Professional Documents
Culture Documents
CHAPTER 1
INTRODUCTION
Elements of Organization
Organization is a mechanism for determining and assigning duties to people
in order to work effectively.
Business Organization in a combination of manpower, money, machines and
methods so coordinated that they can fulfill an economic objective.
Basic Elements of an Organization
1. Division of Responsibility (obligation or duty)
Responsibility must be delegated. The company objectives must be
determined and the organizational plan must be consulted with the aim of achieving
them. The types of work must be identified and grouped logically on related
elements.
2. Delegation of Authority
Authority must be defined and delegated to avoid negligence of duty.
Authority means:
Enforcement of obedience
Ability to make final decisions
3. Determination of the Interrelationship among the Functions of each of the
Components of the Organizational Plan
This interrelationship must be clearly defined to promote harmonious
teamwork.
II.
III.
1. To protect and make the most effective use of the assets of the
company.
2. Establishes objectives and determines the basic policies and general
course of the business.
3. Represents and safeguards the interests of the stockholders.
Level 2 Consists of the president, the function being general management or
administrative. This includes active planning direction, coordination and
control of the business within the scope of policies established and
authorized by the Level 1 management.
Level 3 Consists of the Vice President, General Managers, and Department
Managers. The functions include management of the major departments
of the company. They are fully responsible and accountable to the Level
2 management for the success of their respective operations.
Level 3 embraces the topmost level of executives concerned with a
particular division of the company, rather than the enterprise, as a
whole.
CHAPTER 2
THE PLANT DEPARTMENT
A. Production Control consists of three (3) sections:
1. Purchasing in charge of purchasing requisitioned material (both
packaging materials and raw materials), both form local and imported
sources.
2. Inventory Control watches and monitors closely. Records all materials
used in the Production controls the stocks of both raw materials packaging
materials and finished products. This section therefore is in charge of
checking stocks periodically.
3. Planning and Scheduling coordinates with the Marketing Department on
what products are required for supply, and then plans and schedules the
manufacture of the product. Then, through a manufacturing order (M.O.),
the Production department manufactures the quantity scheduled at the
time limit allowed.
Discussion
I.
CONSTITUENT
Type I
BIO2 + B2O3
Type II
Na2O + CaO
SO2 Treatment
Type III
Na2O + CaO
Type NP
Na2O + CaO
Non parenteral
GENERAL DECRIPTION
Highly Resistant
Borosilicate Glass
Treated Soda lime glass
Soda Lime glass for Dry
Products
General purpose soda
lime glass
Each type of glass is tested according to its resistance to water attack. The degree
of attack is determined by the amount of alkali released from the glass container.
Obviously leaching of the alkali from the glass container into the pharmaceutical
preparation inside could alter the pH and thus the stability of the product.
Type I glass is the most resistant glass of the four categories.
PLASTIC CONTAINER
These are high molecular weight polymers, such as:
Polyethylene
Polystyrene
Polypropylene
Polyvinyl chloride
The interest and widespread use of plastic containers in the pharmaceutical industry
has been generated by a number of factors including:
1.
Today a wide variety of dosage forms maybe found packaged in plastic containers
such as:
a.
b.
c.
d.
e.
Tin
Plastic coated tin
Tin coated lead
Aluminum
Plastic coated aluminum
Tin and tin coated tubes are generally used because of their non-reactive properties
although it was reported that tin tubes can be corroded by chloride or acid
conditions.
RUBBER COMPONENTS
Rubber of varying composition is used in pharmaceuticals and biologicals is
1.
2.
3.
4.
Stoppers
Cap liners
Parts of droper assembles
Components of drip sets/ infusion sets
A major use of the rubber stopper is that the closure for multiple dose vials
continuing solutions for injection.
Problems encountered in the use of rubber closures are:
1. Within contact with the liquid content in the vial. It may cause the absorption
of the native ingredient, preservative on the other components.
Example: the preservative chlorobutanol by the rubber form the solution.
2. The extraction of one or more components of the rubber close into the
solution.
These problems may be corrected by:
a. Using epoxy clinging material (a rosin that glues)
b. Use of Teflon in rubber shoes (tetrafluoroethylenepolymer or plastic)
II. Special techniques required for poorly soluble drugs.
The solubility of most modern chemotherapeutic agents can be favorably altered by:
1. Co-solvency
Weak electrolytes and non-polar molecules frequently possess poor water
solubility. Their solubility usually, can be increased by the addition of a water
miscible solvent in which drug has good solubility.
The approach is successful in some drugs, but is some biological activities toxicity is
to be considered
III. Pharmaceutical elegance is required as to the taste appearance and visocity
Modern pharmaceutical preparations present the drug substance which are
unpalatable and unattractive to the patient as colorful and flavorful formulations
attractive to the sight smell and taste.
FORMULATION OF LIQUIDS
To avoid problems on formulation of liquids the following considerations should be
studied:
1. Solubility
2. Stability
3. Organoleptic characteristics as taste (flavoring) odor and appearance (color
and clarity)
4. Preservatives
5. Sweetening agents
6. Viscocity
Further Discussions
1. Solubility
Co-solvants may be used in the formulation of aqueous liquids, such as
alcohol, sorbitol, glycerin, propylene glycol.
Vehicles used in the formulations are mostly blends of water and
sucrose.
Solubilizing agents are to be selected based on their effect in stability
efficacy and physical character.
2. Stability
Considers both physical and chemical stability
Physical stability is shown by the maintenance of the physical
properties such as the color, clarity, taste, viscocity and odor
throughout its shelf or until the expiry date is reached.
Physical stability includes the package and the label which involves the
effect if the package on the contencs and vice versa. Bottle caps and
liners now used as closures may undergo tests on stress-cracking or
corrosion so that the lner should be compatible with the contents
adequate seal is necessary. A torque tester measures the seal.
Torque is the measure of circular force (in lbs/ sq. inch) because the
instability is magnified in solution as against solid and suspension
systems.
3. Organoleptic Characteristics
a. Taste (flavoring) there are four basic tastes namely sweet, sout, salty
and bitter. A combination of flavoring agents is generally required to
mask these taste sensations.
Example
Menthol and chloroform are used as desensitizing agents since they
impart flavor and odor of their own to their product and have a mild
anesthetic effect on the sensory receptor organ associated with taste
The process of choosing flavouring agents may be divided into two (2)
major categories, such as:
1. Selection depends on an experiment where a panel of formulators
should conduct a trial and error selection of combination of flavors.
2. Evaluation - is conducted by a panel of three (3). They conduct the
taste tests starting from the lowest dilution to increasing
concentration.
b. Appearance depends on the color and clarity. Color should
complement/ harmonize with the flavor
Examples
Strawberry flavor should possess the red color of the strawberry. Kiwi
flavor should possess the green color of the kiwi fruit.
Clarity is improved by the filtration using sintered glass filter aids after
layers of filter or filter cloths.
4. Preservatives there are substances which prevent bacterial and fungal
growth in liquid preparations. Bacteria and fungi affect product stability as
well as health hazard to the patient.
Characteristics of an Ideal Preservative
1. Should be effective against broad spectrum of microbes.
2. Should be physically, chemically and microbiologically stable until the
expiry date of the product.
3. Should be non-toxic, non-sensitizing, adequately soluble and compatible
as well as acceptable to the taste and odor at the amounts used.
Preservatives are classified into four groups:
1. Acidic examples are ethyl asters of phydroxybenzoic acid (PABA) benzoic
acid and its salts. For external use boric acid and phenols are used.
2. Neutral examples are chlorobutanol, benzyl alcohol, and phenylethyl
alcohol.
3. Mercurials examples are thimerosal, nitromersols, phenyl mercuric
acetate/nitrate.
4. Quaternary Ammonium Compounds examples are benzalkonium chloride
and cetyl pyridinium chloride
To avoid the bitter aftertaste of both artificial sweeteners (if used individually)
cyclamate is used in ratio of 20 parts to 2 parts of saccharin to produce a 1%
w/v formulation.
6. Viscosity highly viscous systems are not also desirable since they resist dilution
by gastrointestinal fluid therefore might impede drug release and absorption.
If high concentrations of carboxymethylcellulose (CMC) are used
incorporation of Al*, FC ***, and CA** are done.
Viscosity is sometimes desired either to serve as an adjunct to palatability on
to improve pourability and drainage. Viscocity controlling agents are PVP,
methylcellulose and sodium CMS.
Manufacturing Considerations in Liquids
The basic principles involved in the preparation of homogenous liquids are
the same, regardless of the quantity of materials involved. The solubility of the
solute and the intra/inter molecular interaction in the final solution at equilibrium at
independent of the manner in which the solution is made.
This assumes that the method of compounding does not affect the final
composition of the system, as would be the case of the volatile component were
charged to a heated solution.
The rate at which the equilibrium is achieved is highly dependent in the
details of the following
a.
b.
c.
d.
e.
Equipment
Compounding procedure
Packaging methods
Labelling
Storage
Further discussions
A. Equipment in general the type of equipment used in the manufacture of oral
solutions consist of:
a. Mixing tanks equipped with agitators
This are tanks constructed of polished stainless steel are
jacketed to allow heating and cooling of the contents. They can be
obtained in a number of different sizes. The tanks are completely
covered and equipped with see through charging ports and illumination
for easy observation of the contents.
After compounding the liquid is clarified by filtration into another
adjacent task called storage tanks until release by the quality control
after the release, the liquid may be transported manually by filling into
portable transport tanks or by pumping through suitable liquid delivery
container.
b. Measuring and weighing devices
Used for large and small amounts of liquid and solid ingredients
such as cylinders, pipets and balances.
c. Filtration system for final polishing of the solution.
Filtration is a unit operation in which a mixture of liquids and
solids slurry or feed is forced through a porous medium in which solids
form a cake on the surface and the clear liquid is collected.
The usual objective of filtration or clarification is a sparkling
liquid trace from amorphous/ crystalline precipitates colloidal hazes or
insoluble liquid droplets. IN filtration system, the filter medium is the
surface upon which the solids are deposited on the filter.
Filter Media
1. Filter Cloth
Example
Nylon
Composition
Filter cloth
2. Filter media
Non woven
Stainless wire
cloth
Felt cloth
Bonded fabrics
Kraft paper
3. membrane filter
media
a. esters or
cellulose
b. nylon, Teflon,
PVC silver
Properties
a. Superior type
unaffected by
molds/fungus.
b. can be sterilized
by autoclaving
c. Negligable
absorption
properties
a. For straining
syrupy liquids
a. for gelatinous
solutions
5. Filter Aids
Diatomite
Infusorial earth
Kiesalgur
Celite
Cellulose
asbestos
c. porosity of 0.05
14 microns
d. ideal for microfiltration
a. form highly
porous and noncompressible cake
which retain solid
b. forms a line
surface deposit
which screens out
all solids prevents
the clogging of
supporting filter
media.
Formulation of Adjuvants
Suspension adjuvants the preservatives colorants flavorants and perfume.
These may affect suspension characteristics. The final adjuvant is the package. The
main concern of these adjuvants is compatibility with the vehicle and the active
ingredient.