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Ansel H.C., Allen L.V., “Pharmaceutical Dosage Forms and Drug Delivery System”, 7th edition, Lippincott
Willlams and Wilkens, Baltimore, 2000, 244-246,249-251, 253-255,264-265
3
(A) Solid:
Powder, Aerosol, Plaster
(B) Liquid:
Lotion, Liniment, Solution, Emulsion, Suspension, Aerosol
(C) Semi-solid:
Ointment, Cream, Paste, Gel, Jelly, Suppository
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Advantages: contd…
Relatively large area of application
Drug can be delivered more selectively to a specific site
Avoidance of gastro-intestinal incompatibility
Provide utilization of drugs with short biological half-life &
narrow therapeutic window
Improved physiological and pharmacological response
Improved patient compliance
Suitable for self-medication
Surver, C. and Davis, F.A., Bioaviability and Bioequivalence, In Walter, K.A..(Ed. ) , Dermatological and Transdermal
Formulation, Marcal Dekker, INC. NewYork , 119,2002,pp. 403,323,326,327,403
6
A) Trans-epidermal absorption:
Principally responsible for diffusion across the skin. The resistance
encountered along this pathway mostly arises in the stratum corneum.
Maybe trans-cellular or inter-cellular.
The rate of drug transport across the stratum corneum follows Fick’s Law
of Diffusion
10
Ointment:-
Viscous semisolid preparation
5) Simple base:
Wool fat (5%) + hard paraffin (10%) + yellow soft paraffin (85%)
12
Evaluation Penetration
of ointments
Rate of release of
medicaments
Absorption of
medicaments into
blood stream
Irritant effect
13
Only the medicine that is touching the skin will work, so thin
layer is always preferred to thick layer.
14
Cream:
Viscous semisolid emulsion- medicaments dissolved or suspended in
water removable bases.
Applied to skin or mucous membrane (vagina, rectum)
Most are O/W (small droplets of oil dispersed in a continuous
aqueous phase), only cold creams and emollients are W/O (small
droplets of water dispersed in a continuous oily phase).
O/W (vanishing) - water washable, non greasy, non occlusive, more
cosmetically acceptable.
W/O (oily) - for some hydrophobic drugs, more emollient.
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1. Less greasy
2. Spreads easily
3. Soothing sensation
4. Easily washable
• Uses:-
1. Physical or chemical barrier to protect the skin e.g. sunscreens
2. Cleansing agent
3. Emollient
4. Retention of moisture (especially water-in-oil creams)
5. Vehicle for drug substances such as local anaesthetics, anti-
inflammatory agents, hormones, steroids, antibiotics,
antifungals or counter-irritants
16
Evaluation of
Rheology
cream
Sensitivity
Biological
testing
17
Paste:-
Pastes are basically ointments into which a high percentage of
insoluble solids have been added
Less greasy than ointments
Provide protective coating on skin due to it’s stiff consistency
Poorly occlusive, so suited for application around moist areas
Absorb secretion from the oozing lesions
Forms an unbroken, water impermeable, opaque film on the skin
Effective sun filter & prevent excessive wind dehydration (windburn)
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Abrasiveness
Particle size
Evaluation of
paste
Cleansing
property
Consistency
pH of the
product
Foaming
character
Volatile matters
and moisture
Effect of special
ingredients
19
Types:-
Prepared from either natural gums such as pectin, alginate etc. or from
synthetic derivatives of natural substance such as methylcellulose
21
Applications:
Drug content
Homogeneity
of drug
content
Measurement
of pH
Evaluation
of gel
Viscosity
Spreadability
Extrudability
23
Lotion:
Clear solution/suspension/emulsion containing 25-50% alcohol
Low to medium viscosity
May contain extract of witchhazel, menthol, glycerin, boric acid,
alum, chloroform etc but NOT camphor
Applied without friction
Can be applied on abraded/wounded skin or on mucous membrane
Antiseptic, anti inflammatory, astringent, emollient, cooling,
moisturizing or protective actions
e.g. Calamine lotion
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Antiseptic
property
Evaluation Determination of
of lotion alcohol content
25
Liniment (Balm):
Low- to medium-viscosity emulsions
Formulated from quickly evaporating solvents, contain aromatic
chemical compounds
As a rule contain camphor
Always applied with friction
Applied only on unbroken skin, never on mucus membrane
Mechanism of action:
• Rubefacient
• Local irritant
• Counter irritant
Typically used to relieve pain and stiffness such as from sore muscle
cramp or arthritis
e.g. Turpentine
26
Poultices/Cataplasms:-
Now obsolete
Heated & spread on dressing & applied as hot as the patient can bear
Heat is retained, soothing in pain and inflammation
Ingredients may have counter-irritant/ absorptive properties
e.g. Kaolin poultice
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Solution:
Solutions are liquid preparations of soluble chemicals dissolved in
solvents such as water, alcohol or propylene glycol
E.g:
· Tincture of iodine
· Sterile Indian ink for surgical procedures
28
Emulsion:
Two-phase preparations - the dispensed (internal) phase is finely
dispersed in the continuous (external) phase
Types-
· Water-in-oil emulsion
· Oil-in-water emulsion
· Water-in-oil-in-water emulsion
· Oil-in-water-in-oil emulsion
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Phase separation
Globule size
Evaluation of
emulsions Rheological
properties
Effect of thermal
stresses
30
Suspension:
Heterogeneous system consisting of two phases:
1. The continuous or external phase is generally a liquid or semisolid
2. The disperse or internal phase is made up of particulate matter that
is dispersed throughout the continuous phase
Types:
· Flocculated
· Deflocculated
31
Sedimentation
volume
Evaluation of Rheologic
suspension methods
Electrokinetic
techniques
Particle size
changes
32
Medicated shampoos:-
e.g. Selenium sulphide, Cetrimide, Ketoconazole
Paints:-
Applied to broken skin/mucus membrane
Applied in throat with an applicator
e.g. Mandl’s paint
Nail lacquers:-
e.g. Amorolfine (a newer antifungal) for tinea unguium
33
Collodion:-
• Protective, occlusive, water repellant film on the skin
surface following evaporation of the solvent
• Seals small cuts and scratches
• Occlusion prolongs contact with active medicaments
• Contains pyroxylone (a nitrocellulose) in an ether alcohol
mixture
• Applied using a brush or applicator
• e.g. Salicylic acid collodion
34
Eye/Ear Drops:-
Solution/ suspension
Relatively brief contact time with absorbing surface
pH, tonicity, viscosity important for local comfort.
Sterile; require aseptic handling
Use droppers with attached or separate plastic nozzle, avoid touching
the application surface
Use: to prevent or treat infections
E.g. Ciprofloxacin eye/ear drop, Artificial tear
Ophthalmic strips:-
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Ocular insertion:-
Continuous release multilayered
polymeric insertion in
conjunctival fornix
Ocusert (pilocarpine- for
treatment of glaucoma), Lacrisert
(artificial tear substitute- for
treatment of dry eye)
Not available in India
36
Framycetin dressing
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Suppository:
Advantages:
Disadvantages:
Rectal Suppository:
They are meant for local (e.g. OTC preparation for hemorrhoids
containing a moisturizer or vasoconstrictor; Glycerin or Bisacodyl
as laxative ) and for systemic (e.g. Paracetamol, Aminophylline,
Promethazine) effects
Vaginal suppositories/pessaries:
Globose or oviform, weight=5g
Mostly meant for local effects (clotrimazole, miconazole, metronidazole)
Urethral suppository/bougies:
Cylindrical, longer for males than for females, obsolete now a days
41
Melting range
test
Evaluation of Dissolution
suppository test
Liquefaction or
softening time
test
42
Douche:-
Douche is a device used to rinse any
body cavity but usually applies to
vaginal irrigation
Vaginal douches may consist of water,
water mixed with vinegar, or even
antiseptic chemicals
Disadvantage: Can lead to irritation,
pelvic inflammatory disease (PID),
fertility problems
Use - Treatment of bacterial vaginosis
with a vaginal douche containing a
strain of L. acidophilus
43
Aerosol:
A system that depends on the power of compressed or liquefied gas to expel the
contents from the container.
Topical pharmaceutical aerosols utilize hydrocarbon (propane, butane, and
isobutene) and compressed gases such as nitrogen, carbon dioxide, and nitrous
oxide.
Advantages:
• Rapid onset
• at site delivery
• Less amount of drug required
• Less systemic absorption – less side effects
• No first pass effect
• Dose titration possible
• Acceptable & convenient to patient
46
Disadvantages:
• Difficult to maintain particle size ≈ 2-8 microns and moisture content ≈ 100-300
ppm
• Only 10-20% drug is deposited at site
• Aerosol droplets facilitate microbial invasion
• Propellants can cause ADR
• Proper technique is difficult to maintain
Devices:
MDI ± Spacer
Nebuliser
Rotahaler
Inhaled insulin device
47
Flame projection
Flash point
Vapor pressure
Density
Moisture
Evaluation of aerosol Aerosol valve discharge
rate
Spray patterns
Dosage with metered valves
Net contents
Foam stability
Particle size determination
48
Dusting Powder:-
Free flowing
Applied on skin, wounds, ulcers
Very fine particle size produces large surface area per unit weight
Mechanical protective action against irritation/itching due to friction
Dries the skin by absorbing water & adsorbs toxic material
Medicated powders are used for prickly heat or preventing
microbial growth on skin
e.g. Starch, Talc
49
Pressure testing
Evaluation of powder
Breakage test
Flow property
Dispersion of color
50
TDDS use the percutaneous route for systemic drug delivery, but
the skin is not the primary target organ, active ingredient is moved
across the layers of skin for subsequent systemic distribution.
53
Advantages of TDDS:-
Consistent serum drug levels as IV
The lack of peaks in plasma concentration
Drugs that require relatively consistent plasma levels are very good
candidates
Convenience and high adherence
• non invasive
• usually once weekly /once in 15/30 days application
• removal of the patch in case of toxicity
Avoids FPM and GI irritation
Great advantage in patients who are nauseated or unconscious
Useful for drugs that are degraded by the enzymes and acids in the
gastrointestinal system
54
Disadvantages:-
local irritation
• rotation to minimize
• if severe allergic reactions- discontinue
skin's low permeability limits the number of drugs that can be
delivered
after removal, most patches contain at least 95% of the total amount
of drug initially in the patch
- patients must exercise care when disposing of patches
Damage to a transdermal patch
• patients should be advised to discard a patch if the outer
packaging or the patch itself appears damaged or altered in any
way
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Design of TDDS:
Patch design is the first & commonest type
Factors influencing:-
1. Properties of the drug- Systemic absorption of transdermal is better
with
• low dose
• low molecular weight
• lipid soluble drugs
2. Desired delivery profile
3. Target patient group
-- determine which design is best for a given application
56
Components of a TD patch:-
Liner - protects the patch during storage, removed prior to use
Drug reservoir- drug solution in direct contact with release liner
Adhesive - adhere the components of the patch together and to the skin
Membrane – controls release of the drug from reservoir and multi-layer patches
Backing - protects the patch from the outer environment
57
Types of TD patch:-
Single layer drug in adhesive
Multi -layer drug in adhesive
- immediate drug release layer
Vapour patch
- for releasing of essential oils in decongestion
Reservoir system
- liquid drug solution containing reservoir is embedded between an impervious
backing layer and a rate controlling semi permeable membrane
Matrix system
- similar to that of the reservoir, but the drug is instead provided as a semisolid
formulation, and there is no membrane layer
21-day
cumulative
irritancy patch
test
Kligman
Evaluation “maximization”
of patch test
Draize-shelanski
repeat-insult
patch test
59
Iontophoresis:-
• Technique involving the transport of ionic or charged molecules into tissue
by the passage of direct or periodic electric current through an electrolyte
solution
• Limitations: Hair follicle damage is possible
• E.g. Pilocarpine Iontophoresis in sweat test for Cystic Fibrosis
61
Skin ablation:
• doubling of the TEWL (Trans Epidermal Water Loss) using surgical tapes
• Microsecond thermal ablation- a promising mechanism to increase
permeability of the skin's outer barrier layer of stratum corneum while
sparing deeper living tissues to aid skin permeation
64
Liposomes:-
• frequently used as vehicle for controlled and optimized delivery to skin layers
• spherical phospholipid vesicles whose membrane consists of amphiphilic lipid
(hydrophilic on outer side and lipophilic on the inner side) that enclose an
aqueous core
• thus they may encapsulate hydrophilic substances in their aqueous core and
lipophilic substances in their lipid bilayer.
• unique dual release capability enables the delivery of two types of substances
simultaneously once they are applied on the skin, which may enhance the
desired therapeutic benefit
66
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Niosomes:-
Niosomes are microscopic lamellar structures composed of non-ionic surfactants
and cholesterol
Niosomes and liposomes have similar application in drug delivery but chemically
differ in structure units. Niosomes constitute of non-ionic surfactant whereas
liposomes comprise of phospholipids
Nano-emulsions:-
Polymers:-
Microsponges:-
• biologically inert particles
• made of synthetic polymers with the capacity to store a volume of an active
agent up to their own weight
• the particles serve to protect the entrapped active compound from physical and
environmental degradation
• more frequently manufactured as gels
• once applied on the skin, they slowly release the active agent(s)
71
Emulsifier-free Formulations:-
Fullerenes:-
molecules composed entirely of carbon that resemble a hollow sphere
Rouse, et al., showed that once fullerenes come into contact with the skin, they
migrate through the skin intercellularly, as opposed to moving through cells
therefore, a fullerene could be used to “trap” active compounds and then release
them into the epidermis once they are applied on the skin
moreover, fullerenes, themselves, are thought to be potentially potent
antioxidants
they are well tolerated & hold substantial promise in dermatologic and cosmetic
applications.
Rouse JG, Yang J, Ryman-Rasmussen JP, et al. Effects of mechanical flexion on the penetration of fullerene amino acid- derivatized
peptide nanoparticles through skin. Nano Lett 7(1):155-60 (2007 Jan)
73
Conclusion:-
• Topical preparations are used for the localized effects at the site of their
application by virtue of drug penetration into the underlying layers of skin
or mucous membranes
• The main advantage of topical delivery system is to bypass first pass
metabolism
• Avoidance of the risks and inconveniences of parenteral therapy and of the
varied conditions of absorption, like pH changes, presence of enzymes,
gastric emptying time are other advantage of topical preparations
• Iontophoresis, Electroporation, Sonophoresis, Phonophoresis, Vesicular
concept and Microfabricated microneedles technology are some advanced
technique which are being used to increase delivery through skin
• Semi-solid formulation in all their diversity dominate the system for topical
delivery, but foams, spray, medicated powders, solution, and medicated
adhesive patches are also widely used