SlideShare a Scribd company logo
1 of 71
Pharmaceutical dosage forms
(Unit 3)
Presented by:
Arushe Tickoo
DTU, Delhi
Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are
marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a
particular configuration (such as a capsule shell, for example), and apportioned into a particular dose.
For example, two products may both be amoxicillin, but one is in 500 mg capsules and another is in 250
mg chewable tablets.
Depending on the method/route of administration, dosage forms come in several types. These include
many kinds of
1. liquid,
2. solid, and
3. semisolid dosage forms.
Common dosage forms include pill, tablet, or capsule, drink or syrup, and natural or herbal form such as
plant or food of sorts, among many others.
Dosage forms
Types
OralOphthalmic InhalationalParenteral Topical
• Aerosol
• Inhaler
• Nebulizer
• Smoking
• Vaporizer
• Intradermal (ID)
• Subcutaneous (SC)
• Intramuscular (IM)
• Intra-osseous (IO)
• Intra-peritoneal (IP)
• Intravenous(IV)
• Cream, gel, balm,
lotion or ointment
• Ear drops (otic)
• Eye drops
• Skin patch
• Dermal patch
• Pill
• Thin film
• Liquid solution/
suspension
Powder
• Pastes (e.g.,
Toothpaste)
•Drops
•Ointment
•Liquid solution
An excipient is a pharmacologically inactive substance formulated alongside the active
pharmaceutical ingredient of a medication.
Purposes served by excipients:
 Provide bulk to the formulation.
 Facilitate drug absorption or solubility and other pharmacokinetic considerations.
 Aid in handling of “API” during manufacturing .
 Provide stability and prevent from denaturation
Excipient
Ideal properties
A list of Pharmaceutical Excipients used in
pharmaceutical preparations
Fillers.
Binders.
Disintegrants.
Coatings.
Sorbents.
Antiadherent.
Lubricants.
Glidants.
Preservatives.
Antioxidants.
Flavoring Agents.
Sweeting Agents.
Coloring Agents.
Solvent & Co-solvent.
Buffering Agents.
Chelating Agents.
Viscosity imparting Agents.
Surface Active Agents.
Humectants .
• Fillers:
Fillers typically also fill out the size of a tablet or capsule, making it practical to produce and
convenient for the consumer to use.
Plant cellulose and dibasic calcium phosphate are used popularly as fillers
Function of fillers:
Fillers add volume and/or mass to a drug substance, thereby facilitating precise metering and
handling thereof in the preparation of dosage forms . Used in tablets and capsules.
• Binders:
Binders hold the ingredients in a tablet together . Binders ensure that tablets and granules can be formed
with required mechanical strength, and give volume to low active dose tablets .
Typical features of binders:
A binder should be compatible with other products of formulation and add sufficient cohesion to the
powders .
Examples include gelatin, cellulose, cellulose derivatives, polyvinylpyrrolidone, starch, sucrose and
polyethylene glycol.
• Disintigrants:
Disintegrants are substances or mixture of substances added to the drug formulations, which facilitate
dispersion or breakupa of tablets and contents of capsules into smaller particles for quick dissolution when
it comes in contact with water in the GIT
Examples:
polyvinylpyrrolidone , carboxymethyl cellulose, sodium starch glycolate
• Coating Agent:
Coating is a process by which an essentially dry, outer layer of coatinag material is applied to the surface of
a dosage form. Three types of coating agents are used pharmaceutically, Film coating, Sugar coating,
Compression coating.
Examples: HPMC, MC, HPC
• Sorbents:
Sorbents are materials that soak up oil from the water.
Examples:
i. Natural sorbents- peat moss, sawdust, feathers, and anything else natural that contains carbon.
ii. Synthetic sorbents- polyethylene and nylon
• Glidants
Glidants are used to promote powder flow by reducing interparticle friction and cohesion. These are used in
combination with lubricants as they have no ability to reduce die wall friction.
Examples include fumed silica, talc, and magnesium carbonate.
• Lubricants
Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule
filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between
the solid and die wall.
Examples: Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic
acid are the most frequently used lubricants in tablets or hard gelatin capsules.
Preservatives
Some typical preservatives used in pharmaceutical formulations are:
1) Antioxidants like vitamin A, vitamin E, vitamin C, retinyl palmitate, and selenium
2) The amino acids cysteine and methionine
3) Citric acid and sodium citrate
4) Synthetic preservatives like the parabens: methyl paraben and propyl paraben.
Oral liquid dosage forms include solutions, syrups, suspensions, elixirs and concentrates. They offer better
patient compliance in people who find swallowing pills or capsules difficult, and more flexible dosage control
than a fixed-dose tablet.
Oral liquid
Creams and ointments contain a different proportion of oil to water. Ointments have a higher concentration of
oil, compared to creams. The more oil, the greasier and stickier the product. Creams may work better on larger
areas of the skin because of their "spreadability" factor, compared to ointments.
Several factors are taken into consideration when selecting a topical product. Skin absorbs a cream more
quickly, whereas an ointment will remain on the skin longer and take a longer time to absorb.
Ointments
An ointment is a homogeneous, viscous, semi-solid preparation, most commonly a greasy, thick oil (oil 80% -
water 20%) with a high viscosity, that is intended for external application to the skin or mucous membranes.
Ointments have a water number that defines the maximum amount of water that it can contain.
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.
Granules are produced to enhance the uniformity of the API (active pharmaceutical
ingredient (API) in the final product, to increase the density of the blend so that it occupies less
volume per unit weight for better storage and shipment, to facilitate metering or volumetric
dispensing, to reduce dust during granulation process to reduce toxic exposure and process-related
hazards, and to improve the appearance of the product
Granulation
Techniques
Wet granulation Dry granulation
The dry granulation process is used to
form granules without using a liquid
solution because the product granulated
may be sensitive to moisture and heat.
Forming granules without moisture
requires compacting and densifying the
powders. In this process the primary
powder particles are aggregated under
high pressure. Sweying granulator or a
high-shear mixer-granulator can be used
for the dry granulation.
Dry granulation
Pneumatic Dry Granulation (PDG)
Pneumatic dry granulation (PDG), an innovative dry granulation technology, utilizes roller compaction
together with a proprietary air classification method to produce granules.
• Granules are produced from powder particles by
initially applying mild compaction force by
roller compactor
• The fine particles and/or smaller granules are
separated from the intended size granules in a
fractioning chamber
• The entrained fine particles and/or small
granules are then transferred to a device such as
a cyclone and are either returned to the roller
compactor for immediate re-processing
(recycling or recirculation process)
• Placed in a container for reprocessing later to
achieve the granules of desired size
In wet granulation, granules are formed by the addition of a granulation liquid onto a powder bed which is
under the influence of an impeller (in a high-shear granulator), screws (in a twin screw granulator) or air (in a
fluidized bed granulator). The agitation resulting in the system along with the wetting of the components within
the formulation results in the aggregation of the primary powder particles to produce wet granules
Wet granulation
Reverse wet granulation
Reverse wet granulation or reverse-phase wet granulation is a new development in the wet granulation
technique that involves the immersion of the dry powder formulation into the binder liquid followed by
controlled breakage to form granules
Steam Granulation
In steam granulation as a new wet granulation technique, water steam is used as binder instead of traditional liquid
water as granulation liquid
Moisture-Activated Dry Granulation (MADG)
This technique is a variation of conventional wet granulation technique. It uses very little water to activate a binder and
initiate agglomeration. This technique involves two steps,
1) wet agglomeration of the powder particles, and
2) moisture absorption or distribution.
Freeze granulation
Freeze granulation technology, spray freezing and subsequent freeze drying, involves spraying droplets of a
liquid slurry or suspension into liquid nitrogen followed by freeze-drying of the frozen droplets. By spraying a
powder suspension into liquid nitrogen, the drops are instantly frozen into granules.
Foam granulation
Foam granulation or foamed binder granulation technology, analogous to spray agglomeration, involves the
addition of liquid/aqueous binder as foam instead of spraying or pouring liquid onto the powder particles.
SUSTAINED RELEASE DOSAGE FORMS
Drug delivery systems refer to the technology utilized to present the drug to the desired body site for
drug release and absorption.
IDEAL DRUG DELIVERY SYSTEM should deliver drug at a rate dictated by the needs of the
body over the period of the treatment and it should channel the active entity solely to the site of action.
SUSTAINED RELEASE DRUG DELIVERY is defined as any of the dosage form that maintains
the therapeutic blood or tissue levels of drug by continuous release of medication for a prolonged
period of time, after administration of a single dose.
Sustained release describes the release of drug substance from a dosage form or delivery system over
an extended period of time.
Also referred to as prolonged-release (PR), slow release (SR), sustained action (SA), prolonged action
(PA) or extended-release (ER).
1. SUSTAINED RELEASE DRUG DELIVERY
• Contains loading dose + maintenance dose.
• Loading dose is immediately released to produce quick onset of action.
• Maintenance dose is released at a controlled rate so that the plasma concentration remains
constant above Minimum Effective Concentration (MEC).
• Plasma concentration comes down according to first order elimination kinetics.
2. Delayed release dosage forms
On delayed release dosage forms one or more immediate release units are incorporated into a
single dosage form.
e.g. repeat action tablet, enteric coated tablet.
Sustained release dosage
form
• Constitutes dosage form that provides
medication over extended period of time
• SRDF generally do not attain zero order
release kinetics
• Usually do not contain mechanisms to
promote localization of the drug at active
site.
Controlled release dosage
form
• Constitutes dosage form that maintains
constant drug levels in blood or tissue
• Maintains constant drug levels in the blood
target tissue usually by releasing the drug in a
zero order pattern.
• Controlled dosage forms contain methods to
promote localization of the drug at active site.
Materials Used in Coating of Sustained Release Dosage Forms (Encapsulation)
 Mixtures of waxes [bees wax, carnauba wax, etc] with glyceryl monostearate , stearic
acid , glyceryl mono palmitate and cetyl alcohol.These provide coatings that are
dissolved slowly or broken down in the GIT.
 Shellac and zein – polymers that remain intact until the PH of the GI contents become
less acidic
 Ethyl cellulose , which provides a membrane around the dosage form and remains intact
throughout the GIT. However, it does permit water to permeate the film, dissolve the
drug , and diffuse out again.
 Acrylic resins , which behave similarly to ethyl cellulose as a diffusion controlled drug
release coating material.
 Cellulose acetate [di acetate and tri acetate]
 Silicone elastomers.
Advantages of a controlled drug delivery system
1) Frequency of drug administration is reduced – patient compliance is improved.
2) In multiple dosing of conventional dosage forms the blood level of drug shows oscillatory
characteristic. In controlled release dosage form the blood level is evenly maintained.
3) The safety margin of high potency drugs can be increased and thus side-effects or adverse
effects can be minimized.
4) Total amount of drug administered can be reduced because of maximum utilization.
5) Reduction in health care costs through improved therapy, shorter treatment period, less
frequency of dosing and reduction in personnel time to dispense, administer and monitor
patients.
Disadvantages of controlled release dosage forms
1) Decrease systemic availability in comparison to immediate release conventional dosage forms, this
may be due to incomplete release, increased first-pass metabolism, increased instability, insufficient
residence time for complete release site specific absorption, pH dependent solubility etc.
2) Poor in vitro-in vivo correlation.
3) Possibility of dose dumping due to food, physiologic or formulation variables or chewing or oral
formulations by the patient and thus increased risk of toxicity.
4) Retrieval of drug is difficult in case of toxicity, poisoning or hypersensitivity reactions.
5) Reduced potential for dosage adjustment of drugs normally administered in varying strength.
6) Higher cost of formulation.
Blood products and therapeutic enzymes
Blood and blood products constitute a major group of traditional biologics. The main components of
blood are the red and white blood cells, along with platelets and the plasma in which these cellular
elements are suspended. Whole blood remains in routine therapeutic use, as do red blood cell and
platelet concentrates.
Major blood products that find therapeutic application
Whole blood
Red blood cells
Platelet concentrate
Plasma and plasma protein fraction
Albumin
Clotting factors (particularly factors VIIa, VIII, IX and XIII)
Haemoglobin
Recombinant proteins
1. Insulin
• hormone produced by beta
cells in the pancreas
→ allows glucose to pass into
cells
→ suppresses excess
production of sugar in the liver
and muscles
→ suppresses breakdown of fat
for energy
beta cells in pancreas
preproinsulin
proinsulin
insulin + C-peptide
Producing A and B chains separately
Recombinant glycoproteins
2. Interferons
• glycoproteins that “interfere” with viral propagation in
cell cultures
• group of small proteins with 140-170 amino acids
• secretory protein produced from viral-infected cells,
induces antiviral state in neighboring cells
Interferon interferes with viral replication in protected cells
3 main types of interferons:
1. IFN-α (25 subtypes) – produced from β -lymphocytes
2. IFN-β – fibroblasts – produced from fibroblasts
3. IFN-γ – T-lymphocytes – produced from T-lymphocytes
• mode of action not fully understood → synthesis of host enzymes that
degrade viral RNA and inhibit protein synthesis
1. IFN-alpha – uses transformed human cell lines (B-lympphoblastoid cell line),Grow
well in suspension with serum-free medium, first product from a human tumor line
licensed for human therapy- used to treat leukemia
2. IFN-beta – one of the only human interferons that are glycosylated (along with IFN-
a2), higher activity when glycosylated
Ifn-b secreted in response to viral infection or to double stranded RNA
May be used in treatment of tumors, but has short half-life in blood, can’t make it to
tumor
Recombinant forms may be used to fight other diseases, such as multiple sclerosis
(disease of the central immune system, T-lymphocyte breakdown of nerve cells)
3. IFN-gamma – production stimulated by a variety of antigens, most widely used in
staphylococcal enterotoxin A
Anti-tumor effects of IFN-gamma are strongest of the three
5. Erythropoietin (EPO)
• glycoprotein hormone
produced by the kidney
(hypoxia triggers EPO
production)
• required for continuous red
blood cell production in bone
marrow (erythropoiesis)
• absence of EPO results in
impairment of red blood cell
production → anemia
• anemia treated with exogenous
EPO
Structure of erythropoietin
Fig. 12.11
Recombinant human Erythropoietin
Ser126
Asn24
Asn38
Asn83
Non-glycosylated Glycosylated
18 kDa
39 kDa
Fig. 12.12
3. Plasminogen activators
• thrombosis (formation of
blood clots) is a major cause of
premature death
• deposition of fibrin in the
circulatory system, blocks
blood flow
• formation of insoluble fibrin
controlled by clotting cascade
formed during wound healing
• t-PA (tissue-plasminogen
activator) initiates fibrinolysis
(proteolytic cleavage of fibrin)
disulphide bond
N-glycan
Tissue-plasminogen activator
Plasminogen Plasmin
Coagulation Fibrin
(insoluble)
Fibrin products
(soluble)
Fibrinolysis
Factor VIII
• large glycoprotein (265 kDa)
• gene – 186 kB, 26 exons, 25 introns (overlapping strands of DNA
from genomic and cDNA aligned, without introns)
• BHK cells transfected with expression vector containing gene encoding
Factor VIII
4. Blood-clotting factors
• Hemophilia is a sex-linked (x-chromosome) genetic disease
• inactive clotting cascade in blood, can’t form fibrin
→ hemophilia A – absence of factor VIII
→ hemophilia B – absence of factor IX
Factor IX
• plasma glycoprotein (57 kDa) secreted by hepatocytes
• called “Christmas factor”, after first family diagnosed with clotting
deficiency
• gene cloned into rat hepatoma cell line
→ contains enzymes for post-translation modifications
• produces biologically active protein with correct tertiary folding and
glycosylation
• stabilized by addition of Willebrand factor, normally found as a combined
protein complex in blood
The clotting cascade
Wound surface contact
Factor XII Factor XIIa
Factor XI Factor XIa
Factor IX Factor IXa
+ Factor VIII +
Factor X Factor Xa
Prothrombin Thrombin
Fibrinogen Fibrin clot
+Factor V
Thrombin
Analytical methods and test for various drugs and pharmaceuticals
• In the field of pharmaceutical research, the analytical investigation of bulk drug materials,
intermediates, drug products, drug formulations, impurities and degradation products, and
biological samples containing the drugs and their metabolites is very important.
• From the commencement of official pharmaceutical analysis, analytical assay methods
were included in the compendial monographs with the aim to characterize the quality of
bulk drug materials by setting limits of their active ingredient content.
• In recent years, the assay methods in the monographs include titrimetry, spectrometry,
chromatography, and capillary electrophoresis
The data in Table 2
based on the edition
of European (The
European
Pharmacopoeia and
Council of Europe,
2002) and US
(United States
Pharmacopoeia,
2004)
pharmacopoeias.
Analytical techniques
Titrimetric techniques
Titration, also known as titrimetry, is used to determine the
unknown concentration of an identified analyte. It is also
known as volumetric analysis.
A reagent, called the titrant or titrator is prepared as a standard
solution. A known concentration and volume of titrant reacts
with a solution of analyte or titrand to determine concentration.
Titrimetric methods have been used for the determination of
captopril, albendozole and gabapentin in commercial dosage
forms. Sparfloxacin was determined by the non-aqueous
titration method.
Chromatographic technique
1. Thin layer chromatography
Although an old technique yet it finds a lot of application in the
field of pharmaceutical analysis. In thin layer chromatography, a
solid phase, the adsorbent, is coated onto a solid support as a
thin layer usually on a glass, plastic, or aluminum support.
Several factors determine the efficiency of this type of
chromatographic separation. First the adsorbent should show
extreme selectivity toward the substances being separated so as
to the dissimilarities in the rate of elution be large.
TLC has been utilized for the determination of some steroids,
pioglitazone, celecoxib and noscapine.
2. High-performance liquid chromatography (HPLC)
HPLC is an advanced form of liquid chromatography used in separating the complex mixture of
molecules encountered in chemical and biological systems, in order to recognize better the role of
individual molecules.
The specificity of the HPLC method is excellent and simultaneously sufficient precision is also
attainable.
3. Gas chromatography
Moving ahead with another chromatographic technique, gas chromatography is a powerful separation
technique for detection of volatile organic compounds. Combining separation and on-line detection
allows accurate quantitative determination of complex mixtures, including traces of compounds down
to parts per trillions in some specific cases. The creation of high-molecular mass products such as
polypeptides, or thermally unstable antibiotics confines the scope of this technique.
Recently, gas chromatography has been used for assay of drugs such as isotretinion, cocaine and
employed in the determination of residual solvents in betamethasone valerate
Spectroscopic techniques
1. Spectrophotometry
Another important group of methods which find an important place in pharmacopoeias are
spectrophotometric methods based on natural UV absorption and chemical reactions. Spectrophotometry is
the quantitative measurement of the reflection or transmission properties of a material as a function of
wavelength.
The use of UV–Vis spectrophotometry especially applied in the analysis of pharmaceutical dosage form has
increased rapidly over the last few years
Ultraviolet and visible (UV-Vis) absorption spectroscopy is the measurement of the attenuation of a beam
of light after it passes through a sample or after reflection from a sample surface. Absorption measurements
can be at a single wavelength or over an extended spectral range.
Near infrared spectroscopy (NIRS)
Near-infrared spectroscopy (NIRS) is a spectroscopic method that uses the near-infraredregion of
the electromagnetic spectrum (from about 700 nm to 2500 nm).Near infrared spectroscopy (NIRS) is
a rapid and non-destructive procedure that provides multi component analysis of almost any matrix
Fluorimetry and Phosphorimetry
In fluorescence spectrometry both an excitation spectrum
(the light that is absorbed by the sample) and/or an
emission spectrum (the light emitted by the sample) can be
measured. The concentration of the analyte is directly
proportional with the intensity of the emission.
A form of fluorimetry in which phosphorescence of a sample is
measured in conjunction with a pulsed source of radiation
Phosphorescence is a type of photoluminescence related to
fluorescence. Unlike fluorescence, phosphorescent material does
not immediately re-emit the radiation it absorbs. The slower
time scales of the re-emission are associated with "forbidden"
energy state transitions
Phosphorimetry
INTRODUCTION
• Packaging is the science, art and technology of enclosing or protecting
products for distribution, storage, sale, and use.
• Pharmaceutical packaging can be defined as the economical means of
providing presentation, protection, identification , information, convenience,
compliance , integrity and stability of the product .
FUNCTIONS OF PACKAGING
• Product Identification:- Packaging greatly helps in identification of
products.
• Product Protection:- Packaging protects the contents of a product from
spoilage, breakage, leakage, etc.
• Facilitating the use of product:- Packaging should be convenience to
open, handle and use for the consumers.
• Product Promotion:- Packaging is also used for promotional and
attracting the attention of the people while purchasing.
PHARMACEUTICAL PACKAGING
Secondary packaging -
Is outside the primary packaging perhaps used to
group primary package together.
Ex. Boxes, cartons
Tertiary packaging- is used to bulk handling and shipping.
Ex. Barrel, container, edge protector
TAMPER RESISTANT PACKAGING:
• The requirement for tamper resistant packaging is now one of the major
considerations in the development of packaging for pharmaceutical
products.
• Tamper resistant package is one having an indicator to entry in which, if
missing, can reasonably be expected to provide visible evidence to
consumers that tampering has occurred.
• FDA approves the following configurations as tamper resistant packaging:
Film wrappers, Blister package, Strip package, Bubble pack, Shrink seals,
and bands Oil, paper, plastic pouches, Bottle seals, Tape seals, Breakable
caps, Aerosol containers
Film wrapper
 Film wrapping has been used extensively over the years for products requiring package integrity or
environmental protection.
It is categorizes into following types:
 End folded wrapper
 Fin seal wrapper
 Shrink wrapper
End folded wrapper
 The end folded wrapper is formed by passing the product into a sheet of over wrapping film, which forms the
film around the product and folds the edges in a gift wrap fashion.
 The folded areas are sealed by pressing against a heated bar. The materials commonly used for this purpose are
cellophane and polypropylene.
Fin seal wrapper
• The seals are formed by crimping the film together and sealing together the two inside surfaces of the
film, producing a fin seal.
• Fin sealing is superior than end folded wrapper With good seal integrity the over wrap can removed or
opened by tearing the wrapper
Shrink wrapper
• The shrink wrap concept involves the packaging of the product in a thermoplastic film that has been
stretched and oriented during its manufacture.
• An L shaped sealer seals the over wrap
• The major advantage of this type of wrapper are the flexibility and low cost of packaging equipment .
BLISTER PACKAGE:
 Blister package provides excellent environmental protection, and efficacious appearance.
 It also provides user functionality in terms of convenience , child resistance and tamper resistance
 The blister package is formed by heat softening a sheet of thermoplastic resin and vacuum drawing the
soften sheet of plastic into a contoured mold .
 After cooling the sheet is released from the mold and proceeds to the filling station of the machine. It is then
lidded with heat sealable backing material
 Peel able backing material is used to meet the requirements of child resistance packaging.
 The material such as polyester or paper is used as a component of backing lamination.
 Materials commonly used for the thermo formable blister are PVC, polyethylene combinations ,
polystyrene and polypropylene.
STRIP PACKAGE
• A strip package is a form of unit dose packaging that is commonly used for the packaging of tablets
and capsule .
• A strip package is formed by feeding two webs of a heat sealable flexible through heated crimping
roller.
• The product is dropped into the pocket formed prior to forming the final set of seals. A continuous
strip of packets is formed in general.
• The strip of packets is cut into desired number of packets.
• Different packaging materials used are: paper/polyethylene/foil/PVC.
SEALED TUBES
• Collapsible tubes used for packaging are constructed of metal, plastic or lamination of foil, paper and
plastic.
• Metal tubes are still used for products that required high degree of barrier protection
• . Most of these are made of aluminum .
• Extruded plastic tubes are widely used for products that are compactable and limited protection of
plastic.
BREAKABLE CAPS
Breakable closures come in many different designs.
The roll-on cap design of aluminium shell used for carbonated beverages.
The bottom portion of the cap is rolled around the bottle neck finish.
The lower portion of the cap blank is usually perforated so that it breaks away when the cap is unscrewed.
The bottom portion of the closure has a tear away strip.
TYPES OF PACKAGING MATERIALS USED FOR PHARMACEUTICAL
PACKAGING
• Glass
• Plastics
• Rubbers
• Paper/card boards
• Metals
PACKAGE TESTING
• Drop test
• Vibration test
• Shock test
• Inclined impact test
• Revolving drum test
GLASS:
Glass has been widely used as a drug packaging material
Advantages
• They are transparent.
• They have good protection power.
• They can be easily labelled.
• Variety of sizes and shapes
Disadvantages
 Glass is fragile so easily
broken.
 Release alkali to aqueous
preparation
Type I—Highly resistant borosilicate glass
Type II—Treated soda lime glass
Type III—soda lime glass
NP—soda glass (non parenteral usage)
TYPES OF GLASS
PLASTIC
 Plastics may be defined as any group of substances, of natural or synthetic
origins, consisting chiefly of polymers of high molecular weight that can be
moulded into a shape or form by heat and pressure.
Advantages
 Less weight than glass,
 flexible
 Variety of sizes and shapes
 Essentially chemically inert, strong, rigid
 Extremely resistant to breakage
Disadvantages
 Absorption permeable to
moisture
 Poor printing, thermostatic
charge
Thermosetting type –
When heated they may become flexible but they do not become liquid
e.g. Urea formaldehyde (UF), Phenol formaldehyde, Melamine formaldehyde (MF), Epoxy resins
(epoxides), Polyurethanes (PURs)
Thermoplastics type-
On heating they are soften to viscous fluid which harden again on cooling.
e.g. Polyethylene {HDPE – LDPE}, Polyvinylchloride (PVC), Polystyrene Polypropylene, Nylon
(PA), Polyethylene terephthalate (PET), Polyvinylidene chloride (PVdC), Polycarbonate
Acrylonitrile butadiene styrene (ABS)
TYPES OF PLASTICS
METALS :
Metals are used for construction of containers. The metals commonly used for this purpose are
aluminium ,tin plated steel, stainless steel, tin and lead
Advantages:
• They are impermeable to light, moisture and gases.
• They are made into rigid unbreakable containers by impact extrusion.
• They are light in weight compared to glass containers.
• Labels can printed directly on to their surface.
Disadvantages:
They are expensive.
They react with certain chemicals
Tin:
• Tin containers are preferred for food, pharmaceuticals and any product for
which purity is considered.
• Tin is the most chemically inert of all collapsible metal tubes .
Aluminium:
• Aluminium tubes offer significant savings in product shipping costs
because of their light weight .
• They are attractive in nature
Lead:
• Lead has the lowest cost of all tube metals and is widely used for non food
products such as adhesives, inks. paints and lubricants.
• Lead should never be used alone for anything taken internally because of
the risk lead poison .
• With internal linings, lead tubes are used for products such as chloride
toothpaste.
RUBBER:
 Rubber is used mainly for the construction of closure meant for vials, transfusion fluid
bottles, dropping bottles and as washers in many other types of product.
BUTYL RUBBER:
Advantages:
 Permeability to water vapour .
 Water absorption is very low.
 They are relatively cheaper compared to other synthetic rubbers.
Disadvantages:
 Slow decomposition takes place above 130 ▫ C.
 Oil and solvent resistance is not very good.
SILICON RUBBERS:
Advantages:
• Heat resistance.
• Extremely low absorption and permeability of water.
• Excellent aging characteristic.
Disadvantages:
• They are very expensive.
NITRILE RUBBER:
Advantages : Oil resistant due to polar nitrile group. Heat resistant.
Disadvantages:
Absorption of bactericide and leaching of extractives are considerable.
CHLOROPRENE RUBBERS :
Advantages: Oil resistant. heat stability is good.
biopharmaceuticals

More Related Content

What's hot

Parenteral controlled drug delivery system sushmitha
Parenteral controlled drug delivery system sushmithaParenteral controlled drug delivery system sushmitha
Parenteral controlled drug delivery system sushmitha
Danish Kurien
 

What's hot (20)

Parentral emulsion and suspension sunil kokate
Parentral emulsion and suspension  sunil kokateParentral emulsion and suspension  sunil kokate
Parentral emulsion and suspension sunil kokate
 
Chapter on Pellets
Chapter on PelletsChapter on Pellets
Chapter on Pellets
 
Pharmaceuticals excipients
Pharmaceuticals excipientsPharmaceuticals excipients
Pharmaceuticals excipients
 
parenteral dosage form
parenteral dosage formparenteral dosage form
parenteral dosage form
 
parentral controlled drug delivery system
parentral controlled drug delivery systemparentral controlled drug delivery system
parentral controlled drug delivery system
 
Solid dosage forms (capsules)
Solid dosage forms (capsules)Solid dosage forms (capsules)
Solid dosage forms (capsules)
 
Diluent ppt
Diluent pptDiluent ppt
Diluent ppt
 
Direct compression method..Mominul Islam
Direct compression method..Mominul IslamDirect compression method..Mominul Islam
Direct compression method..Mominul Islam
 
Manufacturing of capsule
Manufacturing of capsuleManufacturing of capsule
Manufacturing of capsule
 
Parenteral controlled drug delivery system sushmitha
Parenteral controlled drug delivery system sushmithaParenteral controlled drug delivery system sushmitha
Parenteral controlled drug delivery system sushmitha
 
Nanoparticles
NanoparticlesNanoparticles
Nanoparticles
 
Preformulations
PreformulationsPreformulations
Preformulations
 
Tablet coating.pptx
Tablet coating.pptxTablet coating.pptx
Tablet coating.pptx
 
Sterile dosage form
Sterile dosage formSterile dosage form
Sterile dosage form
 
Hard gelatin capsules - a detailed study
Hard gelatin capsules - a detailed studyHard gelatin capsules - a detailed study
Hard gelatin capsules - a detailed study
 
Theories of dissolution
Theories of dissolutionTheories of dissolution
Theories of dissolution
 
Comparison between conventional and sustained-release drugs
Comparison between conventional and sustained-release drugs Comparison between conventional and sustained-release drugs
Comparison between conventional and sustained-release drugs
 
Novel Drug Delivery Systems
Novel Drug Delivery SystemsNovel Drug Delivery Systems
Novel Drug Delivery Systems
 
Floating drug delivery systems
Floating drug delivery systemsFloating drug delivery systems
Floating drug delivery systems
 
DILUENTS AND DISINTEGRANTS
DILUENTS AND DISINTEGRANTSDILUENTS AND DISINTEGRANTS
DILUENTS AND DISINTEGRANTS
 

Similar to biopharmaceuticals

powders and graWRGVBDBUHURHGJRHGBnules.pptx
powders and graWRGVBDBUHURHGJRHGBnules.pptxpowders and graWRGVBDBUHURHGJRHGBnules.pptx
powders and graWRGVBDBUHURHGJRHGBnules.pptx
interaman123
 
Unit 3 - Pellets -Rajesh.pdf
Unit 3 - Pellets -Rajesh.pdfUnit 3 - Pellets -Rajesh.pdf
Unit 3 - Pellets -Rajesh.pdf
Rajesh M
 

Similar to biopharmaceuticals (20)

pellets final
pellets finalpellets final
pellets final
 
All about Tablets (Pharma)
All about Tablets  (Pharma)All about Tablets  (Pharma)
All about Tablets (Pharma)
 
Tablets
Tablets Tablets
Tablets
 
Tablet Manufacturing Technique.ppt
Tablet Manufacturing Technique.pptTablet Manufacturing Technique.ppt
Tablet Manufacturing Technique.ppt
 
PELLETS.pptx
PELLETS.pptxPELLETS.pptx
PELLETS.pptx
 
Pellets
PelletsPellets
Pellets
 
Processing of tablet
Processing of tabletProcessing of tablet
Processing of tablet
 
Pharmaceutical powders classification etc
Pharmaceutical powders classification etcPharmaceutical powders classification etc
Pharmaceutical powders classification etc
 
powders and graWRGVBDBUHURHGJRHGBnules.pptx
powders and graWRGVBDBUHURHGJRHGBnules.pptxpowders and graWRGVBDBUHURHGJRHGBnules.pptx
powders and graWRGVBDBUHURHGJRHGBnules.pptx
 
tabletsformulation2.pptx
tabletsformulation2.pptxtabletsformulation2.pptx
tabletsformulation2.pptx
 
Unit 3 - Pellets -Rajesh.pdf
Unit 3 - Pellets -Rajesh.pdfUnit 3 - Pellets -Rajesh.pdf
Unit 3 - Pellets -Rajesh.pdf
 
Pharmaceutical excipient
Pharmaceutical excipientPharmaceutical excipient
Pharmaceutical excipient
 
Tablet ppt
Tablet pptTablet ppt
Tablet ppt
 
Solid dosage forms
Solid dosage formsSolid dosage forms
Solid dosage forms
 
Tablet a solid dosage form.
Tablet a solid dosage form.Tablet a solid dosage form.
Tablet a solid dosage form.
 
Tablet.2.0
Tablet.2.0Tablet.2.0
Tablet.2.0
 
Tablets
TabletsTablets
Tablets
 
Manufacturing of pharmaceutical dosage forms
Manufacturing of pharmaceutical dosage formsManufacturing of pharmaceutical dosage forms
Manufacturing of pharmaceutical dosage forms
 
Granulation
GranulationGranulation
Granulation
 
Tablet Granulation Process by Gaurav Kumar Sharma
Tablet Granulation Process by Gaurav Kumar SharmaTablet Granulation Process by Gaurav Kumar Sharma
Tablet Granulation Process by Gaurav Kumar Sharma
 

More from arushe143 (11)

Landfill design and operation
Landfill design and operationLandfill design and operation
Landfill design and operation
 
Memberane used in Biosensor
Memberane used in BiosensorMemberane used in Biosensor
Memberane used in Biosensor
 
Environment biotechnology
Environment biotechnologyEnvironment biotechnology
Environment biotechnology
 
Bio-Molecular motors
Bio-Molecular motorsBio-Molecular motors
Bio-Molecular motors
 
Isoelectric focussing
Isoelectric focussingIsoelectric focussing
Isoelectric focussing
 
Catalytic antibodies
Catalytic antibodiesCatalytic antibodies
Catalytic antibodies
 
Himalaya ppt
Himalaya pptHimalaya ppt
Himalaya ppt
 
Gene therapy
Gene therapy Gene therapy
Gene therapy
 
Antibody based techniques
Antibody based techniquesAntibody based techniques
Antibody based techniques
 
Mass spectrometry
Mass spectrometryMass spectrometry
Mass spectrometry
 
Tissue engg.
Tissue engg. Tissue engg.
Tissue engg.
 

Recently uploaded

Integrated Test Rig For HTFE-25 - Neometrix
Integrated Test Rig For HTFE-25 - NeometrixIntegrated Test Rig For HTFE-25 - Neometrix
Integrated Test Rig For HTFE-25 - Neometrix
Neometrix_Engineering_Pvt_Ltd
 
Standard vs Custom Battery Packs - Decoding the Power Play
Standard vs Custom Battery Packs - Decoding the Power PlayStandard vs Custom Battery Packs - Decoding the Power Play
Standard vs Custom Battery Packs - Decoding the Power Play
Epec Engineered Technologies
 

Recently uploaded (20)

Integrated Test Rig For HTFE-25 - Neometrix
Integrated Test Rig For HTFE-25 - NeometrixIntegrated Test Rig For HTFE-25 - Neometrix
Integrated Test Rig For HTFE-25 - Neometrix
 
Employee leave management system project.
Employee leave management system project.Employee leave management system project.
Employee leave management system project.
 
Thermal Engineering Unit - I & II . ppt
Thermal Engineering  Unit - I & II . pptThermal Engineering  Unit - I & II . ppt
Thermal Engineering Unit - I & II . ppt
 
Introduction to Data Visualization,Matplotlib.pdf
Introduction to Data Visualization,Matplotlib.pdfIntroduction to Data Visualization,Matplotlib.pdf
Introduction to Data Visualization,Matplotlib.pdf
 
PE 459 LECTURE 2- natural gas basic concepts and properties
PE 459 LECTURE 2- natural gas basic concepts and propertiesPE 459 LECTURE 2- natural gas basic concepts and properties
PE 459 LECTURE 2- natural gas basic concepts and properties
 
Theory of Time 2024 (Universal Theory for Everything)
Theory of Time 2024 (Universal Theory for Everything)Theory of Time 2024 (Universal Theory for Everything)
Theory of Time 2024 (Universal Theory for Everything)
 
NO1 Top No1 Amil Baba In Azad Kashmir, Kashmir Black Magic Specialist Expert ...
NO1 Top No1 Amil Baba In Azad Kashmir, Kashmir Black Magic Specialist Expert ...NO1 Top No1 Amil Baba In Azad Kashmir, Kashmir Black Magic Specialist Expert ...
NO1 Top No1 Amil Baba In Azad Kashmir, Kashmir Black Magic Specialist Expert ...
 
FEA Based Level 3 Assessment of Deformed Tanks with Fluid Induced Loads
FEA Based Level 3 Assessment of Deformed Tanks with Fluid Induced LoadsFEA Based Level 3 Assessment of Deformed Tanks with Fluid Induced Loads
FEA Based Level 3 Assessment of Deformed Tanks with Fluid Induced Loads
 
AIRCANVAS[1].pdf mini project for btech students
AIRCANVAS[1].pdf mini project for btech studentsAIRCANVAS[1].pdf mini project for btech students
AIRCANVAS[1].pdf mini project for btech students
 
COST-EFFETIVE and Energy Efficient BUILDINGS ptx
COST-EFFETIVE  and Energy Efficient BUILDINGS ptxCOST-EFFETIVE  and Energy Efficient BUILDINGS ptx
COST-EFFETIVE and Energy Efficient BUILDINGS ptx
 
HAND TOOLS USED AT ELECTRONICS WORK PRESENTED BY KOUSTAV SARKAR
HAND TOOLS USED AT ELECTRONICS WORK PRESENTED BY KOUSTAV SARKARHAND TOOLS USED AT ELECTRONICS WORK PRESENTED BY KOUSTAV SARKAR
HAND TOOLS USED AT ELECTRONICS WORK PRESENTED BY KOUSTAV SARKAR
 
DC MACHINE-Motoring and generation, Armature circuit equation
DC MACHINE-Motoring and generation, Armature circuit equationDC MACHINE-Motoring and generation, Armature circuit equation
DC MACHINE-Motoring and generation, Armature circuit equation
 
Online food ordering system project report.pdf
Online food ordering system project report.pdfOnline food ordering system project report.pdf
Online food ordering system project report.pdf
 
Standard vs Custom Battery Packs - Decoding the Power Play
Standard vs Custom Battery Packs - Decoding the Power PlayStandard vs Custom Battery Packs - Decoding the Power Play
Standard vs Custom Battery Packs - Decoding the Power Play
 
Bhubaneswar🌹Call Girls Bhubaneswar ❤Komal 9777949614 💟 Full Trusted CALL GIRL...
Bhubaneswar🌹Call Girls Bhubaneswar ❤Komal 9777949614 💟 Full Trusted CALL GIRL...Bhubaneswar🌹Call Girls Bhubaneswar ❤Komal 9777949614 💟 Full Trusted CALL GIRL...
Bhubaneswar🌹Call Girls Bhubaneswar ❤Komal 9777949614 💟 Full Trusted CALL GIRL...
 
Unit 4_Part 1 CSE2001 Exception Handling and Function Template and Class Temp...
Unit 4_Part 1 CSE2001 Exception Handling and Function Template and Class Temp...Unit 4_Part 1 CSE2001 Exception Handling and Function Template and Class Temp...
Unit 4_Part 1 CSE2001 Exception Handling and Function Template and Class Temp...
 
Tamil Call Girls Bhayandar WhatsApp +91-9930687706, Best Service
Tamil Call Girls Bhayandar WhatsApp +91-9930687706, Best ServiceTamil Call Girls Bhayandar WhatsApp +91-9930687706, Best Service
Tamil Call Girls Bhayandar WhatsApp +91-9930687706, Best Service
 
Computer Networks Basics of Network Devices
Computer Networks  Basics of Network DevicesComputer Networks  Basics of Network Devices
Computer Networks Basics of Network Devices
 
S1S2 B.Arch MGU - HOA1&2 Module 3 -Temple Architecture of Kerala.pptx
S1S2 B.Arch MGU - HOA1&2 Module 3 -Temple Architecture of Kerala.pptxS1S2 B.Arch MGU - HOA1&2 Module 3 -Temple Architecture of Kerala.pptx
S1S2 B.Arch MGU - HOA1&2 Module 3 -Temple Architecture of Kerala.pptx
 
Double Revolving field theory-how the rotor develops torque
Double Revolving field theory-how the rotor develops torqueDouble Revolving field theory-how the rotor develops torque
Double Revolving field theory-how the rotor develops torque
 

biopharmaceuticals

  • 1. Pharmaceutical dosage forms (Unit 3) Presented by: Arushe Tickoo DTU, Delhi
  • 2. Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a capsule shell, for example), and apportioned into a particular dose. For example, two products may both be amoxicillin, but one is in 500 mg capsules and another is in 250 mg chewable tablets. Depending on the method/route of administration, dosage forms come in several types. These include many kinds of 1. liquid, 2. solid, and 3. semisolid dosage forms. Common dosage forms include pill, tablet, or capsule, drink or syrup, and natural or herbal form such as plant or food of sorts, among many others. Dosage forms
  • 3. Types OralOphthalmic InhalationalParenteral Topical • Aerosol • Inhaler • Nebulizer • Smoking • Vaporizer • Intradermal (ID) • Subcutaneous (SC) • Intramuscular (IM) • Intra-osseous (IO) • Intra-peritoneal (IP) • Intravenous(IV) • Cream, gel, balm, lotion or ointment • Ear drops (otic) • Eye drops • Skin patch • Dermal patch • Pill • Thin film • Liquid solution/ suspension Powder • Pastes (e.g., Toothpaste) •Drops •Ointment •Liquid solution
  • 4. An excipient is a pharmacologically inactive substance formulated alongside the active pharmaceutical ingredient of a medication. Purposes served by excipients:  Provide bulk to the formulation.  Facilitate drug absorption or solubility and other pharmacokinetic considerations.  Aid in handling of “API” during manufacturing .  Provide stability and prevent from denaturation Excipient
  • 6. A list of Pharmaceutical Excipients used in pharmaceutical preparations Fillers. Binders. Disintegrants. Coatings. Sorbents. Antiadherent. Lubricants. Glidants. Preservatives. Antioxidants. Flavoring Agents. Sweeting Agents. Coloring Agents. Solvent & Co-solvent. Buffering Agents. Chelating Agents. Viscosity imparting Agents. Surface Active Agents. Humectants .
  • 7. • Fillers: Fillers typically also fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use. Plant cellulose and dibasic calcium phosphate are used popularly as fillers Function of fillers: Fillers add volume and/or mass to a drug substance, thereby facilitating precise metering and handling thereof in the preparation of dosage forms . Used in tablets and capsules. • Binders: Binders hold the ingredients in a tablet together . Binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dose tablets . Typical features of binders: A binder should be compatible with other products of formulation and add sufficient cohesion to the powders . Examples include gelatin, cellulose, cellulose derivatives, polyvinylpyrrolidone, starch, sucrose and polyethylene glycol.
  • 8. • Disintigrants: Disintegrants are substances or mixture of substances added to the drug formulations, which facilitate dispersion or breakupa of tablets and contents of capsules into smaller particles for quick dissolution when it comes in contact with water in the GIT Examples: polyvinylpyrrolidone , carboxymethyl cellulose, sodium starch glycolate • Coating Agent: Coating is a process by which an essentially dry, outer layer of coatinag material is applied to the surface of a dosage form. Three types of coating agents are used pharmaceutically, Film coating, Sugar coating, Compression coating. Examples: HPMC, MC, HPC • Sorbents: Sorbents are materials that soak up oil from the water. Examples: i. Natural sorbents- peat moss, sawdust, feathers, and anything else natural that contains carbon. ii. Synthetic sorbents- polyethylene and nylon
  • 9. • Glidants Glidants are used to promote powder flow by reducing interparticle friction and cohesion. These are used in combination with lubricants as they have no ability to reduce die wall friction. Examples include fumed silica, talc, and magnesium carbonate. • Lubricants Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall. Examples: Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules. Preservatives Some typical preservatives used in pharmaceutical formulations are: 1) Antioxidants like vitamin A, vitamin E, vitamin C, retinyl palmitate, and selenium 2) The amino acids cysteine and methionine 3) Citric acid and sodium citrate 4) Synthetic preservatives like the parabens: methyl paraben and propyl paraben.
  • 10. Oral liquid dosage forms include solutions, syrups, suspensions, elixirs and concentrates. They offer better patient compliance in people who find swallowing pills or capsules difficult, and more flexible dosage control than a fixed-dose tablet. Oral liquid
  • 11. Creams and ointments contain a different proportion of oil to water. Ointments have a higher concentration of oil, compared to creams. The more oil, the greasier and stickier the product. Creams may work better on larger areas of the skin because of their "spreadability" factor, compared to ointments. Several factors are taken into consideration when selecting a topical product. Skin absorbs a cream more quickly, whereas an ointment will remain on the skin longer and take a longer time to absorb. Ointments An ointment is a homogeneous, viscous, semi-solid preparation, most commonly a greasy, thick oil (oil 80% - water 20%) with a high viscosity, that is intended for external application to the skin or mucous membranes. Ointments have a water number that defines the maximum amount of water that it can contain.
  • 12. 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. Granules are produced to enhance the uniformity of the API (active pharmaceutical ingredient (API) in the final product, to increase the density of the blend so that it occupies less volume per unit weight for better storage and shipment, to facilitate metering or volumetric dispensing, to reduce dust during granulation process to reduce toxic exposure and process-related hazards, and to improve the appearance of the product Granulation Techniques Wet granulation Dry granulation
  • 13.
  • 14. The dry granulation process is used to form granules without using a liquid solution because the product granulated may be sensitive to moisture and heat. Forming granules without moisture requires compacting and densifying the powders. In this process the primary powder particles are aggregated under high pressure. Sweying granulator or a high-shear mixer-granulator can be used for the dry granulation. Dry granulation
  • 15. Pneumatic Dry Granulation (PDG) Pneumatic dry granulation (PDG), an innovative dry granulation technology, utilizes roller compaction together with a proprietary air classification method to produce granules. • Granules are produced from powder particles by initially applying mild compaction force by roller compactor • The fine particles and/or smaller granules are separated from the intended size granules in a fractioning chamber • The entrained fine particles and/or small granules are then transferred to a device such as a cyclone and are either returned to the roller compactor for immediate re-processing (recycling or recirculation process) • Placed in a container for reprocessing later to achieve the granules of desired size
  • 16. In wet granulation, granules are formed by the addition of a granulation liquid onto a powder bed which is under the influence of an impeller (in a high-shear granulator), screws (in a twin screw granulator) or air (in a fluidized bed granulator). The agitation resulting in the system along with the wetting of the components within the formulation results in the aggregation of the primary powder particles to produce wet granules Wet granulation
  • 17. Reverse wet granulation Reverse wet granulation or reverse-phase wet granulation is a new development in the wet granulation technique that involves the immersion of the dry powder formulation into the binder liquid followed by controlled breakage to form granules
  • 18. Steam Granulation In steam granulation as a new wet granulation technique, water steam is used as binder instead of traditional liquid water as granulation liquid
  • 19. Moisture-Activated Dry Granulation (MADG) This technique is a variation of conventional wet granulation technique. It uses very little water to activate a binder and initiate agglomeration. This technique involves two steps, 1) wet agglomeration of the powder particles, and 2) moisture absorption or distribution.
  • 20. Freeze granulation Freeze granulation technology, spray freezing and subsequent freeze drying, involves spraying droplets of a liquid slurry or suspension into liquid nitrogen followed by freeze-drying of the frozen droplets. By spraying a powder suspension into liquid nitrogen, the drops are instantly frozen into granules.
  • 21. Foam granulation Foam granulation or foamed binder granulation technology, analogous to spray agglomeration, involves the addition of liquid/aqueous binder as foam instead of spraying or pouring liquid onto the powder particles.
  • 22. SUSTAINED RELEASE DOSAGE FORMS Drug delivery systems refer to the technology utilized to present the drug to the desired body site for drug release and absorption. IDEAL DRUG DELIVERY SYSTEM should deliver drug at a rate dictated by the needs of the body over the period of the treatment and it should channel the active entity solely to the site of action. SUSTAINED RELEASE DRUG DELIVERY is defined as any of the dosage form that maintains the therapeutic blood or tissue levels of drug by continuous release of medication for a prolonged period of time, after administration of a single dose. Sustained release describes the release of drug substance from a dosage form or delivery system over an extended period of time. Also referred to as prolonged-release (PR), slow release (SR), sustained action (SA), prolonged action (PA) or extended-release (ER).
  • 23. 1. SUSTAINED RELEASE DRUG DELIVERY • Contains loading dose + maintenance dose. • Loading dose is immediately released to produce quick onset of action. • Maintenance dose is released at a controlled rate so that the plasma concentration remains constant above Minimum Effective Concentration (MEC). • Plasma concentration comes down according to first order elimination kinetics. 2. Delayed release dosage forms On delayed release dosage forms one or more immediate release units are incorporated into a single dosage form. e.g. repeat action tablet, enteric coated tablet.
  • 24. Sustained release dosage form • Constitutes dosage form that provides medication over extended period of time • SRDF generally do not attain zero order release kinetics • Usually do not contain mechanisms to promote localization of the drug at active site. Controlled release dosage form • Constitutes dosage form that maintains constant drug levels in blood or tissue • Maintains constant drug levels in the blood target tissue usually by releasing the drug in a zero order pattern. • Controlled dosage forms contain methods to promote localization of the drug at active site.
  • 25. Materials Used in Coating of Sustained Release Dosage Forms (Encapsulation)  Mixtures of waxes [bees wax, carnauba wax, etc] with glyceryl monostearate , stearic acid , glyceryl mono palmitate and cetyl alcohol.These provide coatings that are dissolved slowly or broken down in the GIT.  Shellac and zein – polymers that remain intact until the PH of the GI contents become less acidic  Ethyl cellulose , which provides a membrane around the dosage form and remains intact throughout the GIT. However, it does permit water to permeate the film, dissolve the drug , and diffuse out again.  Acrylic resins , which behave similarly to ethyl cellulose as a diffusion controlled drug release coating material.  Cellulose acetate [di acetate and tri acetate]  Silicone elastomers.
  • 26. Advantages of a controlled drug delivery system 1) Frequency of drug administration is reduced – patient compliance is improved. 2) In multiple dosing of conventional dosage forms the blood level of drug shows oscillatory characteristic. In controlled release dosage form the blood level is evenly maintained. 3) The safety margin of high potency drugs can be increased and thus side-effects or adverse effects can be minimized. 4) Total amount of drug administered can be reduced because of maximum utilization. 5) Reduction in health care costs through improved therapy, shorter treatment period, less frequency of dosing and reduction in personnel time to dispense, administer and monitor patients.
  • 27. Disadvantages of controlled release dosage forms 1) Decrease systemic availability in comparison to immediate release conventional dosage forms, this may be due to incomplete release, increased first-pass metabolism, increased instability, insufficient residence time for complete release site specific absorption, pH dependent solubility etc. 2) Poor in vitro-in vivo correlation. 3) Possibility of dose dumping due to food, physiologic or formulation variables or chewing or oral formulations by the patient and thus increased risk of toxicity. 4) Retrieval of drug is difficult in case of toxicity, poisoning or hypersensitivity reactions. 5) Reduced potential for dosage adjustment of drugs normally administered in varying strength. 6) Higher cost of formulation.
  • 28. Blood products and therapeutic enzymes Blood and blood products constitute a major group of traditional biologics. The main components of blood are the red and white blood cells, along with platelets and the plasma in which these cellular elements are suspended. Whole blood remains in routine therapeutic use, as do red blood cell and platelet concentrates. Major blood products that find therapeutic application Whole blood Red blood cells Platelet concentrate Plasma and plasma protein fraction Albumin Clotting factors (particularly factors VIIa, VIII, IX and XIII) Haemoglobin
  • 29. Recombinant proteins 1. Insulin • hormone produced by beta cells in the pancreas → allows glucose to pass into cells → suppresses excess production of sugar in the liver and muscles → suppresses breakdown of fat for energy
  • 30. beta cells in pancreas preproinsulin proinsulin insulin + C-peptide
  • 31. Producing A and B chains separately
  • 32. Recombinant glycoproteins 2. Interferons • glycoproteins that “interfere” with viral propagation in cell cultures • group of small proteins with 140-170 amino acids • secretory protein produced from viral-infected cells, induces antiviral state in neighboring cells
  • 33. Interferon interferes with viral replication in protected cells
  • 34. 3 main types of interferons: 1. IFN-α (25 subtypes) – produced from β -lymphocytes 2. IFN-β – fibroblasts – produced from fibroblasts 3. IFN-γ – T-lymphocytes – produced from T-lymphocytes • mode of action not fully understood → synthesis of host enzymes that degrade viral RNA and inhibit protein synthesis 1. IFN-alpha – uses transformed human cell lines (B-lympphoblastoid cell line),Grow well in suspension with serum-free medium, first product from a human tumor line licensed for human therapy- used to treat leukemia 2. IFN-beta – one of the only human interferons that are glycosylated (along with IFN- a2), higher activity when glycosylated Ifn-b secreted in response to viral infection or to double stranded RNA May be used in treatment of tumors, but has short half-life in blood, can’t make it to tumor Recombinant forms may be used to fight other diseases, such as multiple sclerosis (disease of the central immune system, T-lymphocyte breakdown of nerve cells) 3. IFN-gamma – production stimulated by a variety of antigens, most widely used in staphylococcal enterotoxin A Anti-tumor effects of IFN-gamma are strongest of the three
  • 35. 5. Erythropoietin (EPO) • glycoprotein hormone produced by the kidney (hypoxia triggers EPO production) • required for continuous red blood cell production in bone marrow (erythropoiesis) • absence of EPO results in impairment of red blood cell production → anemia • anemia treated with exogenous EPO
  • 38. 3. Plasminogen activators • thrombosis (formation of blood clots) is a major cause of premature death • deposition of fibrin in the circulatory system, blocks blood flow • formation of insoluble fibrin controlled by clotting cascade formed during wound healing • t-PA (tissue-plasminogen activator) initiates fibrinolysis (proteolytic cleavage of fibrin) disulphide bond N-glycan
  • 39. Tissue-plasminogen activator Plasminogen Plasmin Coagulation Fibrin (insoluble) Fibrin products (soluble) Fibrinolysis
  • 40. Factor VIII • large glycoprotein (265 kDa) • gene – 186 kB, 26 exons, 25 introns (overlapping strands of DNA from genomic and cDNA aligned, without introns) • BHK cells transfected with expression vector containing gene encoding Factor VIII 4. Blood-clotting factors • Hemophilia is a sex-linked (x-chromosome) genetic disease • inactive clotting cascade in blood, can’t form fibrin → hemophilia A – absence of factor VIII → hemophilia B – absence of factor IX
  • 41. Factor IX • plasma glycoprotein (57 kDa) secreted by hepatocytes • called “Christmas factor”, after first family diagnosed with clotting deficiency • gene cloned into rat hepatoma cell line → contains enzymes for post-translation modifications • produces biologically active protein with correct tertiary folding and glycosylation • stabilized by addition of Willebrand factor, normally found as a combined protein complex in blood
  • 42. The clotting cascade Wound surface contact Factor XII Factor XIIa Factor XI Factor XIa Factor IX Factor IXa + Factor VIII + Factor X Factor Xa Prothrombin Thrombin Fibrinogen Fibrin clot +Factor V Thrombin
  • 43. Analytical methods and test for various drugs and pharmaceuticals • In the field of pharmaceutical research, the analytical investigation of bulk drug materials, intermediates, drug products, drug formulations, impurities and degradation products, and biological samples containing the drugs and their metabolites is very important. • From the commencement of official pharmaceutical analysis, analytical assay methods were included in the compendial monographs with the aim to characterize the quality of bulk drug materials by setting limits of their active ingredient content. • In recent years, the assay methods in the monographs include titrimetry, spectrometry, chromatography, and capillary electrophoresis
  • 44. The data in Table 2 based on the edition of European (The European Pharmacopoeia and Council of Europe, 2002) and US (United States Pharmacopoeia, 2004) pharmacopoeias.
  • 45. Analytical techniques Titrimetric techniques Titration, also known as titrimetry, is used to determine the unknown concentration of an identified analyte. It is also known as volumetric analysis. A reagent, called the titrant or titrator is prepared as a standard solution. A known concentration and volume of titrant reacts with a solution of analyte or titrand to determine concentration. Titrimetric methods have been used for the determination of captopril, albendozole and gabapentin in commercial dosage forms. Sparfloxacin was determined by the non-aqueous titration method.
  • 46. Chromatographic technique 1. Thin layer chromatography Although an old technique yet it finds a lot of application in the field of pharmaceutical analysis. In thin layer chromatography, a solid phase, the adsorbent, is coated onto a solid support as a thin layer usually on a glass, plastic, or aluminum support. Several factors determine the efficiency of this type of chromatographic separation. First the adsorbent should show extreme selectivity toward the substances being separated so as to the dissimilarities in the rate of elution be large. TLC has been utilized for the determination of some steroids, pioglitazone, celecoxib and noscapine.
  • 47. 2. High-performance liquid chromatography (HPLC) HPLC is an advanced form of liquid chromatography used in separating the complex mixture of molecules encountered in chemical and biological systems, in order to recognize better the role of individual molecules. The specificity of the HPLC method is excellent and simultaneously sufficient precision is also attainable.
  • 48. 3. Gas chromatography Moving ahead with another chromatographic technique, gas chromatography is a powerful separation technique for detection of volatile organic compounds. Combining separation and on-line detection allows accurate quantitative determination of complex mixtures, including traces of compounds down to parts per trillions in some specific cases. The creation of high-molecular mass products such as polypeptides, or thermally unstable antibiotics confines the scope of this technique. Recently, gas chromatography has been used for assay of drugs such as isotretinion, cocaine and employed in the determination of residual solvents in betamethasone valerate
  • 49. Spectroscopic techniques 1. Spectrophotometry Another important group of methods which find an important place in pharmacopoeias are spectrophotometric methods based on natural UV absorption and chemical reactions. Spectrophotometry is the quantitative measurement of the reflection or transmission properties of a material as a function of wavelength. The use of UV–Vis spectrophotometry especially applied in the analysis of pharmaceutical dosage form has increased rapidly over the last few years Ultraviolet and visible (UV-Vis) absorption spectroscopy is the measurement of the attenuation of a beam of light after it passes through a sample or after reflection from a sample surface. Absorption measurements can be at a single wavelength or over an extended spectral range.
  • 50. Near infrared spectroscopy (NIRS) Near-infrared spectroscopy (NIRS) is a spectroscopic method that uses the near-infraredregion of the electromagnetic spectrum (from about 700 nm to 2500 nm).Near infrared spectroscopy (NIRS) is a rapid and non-destructive procedure that provides multi component analysis of almost any matrix
  • 51. Fluorimetry and Phosphorimetry In fluorescence spectrometry both an excitation spectrum (the light that is absorbed by the sample) and/or an emission spectrum (the light emitted by the sample) can be measured. The concentration of the analyte is directly proportional with the intensity of the emission.
  • 52.
  • 53. A form of fluorimetry in which phosphorescence of a sample is measured in conjunction with a pulsed source of radiation Phosphorescence is a type of photoluminescence related to fluorescence. Unlike fluorescence, phosphorescent material does not immediately re-emit the radiation it absorbs. The slower time scales of the re-emission are associated with "forbidden" energy state transitions Phosphorimetry
  • 54. INTRODUCTION • Packaging is the science, art and technology of enclosing or protecting products for distribution, storage, sale, and use. • Pharmaceutical packaging can be defined as the economical means of providing presentation, protection, identification , information, convenience, compliance , integrity and stability of the product . FUNCTIONS OF PACKAGING • Product Identification:- Packaging greatly helps in identification of products. • Product Protection:- Packaging protects the contents of a product from spoilage, breakage, leakage, etc. • Facilitating the use of product:- Packaging should be convenience to open, handle and use for the consumers. • Product Promotion:- Packaging is also used for promotional and attracting the attention of the people while purchasing. PHARMACEUTICAL PACKAGING
  • 55. Secondary packaging - Is outside the primary packaging perhaps used to group primary package together. Ex. Boxes, cartons
  • 56. Tertiary packaging- is used to bulk handling and shipping. Ex. Barrel, container, edge protector
  • 57. TAMPER RESISTANT PACKAGING: • The requirement for tamper resistant packaging is now one of the major considerations in the development of packaging for pharmaceutical products. • Tamper resistant package is one having an indicator to entry in which, if missing, can reasonably be expected to provide visible evidence to consumers that tampering has occurred. • FDA approves the following configurations as tamper resistant packaging: Film wrappers, Blister package, Strip package, Bubble pack, Shrink seals, and bands Oil, paper, plastic pouches, Bottle seals, Tape seals, Breakable caps, Aerosol containers
  • 58. Film wrapper  Film wrapping has been used extensively over the years for products requiring package integrity or environmental protection. It is categorizes into following types:  End folded wrapper  Fin seal wrapper  Shrink wrapper End folded wrapper  The end folded wrapper is formed by passing the product into a sheet of over wrapping film, which forms the film around the product and folds the edges in a gift wrap fashion.  The folded areas are sealed by pressing against a heated bar. The materials commonly used for this purpose are cellophane and polypropylene.
  • 59. Fin seal wrapper • The seals are formed by crimping the film together and sealing together the two inside surfaces of the film, producing a fin seal. • Fin sealing is superior than end folded wrapper With good seal integrity the over wrap can removed or opened by tearing the wrapper Shrink wrapper • The shrink wrap concept involves the packaging of the product in a thermoplastic film that has been stretched and oriented during its manufacture. • An L shaped sealer seals the over wrap • The major advantage of this type of wrapper are the flexibility and low cost of packaging equipment .
  • 60. BLISTER PACKAGE:  Blister package provides excellent environmental protection, and efficacious appearance.  It also provides user functionality in terms of convenience , child resistance and tamper resistance  The blister package is formed by heat softening a sheet of thermoplastic resin and vacuum drawing the soften sheet of plastic into a contoured mold .  After cooling the sheet is released from the mold and proceeds to the filling station of the machine. It is then lidded with heat sealable backing material  Peel able backing material is used to meet the requirements of child resistance packaging.  The material such as polyester or paper is used as a component of backing lamination.  Materials commonly used for the thermo formable blister are PVC, polyethylene combinations , polystyrene and polypropylene.
  • 61. STRIP PACKAGE • A strip package is a form of unit dose packaging that is commonly used for the packaging of tablets and capsule . • A strip package is formed by feeding two webs of a heat sealable flexible through heated crimping roller. • The product is dropped into the pocket formed prior to forming the final set of seals. A continuous strip of packets is formed in general. • The strip of packets is cut into desired number of packets. • Different packaging materials used are: paper/polyethylene/foil/PVC.
  • 62. SEALED TUBES • Collapsible tubes used for packaging are constructed of metal, plastic or lamination of foil, paper and plastic. • Metal tubes are still used for products that required high degree of barrier protection • . Most of these are made of aluminum . • Extruded plastic tubes are widely used for products that are compactable and limited protection of plastic. BREAKABLE CAPS Breakable closures come in many different designs. The roll-on cap design of aluminium shell used for carbonated beverages. The bottom portion of the cap is rolled around the bottle neck finish. The lower portion of the cap blank is usually perforated so that it breaks away when the cap is unscrewed. The bottom portion of the closure has a tear away strip.
  • 63. TYPES OF PACKAGING MATERIALS USED FOR PHARMACEUTICAL PACKAGING • Glass • Plastics • Rubbers • Paper/card boards • Metals PACKAGE TESTING • Drop test • Vibration test • Shock test • Inclined impact test • Revolving drum test
  • 64. GLASS: Glass has been widely used as a drug packaging material Advantages • They are transparent. • They have good protection power. • They can be easily labelled. • Variety of sizes and shapes Disadvantages  Glass is fragile so easily broken.  Release alkali to aqueous preparation Type I—Highly resistant borosilicate glass Type II—Treated soda lime glass Type III—soda lime glass NP—soda glass (non parenteral usage) TYPES OF GLASS
  • 65. PLASTIC  Plastics may be defined as any group of substances, of natural or synthetic origins, consisting chiefly of polymers of high molecular weight that can be moulded into a shape or form by heat and pressure. Advantages  Less weight than glass,  flexible  Variety of sizes and shapes  Essentially chemically inert, strong, rigid  Extremely resistant to breakage Disadvantages  Absorption permeable to moisture  Poor printing, thermostatic charge
  • 66. Thermosetting type – When heated they may become flexible but they do not become liquid e.g. Urea formaldehyde (UF), Phenol formaldehyde, Melamine formaldehyde (MF), Epoxy resins (epoxides), Polyurethanes (PURs) Thermoplastics type- On heating they are soften to viscous fluid which harden again on cooling. e.g. Polyethylene {HDPE – LDPE}, Polyvinylchloride (PVC), Polystyrene Polypropylene, Nylon (PA), Polyethylene terephthalate (PET), Polyvinylidene chloride (PVdC), Polycarbonate Acrylonitrile butadiene styrene (ABS) TYPES OF PLASTICS
  • 67. METALS : Metals are used for construction of containers. The metals commonly used for this purpose are aluminium ,tin plated steel, stainless steel, tin and lead Advantages: • They are impermeable to light, moisture and gases. • They are made into rigid unbreakable containers by impact extrusion. • They are light in weight compared to glass containers. • Labels can printed directly on to their surface. Disadvantages: They are expensive. They react with certain chemicals
  • 68. Tin: • Tin containers are preferred for food, pharmaceuticals and any product for which purity is considered. • Tin is the most chemically inert of all collapsible metal tubes . Aluminium: • Aluminium tubes offer significant savings in product shipping costs because of their light weight . • They are attractive in nature Lead: • Lead has the lowest cost of all tube metals and is widely used for non food products such as adhesives, inks. paints and lubricants. • Lead should never be used alone for anything taken internally because of the risk lead poison . • With internal linings, lead tubes are used for products such as chloride toothpaste.
  • 69. RUBBER:  Rubber is used mainly for the construction of closure meant for vials, transfusion fluid bottles, dropping bottles and as washers in many other types of product. BUTYL RUBBER: Advantages:  Permeability to water vapour .  Water absorption is very low.  They are relatively cheaper compared to other synthetic rubbers. Disadvantages:  Slow decomposition takes place above 130 ▫ C.  Oil and solvent resistance is not very good.
  • 70. SILICON RUBBERS: Advantages: • Heat resistance. • Extremely low absorption and permeability of water. • Excellent aging characteristic. Disadvantages: • They are very expensive. NITRILE RUBBER: Advantages : Oil resistant due to polar nitrile group. Heat resistant. Disadvantages: Absorption of bactericide and leaching of extractives are considerable. CHLOROPRENE RUBBERS : Advantages: Oil resistant. heat stability is good.