Topical drug delivery system

1. TOPICAL DRUG
DELIVERY SYSTEM
Prepared By: Nishant Shrestha

2. Introduction
• Topical drug delivery system is defined as the application of a drug
containing formulation to the skin or mucous membrane, to treat
specific cutaneous disorders (e.g. acne) or cutaneous manifestations of
a generalized disease (e.g. psoriasis), with the intent of containing the
pharmacological effect of the drug only to the surface or within the
layers of skin or mucous membrane.

3. Types of Topical Drug Delivery System
• Includes two types of Topical Drug Delivery System:
• External- that are spread or dispersed on the cutaneous surface covering the
affected area.
• Internal- that are applied to the mucous membrane of eye (conjunctiva), ear,
oropharyngeal cavity, nasal cavity, vagina or anorectal region for local activity.
• Classification Based on physical state-
• Solid: Powder, Aerosol, Plaster
• Liquid: Lotion, Liniment, Solution, Emulsion, Suspension, Aerosol
• Semi-solid: Ointment, Cream, Paste, Gel, Jelly, Suppository

4. Advantages of Topical Drug Delivery
System:
• Avoidance of first pass metabolism
• Easy application
• Avoidance of the risks and inconveniences of administration and the
varied conditions of absorption, like pH changes, presence of
enzymes, gastric emptying time etc. in enteral or parenteral routes
• Achievement of efficacy with lower total daily dosage of drug by
continuous drug input
• Avoids fluctuation in drug levels, inter- and intra-patient variations
• Easy termination of medications, when needed

5. Adv. Continue
• 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

6. Disadvantages of Topical Drug Delivery
System:
• Skin irritation/contact dermatitis due to drug and/or excipients
• Poor permeability of some drugs through the skin
• Possibility of allergic reactions
• Can be used only for those drugs which require low plasma
concentration for action
• Enzymes in epidermis may denature the drugs
• Drugs with larger particle size are difficult to get absorbed through the
skin

7. Fig: Structure of Skin

8. Absorption Through Skin
• Absorption through skin: Two principal absorption route are
identified:
• 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.
• Trans-follicular (shunt pathway) absorption: The skin’s appendages,
mainly sebaceous glands, sweat glands, hair follicles offer secondary
avenues for permeation, which are considered as shunts bypassing the
trans-epidermal route.

9. Factors Affecting the Extent and Rate of Topical and
Percutaneous Drug Absorption and Transportation:-
• Skin physiology & pathology:- hydration, blood flow, lipid content
• Physio-chemical properties of drugs and excipients:-
• Partition coefficient
• pH-condition
• Drug solubility
• Concentration
• Particle size
• Polymorphism
• Molecular weight
• Fabrication and design of the delivery systems:- release characteristics,
composition, nature of vehicle, presence of penetration enhancers
• The rate of drug transport across the stratum corneum follows Fick’s Law of
Diffusion

10. Types of Topical Dosage Form
Topical Dosage Form
Solid
Semi Solid
Lotion
Powder
Ointment
Paste
Aerosol
Cream
Liquid
Liniment
Solution
Plaster
Emulsion
Suspension
Gel
Aerosol
Jelly
Suppository

11. 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

12. Fig: Evaluation of powder Shade control and lighting Pressure testing Breakage test Flow property Particle size
and abrasiveness Dispersion of color

13. Ointment:
• Ointment are viscous semisolid preparation.
• Applied externally to skin or mucous membrane (eye, nose, vagina,
rectum)

14. Vehicle of an ointment (ointment base )
• Hydrocarbon (oleaginous) bases: Emollient, occlusive, greasy, non water
washable, prolonged contact period E.g.- white/yellow petrolatum
• Absorption (anhydrous) bases: Permits the incorporation of additional
quantities of aqueous solutions E.g.- Lanolin
• Water removable Bases: Oil in water type, non occlusive, less greasy,
creamy in appearance, water-washable.
• Water soluble Bases: Do not contain oleaginous components, completely
water-washable, greaseless, mostly used for the incorporation of solid
substances. E.g.- Polyethylene Glycol
• Simple base: Wool fat (5%) + hard paraffin (10%) + yellow soft paraffin
(85%)

15. Fig: Evaluation of ointments Penetration Rate of release of medicaments Absorption of medicaments into
blood stream Irritant effect

16. 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.

17. Advantages
• Less greasy
• Spreads easily
• Soothing sensation.
• Easily washable
Uses:
• Physical or chemical barrier to protect the skin e.g. sunscreens
• Cleansing agent
• Emollient
• Retention of moisture (especially water-in-oil creams)
• Vehicle for drug substances such as local anaesthetics, anti-inflammatory
agents, hormones, steroids, antibiotics, antifungals or counter-irritants

18. Fig: Evaluation of cream Rheology Sensitivity Biological testing

19. 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)

20. Fig: Evaluation of paste Abrasiveness Particle size Cleansing property Consistency pH of the
product Foaming character Limit test for arsenic and lead Volatile matters and moisture Effect of
special ingredients

21. Gels & Jellies:
• Semisolid systems- dispersions of small or large molecules in an
aqueous liquid vehicle by addition of gelling agent
• Gelling agents- either Synthetic macromolecules (Carbomer 934) or
Cellulose derivatives (Carboxymethylcellulose)
• Non greasy, moisture rich
• Compatible with many substances
• May contain penetration enhancers for anti-inflammatory and some
other medications

22. Applications:
• Sustained-release delivery system
• Dressings for healing of burn or other hard-to-heal wounds
• Reservoirs in topical drug delivery, particularly ionic drugs, delivered
by iontophoresis e.g. Diclofenac gel, Lignocaine jelly

23. Fig: Evaluation of gel Drug content Homogeneity of drug content Measurement of pH Viscosity
Spread ability Extrudability

24. Lotion:
• Clear solution/suspension/emulsion containing 25-50% alcohol
• Low to medium viscosity
• May contain extract of witch-hazel, 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

25. Fig: Evaluation of lotion Antiseptic property Determination of alcohol content

26. 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
• Typically used to relieve pain and stiffness such as from sore muscle
cramp or arthritis e.g. Turpentine

27. 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
• Because there are two incompatible phases in close conjunction, a
physical stabilizing system is needed- surfactant (ionic or nonionic),
polymers, polyelectrolytes etc.
• Types-
• Water-in-oil emulsion
• Oil-in-water emulsion
• Water-in-oil-in-water emulsion
• Oil-in-water-in-oil emulsion

29. Fig: valuation of emulsions Phase separation Globule size 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
• Almost all suspension systems get separated on standing, the rate of settling
and ease of re-suspendability is the concern
• A satisfactory suspension must remain sufficiently homogenous for at least
the time necessary to remove and administer the dose after shaking its
container
• Types:
• Flocculated
• Deflocculated

31. Fig: Evaluation of suspension Sedimentation volume Rheologic methods Electro-kinetic
techniques Particle size changes

32. 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

33. Ophthalmic Strips:
• Used for delivering diagnostic dyes topically for eye, by simply
touching the conjunctival surface
• e.g. Fluorescein sodium 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)

34. Suppository:
• Solid dosage forms intended to deliver medicine into rectal, vaginal or
urethral orifice
• Prepared by cold compression or fusion technique
• An appropriate base is selected for its compatibility, stability, melting
point, and aesthetics.
• Commonly used bases are cocoa butter, glycerin, hydrogenated
vegetable oils, and polyethylene glycol

35. Advantages:
• Bypasses first pass metabolism
• Suitable when oral route cannot be used (e.g. patient unconscious, excessive
nausea, vomiting, malabsorption disorder)
• Suitable when drug is not suitable for oral use (unstable in GI tract,
degraded by digestive enzymes )
Disadvantages:
• Absorption slower & unpredictable (BA ~50%)
• Inconvenient & embarrassing
• The contained fat often melts at the high temperatures of the tropics
• Used in kids only where controlled delivery possible

36. Fig: Evaluation of suppository Melting range test Dissolution test Liquefaction or softening
time test

37. Medicated Vaginal Rings:
• Doughnut-shaped polymeric drug delivery devices designed to provide
controlled release of drugs to the vagina over extended periods of time
• Vaginal ring products are used for the treatment of vaginal atrophy,
relief of hot flashes and as a contraceptive
• Vaginal ring technology is currently being developed for the controlled
release of microbicides and vaccines for the prevention of HIV/HPV
infection

38. 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

39. Fig: Evaluation of aerosol Flame projection Flash point Vapor pressure Density Moisture Aerosol valve discharge
rate Spray patterns Dosage with metered valves Net contents Foam stability Particle size determination

40. Hydrogels
• Hydrogels are three-dimensional network of hydrophilic cross-linked
polymer that do not dissolve but can swell in water or can respond to
the fluctuations of the environmental stimuli
• Hydrogels are highly absorbent (they can contain over 90% water)
natural or synthetic polymeric networks
• Hydrogels also possess a degree of flexibility very similar to natural
tissue, due to their significant water content Colorful hydrogels

41. Various criteria for the classification of
hydrogels Classification

42. Classification
• On the basis of Preparation
• homo-polymer
• copolymer
• Semi-interpenetrating network
• interpenetrating network
• On the basis of cross linking
• Chemical hydrogels
• Physical hydrogels

43. Advantages of Hydrogels
• Hydrogels possess a degree of flexibility very similar to natural tissue, due to their
significant water content
• Entrapment of microbial cells within Hydrogel beads has the advantage of low
toxicity
• Environmentally sensitive Hydrogels have the ability to sense changes of pH,
temperature, or the concentration of metabolite and release their load as result of
such a change
• Timed release of growth factors and other nutrients to ensure proper tissue growth
• Hydrogels have good transport properties
• Hydrogels are Biocompatible
• Hydrogels can be injected
• Hydrogels are easy to modify

44. Applications of Hydrogels in Drug Delivery
• Benefits of controlled drug delivery
• more effective therapies with reduced side effects
• the maintenance of effective drug concentration levels in the blood
• patient’s convenience as medicines hence increased patient compliance
• Hydrogels that are responsive to specific molecules, such as glucose or
antigens, can be used as biosensors as well as drug delivery systems
• Sensitive hydrogels like temperature, pH sensitive, which are used for the
targeted delivery of proteins to colon, and chemotherapeutic agents to
tumors
• Hydrogels will provide new and improved methods of regenerative
medicine, biotechnology, pharmacology, and biosensors in the near future
• Hydrogels can influence the cell behavior and its biochemical and
biophysical processes

45. Limitation of Hydrogels
• Hydrogels are expensive
• Hydrogels causes sensation felt by movement of the maggots
• The surgical risk associated with the device implantation and retrieval
• Hydrogels are non-adherent, they may need to be secured by a secondary
dressing
• Hydrogels used as contact lenses causes lens deposition, hypoxia,
dehydration and red eye reactions
• Hydrogels have low mechanical strength
• Difficulty in handling
• Difficulty in loading

46. Organo-gel
• An organo-gel is a class of gel composed of a liquid organic phase
within a three-dimensional, cross-linked network.
• Organo-gel networks can form in two ways.
• The first is classic gel network formation via polymerization.
• The gel is said to be a hydrogel or an organo-gel depending on the
nature of the liquid component: water in hydrogels and an organic
solvent in organo-gels.

47. Advantages
• Ease of administration
• Avoids first pass effect
• Absorption enhancement
• Overcome the problems of conventional dosage forms
• Site specific drug delivery
• Avoid systemic adverse effects associated with oral administration of
drug.

48. Application
• Ease of preparation & scale up, easier quality monitoring,
thermodynamic stability, enhanced topical performance,
biocompatibility, safety upon applications for prolonged period make
the organo-gels a vehicle of choice for topical drug delivery
• Ease of administration.
• Site specific drug delivery.
• Avoids first pass effect.
• Absorption enhancement.
• Overcome the problems of conventional dosage forms.

49. Limitation
• The major limitation in the formation of Los is the requirement of high
purity lecithin
• High purity lecithin is expensive
• Difficult to obtain in large quantities
• Inclusion of pluronics as co-surfactant makes organo-gelling feasible
with lecithin of relatively less purity

50. In situ gels
• It is a drug delivery system which is in a solution form before the
administration in the body but it converts in to a gel form after the
administration
• There are various routes such as oral, ocular, vaginal, rectal, I/V ,
intraperitoneal etc.
• The formation of gels depends on factors like temperature modulation,
pH change, presence of ions and ultra violet irradiation, from which
the drug gets released in a sustained and controlled manner.
• Various polymers that are used for the formulation of in situ gels
include gellan gum, alginic acid, xyloglucan, pectin etc.

51. Advantages
• Increased contact time
• Ease of administration
• Improved local bioavailability
• Reduced dose concentration
• Reduced dosing frequency
• Improved patient compliance and comfort
• Simple formulation and manufacturing so less investment and cost

52. Applications
• Oral Delivery
• Parenteral Delivery
• Ocular Delivery
• Vaginal Delivery
• Dermal and Transdermal Delivery
• Nasal Delivery

53. Limitation
• Rapid precorneal elimination.
• Loss of drug by drainage.
• Non-sustained action.
• Patients non-compliance.
• Possible oil entrapment.
• Sticking of eyelids
• No rate control on diffusion.
• Drug choice limited by partition coefficient.