Drug Delivery through topical

1. NEWER RAW MATERIALS
IN TOPICAL / DERMAL
DRUG DELIVERY SYSTEMS
Prof. M. VIMALA DEVI
CEO - AURO PHARMA
PONDICHERRY

2.  FORMULATION
 CHOICE OF VEHICLE,
RATIONALE ADDITIVES
 DRUG RELEASE KINETICS
FROM THE VEHICLE
 ABSORPTION AND HEAL
HASTENING

3. SELECTION OF APPROPRIATE
BASE/VEHICLE
 The selection of the base to use in the formulation of an
ointment depends upon the careful assessment of a number
of factors, including the:
 Desired release rate of the drug substance from the
ointment base.
 Desirability for topical or percutaneous drug absorption
 Desirability of occlusion of moisture from the skin
 Stability of the drug in the ointment base
 Effect, if any, of the drug on the consistency or other
features of the ointment base
 The desire for a base that is easily removed by washing
with water
The base that provides the majority of the most desired
attributes should be selected.

4. TYPES OF VEHICLES/BASES
Hydrophobic Bases – Emollient, occlusive, Non-
water washable Greasy eg. Analgesic like
Methyl salicylate ointment
Hydrophilic bases – Absorption Bases Anhydrous
 Emollient, Occlusive, Absorb water,
Anhydrous, Greasy
Water removable bases or Creams/Maximum in use
are hydrated emollient base

5. Emulsion Bases – o/w type, water washable
Non- greasy can be diluted with water
Non- occlusive
Water Soluble Bases – Anhydrous water
soluble, washable Non-greasy, Lipid free.
Mineral gel bases - water washable non-
occlusive better absorption.
Veegum / Bentonite / Sodium Alginate
(Ketocolid) Propylene Glycol ester of alginic
acid)

6. Glycerogelatins
– Glycerogelatins are plastic masses containing
gelatin (15%), glycerin (40%), water (35%),
and an added medicinal substance (10%) as
zinc oxide. They are prepared by first softening
the gelatin in the water for about 10 mins,
heating on a steam bath until the gelatin is
dissolved, adding the medicinal substance
mixed with the glycerin, and allowing the
mixture to cool with stirring until congealed.

7. Glycerogelatins are applied to the skin for long-
term residence. They are melted before
application, cooled to slightly above body
temp, and applied to the affected area with a
fine brush. Following application the
glycerogelatin hardens, is usually covered with
a bandage and is allowed to remain in place for
a period of weeks. The most recently official
glycerogelatin was zinc gelatin, used in the
treatment of various ulcers. It was also known
as “zinc gelatin boot” due to its ability to form
a pressure bandage.

8. TOPICAL DRUGS
Drugs of choice to be formulated into topical dosage
forms
1. Antimicrobial agents – Antiseptics, Antibiotics/
Sulpha drugs etc.
2. Anti-allerginic drugs – for urticaria, skin-rasher etc.
Pain relievers/ anti-inflammatory agents.
3. Special skin diseases, Psoriasis, wet and dry
eczema. Special skin allergies like sun allergy, heat
allergy burn (antimicrobial – with special heal
hasteners detranomer
4. Antifungal – Thiabendazole, Tinidazole

9. Bedsores
(Chronic disorders)
Melanisers, Scar removers, Scar preventives
Sunscreens –Cinoxate type
Dental Creams / patches / 1-4% creams
Sclerozing agents – e.g. quinine and urea
hydrochloride
Cosmetics
Podophyllum resin :- Topicalsolutions or ointments
(rare) 25% - alcoholic extract of Podophyllum 10% -
benzoin extract in alcohol suitable base q.s.
Papillomas worts

10. CLASSIFICATION OF TOPICAL
DRUGS
Astringents
Irritants
Rubefacients
Vesicants
Scleroing agents

11. Caustics Podophyllum resin –
Keratolytic, cauterizing agents, remove fibroids
at the site
Papillomas / worts
Personal Care, Topical Products
Cosmetics Creams

12. Special & Misallaneous drugs – special skin
allergies, sunburn
For medicated creams – eg. Psoriasis, Eczemz,
Chronic dermaloses
Eg. Anthralin – (Sulfonater Anthraquinone)
Melanisers, Scar removers, Scan preventives
Sunscreens (sunoxate 1-4%)
Sclerosing agents (Quinine + Urea hydrochloride)

13. DOSAGE FORM DESIGN AND
DEVELOPMENT
1. Physico-chemical factors of vehicles
2. Type of skin
3. Application site
4. Lesion type
5. Physico-chemical action of the base
6. Drug stability
7. Product type
8. Penetration enhancers – DMSO, DMA / DMFA
9. Incompatibilities
a) Drug + additives
b) Drug + Vehicles
Priority or foremost, expectation from the product drug
release from the vehicle.

14. Parameters or Conditions :
That promotes the drug release from the
vehicle:
1.Nature of vehicle
2.Nature of drug
3.Additives that help- e.g. sulphur +silver ions
4. Role of preservatives - ??
5.Absorption of drug released from base at the
sites of application

15. Percutaneous Absorption
The usual of dermatological drug therapy is
to produce a desired therapeutic effecty
(action) at specific sites on the epidermal
tissue. While certain topical drugs such as
emollients, antimicrobials, & deodorants act
primarily on the surface of skin, the target
lies in the viable epidermis or upper dermis.
This requires diffusive penetration of the
skin or percutaneous absorption.

16. Rationale for choice of vehicle vs drug
Main criteria are on release rate.
Therapeutic efficacy spreadability adherence at
the site of application
Compatibility, sterility, aesthetic appearance /
elegance
(Or Cosmetic touch)
Desired release rate of drug from the base.

17. FORMULA OF A FEW BASES
 Hydrophobic – All oleaginous bases (outdated) only for
analgesics.
 Hydrophilic
A. Mineral oil 20.0
Cetyl Alcohol 5.0
Arlacel 60 (Sorbitan Stearate) 2.5
Tween 60 7.5
PPG-15 Stearyl Ether 2.0
Glyceryl stearate (and)
PEG-100 Stearate 1.5
B. Sorbital 2.5
Water to 100
Preservatives qs

18. EMULSION BASES
Hydrophilic Ointment Base
 SLS 1%
 Stearyl Alcohol 25%
 Petrolactum (White) 25%
 Propylene Glycol 12%
 Water 37%
Water Removable / Water Soluble
 PEG 400 60%
 PEG 4000 40%
 Water

19. Mineral Bases
Example- Bentonite Base
13% of Bentonite
Petroleum jelly
SLS
Water qs
Sodium alginate base
Sodium alginate + Ca
Or Calcium alginate – gelforms

20. Cosmetic Creams
Propylene Glycol Monostearate 3.5
Stearic acid (T.P) 12.5
Mineral oil 65/75 3.0
Glycerine 2.0
Triethanolamine 1.5
Water to make qs

21. Components Of Some Typical
Corticosteroid Cream Bases
Emulsifiers
 Sorbitan monostearate - Kenalog Cream, Synalar Cream
Synalar Emollient Cream
 Sorbitan monooleate – Synalar Cream
 SLS - Locorten Cream
 Polyoxyethylene sorbitan - Aristocrat Cream,
monostearate Synalar Cream, Synalar
Emollient Cream
 Polyoxy 40 stearate - Cordran Cream
 Polyethylene glycol 100 - Valisone Cream
monocetyl ether
 Polysorbate 80 - Aristocrat Cream

22. Fat Phase Components
 Glyceryl monostearate - Kenalog Cream, Aristocrat Cream,
Oxylone Cream
 Cetyl alcohol - Cordran Cream, Kenalog Cream,
Locorten Cream, Synalar Emollient
Cream
 Spermaceti - Kenalog Cream, Aristocrat Cream,
Oxylone Cream
 Stearyl alcohol - Lidex Cream, Aristocrat Cream,
Synalar Emollient Cream
 Stearic acid - Cordran Cream, Synalar Cream
 Petrolatum - Valisone Cream
 Liquid petrolatum - Cordran Cream, Synalar Emollient
Cream, Valisone Cream
 Cetostearyl alcohol - Valisone Cream
 Isopropyl palmitate - Kenalog Cream
 Squalane - Kenalog Cream

23. Polyols
 Glycerine - Cordran Cream
 Propylene glycol - Kenalog Cream, Lidex Cream, Locorten
Cream, Synalar Cream, Synalar
Emollient Cream
 Propylene glycol 400 - Oxylone Cream
 Polyethylene glycol 6000 - Lidex Cream
 1,2,6 Hexanetriol - Lidex Cream
 Sorbitol solution - Aristocrat Cream

24. Antimicrobial agents
 Methylparaben - Kenalog Cream, Locorten Cream,
Oxylone Cream, Synalar Cream
 Propylparaben - Kenalog Cream, Locorten Cream,
Synalar Cream
 Ethylparaben - Cordran Cream
 Butylparaben - Oxylone Cream
 4-chloro-m-cresol - Valisone Cream
 Thimerosol - Synalar Emollient Cream
 Sorbic acid - Aristocrat Cream
 Potassium sorbate - Aristocrat Cream

25. Buffering agents
 Citric acid - Lidex Cream, Synalar Cream,
Synalar Emollient Cream
 Phosphoric acid - Valisone Cream
 Monobasic sodium phosphate - Valisone Cream
 Purified water - Cordran Cream, Kenalog Cream,
Locorten Cream,Aristocrat Cream,
Oxylone Cream, Synalar Cream,
Synalar Emollient Cream, Valisone
Cream

26. Examples of Dermatologic Ointments and
Creams by Therapeutic Category -
Adrenocortical Steroids
 Preparation
– Alclometasone Diproprionate Cream and Ointment
 Corresponding Commercial Product
- Aclovate Cream and ointment (Glaxo Dermatology)
 Usual Percentage Strength Of Active Ingredient
- 0.05% cream and ointment
 Use
- For the relief of inflammatory dermatoses

27. Adrenocortical Steroids
 Preparation
– Fluocinolone Acetonide Cream and Ointment
 Corresponding Commercial Product
- Synalar Cream & Ointment (Medicis)
 Usual Percentage Strength Of Active Ingredient
- 0.025% cream and ointment
 Use
- For the relief of inflammatory dermatoses

28. Adrenocortical Steroids
 Preparation
– Hydrocortisone Acetate Cream and Ointment
 Corresponding Commercial Product
- Cortaid Cream and Ointment (Upjohn)
 Usual Percentage Strength Of Active Ingredient
- 0.5% and 1%
 Use
- For the relief of inflammatory dermatoses

29. Adrenocortical Steroids
 Preparation
– Triamcinolone Acetonide Cream and Ointment
 Corresponding Commercial Product
- Aristocort A Cream and Ointment (Fujisawa)
 Usual Percentage Strength Of Active Ingredient
- 0.1% (ointment) and 0.1%, 0.025% and 0.5% (cream)
 Use
- For the relief of inflammatory dermatoses

30. Adrenocoricoid/Antifungal Combination
 Preparation
– Betamethasone and Clotrimazole Cream
 Corresponding Commercial Product
- Lotrisone Cream (Schering)
 Usual Percentage Strength Of Active Ingredient
- 1% betamethasone and 0.05% clotrimazole
 Use
- For the relief and treatment of inflammatory and pruritic
manifestations that could be complicated by fungal overgrowth.

31. Analgesic
 Preparation
– Capsaicin Cream
 Corresponding Commercial Product
- Zostrix Cream (Genderm)
 Usual Percentage Strength Of Active Ingredient
- 0.025%
 Use
- For the relief of arthritic pain

32. Antiacne
 Preparation
– Tretinoin Cream
 Corresponding Commercial Product
- Retin-A (Ortho)
 Usual Percentage Strength Of Active Ingredient
- 0.025%, 0.05% and 0.1%
 Use
- A derivative of vitamin A used for the topical treatment of acne
vulgaris

33. Antianginal
 Preparation
– Nitroglycerin Ointment
 Corresponding Commercial Product
- Nitro-Bid Ointment
(Hoechst Marion Roussel)
 Usual Percentage Strength Of Active Ingredient
- 2%
 Use
- Used for systemic nitroglycerin effects to reduce the workload of
the heart by smooth muscle relaxation of peripheral arteries and
veins

34. Antibacterial/Anti-infectives
 Preparation
– Gentamicin Sulfate Cream and Ointment
 Corresponding Commercial Product
- Garamycin Cream and Ointment (Schering)
 Usual Percentage Strength Of Active Ingredient
- 0.1%
 Use
- For the treatment of skin infections caused by susceptible
microorganisms affected by local treatment

35. Antibacterial/Anti-infectives
 Preparation
– Nystatin Cream
 Corresponding Commercial Product
- Mycostatin Cream
(westwood-Squibb)
 Usual Percentage Strength Of Active Ingredient
- 0.5% 100,000 units/g
 Use
- For the treatment of skin infections caused by susceptible
microorganisms affected by local treatment

36. Antibacterial/Anti-infectives
 Preparation
– Polymyxin B sulfate, Bacitracin zinc and Neomycin ointment
 Corresponding Commercial Product
- Neosporin Ointment
(Warner Wellcome)
 Usual Percentage Strength Of Active Ingredient
- 5,000 units/g polymixin B; 400 units/g bacitracin zinc; and
3.5mg/g neomycin
 Use
- For the treatment of minor cuts and scrapes.

37. Antifungals
 Preparation
– Miconazole Nitrate Cream
 Corresponding Commercial Product
- Monistat-Derm Cream (Ortho)
 Usual Percentage Strength Of Active Ingredient
- 2%
 Use
- For the cutaneous candidiasis and treatment of tinea infections
caused by Trichophyton sp.

38. Antifungals
 Preparation
– Tolnaftate Cream
 Corresponding Commercial Product
- Tinactin Cream
(Schering-Plough)
 Usual Percentage Strength Of Active Ingredient
- 1%
 Use
- For topical treatment of tinea pedis, tinea cruris, tinea corporis
and tinea manuum

39. Antineoplastic
 Preparation
– Fluorouracil Cream
 Corresponding Commercial Product
- Efudex Cream (Roche)
 Usual Percentage Strength Of Active Ingredient
- 5%
 Use
- For treatment of multiple actinic or solar keratoses

40. Antipruritic/Analgesic
 Preparation
– Lidocaine Ointment
 Corresponding Commercial Product
- Xylocaine Ointment
 Usual Percentage Strength Of Active Ingredient
- 2.5%
 Use
- For the relief of pain and itching due to minor skin irritation and
insect bites.

41. Astringent/Protectant
 Preparation
– Zinc Oxide Ointment
 Corresponding Commercial Product
- Desitin Ointment (Pfizer)
 Usual Percentage Strength Of Active Ingredient
- 40%
 Use
- Used topically as an astringent and protective in various skin
conditions as diaper rash

42. Depigmenting Agents
 Preparation
– Hydroquinone Cream
 Corresponding Commercial Product
- Eldopaque Cream
(ICN Pharmaceutical)
 Usual Percentage Strength Of Active Ingredient
- 4%
 Use
- Used in the temporary bleaching of hyperpigmented skin
blemished due to freckles, old age spots, and cholasma

43. Scabicide
 Preparation
– Crotamiton Cream
 Corresponding Commercial Product
- Eurax Cream
(Westwood- Squibb)
 Usual Percentage Strength Of Active Ingredient
- 10%
 Use
- For eradication of scabies and symptomatic treatment of
pruritus.

44. Examples of ophthalmic ointments
 Ophthalmic Ointment
– Chloramphenicol Opthalmic Ointment
 Corresponding Commercial Product
- Chloromycetin Opthalmic Ointment (Park-Davis)
 % of Active Ingredient
- 1%
 Category
- Antibacterial antibiotic

45. Examples of ophthalmic ointments
 Ophthalmic Ointment
– Dexamethasone Sodium Phosphate Ophthalmic Ointment
 Corresponding Commercial Product
- Decadron Phosphate Ophthalmic Ointment (Merck Sharp &
Dohme)
 % of Active Ingredient
- 0.05%
 Category
- Anti-inflammatory adrenocortical steroid

46. Examples of ophthalmic ointments
 Ophthalmic Ointment
– Gentamicin Sulfate Ophthalmic Ointment
 Corresponding Commercial Product
- Garamycin Ophthalmic Ointment (Schering)
 % of Active Ingredient
- 0.3%
 Category
- Antibacterial antibiotic

47. Examples of ophthalmic ointments
 Ophthalmic Ointment
– Isoflurophate Ophthalmic Ointment
 Corresponding Commercial Product
- Floropryl Sterile Ophthalmic Ointment (Merck)
 % of Active Ingredient
- 0.025%
 Category
- Cholinesterase inhibitor

48. Examples of ophthalmic ointments
 Ophthalmic Ointment
– Neomycin Sulfate and Dexamethasone Sodium Phosphate
Ophthalmic Ointment
 Corresponding Commercial Product
- NeoDecadron Ophthalmic Ointment (Merck)
 % of Active Ingredient
- 0.35% neomycin base and 0.05% dexamethasone phosphate
equivalents
 Category
- Antibacterial / Anti-inflammatory

49. Examples of ophthalmic ointments
 Ophthalmic Ointment
– Polymyxin B-Bacitracin Ophthalmic Ointment
 Corresponding Commercial Product
- Polysporin Ophthalmic Ointment (Burroughs Wellcome)
 % of Active Ingredient
- Per g: polymyxin B sulfate, 10,000 units and bacitracin zinc, 500
units
 Category
- Antimicrobial