Pharmaceutical Processing is the process of drug manufacturing and can be broken down into a range of unit operations, such as blending, granulation, milling, coating, tablet pressing, filling, and others.

1. Dissolution
Dr. Sarad Pawar Naik B
Associate Professor, Dept. of Pharmaceutics, KIU-WC

2. Defination - Dissolution is a defined as a process in which
a solid substance solubilizes in a given solvent i.e., mass
transfer from the solid surface to the liquid phase.
Dissolution is a process which is used to measure
the release profile of the drugs from formulations
which are commonly solid oral dosage forms like
tablets and capsules.
 Dissolution rate is defined as the amount of solute dissolved in a given
solvent under standard conditions of temperature, pH, solvent composition and
constant solid surface area.
It is a dynamic process.
Dissolution is expressed in terms of a rate process.
 If the rate increases, the dissolution process also increases.
The rate of dissolution of drug substance is determined by the rate at which
solvent-solute forces of attraction overcome the cohesive forces present in solid.

3. Drug Dissolution Process

4. dC/dt = k (Cs- Cb)…………(1)
where, dC/dt = dissolution rate of the drug
k = dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the solution at time
(1)
(2)
1) Diffusion model / film theory
The rate of dissolution is given by Noyes and Whitney:
THEORIES OF DISSOLUTION
Several theories have been proposed to explain the process of dissolution.
Some of the important ones are –
A) Diffusion model / film theory
B) Danckwert’s model / surface renewal theory
C) Interfacial barrier model / limited solvation theory

5. The Danckwert’s model is expressed by equation:
where, m = mass of solid dissolved
γ = rate of surface renewal
2) Danckwert’s model / surface renewal theory
3) Interfacial barrier model / limited solvation theory
In this model it is assumed that the reaction at solid surface is nor instantaneous i.e., the reaction
at solid surface and its diffusion across the interface is slower than diffusion across liquid film.
therefore the rate of solubility of solid in liquid film becomes the rate-limiting than the diffusion
of dissolved molecules equation:
Such a concept is given by the following equation :
G = Ki (Cs-Cb)………………….(4)
where, G = dissolution rate per unit area
Ki = effective interfacial transport constant
Cs = concentration of drug in stagnant layer
Cb = concentration of drug in the bulk of the solution at time
3

6. Dissolution apparatus from different official

7.  Dissolution is the process in which a substance forms a solution.
 Dissolution testing measures the extent and rate of solution formation from a
dosage form, such as tablet, capsule, ointment, etc.
 The dissolution of a drug is important for its bioavailability and therapeutic
effectiveness.
Dissolutions used in pharmacy

8. Solubilisation

9. Uses of solubilization:
 Micellar solubilization is widely utilized,
E.g., in laundry washing using detergents, and in cleanup of oil
spills using dispersants.
Solubilization used in pharmacy
 Solubility, the phenomenon of dissolution of solute in solvent to give a
homogenous system, is one of the important parameters to achieve desired
concentration of drug in systemic circulation for desired (anticipated)
pharmacological response.
 Solubilization is the increase in solubility of a poorly water–soluble substance
with surface-active agents.

10. DISTILLATION
It is defined as the separation of the components of the liquid mixture by process
involving vaporization and subsequent condensation at another place.
Psolution = Xsolvent . Psolvent
Raoult’s law: It states that a solvent's partial vapour
pressure in a solution (or mixture) is equal or identical to the
vapour pressure of the pure solvent multiplied by its mole
fraction inthe at given temperature.
Psolution = Vapor pressure of the solution
Xsolvent = mole fraction of the solvent
Psolvent = vapor pressure of the pure solvent.
 Ideal solution obeys (behaves) Raoult’s law.
 Raoult’s law is obeyed by only a few solution of liquid in
liquids.
Examples are benzene, toluene, n-hexane, n-heptane, ethyl
bromide, ethyl iodide.
Dalton’s law: It states that the total pressure p of moist air is the sum of
partial pressures of dry air pa and water vapor pv :
p = pa + pv

11. Evaporation
Defined as a process by which a liquid is transformed into vapour.
Evaporation used in pharmacy
 Evaporation is also used to concentrate liquid foods such as noodles and make condensed milk,
the product of a process that removes water from milk.
 Similarly, pharmaceutical companies use evaporators to remove excess moisture from drugs,
thus improving product stability.

12. Drying
 Drying is the process of using evaporation to remove water from a solution,
suspension, or other solid-liquid mixture.
 In addition to solids, the process can also be used to remove water from liquids or gases.
Drying used in pharmacy
 Drying is a common unit operation used to reduce the levels of water or organic solvent in
pharmaceutical materials to acceptable levels.
 Purification and drying of inorganic salts (sodium chloride, calcium carbonate etc.).

13. Crystallization
Crystallization is the physical transformation (phase transition) of a liquid,
solution, or gas to a crystal, which is a solid with an ordered internal arrangement
of molecules, ions, or atoms.
Crystallization used in pharmacy
 Crystallization is a key unit operation and an important step in processing and development
within the pharmaceutical industry, and
 It is used in the separation and purification of intermediate compounds and Active
Pharmaceutical Ingredients (APIs).
 Over 80% of drug products involving at least one crystallization step.

14. Particle Size Reduction
 Size reduction is a process in which the particle size of a solid is made smaller.
 The term size reduction is applied to ways in which particles of solids are cut or
broken into smaller pieces.
1. Hardness: Harder the material, more difficult to reduce its size.
2. Toughness: Soft but tough material creates problem in size reduction and
its toughness is reduced by decrease temperature.
3. Stickness: Gum and resinous substances cause problem in size reduction.
4. Moisture content: <5% moisture suitable for dry grinding and >50% for
wet grinding.
Factors affecting size reduction
Particle Size Reduction used in pharmacy
 Particle size reduction is a fast and cost-effective answer to increasing the
exposure of poorly soluble oral drugs by increasing surface area and thereby
improving dissolution rate.

16. Mixing
Definition: It is a unit operation in which two or more than two components in
separately or roughly mixed. Example of mixer- Blender, Planetary mixers, Propellers etc.,
Mixing Equipments
1. Liquid mixers 3. Semi-solid mixers
A. Agitator mixers
B. Shear mixers

17. APPLICATION OF MIXING
 To get true solution after mixing two miscible liquids.
 To provide uniformity of composition between the mixed
ingredients.
 To enhance the physical or chemical reactions.
 To improve dissolution & diffusion of mixture.
 To produce suspension when an insoluble solid is mixed
with a vehicle.

18. Sterilization is a process of killing or removal of all microorganisms,
including highly resistant bacterial endospores. Depending on the
material, sterilization can be achieved by moist heat (autoclave), dry
heat (hot-air oven), ethylene oxide gas, or filtration.
Sterilization
WHAT IS STERILIZATION?
Sterilization can be defined as any process that effectively kills or
eliminates transmissible agents (such as fungi, bacteria, viruses and
prions) from a surface, equipment, foods, medications, or biological
culture medium. METHODS OF STERILIZATION
The various methods of sterilization are:
1. Physical Method
a. Thermal (Heat) methods
b. Radiation method
c. Filtration method
2. Chemical Method
a. Gaseous method

19. Thermal methods includes:
i) Dry Heat Sterilization – Higher temperatures in the range of 160-180˚C and
requires exposures time upto 2 hours, depending upon the temperature
employed.
Eg: Incineration(Rapid oxdn of a waste), Red heat, Flaming, Hot air oven
 It is used for sterilizing non-aqueous thermo stable liquids and
thermo stable powders.
ii) Moist Heat Sterilization - Moist heat sterilization involves the use of steam in
the range of 121-134˚C. Steam under pressure is used to generate high
temperature needed for sterilization. Saturated steam acts as an effective
sterilizing agent.
1. Dry saturated steam –
 Use pressurized steam to destroy microorganisms.
 Generally the conditions employed are Temperature
upto 121-134˚C for 15-20 min under 15 lbs (pound) pressure,
based on type of material used.
2. Boiling water/ steam at atmospheric pressure
3. Hot water below boiling point
PHYSICAL STERILIZATION METHOD
THERMAL (HEAT) METHODS
Autoclaving

20. Radiation method
 Many types of radiation are used for sterilization like electro-magnetic radiation
(e.g. gamma rays and UV light), particulate radiation (e.g. accelerated electrons).
 The major target for these radiation is microbial DNA.
 Radiation sterilization with high energy gamma rays or accelerated electrons has
proven to be a useful method for the industrial sterilization of heat sensitive products.
 Radiation sterilization is generally applied to the dry state; including
 Surgical instruments,
 Sutures,
 Prostheses,
 Unit dose ointments,
 Plastic syringes and
 Dry pharmaceutical products.

21. Filtration method
 Filtration process does not destroy but removes the microorganisms.
 It is used for both the clarification and sterilization of liquids and gases as it is capable of
preventing the passage of both viable and non viable particles.
 The major mechanisms of filtration are sieving, adsorption and trapping within the matrix
of the filter material. Ex: HEPA Filters [ High Efficiency Particulate Air]
 Sterilizing grade filters are used in the treatment of heat sensitive injections and ophthalmic
solutions, biological products and air and other gases for supply to aseptic areas.
 They are also used in industry as part of the venting systems on fermentors, centrifuges,
autoclaves and freeze driers.
 Membrane filters are used for sterility testing.
 There are two types of filters used in filtration sterilization:
(a) Depth filters
(b) Membrane filters: These are porous membrane about 0.1 mm thick, made of cellulose
acetate, cellulose nitrate, polycarbonate, and poly-vinyl-pyrolidene fluoride, or some other
synthetic material.
This type of air filter can remove at least 99.97% of dust, mold,
bacteria and any airborne particles with a size of 0.3 µm.
Mold : a fungal growth
That forms & spreads on
Various kids of damp/ plant/
Animal matter.

22. CHEMICAL STERILIZATION METHOD
GASEOUS METHOD
 The chemically reactive gases such as formaldehyde, (methanol, H.CHO) and
ethylene oxide (CH2)2O possess bio-cidal activity.
 Ethylene oxide is a colorless, odorless, and flammable gas.
 The mechanism of antimicrobial action of the two gases is assumed to be
through alkylations of sulphydryl, amino, hydroxyl and carboxyl groups on
proteins and amino groups of nucleic acids.
 The concentration ranges (weight of gas per unit chamber volume) are
usually in range of 800- 1200 mg/L for ethylene oxide and 15-100 mg/L for
formaldehyde with operating temperatures of 45-63°C and 70-75°C respectively.
 Both of these gases being alkylating agents are potentially mutagenic and
carcinogenic. They also produce acute toxicity including irritation of the skin,
conjunctiva & nasal mucosa.

23. Merits, Demerits and Applications of Different Methods of Sterilization

26. Surface and interfacial phenomena
Surface tension: A force pulls the molecules of the interface together.
Unit: dyne/cm
Interfacial tension: The force per unit length existing at the interface between two
immiscible liquid phases.
Unit: dyne/cm
Important of Interfacial phenomena in pharmacy
1. Adsorption of drugs onto solid adjuncts in dosage forms.
2. Penetration of molecules through biological membranes.
3. Emulsion formation and stability.
4. The dispersion of insoluble particles in liquid media to
form suspensions.

27. Surface-Active Agents (or) Surfactants
 Surface-active agents or surfactants are molecules and ions that are adsorbed at
interfaces.
 Surfactants are materials that lower the surface tension (or interfacial tension)
between two liquids or between a liquid and a solid.
 An alternative term is amphiphile, which suggests that the molecule or ion has
a certain affinity for both polar and non-polar solvents.
 When such molecule is placed in an air-water or oil-water system, the polar
groups are attached or oriented toward the water, and the non-polar groups are
oriented toward the air or oil.
Introduction:
 They are used in many pharmaceutical
preparations as wetting agents, emulsifiers,
solubilizing and anti-foaming agents.
 At the air-water interface, the lipophilic chains
are directed upward into the air; at the oil-water
interface, they are associated with the oil phase.
Fig: Adsorption of fatty acid molecule
at a water-oil interface (left panel) and
a water-air interface (right panel).
(Below figure).

28. Surfactants are classified
According to their chemical structure and, more specifically, their polar group:
Anionic surfactant such as sodium
dodecyl sulfate (SDS®)
Cationic surfactant such as cetyl trimethyl
ammonium bromide (CTAB®)
Ampholytic (Zwitterionic®) surfactant
such as phospholipids
Non-ionic surfactant such as poly oxy
ethylene (Tween®)

29. HLB (Hydrophilic -Lipophilic Balance)
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
Solubilizing agents (15-18)
Detergents (13-15)
o/w Emulsifying agents (8-16)
Wetting & Spreading agents (3-6)
w/o Emulsifying agents (3-6)
Antifoaming agents (2-3)
Hydrophilic
(water soluble)
Hydrophobic /
Lipophilic
(oil soluble)
Water
dispersible

30.  There is an arbitrary scale that has been set up for expressing the
hydrophilic and lipophilic characteristics of an emulsifying agent is
known as HLB (hydrophilic -lipophilic balance).
 The higher HLB the more hydrophilic it is.
 The Spans, sorbitan ester are lipophilic and have low HLB;
 The Tween, polyoxyethylene derivetives of Spans, are hydrophilic and
have high HLB.
 Anionic surfactants.  Cationic surfactants.  Amphoteric surfactants.  Non-ionic surfactants.
Surface active agent in pharmacy
 Surface active agents (SAAs) are molecules with the capacity to adsorb to solid
surfaces and/or fluid interfaces, a property that allows them to act as
multifunctional ingredients. (E.g., wetting and dispersion agents, emulsifiers,
foaming and anti-foaming agents, lubricants, etc.)

31. Granulation
 Granulation is the process of forming grains or granules from a powdery or
solid substance, producing a granular material.
 It is applied in several technological processes in the chemical and
pharmaceutical industries.
 Granulation done to
 Improve flow properties of the mix
 Improve compression properties of the mix
 Prevent segregation of components in powder mix
 Reduce production of toxic dust
 Reduce possibility of ‘cake’ formation
 Increase convenience of transport.
Types of Granulation
1. Wet granulation
Shear granulators
High speed mixer/granulators
Fluidized bed granulators
2. Dry granulation
other more specialized granulators - Spray driers & Pelletizers
Roller compactors
Sluggers

32.  Granulation, the process of particle enlargement by agglomeration technique,
is one of the most significant unit operations in the production of
pharmaceutical dosage forms, mostly tablets and capsules.
 Granulation process transforms fine powders into free-flowing, dust-free
granules that are easy to compress.
Granulation used in pharmacy

33. Packaging (primary and secondary packaging)
Packaging Definition:
Packaging is the science, art and technology of enclosing, protecting a
product and providing information about the product for distribution,
storage, sale and use.
Role of packaging:
 Protection
 Identification
 Information transmission
 Storage
 Convenience
Types of packaging for tablets and capsules
HDPE Container Good barrier for moisture,
gas and light
All kind of products from
solid orals and dry syrup
PET/PP (Amber) Moderate barrier to
moisture and gas
Light sensitive
products
1. Blister package 2. Strip package
3. Alu-alu packaging 4. Bottle packaging
Materials Critical properties Area of use

34.  Primary packaging could be blister packs which are used to
contain the correct dosage of pills.
 For secondary packaging, you'd often see the paperboard
boxes used to display the packets on the pharmacy.
Primary, Secondary Packaging Used in Pharmacy