition Equation

ll'ag diameter (or d.i llameter of a sphere huving the same resistance to
frictional dmg imtion in a fuid as the particle in a fuid of the same
diameter) den.~ity (p 1) and sa m! viscosity (11 ), w1d moving at the
same ,elocily (v) (d.i approximates to d, when the where C,A= f(d.i)
particle Reynolds number (Rep) is small and particle (i.e fii = 3,rcJ.i,/ V)
motion i<; streamlined. i.e. Re 1, < 0.2)
Feret's diameter The mean value of the distance between pairs of 1'bne
parallel tangents to the projected outline of the
particle. lhis can be considered as the boundary
separating equal particle areas (see text and Fig. 9 3)
Free-falling diameter llameter of a sphere having the same density and Nine
same free-falling speed as the particle in a fuid of
the same density and viscosity
Hydrodynamic Ilameter calculated from the diffusion coefficient 1.38 x 10- 12T
D= ----1n1s-1
diameter according to the Stokcs-Gnstein equation (see text) 3.irr,d
l\ihrtin 's diaireter C4t The mean chord length of the projected outline of ~ie 1'bne
particle (see text and rig. 9 .3)
Projected a rca Jlameter of a circle having the same area (A) as the
diameter prqjected area of the particle resting in a stable A= ,r dl
4 •
position (see text and Fig. 9.2)
Perinieter diameter namctcr of a circle having the same perimeter as the Nine
projected outline of the particle (see text and 1-ig. 9.2)
Sie,e diarrieter The width of the minimum square aperture through Nine
wbicb the particle will pass (see text and rig. 9.7)
Stokes diameter d~ ·!he free-falling diameter (cl,, see abo\e) of a particle Lhder these conditions
in the laminar f ow region (Pep < 0.2) dl = d!
" dd

Swface diameter Clameter of a sphere having the same external S=,rdl•

swface area (S) as the particle
Surtace ,ulume cl,. Clarrieter of a sphere having the same external d1
d -
,v- d!
V

diameter swface area lo ~olume ratio as the particle

\olurrie diameter d. Dameter of a sphere having the same \Olume N as
the article
Table 9.2 Frequency and cumulative frequency distribution data for a nominal particle size analysis procedure

Percent N.lmber of Cllmula tive Nimber of Cll1nula tive

Range of M!an N.lmber of
particles in particles in percent particles percent
equivalent diameter particles in
each size the sample frequency in the frequency
diameters of of each each size
fraction(% smaller smaller sample larger than
particles stze fraction
(frequency) frequency) than the than the larger the mean
measured fraction
mean mean than the diameter
(known as the (µm)
diameter of diameter of mean of each
size fraction)
each size each size diameter stze
(µm)
fraction fraction of each fraction
(cum.% size (cum.%
undersize) fraction oversize)

0 0.0 0 0 2200 100.0

<9.9

10-29.9 20 JOO 4.5 50 2.3 2150 97.7

30-49.9 40 200 9.1 200 9.1 2000 90.9

50-69.9 60 400 18.2 500 227 1700 77.3

70-89.9 80 800 36.4 1100 50.0 1100 50.0

90-109.9 100 400 18.2 1700 77.3 500 22.7

110-129.9 120 200 9.1 2000 90.9 200 9.1

130-149.9 140 100 4.5 2 150 97.9 50 2.3

150> 0 0.0 2200 100.0 0 0.0

Table 10.2 Fxample of pow der grad es as spec ified
in phar maco poei as

Ths cription Coar sest sieve Sieve diam eter

of grad e of diam eter (µm) throu gh whic h
pow der no more than
40% of pow der
mus t pass (µm)

Coarse 1700 355

:Mxlerately 710 250
coarse

:Mxlerately fine 355 180

Fme 180
\ery fine 125
Some pbannacopoeias define another size fraction, known as ultrafne
poooer, in wuch the maximum diameter of at least 90% of the
particles must be no greater than 5 µm and none of the particles
should have diameters greater than 50 µm
Table 11.1 Nimber of particles of a minor active
constituent present in samples taken from a 1 : 1000
random powder mix with different numbers of particles
in the scale of scrutiny

Sample Nnnber of particles in scale

number of scrutiny
1000 10000 100000
1 1 7 108
2 0 10 91
3 1 15 116
4 2 8 105
5 0 13 84
6 1 10 93
7 1 6 113
8 2 5 92
9 0 12 104
10 1 13 90

The figures in the table are the numbers of particles of the minor
constituent in the samples.
 Angle defined ~para tus M!thod Angle de fined
~para tus M!thod

Fixed height cooe .dngleofrepose a b ledge Dained angle of

repose

Crater Q-a ined angle of

repo.se
Fixed base cooe .Angle of repose a

~( b ~~
Aatbm Dained angle of

I
• liking table lf18k: of repose
a~ ( repose

Rotatilg cylinder ~rm ; angle of b ~(

repose
Table 12.2 Angle of repose as an indication of Table 12.3 Relationship between powder f owability, %
powder f ow properties (based on Carr) compressibility and Htusner ratio

Angle of repose Type of fow Compressibility Type of fow Htusner ratio

(degrees) index(%)
(Carr's index)
25-30 Fxcellent
1-10 Excellent 1.00--1.11
31- 35 Gxxl
11-15 Gxxl 1.12-1.18
36-40 Fair (f ow aid not needed)
16--20 Fair 1.19-1.25
41-45 Passable (may hang up, f ow aid
might be needed) 21-25 Passable 1.26--1 .34

46--55 Poor (agitation or VIbration needed) 26--31 Poor 1.35-1.45

56--65 \ery poor 32-37 \erypoor 1.46--1.59

Oler 66 \ery, very poor >38 \ery, very poor >l.60
Table 13.1 OOerences between prokaryotic and
eukaryotic organisms

Structure Prokaryotes E1karyotes

Cell wall U;ually contains Peptidoglycan

structure peptidogl)can absent

N.iclear Pbsent Present. Possess

membrane a true nucleus

N.icleolus Pbsent Present

N.nnber of Ole rvt>re than one

chromosomes
Mtochondria Pbsent Present
~sosomes Present Pbsent
Ribosomes 70S 80S
Table 132 The major groups of viruses that infect humans

Family Caps id J\licleic acid Envelope Example

Pdenovindae Icosahedral dsfN.\. !'It> 1-lunan adcnovirus

lrenaviridae H!lical ssRNA. 'res lassa rever virus

Aaviviridac Icosahedral ssRNA. 'res Yellow fever virus

1-l!patitis C virus

1-l!padna viridac Icosahedral dsCN.<\ !'It> li:patitis B virus

H:rpesviridae Icosahedral dsfN.\ Yes 1-l!rpes simplex virus

Cytorregalovirus
\oricclla zostcr virus

Othomyxoviridae H::lical ssRN.A. 'res Influenza virus

Papoviridae Icosahedral dsCNA. 1't> Papilloma virus

Paramyxoviridae 1-t:lical ssRNA. 'res Respiratory syncytial virus

~asles virus
~ virus

Picomaviridae Icosahedral ssRNA. Rhinovirus

Poliovirus
Coxsackie virus

Pox'Viridae Complex dsCNA. 'res M>lluscum contagiaium

\ecc inia virus
\eriola virus

Rcoviridae Icosahedral dsRNA. Rota\,jrus

Colorado tick lever virus

Rctroviridae Icosahedral ssRNA. 'res I-IV

Rha txloviridae H:lical ssRNA. Yes Rabies virus

Togaviridae Icosahedral ssRN.A. 'res Jqilx:lla virus

 1 2 3 4 5 6

0 0

Chromatin Spore Engulfment Cortex Coat Maturation

filame nt sectrum of fores pore formation formation
Antibiotic Alanine Alkaline Dipicolinic Cysteine Alanine
dehydrogenase phosphatase acid incorporation racemase
Protease

Protein G lucose Uptake of Octa no I Heat

turnover Dehydrogenase ca lcium resistance resistance

Amylase Re fra c tility

Fig. 13.5 • Morphologica l and b ioc hemical c hanges during spore formation.
Table 14.1 Relative merits of alternative antibiotic assay methods
A5say method .Advantages
Biological Inactive .impurities or degradation
methods properties do not interfere
Easily scaled up for multiple samples
lli not require expensive equipment
Nln-biological Thually rapid, accurate and precise.
methods Nhy be more sensitive than biological
assays
Fnzyme and immunological methods are
usually assay kits, which give reliable
resuhs with inexperienced operators
Ilsadvantages
Slow, usually requmng overnight incubation
Relatively labour-intensive
Relatively inaccurate and imprecise, particularly with
inexperienced operators
Nhy require expensive equipment (e.g. 1-Pl.C) or expensive
reagents or assay kits (enzyme and immunological methods)
1-Pl.C can only assay samples sequentially, so unusually large
sample numbers may cause problems
Table 14.2 log reductions required in viable counts of microorganisms used in EP (2011) preservative efficacy tests

Mcroorganis m Oiteria 6h 24 h 48 h 7d 14 d 28 d
Product type

Parenteral and ophthalmic :Ebcteria A 2 3 IB

Pseudomonas aeruginosa B 1 3 NI
Staphylococcus aureus
Escherichia coli *
Fungi A 2 NI
Ac;pergillus niger B 1 NI
Candida albicans

Topical :Ebcteria A 2 3 NI
B 3 NI
Fungi A 2 N[

B 1 N[

:Ebcteria 3 N[
Gal
Fungi 1 N[

~ oral prcx:lucts only

Nl no recmery,
NI. no increase (see text}