INDUSTRIAL

PHARMACEUTICAL
TECNOLOGY
(ESSENTIALS)

Part 1

Yauheni Hryniuk,
Associate professor
 History

Real birth of industrial Pharmaceutical Technology –

first half of XIX century
Merck – established in 1668. But it was only a
drugstore, in XIX c. on the drugstore basis factory was
established. Today – huge company (~ 40 000
employees).
Shering – drugstore – 1851, factory – 1864. In 2006 –
takeover by Bayer.
Bayer – 1863. Today – one of the biggest company
with 111500 workers among the world.
 Pfizer 182.15 B
Johnson & Johnson 180.88 B
GlaxoSmithKlein 141.87 B
Roche Holding 135.28 B
Novartis 128.65 B
Sanofi-Aventis 122.80 B
Astra Zeneca 75.70 B
Merck 72.71 B
Eli Lilly & Co. 64.67 B
Wyeth 62.78 B

Source: Yahoo Finance

History
in Belarus

JSC “Borisovsky zavod

medpreparatov” - 1962
RUE “Belmedpreparaty” - 1929
RUE “Minskinterkaps” - 1995
Modern-day drug discovery and
development
L eading Pharmaceutical Companies Ranked
by R&D Spending (US$ in Billions) in 2010
Advantages of the industrial production

Low prime cost (including

innovations)
Large scale production
Unified package (good for
transportation)
Quality control processes (standard
technical documentation)
Standard technical
documentation
Pharmacopoeia
Technology and technical regulations
State standards
Producer Pharmacopoeia articles
SOPs
…
It is extremely needed to provide us
with safe, effective and
qualitative medicines
Basis of the most tecnological
processes – dosage form of drug
Solid dosage forms (tablets, capsules,
powders, granules, dragee, …)
Liquid dosage forms (solutions,
suspension, emulsion)
 Soft dosage forms (ointments,
liniments, capsules, patches, gels…)
Gaseous dosage forms (gases, aerosols)
 Some special areas of drug
production
drugs Galenical (extraction of medicinal
plants: tinctures, extracts …)
biotech pharmaceuticals
children's medicines
ophthalmic formulations
geriatric medicines
…
Tecnology of drug production
according to the peculiarities of
production and dosage form
 Drugs Galenical

The process of extraction

refers to the mass-transfer
processes and flows through
the diffusion laws
The main factors are:
1)nature and characteristics of medicinal
herbs
2)Properties of the extracting agent (water,
ethanol, ethyl ether, chloroform, acetone,
liquefied gases )
Main stages of production:
Raw material preparation
Extraction process
Purification (settling, filtration,
centrifugation)
Concentration or drying
Filling and packing
Quality control
Organoleptic characteristics (transparency,
chromaticity, taste, flavor)
Ethanol content and dencity (in tinctures)
Dry residue
Heavy metals
 Solid dosage forms

tablets
capsules
sugar-coated tablets (dragee)
powders
granules
sachets
 Powders
latin - pulvis (pulv.)
Powders are drugs or drug extracts that are
dried and ground and micronized into fine
particles.
According to the division into prescribed doses
powders are pulveres indivisi (all doses are given
inseparably) and pulveres divisi (they are divides
into the prescribed number of doses).
According to the composition are simplex
powders (consist one active ingredient) and
complex powders (a mixture of more than one
active ingredient).
 Solid dosage forms

Тablets
A tablet is a solid dosage form that is
prepared by compressing or molding of
the drug into various sizes and shapes.
Dissolution is the rate-limiting step in
the delivery of drug from a tablet to the
systemic circulation.
Advantages
 Production aspect
 Large scale production at
lowest cost
 Easiest and cheapest to
package and ship
 High stability
 User aspect (doctor, pharmacist,
patient)
 Easy to handling
 Lightest and most compact
 Greatest dose precision &
least content variability
Disadvantages
 Some drugs resist compression
into dense compacts
 Drugs with poor wetting, slow
dissolution, intermediate to
large dosages may be difficult or
impossible to formulate and
manufacture as a tablet that
provide adequate or full drug
bioavailability
 Bitter taste drugs, drugs with an
objectionable odor, or sensitive
to oxygen or moisture may
require encapsulation or
entrapment prior to
compression or the tablets may
require coating
Types of tablets:

Tablets for oral administration

Tablets for vaginal administration

Tablets for implantation (pellets)

 Solid dosage forms

Tablets for oral administration

Film coated tablets
Enteric coated tablets
Effervescent tablets
Sublingual tablets
Buccal tablets
Troches (lozenges)
Chewable tablets
Controlled release tablets - slow release tablets
(SR) and modified release tablets (MR)
Compressed Tablets contains:
Medicinal agent
Diluents or filler
Binders or adhesives
Disintergrants
Lubricants
Miscellaneous adjuncts
Colorants and flavorants
DILUENTS
Diluents increase the volume to a formulation to
prepare tablets of the desired size. Widely used
fillers are lactose, dextrin, microcrystalline cellu-
lose starch, pregelatinized starch, powdered
sucrose, and calcium phosphate.
BINDERS
Binders promote the adhesion of particles of the

formulation. Such adhesion enables preparation of

granules and maintains the integrity of the final tablet.
Commonly used binding agents include: water, ethanol,
starch, gelatin and sugars (sucrose, glucose, dextrose,
and lactose).
DISINTEGRANTS
 The breakup of the tablets to smaller particles is important for
dissolution of the drug and subsequent bioavailability.
Disintegrators promote such breakup. To rupture or breakup of
tablets, disintegrating agents must swell or expand on exposure to
aqueous solution. Thus, the most effective disintegrating agents in
most tablet systems are those with the highest water uptake
property. In general, the more hydrophilic, the better disintegrating
agents are therefore highly hydrophilic.
LUBRICANTS
Lubricant is a substance capable of reducing or preventing
friction, heat, and wear when introduced as a film between solid
surfaces. It works by coating on the surface of particles, and thus
preventing adhesion of the tablet material to the dies and
punches.
Lubricants play more than one role in the preparation of tablets.

Commonly used lubricants include: talc, magnesium stearat,

calcium stearate ,stearic acid, hydrogenated vegetable oils and
PEG.
 Compressed tablet manufacturing
•The classification of manufacturing methods

wet granulation: suitable for drugs that are stable to moisture and
granulation heat
dry granulation: suitable for drugs that are sensitive to moisture
and heat
powder compression : suitable for drugs that are sensitive to
moisture and heat, fill material possessing, good flowability and
direct compressibility
compression
crystal compression ： suitable for drugs with proper
crystal form and good flowability
The classification of tablet presses
Tablet presses:

a. single-punch presses

b. multi-station rotary presses

The main components of single-punch
tablet presses t a b l e t
h o p p e r

h a r d n e s s

a d j u s t o r

Core components:
f e e d

s h o e

die d i e

u p p e r

c a v i t y

lower punch p u n c h

upper punch d i e

l o w e r

p u n c h

t a b l e t e j e c t o r

a d j u s t o r

t a b l e t w e i g h t

a d j u s t o r
 Tablet coating
The reasons for tablet coating
1) to protect the medicinal agent against destructive
exposure to air and/or humidity;
2) to mask the taste of the drug;
3) to provide special characteristics of drug release;
4) to provide aesthetics or distinction to the
product;
5) to prevent inadvertent contact by nonpatients
with the drug substance
 Tablet coating

The general methods involved in coating

tablets are as follows
1) sugarcoating tablets
2) film-coating tablets
3) fluid-bed or air suspension coating
4) compression coating
Quality standards and compendial
requirements
The apparent physical features of compressed tablets:
1) shape: round, oblong, unique
2) thickness: thick or thin
3) diameter: large or small
4) flat or convex
5) unscored or scored in halves, thirds and quadrants
6) engraved or imprinted with an identifying symbol and/or
code number
7) coated or uncoated
8)colored or uncolored
9) number of layers.
Quality standards and compendial
requirements
Other physical specifications and quality
standards:
tablet weight weight variation
content uniformity tablet thickness
tablet hardness tablet disintegration
drug dissolution
in-process controls
verification after the production
Quality standards and compendial
requirements
Tablet hardness
1)The greater the pressure applied, the harder the
tablets.
2) The hardness required by different tablets
a) lozenges and buccal tablets: hard (dissolve slowly)
b) the tablets for immediate drug release: soft
3) Measurement
a) special dedicated hardness testers
b) multifunctional equipment
Quality standards and compendial
requirements
Friability
1) It is used to determine a tablet’s durability
2) Method: allowing the tablets to roll and
fall within the rotating apparatus
(friabilator); determine the loss in weight;
3) requirement: weight loss ≤1%
Quality standards and compendial
requirements — tablet dissolution
1) The importance of in vitro dissolution test
a) to guide the formulation and product
development process toward product optimization
b) to monitor the performance of manufacturing
process
c) to assure bioequivalence from batch to batch
d) as a requirement for regulatory approval for
product marketing for products registered with the
FDA and regulatory agencies of other countries.
2) The goal of in vitro dissolution is to provide a
reasonable prediction of the product’s in vivo
bioavailability.

Basis: The combinations of a drug’s solubility and

its intestinal permeability are supposed as a basis
for predicting the likelihood of achieving a
successful in vivo – in vitro correlation (IVIVC).
3) The formulation and manufacturing factors affecting
the dissolution of a tablet
a) the particle size of the drug substance
b) the solubility and hygroscopicity of the formulation
c) the type and concentration of the disintegrant,
binder, and lubricant used
d) the manufacturing method, particularly, the
compactness of the granulation and the compression
force
e) the in-process variables