SPLE

Saudi Pharmacist Licensure Examination

Preparation course

Dr. Osama Madkhali

Assistant Professor
Department of Pharmaceutics
College of Pharmacy
Jazan University
Pharmaceutics and Biopharmaceutics
Lecture Outlines
• Introduction to pharmaceutics and biopharmaceutics
• Physicochemical behavior
• Biological principles of dosage forms and delivery systems
• Materials and methods used in preparation and use of drug forms
• Biotechnology and its applications
Introduction
Introduction
Pharmaceutics is converting the drug into a medicine and
the science that deals with different dosage forms.

Drugs are rarely administered as pure chemical substances

but are almost always given in formulated preparation.
These can vary from relatively simple solutions to complex
drug delivery system.
Introduction
• Pharmaceutical principles are the underlying physicochemical
principles that allow a drug to be incorporated into a pharmaceutical
dosage form (e.g., solution, capsule).

• These principles apply whether the drug is compounded by the

pharmacist or manufactured for commercial distribution as a drug
product.
Introduction
• The finished dosage form contains the active drug ingredient in
association with nondrug (usually inert) ingredients (excipients) that
make up the vehicle, or formulation matrix.
• The drug delivery system concept holds not only the drug (or
prodrug) and its formulation matrix, but also the dynamic interactions
among the drug, its formulation matrix, its container, and the
physiologic milieu of the patient.
• These dynamic interactions are the subject of biopharmaceutics.
Introduction
• The usual relevant states of matter are gases, liquids, and solids.

• Intermolecular forces of attraction are weakest in gases and strongest

in solids. Conversions from one physical state to another can involve
simply overcoming intermolecular forces of attraction by adding
energy (heat)

• Chemical composition can have a dramatic effect on physicochemical

properties and behavior.
Introduction
• Gasses are composed of particles called molecules, continue to
collides with other molecules and with boundaries of the system.
These repletion collisions called pressure. Volume is also another
important factor that affect gases.
• Liquid show important properties such as vapor pressure and boiling
point. Molecules in the bulk phase are surrounded by similar
molecules (liquid-liquid interface) but at the surface, they are
surrounded by different molecules (liquid-air interface), which
produce surface tension.
• Solids show higher order of geometry and have stronger
intermolecular attractions than liquid and gases.
Types of systems
PHYSICOCHEMICAL BEHAVIOR
• Types of Systems:

1- Homogeneous systems
• A solution is a homogeneous system in which a solute is
molecularly dispersed, or dissolved, in a solvent.

2- Heterogeneous systems
• A heterogeneous system can be defined as a chemical system that
contains various distinct and mechanically separable parts or
phases (e.g., suspensions, emulsions).
Homogeneous Systems
The Colligative properties considered in the homogeneous
systems are:
• Vapor pressure lowering.
• Boiling point elevation.
• Freezing point depression
• Osmotic pressure.
Homogeneous Systems
• Vapor pressure lowering:
• The lowering of the vapor pressure of the solution relative to
the vapor pressure of the pure solvent is proportional to the
number of molecules of solute in the solution.
• Boiling point elevation:
• A solution of a nonvolatile solute has a higher boiling point
than a pure solvent because the solute lowers the vapor
pressure of the solvent.
• Freezing point depression
• The freezing point, or melting point, of a pure compound is
the temperature at which the solid and the liquid phases are
in equilibrium under a pressure of 1 atmosphere (atm).
• The amount of depression of the freezing point depends on
the molality of the solution
 Homogeneous Systems
• Osmosis is passive transport process
by which solvent molecules pass
through a semipermeable membrane
(a barrier through which only solvent
molecules may pass) from a region of
dilute solution to one of more
concentrated solution.
• Osmotic pressure may be defined as
the excess pressure on the solution
side to prevent the passage of solvent
into it through a semipermeable
membrane.
 Buffer

• A buffer is a mixture of salt with acid or base that resists changes in pH

when small quantities of acid or base are added.

• A buffer can be a combination of a weak acid and its conjugate base

(salt) or a combination of a weak base and its conjugate acid (salt).
 Heterogeneous systems

• A heterogeneous system can be defined as a chemical system that

contains various distinct and mechanically separable parts or phases
(e.g., suspensions, emulsions).
• Colloidal dispersions: consist of two distinct immiscible entities, the
dispersed phase (internal phase) and the dispersion medium (external
phase).
• The particles of the dispersed substance are only suspended in the
mixture, unlike a solution, within which they are completely dissolved.
 Heterogeneous systems

• Coarse dispersed systems can be classified broadly into two

pharmaceutically relevant systems:

• Suspensions.
• Emulsions.
 Heterogeneous systems

Suspensions:
• A suspension is a two-phase coarse dispersion system that is composed of
insoluble solid material dispersed in an oily or aqueous liquid medium.
• The particle size of the dispersed solid is usually 0.5 µm.
 Heterogeneous systems

Emulsions:
• An emulsion is a heterogeneous system that consists of at
least one immiscible liquid that is intimately dispersed in
another in the form of droplets.
• Emulsions are inherently unstable because the droplets
of the dispersed liquid tend to coalesce to form large
droplets until all of the dispersed droplets have coalesced
 Heterogeneous systems
Types of emulsions:

1- Oil-in-water emulsion (O/W): When the

oil phase is dispersed into a continuous
aqueous phase

2- Water-in-oil emulsion (W/O): if the

water phase is dispersed in a continuous
oil phase

Adapted from: Current trends in water-in-diesel emulsion as a fuel." The Scientific World Journal 2014
 Dispersion stability

• Particle size should be as small as possible. Smaller particles yield

slower sedimentation, or flotation, rates.
• High particulate (dispersed phase) concentrations increase the rate
of particle–particle collisions and interaction leading to instability.
• Avoidance of particle–particle interactions:
• Aggregation can be prevented by difference in electrical potential between
the charged surface of the particle and the bulk of the dispersion medium.
• The sedimentation, or flotation, rate is inversely proportional to the viscosity.
An increase in the viscosity of the dispersion medium decreases the rate of
settling, or flotation.
 Solubility

• The solubility of a compound depends on the physical and chemical

properties of the solute and the chemical properties of the solvent.

• Other factors, such as temperature, pressure, and the pH of the

solvent, also affect the solubility of solutes.

As you know that solubility is an important issue

in pharmaceutical preparations. Depending on
weather or not the drug is soluble in water, we
can determine the proper delivery system and
the route of administration.
 Solubility
• Solubility terms according to the U.S. Pharmacopeia
Solubility Term Parts of solvent required to dissolve
1 g of solute
Very soluble Fewer than 1 mL
Freely soluble 1-10
Soluble 10-30
Sparingly soluble 30-100
Slightly soluble 100-1,000
Very slightly soluble 1,000-10,000
Insoluble More than 10,000
Solubility
• Temperature significantly affects the solubility of solutes.
• As the temperature increases, the solubility of a solid increases
proportionally, for an endothermic change of state.

• However, as the temperature of a system containing a gas in

liquid is increased, the solubility decreases because of the
change in vapor pressure.
 Solubility
• Partition Coefficient (P) is useful in estimating distribution of
drugs within the body.
• Defined as the ratio of concentrations of a compound in a
mixture of two immiscible phases at equilibrium.
• Estimating distribution of drugs within the body
• {1-Octanol}
• Water

• Drugs: high P = hydrophobic

: low P = hydrophilic
Chemical kinetics and drug stability
Chemical kinetics and drug stability
• The stability of the pharmaceutical preparation is fundamental
concept in determining whether a given formulation is accepted or
rejected.

• Unstable formulation could lead to:

• Substantial loss of active ingredient from the dosage form
• Produce a toxic product that has undesirable side effects.
• Decreased bioavailability
 Rates and orders of reactions
• The rate of a reaction, or degradation rate, is the velocity with which
the reaction occurs.
• This rate is expressed as dC/dt
• dC: is the change in concentration
• dt : The given time interval
• Reaction rates depend on certain conditions:
• Reactant concentration
• Temperature
• pH
• Additives
• Radiation and catalytic agents
Rates and orders of reactions
• The order of a reaction is the way in which the concentration of the
drug or reactant in a chemical reaction affects the rate.

• The rate of a reaction, dC/dt, is proportional to the concentration to

the nth power, where n is the order of the reaction—that is, dC/dt ∞ Cn

• Usually, pharmaceutical degradation can be treated as a zero-order,

first-order, or higher order reaction
 Rates and orders of reactions
• In a zero-order reaction, the rate is
independent of the concentration of the
reactants.

• Other factors, such as absorption of light

in certain photochemical reactions,
determine the rate.

• In a first-order reaction, the rate depends

on the first power of the concentration of
a single reactant.
• In a first-order reaction, drug
concentration decreases exponentially
with time
 Rates and orders of reactions
• The half-life (t½) of a reaction is the time required for the
concentration of a drug to decrease by one-half.

• The time required for a drug to degrade to 90% of its original

concentration (t90%)
 Determination of shelf life
• The shelf life of a drug preparation is the amount of time that the
product can be stored before it becomes unfit for use, through either
chemical decomposition or physical deterioration.

• Storage temperature affects shelf life. It is generally understood to

be ambient temperature unless special storage conditions are
specified.
 Shelf-life testing
• Samples are stored at 3° to 5°C and at room temperature (20° to
25°C). The samples are then analyzed at various intervals to
determine the rate of decomposition. Shelf life is calculated from this
rate.

• Temperature-accelerated stability testing is conducted with a range

of higher temperatures. The rate constants obtained from these
samples are used to predict shelf life at ambient or refrigeration
temperatures.
Biological principle of dosage forms
Biological principle of dosage forms
• Absorption, regardless of the site depends on the drug solubility. Drugs
given in aqueous are more soluble than those given in oily solution,
suspension, or in solid form.

• Small intestine is responsible for majority of drug absorption because:

oIt has large surface area (due to villi, microvilli and valves of kreckring)
oHigh blood supply
opH range (5-8)
oSmall intestine is the most important region of GIT with respect to carrier
mediated transport.
Biological principle of dosage forms
Stomach
oThe pH of the stomach ranges 1.5-3.5 (average of 2.5) in the fasted
state, while it increases initially after meals.
oBasic drugs are solubilized rapidly in the gastric fluid.

Large intestine and colon

oThey have limited absorption compared to stomach and small
intestine.
oRestricted surface area due to lack of villi and microvilli.
 Mechanism involve in passages of drugs
across the cell membrane
• Passive transport (also called simple or lipid diffusion)
oDrugs transfer across cell membrane from high conc. to lower conc.
oNo energy is required.
oMost lipid molecules and some small hydrophilic and gases

https://www.youtube.com/watch?v=I1MZG6508IM
 Mechanism involve in passages of drugs
across the cell membrane
• Active transport
oEnergy is required
oCarrier mediated process
oAgainst concentration gradient

https://www.youtube.com/watch?v=I1MZG6508IM
Drug dosage forms and delivery systems
Drug dosage forms and delivery systems
• Oral solutions: USP “liquid preparations, intended for oral
administration, that contain one or more substances with or without
flavoring, sweetening, or coloring agents dissolved in water or
cosolvent-water mixtures.”
Drug dosage forms and delivery systems
• Oral drug solutions:

• Syrups are traditionally per oral solutions that contain high concentrations of
sucrose or other sugars.

• Elixirs are traditionally per oral solutions that contain alcohol as a cosolvent.

• Miscellaneous solutions:
• Aromatic waters
• Spirits
• Tinctures
• Mouthwashes
• Astringents : locally applied solutions that precipitate protein
Suspension
• A suspension is a heterogeneous mixture that contain solid
in liquid dispersion.
• Classification based on general classes:
• Oral suspension
• eg: Paracetamol suspension, antacids, Tetracycline HCl.
• Externally applied suspension
• eg :Calamine lotion
• Parenteral suspension
• eg: Procaine penicillin G, Insulin Zinc Suspension
Suspension
• Advantages:
• Suspension can improve chemical stability of certain drug. E.g. Procaine
penicillin G.
• Drug in suspension exhibits higher rate of bioavailability than other dosage
forms.
Order of bioavailability : Solution > Suspension > Capsule > Compressed
Tablet
• Disadvantages:
• Physical stability , sedimentation and compaction can cause problems.
• Uniform and accurate dose can not be achieved unless suspension are
packed in unit dosage form.
Suspension
• Special labels and advice for Suspensions
“Shake well before use”
“Store in a cool place”
• Suspensions have a relatively short shelf life. They are
usually required to be recently or freshly prepared, with a 1 -
4 weeks expiry date.
Suspension
Preparation
Adding the
Mixing
aqueous
suspending
Wetting solids dispersion to The
agent with the
with dispersion the solid (or preparation is
active
medium the levigated brought to the
ingredients in
(Levigation) solid) by desired volume
an aqueous
geometric
dispersion
dilution

Geometric dilution

Levigation: is the process of grinding an insoluble substance to a fine powder, while wet addition of a
suitable nonsolvent, or levigating agent, to the solid material, followed by blending to form a paste
Emulsion
• An emulsion is a heterogeneous mixture that contain liquid in liquid
dispersion

• Purposes of emulsions:
• Increased drug solubility
• Increased drug stability
• Prolonged drug action
• Improved taste
• Improved appearance
Emulsion
• Preparation:
• Wet gum method
• Dry gum method
• Bottle method
• Nascent soap method
• Wet gum method: Trituration: it is a form of comminution
(reducing the particle size of a
Emulgent is placed in the mortar substance)

Water is added to the emulgent and

is dispersed to form a mucilage

Oil is added in small amounts with

continuous trituration
Emulsion
Dry gum method:

Emulgent is placed in the mortar

Oil is added to the emulgent and is

dispersed to form a mucilage

Water is added at a time with rapid

continuous trituration
Ointments
• Ointments are semisolid preparations intended for external use.
• Purpose of ointment:
• Emollients.
• Protective.
• Vehicles
• Ideally, an ointment base should be compatible with the skin, stable,
smooth, non-irritating, non-sensitizing.
Preparation of ointment
• Incorporation Method :
• Involves the blending of an ingredient into the vehicle.
• This is done using a glass slab and a pair of spatulas for small
volumes or using a mortar and pestle for larger volumes.

• Fusion Method :
• Used to incorporate ingredients with solid, hard properties such as
waxes.
• All or some of the components of an ointment are combined by
being melted together and cooled with constant stirring until
solidified.
Suppositories
• A suppository is a solid or semisolid mass intended to be inserted into a body
orifice (i.e., rectum, vagina, urethra).
• After it is inserted, a suppository either melts at body temperature or dissolves
(or disperses) into the aqueous secretions of the body cavity.
• Suppositories are often used for local effects (e.g., relief of hemorrhoids or
infection).
• When used rectally, suppositories can provide systemic medication
Suppositories
• Rectal suppositories are useful when oral administration is
inappropriate:
• Infants
• Comatose patients
• Patients who have nausea, vomiting, or gastrointestinal disturbances
• Types of suppositories:
• Rectal suppositories
• a bullet-like shape, as the rectum contracts, a suppository of this shape moves inward.
• Suppositories for adults weigh approximately 2 g. Suppositories for infants and children
are smaller.
Suppositories
• Vaginal suppositories
• oval and typically weigh approximately 5 g.
• Antiseptics, contraceptive agents, and drugs used to treat trichomonal, monilial, or
bacterial infections are often formulated as vaginal suppositories.

• Urethral suppositories
• Typically long and tapered. They are approximately 60 mm long and 4 to 5 mm in
diameter.
• They are administered for a local effect and are most often used for anti-infective agents.
Suppositories
Some examples for suppository bases

Note: Adopted from “Comprehensive pharmacy review,” by Shargel, L et al., (2013),

Philadelphia: Lippincott Williams & Wilkins
Preparation of suppositories
1- Hand-rolling:
• Simple and old method, useful when we are preparing a small number of
suppositories.
Mixing with the grated base
in a mortar and pestle The uniformly mixed semi
The drug is made into fine
(levigation plastic mass is rolled into a
powder
and geometric dilution cylinder
techniques)

Each small cylinder is rolled

by hand divided into the requisite
until a suppository shape is number of suppositories
fashioned
 Preparation of suppositories
2- Compression Method:
• Generally used when cocoa butter is used as a base.
• This procedure generally produces a 2-g suppository.
• Used for thermolabile and insoluble drugs.
The mixture is placed into a
A uniform mixture
suppository compression
of drug and base is
device, then pressure is
prepared
applied

The mold is then

cooled and mixture is forced into
lubricated compression mold
the suppositories cavities
ejected.
 Preparation of suppositories
3- Fusion method:
• The principal way that suppositories are made commercially
• Can be used with all types of suppositories

First melting the then dispersing or dissolving

suppository base the drug in the melted base

When the mixture

has congealed, the The mixture is removed from
suppositories are the heat and poured into a
removed from the suppository mold
mold.
Powder
• A pharmaceutical powder is a mixture of finely divided drugs or
chemicals in dry form. The powder may be used internally or externally.
• Advantages of powders:
• Flexibility of compounding
• Good chemical stability
• Rapid dispersion of ingredients because of the small particle size
• Disadvantages of powders:
• Time-consuming preparation
• Inaccuracy of dose
• Unsuitability for many unpleasant-tasting, hygroscopic, and deliquescent drugs
Mixing powders
• Sifting
• Powders are mixed by passing them through sifters similar to
those used to sift flour
• Tumbling
• Is the process of mixing powders in a large container rotated by a
motorized process.
• These blenders are widely used in industry.
Capsules
• The European Pharmacopoeia (Eur. Ph.) describes capsules as follows:
'Capsules are solid preparations with hard or soft shells of various
shapes and capacities, usually containing a single dose of active
ingredient. They are intended for oral administration.”
• Most capsules are intended to be swallowed whole
• There are two types of capsules, “hard” and “soft.”
Advantages of capsules
• Capsules mask the taste and odor of unpleasant drugs and can be
easily administered.
• They are attractive
• They are slippery when moist and, hence, easy to swallow with a
draught of water.
• As compared to tablets less additives are required.
• Allow powders to be dispensed in an uncompressed form, thus
allowing for quicker dissolution and absorption of the drug following
oral dosing
Disadvantages of capsules
• They are subject to the effects of relative humidity and to microbial
contamination.
• Highly Moisture sensitive Efflorescent material cannot be
incorporated, they may cause softening / leaching
• Deliquescent materials cannot be incorporated, they may cause
hardening or brittle capsules
• The drugs which are hygroscopic absorb water from the capsule shell
making it brittle and hence are not suitable for filling into capsules.
 Hard gelatin capsules
• Preparation of filled hard capsules:
1- Preparing the formulation
2- Selecting the appropriate capsule
3- Filling the capsule shells
4- Cleaning and polishing the filled capsules
• Empty hard capsule shells are manufactured from a mixture of
gelatin, colorants.
 Hard gelatin capsules
• Storage:
• Hard capsules should be stored in tightly closed glass containers and
protected from dust and extremes of humidity and temperature.
• Sizes:

• For human use: 000(the largest) to size 5 (the smallest)

• For veterinary use: Nos. 10, 11 and 12 having capacities of 30, 15 and 7.5 g,
respectively.
Soft gelatin capsules
• Preparation:
• Soft gelatin capsules are prepared from gelatin shells. Glycerin or a
polyhydric alcohol (e.g., sorbitol) is added to these shells to make
them elastic or plastic-like. Also called a plasticizer.
• These shells contain preservatives (e.g., methyl and propyl parabens,
sorbic acid) to prevent the growth of fungi.
Soft gelatin capsules
Soft gelatin capsules may be prepared by
• Plate process, using a set of molds to form the capsules.
• By the Rotary or reciprocating die processes by which they are
produced, filled, and sealed in a continuous operation.
• Most soft gelatin capsules are prepared by the rotary die process.

Rotary die
Soft gelatin capsules
Uses:
• Soft gelatin shells are oblong, elliptical, or spherical.
• They are used to contain liquids, suspensions, pastes, dry powders,
or pellets.
• Ex: Demeclocycline hydrochloride (Declomycin, Lederle), Chloral
hydrate, digoxin (Lanoxicaps, GlaxoSmithKline), vitamin A, and vitamin
E.
Tablets
• Tablets are the most commonly used solid dosage form.

• Advantages:
• Easy to swallow and least tendency for "hang-up".
• Light, compact and simple to identify.
• Large-scale production at low cost.
• Modified-release products can be made.
• Physical or chemical incompatible active pharmaceutical substances can be
incorporated.
Tablets
• Disadvantages:
• Difficult to take by children and the elderly.
• Absorption depend on physiological factors.
• Low-density, amorphous or flocculent drugs resist compression.
• Poor wetting and slow dissolution drugs are difficult to formulate.
• Coating required to mask objectionable taste or odor, or to protect
drug from oxygen or moisture.
Types of tablets
• Uncoated • Coated
A. Oral compressed tablets i. Film coated tablet
ii. Sugar coated tablet
B. Used in oral cavity iii. Enteric coated tablet
i. Chewable tablet iv. Implant
ii. Sublingual tablet v. Modified-release tablet.
iii. Lozenge tablet
iv. Dental cone
C. Used to prepare solution
i. Soluble tablet
ii. Effervescent tablet
iii. Dispensing tablet
iv. Hypodermic tablets
D. Administered by other route
i. Vaginal tablets
ii. Implants
Types of tablets

Film-coated tablets are compressed tablets that are coated with a thin layer of a
water insoluble or water-soluble polymer (e.g., hydroxypropyl methylcellulose
[hypromellose], ethylcellulose, povidone, PEG).

Note: Adopted from “Comprehensive pharmacy review,” by Shargel, L et al., (2013), Philadelphia:
Lippincott Williams & Wilkins
Tablets used in the oral cavity
Buccal and sublingual tablets:
1. They are generally small, flat, oval tablets.
2. Allow absorption through the oral mucosa after they dissolve in the
buccal pouch (buccal tablets) or below the tongue (sublingual tablets).
3. Useful for drugs that are destroyed by gastric juice or poorly absorbed
from the intestinal tract.
Eg. sublingual nitroglycerin tablets, which dissolve very promptly to give
rapid effects in angina pain.
Effervescent tablet:
a. Prepared by compressing granular effervescent salts or other
materials (e.g., citric acid, tartaric acid, sodium bicarbonate)
b. Release carbon dioxide gas when they come into contact with
water.
Sugar coated Tablets
• Steps in Sugar coating
1. Water proofing and sealing of tablets (if needed)
2. Subcoating
3. Smoothing and final rounding
4. Finishing and coloring
5. Polishing
6. Printing
 Film-Coated Tablets
• The film-coating process, which places a thin, skintight coating of a
plastic-like material over the compressed tablet, was developed to
produce coated tablets having essentially the same shape, and size as the
originally compressed tablet.

• Film coating has proved successful as a result of the many advantages

offered, including:

1. Minimal weight increase (typically 2 to 3% of table core weight)

2. Significant reduction in processing times.
3. Increased process efficiency and output.
4. Increased flexibility in formulations.
5. Improved resistance to chipping of the coating.
 Enteric Coated tablets

• Enteric coating tablets have delayed-release

feature.
• The design of an enteric coating may be based
upon the transit time required for the
passage of the dosage form from the stomach
into the intestines.
• More usually, an enteric coating is based upon
the pH of the environment, being designed to
resist dissolution in the highly acid
environment of the stomach but yielding to
the less acid environment of the intestine.
Tablet preparation
• The methods used for tablet
manufacture are :
• Direct Compression
• Granulation Method
• Dry Granulation
• Wet Granulation
Processing problems (defects)
• Capping is the partial or complete separation of the top or bottom
crown from the main body of the tablet. Lamination is separation of a
tablet into two or more distinct layers. These problems are usually
caused by entrapment of air during processing.
Processing problems
• Picking is removal of the surface material of a tablet by a punch.
Sticking is adhesion of tablet material to a die wall.
• These problems are caused by excessive moisture or the inclusion of
substances with low melting temperatures in the formulation.
Processing problems
• Mottling is unequal color distribution, with light or dark areas
standing out on an otherwise uniform surface.
• This problem occurs when a drug has a different color than the
tablet excipients or when a drug has colored degradation products.
• Colorants solve the problem but can create other problems.
Tablet evaluation and control
• The appearance of the tablet
• size, shape, color, odor, taste, surface, texture, physical flaws, consistency

• Hardness and resistance to friability

• Tablet hardness testers measure the degree of force required to break a
tablet.
• Friabilators determine friability (the tendency of the tablet to crumble).
Tablet evaluation and control
• Resistance to weight loss indicates the ability of the tablet to
withstand abrasion during handling, packaging, and shipping.
• Compressed tablets that lose 0.5% to 1% of their weight are usually
considered acceptable.
• Weight variation standard:
• Applied to tablets that contain 50 mg or more of drug substance when the
drug substance is 50% or more (by weight) of the dosage form unit.
• Content uniformity:
• The USP defines content uniformity tests for tablets that contain 50 mg or less
of drug substance.
Tablet evaluation and control
• Disintegration: is evaluated to ensure that the drug substance is fully
available for dissolution and absorption from the gastrointestinal tract.
• Disintegration time: is the time required for complete break down of
tablets into small fragments that passed from 10 mesh sieve.

• Disintegration time limit:

1. Uncoated and film coated tablet: 5-30 minutes
2. Enteric coated tablet: Not dissolve in 0.1 N HCl for1 hr and should
dissolve within 2 hours in pH 6.8 buffer.
3. Sugar coated: 45 minutes.
4. Buccal tablets: Up to 4 hrs
Aerosol products
• Aerosol products are pressurized dosage forms.
• They deliver drug systemically or topically.
• Aerosols consist of:
• Propellants
• Product concentrate
• Container
• Valves and actuators
• Aerosols are used for topical drug delivery, and systemic delivery
(metered dose inhalers MDIs)
Aerosol products
• Propellants used in aerosol products:
• Compressed gases: carbon dioxide,
nitrogen, and nitrous oxide.

• Liquefiable gases:
• saturated hydrocarbons (n-butane,
isobutane, propane)
• chlorofluorocarbons (CFCs)
Aerosol products
• Advantages:
• Easy and convenient to application
• Stability is enhanced
• Irritation produced by mechanical application of topical medication is reduced
or eliminated.
• Disadvantages:
• Expensive
• Not environmentally friendly.
Controlled-release dosage forms
• Introduction:
• The United States Pharmacopoeia (USP) defines the modified-release (MR)
dosage form as “the one for which the drug release characteristics of time
course and/or location are chosen to accomplish therapeutic or convenience
objectives not offered by conventional dosage forms such as solutions,
ointments, or promptly dissolving dosage forms”.
• They are designed to release drug substance slowly to provide prolonged
action in the body.
• Terms used: delayed-release, sustained-action, prolonged-action, sustained-
release, prolonged-release, timed-release, slow-release, extended-action, and
extended-release forms.
Controlled-release dosage forms
• Advantages of controlled-release forms
• Fewer problems with patient compliance
• Use of less total drug
• Fewer local or systemic side effects
• Improved treatment efficiency
• More rapid control of the patient’s condition
• Improved bioavailability for some drugs
• Improved ability to provide special effects (e.g., morning relief of arthritis by
bedtime dose)
 Controlled-release dosage forms
• Pharmaceutical mechanisms of Sustained-release DDS:
Coated beads
• Coated beads or granules: e.g., Spansules, GlaxoSmithKline,
Sequels, Wyeth

• Microencapsulation: is a process by which solids, liquids, or

gases are encased in microscopic capsules. Microencapsulation

• Matrix tablets: The most common method of preparation is

mixing of the drug with the matrix material followed by
compression of the material into tablets. Examples include
Gradumet (Abbott) and Dospan (Aventis). Matrix
Controlled-release dosage forms
• Osmotic systems: This system requires only osmotic pressure to
be effective. It is essentially independent of pH changes in the
environment. Ex: the Oros system (Alza), Glucotrol XL, Procardia XL

• Ion-exchange resins: Ion-exchange preparations usually involve an

insoluble resin capable of reacting with either an anionic or
cationic drug. Examples include Ionamin capsules
 Parenteral Administration
A. Intravenous injection.
o (100% bioavailability)
o Immediate onset of action,
o Large quantities can be given, fairly pain free
o Greater risk of adverse effects
B. Intramuscular injection.
o The rate of absorption depends on the vascularity of the muscle site, the lipid solubility
of the drug, and the formulation matrix.
o Very rapid absorption of drugs in aqueous solution
o Pain at injection sites
C. Subcutaneous injection.
o Slow and constant absorption
o Absorption is limited by blood flow, affected if circulatory problems exist
o Concurrent administration of vasoconstrictor will slow absorption
Materials and methods used
Materials and methods used in preparation
and use of drug forms
• Commonly Used Excipients in Tablets

Adopted from “The APhA complete review for the FPGEE,” by Gourley, D. R. (2010), Washington, D.C.: American
Pharmacists Association.
 Materials and methods used in preparation
and use of drug forms
• Commonly Used Excipients in Capsules

Adopted from “The APhA complete review for the FPGEE,” by Gourley, D. R. (2010), Washington, D.C.: American
Pharmacists Association.
Materials and methods used in preparation
and use of drug forms
• Commonly Used Excipients in Liquid dosage forms

Adopted from “The APhA complete review for the FPGEE,” by Gourley, D. R. (2010),
Washington, D.C.: American Pharmacists Association.
Biotechnology
What is biotechnology?
• The term biotechnology was coined in
1917, by Hungarian engineer, karl Erky, to
describe a process for large scale
production of pigs

• Biotechnology can be defined as the

application of technology using the living
organism to obtain useful products.
Development of biotechnology
• Ancient Biotechnology: early history relates to food and shelter,
includes domestication.

• Classical Biotechnology: fermentation food production and medicine.

• Modern Biotechnology: manipulates genetic information in an

organism. genetic engineering.
Modern biotechnology process
• Genetic engineering: It is in vitro
DNA technology used to isolate
genes from an organism
manipulating them in the
laboratory as per desire and insert
them into other cell or system for
specific character.
Recombinant DNA (rDNA)
• Recombinant DNA technology is one of the recent Stanely Cohen Herbert Boyer
advances in biotechnology, which was developed by
two scientists named Boyer and Cohen in 1973.
• Recombinant DNA technology works by taking DNA
from two different sources and combining that DNA
into a single molecule. That alone, however, will not do
much.
• Recombinant DNA technology only becomes useful
when that artificially-created DNA is reproduced. This is
known as DNA or gene cloning.
 Structure of DNA
Structurally it forms a large
sequence of nucleotides
attached covalently to each
other.

Nucleotides are composed of a

nitrogenous base, a five-carbon
sugar, and a phosphate group.

DNA is composed of a
phosphate-deoxyribose sugar
backbone and the nitrogenous
bases adenine (A), guanine (G),
cytosine (C), and thymine (T).
RNA has ribose sugar and the
nitrogenous bases A, G, C, and
uracil (U).

Bailey, Regina. "Learn About Nucleic Acids and Their Function." ThoughtCo, Feb. 11, 2020, thoughtco.com/nucleic-acids-373552.
 Restriction and ligase enzymes

Restriction enzyme

Ligase enzyme

Recombinant DNA

https://socratic.org/questions/why-are-restriction-enzymes-important-for-recombinant-dna-technology
 Six steps of rDNA

1. Isolating (vector and target gene)

2. Cutting (Cleavage)
3. Joining (Ligation)
4. Transforming
5. Cloning
6. Selecting (Screening)

Different steps involved in cloning of foreign DNA into plasmid vector. Adapted from
https://www.researchgate.net/publication/322152584_Practical_Manual_Plant_Genetic_Engineering
Overview of protein expression

Adapted from
http://www.bio.utexas.edu/faculty/sjasper/bio212/biotech.html
Applications of rDNA technology
• 1. Analysis of Gene Structure and expression
• 2. Pharmaceutical Products
o Drugs- human insulin
o Vaccines-recombinant vaccines
• 3. Genetically modified organisms (GMO)
o Transgenic plants (Bt.crops)
o Transgenic animal
• 4. Application in medicine
o Gene therapy
Applications of rDNA technology
• Pharmaceutical companies already are producing molecules
made by recombinant DNA to treat human diseases.

• Recombinant bacteria are used in the production of human

growth hormone and human insulin
Applications of rDNA technology (examples)
Therapeutic proteins Potential applications Expression cells

Insulin Diabetes mellitus E.coli

Erythropoietin Anemia Mammalian cell lines
Hepatitis B vaccine Hepatitis B S. cerevisiae
α interferon Leukemia E. coli
β interferon Sclerosis Chinese hamster ovary
cells
ℽ interferon Chronic granulomatous E. coli
disease
Streptokinase Acute myocardial E.coli
infarction
Analysis of Gene Structure and Expression
• Using specialized recombinant DNA techniques, researchers have
determined vast amounts of DNA sequence including the entire genomic
sequence of humans and many key experimental organisms.
• This enormous volume of data, which is growing at a rapid pace, has
been stored and organized in two primary data banks:

1- the GenBank at the National Institutes of Health, Bethesda,

Maryland, and
2- the EMBL Sequence Data Base at the European Molecular Biology
Laboratory in Heidelberg, Germany
Vaccines
• Vaccines-administration of antigen to elicit an immune response that
shall Protect against infections •
• Types of vaccines:
1.Dead bacteria or inactivated viruses
2.Attenuated bacteria
3.Subunit vaccines –viral fragments.

• New generation vaccines –recombinant vaccines 1987- first

recombinant vaccine for hepatitis came for public use (S. cerevisiae)
 Insulin using r-DNA

• Diabetes-increased glucose concentration

180mg/dl
• Early years –insulin isolated and purified from pigs and
cow...
• leads problems -allergy in some people, sacrifice of
animals???
• Attempts to make rec –insulin started in 1970.
• Technique involves - inserting human insulin gene in
promoter of lac operon of the plasmid of E.coli Bacteria .
1980- rec insulin produced and ready for clinical trials.
1982-approval for human use.
• 1986-ELI- LILLY approval to market HUMULIN..
Gene therapy
Gene therapy
gives
patients a healthy
version of a
defective gene

Cell has defective Healthy gene is Cell function is

gene introduced restored

PAGE 115
Naked DNA

• A naked DNA injection, without any carrier, is the simplest and safest physical/mechanical approach of gene
delivery.
Naked DNA
degradation
after systemic
administration

Naked DNA injection The human cell

PAGE 116
CONTACT ME ON

@oa_madkhali

omadkhali@jazanu.edu.sa
omadkhal@gmail.com
References
• Gourley, D. R. (2010). The APhA complete review for the Foreign Pharmacy Graduate Equivalency Examination. Washington, D.C.:
American Pharmacists Association.
• Shargel, L., Mutnick, A. H., Souney, P. F., Swanson, L. N., & Shargel, L. (2013). Comprehensive pharmacy review. Philadelphia:
Lippincott Williams & Wilkins.
• Sharma, A. (1970, January 01). Retrieved February 25, 2019, from
https://pharmaceuticaleducation.blogspot.com/2017/06/capping-lamination-capping-is-partial.html
• Cutter Mill:Operating Principle, Uses, advantages and Disadvantag. (2018, March 23). Retrieved February 25, 2019, from
https://www.pharmapproach.com/cutter-mill/
• (2016, January 29). Retrieved February 25, 2019, from http://present5.com/suppositories-author-as-yu-plaskonis/
• Intramolecular and intermolecular forces. (n.d.). Retrieved February 25, 2019, from https://www.khanacademy.org/test-
prep/mcat/chemical-processes/covalent-bonds/a/intramolecular-and-intermolecular-forces
• 3,000 Solved Problems In Chemistry. (n.d.). Retrieved February 25, 2019, from https://www.mhprofessional.com/9780071755009-
usa-3000-solved-problems-in-chemistry
• Libretexts. (2019, February 23). 12.1: Crystalline and Amorphous Solids. Retrieved February 25, 2019, from
https://chem.libretexts.org/Bookshelves/General_Chemistry/Map:_Chemistry_(Averill_and_Eldredge)/12:_Solids/12.1:_Crystallin
e_and_Amorphous_Solids
• https://www.slideshare.net/sardar1109/biotechnology-and-its-application-37416651