Topical Drug Delivery Systems

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Topical Drug Delivery Systems : A ReviewMr.J.P.GoswamiShailesh SharmaDr.G.D.GuptaMr.Anis Mustafa

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 oftopical delivery system is to bypass first pass metabolism. Avoidance of the

risks and inconveniences of intravenous therapy and of the varied conditions of absorption, like pH

changes, presence of enzymes, gastric emptying time are other advantage of topical preparations.

Semi-solid formulation in all their diversity dominate the system for topical delivery, but foams,

spray, medicated powders, solution, and even medicated adhesive systems are in use. The topical

drug delivery system is generally used where the others system of drug administration fails or it is

mainly used in pain management, contraception, and urinary incontinence. This review describes the

various formulation aspects, variousexcipients, evaluation tests, challenges and drugs explored in

the field of topical drug delivery.

Introduction

Over the last decades the treatment of illness has been accomplished by administrating drugs tohuman body via various routes namely oral, sublingual, rectal, parental, topical, inhalation etc.

Topical delivery can be defined as the application of a drug containing formulation to the skin to

directly treat cutaneous disorders (e.g. acne) or the cutaneous manifestations of a general disease

(e.g. psoriasis) with the intent of containing the pharmacological or other effect of the drug to the

surface of the skin or within the skin. Semi-solid formulation in all their diversity dominate the

system for topical delivery, but foams, spray, medicated powders, solution, and even medicated

adhesive systems are in use1.

Topical delivery includes two basic types of product:

External topicals that are spread, sprayed, or otherwise dispersed on to cutaneous tissues tocover the affected area.

Internal topicals that are applied to the mucous membrane orally, vaginally or on anorectaltissues for local activity

2.

For the most part 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. Although

some unintended drug absorption may occur, it is sub therapeutics quantities and generally of minor

concern3.

Advantages of Topical Drug Delivery Systems:4-7
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Avoidance of first pass metabolism. Convenient and easy to apply. Avoidance of the risks and inconveniences of intravenous therapy and of the varied conditions

of absorption, like pH changes, presence of enzymes, gastric emptying time etc.

Achievement of efficacy with lower total daily dosage of drug by continuous drug input. Avoids fluctuation in drug levels, inter- and intrapatient variations. Ability to easily terminate the medications, when needed. A relatively large area of application in comparison with buccal or nasal cavity Ability to deliver drug more selectively to a specific site. Avoidance of gastro-intestinal incompatibility. Providing utilization of drugs with short biological half-life, narrow therapeutic window. Improving physiological and pharmacological response. Improve patient compliance. Provide suitability for self-medication.

Disadvantages of Topical Drug Delivery Systems:8-10

Skin irritation of contact dermatitis may occur due to the drug and/orexcipients. Poor permeability of some drugs through the skin. Possibility of allergenic reactions. Can be used only for drugs which require very small plasma concentration for action Enzyme in epidermis may denature the drugs Drugs of larger particle size not easy to absorb through the skin

Classification ofTopical Drug Delivery Systems:11

Classification of Topical Drug Delivery Systems based on physical state

(A) Solid:

Powder Aerosol Plaster

(B)Liquid :

Lotion Liniment Solution Emulsion Suspension Aerosol

(c) Semi-solid :

Ointment Cream
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Paste Gel Jelly Suppository

Figure 1 -Topical dosage form for dermatological application

Permeation through skin

Most of topical preparations are meant to be appliedto the skin. So basic knowledge of skin and its

physiology, function and biochemistry is very important for designing topicals. The skin is the

heaviest single organ of the body, combines with the mucosal lining of the respiratory, digestive and

urogenital tracts to from a capsule, which separates the internal body structures from the external

environment. The pH of the skin varies from 4 to 5.6. Sweat and fatty acids secreted from sebum

influence the pH of the skin surface. It is suggested that acidity of the skin helps in limiting or

preventing the growth of pathogens and other organisms11.


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Physiology of the skin:11-14

The skin has several layers. The overlaying outer layer is called epidermis, the layer below epidermis

is called dermis. They dermis contain a network of blood vessels, hair follicle, sweat gland &

sebaceous gland. Beneath the dermis are subcutaneous fatty tissues. Bulbs of hair project in to these

fatty tissues.

Figure 2 -Cross section of human skin

The layers of epidermis are:

Stratum Germinativum (Growing Layer) Malpighion Layer (pigment Layer) Stratum Spinosum (Prickly cell Layer) Stratum Granulosum (Granular Layer) Stratum Lucidum Stratum Corneum (Horny Layer)

Epidermis

It is the outermost layer of the skin, which is approximately 150 micrometers thick. Cell from lowers

layers of the skin travel upward during their life cycle and become flat dead cell of the corneum. The

source of energy for lower portions of epidermis is also glucose, and the end product of metabolism,lactic acid accumulates in skin.

Stratum Germinativum: Basal cells are nucleated, columnar. Cells of this layer have high mitotic

index and constantly renew the epidermis and this proliferation in healthy skin balances the loss of

dead horny cells from the skin surface.

Malpighion Layer: The basal cell also include melanocytes which produce the distribute melanin

granules to the keratinocytes required for pigmentation a protective measure against radiation.

Stratum Spinosum: The cell of this layer is produced by morphological and histochemical alteration

of the cells basal layers as they moved upward. The cells flatten and their nuclei shrink. They are


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interconnected by fine prickles and form intercellular bridge the desmosomes. These links maintain

the integrity of the epidermis.

Stratum Granulosum: This layer is above the keratinocytes. They manufacturing basic staining

particle, the keratinohylline granules. This keratogenous or transitional zone is a region of intense

biochemical activity and morphological change.

Stratum Lucidum: In the palm of the hand and sole of the foot, and zone forms a thin, translucent

layer immediately above the granule layer. The cells are non-nuclear.

Stratum corneum: At the final stage of differentiation, epidermal cell construct the most superficial

layer of epidermis, stratum corneum. At friction surface of the body like palms and soles adapt for

weight bearing and membranous stratum corneum over the remainder of the body is flexible but

impermeable. The horny pads (sole and palm) are at least 40 times thicker than the membranous

horny layer

Dermis

Non-descriptive region lying in between the epidermis and the subcutaneous fatty region. It consist

mainly of the dense network of structural protein fibre i.e. collagen, reticulum and elastin, embedded

in the semigel matrix of mucopolysaccaridic 'ground substance'. The elasticity of skin is due to the

network or gel structure of the cells. Beneath the dermis the fibrous tissue open outs and merges

with the fat containing subcutaneous tissue. Protein synthesis is a key factor in dermal metabolism.

Subcutaneous tissue

This layer consist of sheet of fat rich areolar tissue, know as superficial fascia, attaching the dermis

to the underlying structure. Large arteries and vein are present only in the superficial region.

Skin Appendages

The skin is interspersed with hair follicle and associated sebaceous gland like regions two types of

sweat glands eccrine and apocrine. Collectively these are referred to as skin appendages.

Functions of skin:15

Containment of body fluids and tissues. Protection from external stimuli like chemicals, light, heat, cold and radiation. Reception of stimuli like pressure, heat, pain etc. Biochemical synthesis. Metabolism and disposal of biochemical wastes. Regulation of body temperature. Controlling of blood pressure. Prevent penetration of noxious foreign material & radiation. Cushions against mechanical shock. Interspecies identification and/ or sexual attraction.

Biochemistry of skin:

15-16

Epidermis


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The source of energy for the lower portion of epidermis is also glucose and the end product of

metabolism; lactic acid accumulates in the skin, which result in a drop in tissue pH from the usual 7

to less then 6. During differentiation from basal cells to stratum corneum by degradation of the

existing cellular components, the entire cellular make-up changes. Specialized cellular organelles

called lysosomes contain a host lytic enzyme, which they release for intracellular lysis. The epidermisis reservoir of such lytic enzymes. Many of these enzymes are inactivated (probably by auto catalytic

processes) in upper granular layer; however, many also survive into the stratum corneum. The

stratum corneum also has proteolytic enzymes involved in this desquamation.

Dermis

Despite its greater volume, the dermis contains far fewer cells than the epidermis and instead much

of its bulk consists of fibrous and amorphous extra cellular matrix interspersed between the skin's

appendages, nerves, vessels, receptors and the dermal cells. The main cell type of the dermis is the

fibroblast, a heterogeneous migratory cell that makes and degrades extracellular matrix extracellular

matrix components. There is significant current interest in the factors that control the differentiation

of the dermal fibroblast, particularly in the context of their increased synthetic and proliferative

activity during wounding healing. The dermis is home to several cell types including multi-functional

cells of the immune system like macrophages and mast cells, the latter which can trigger allergic

reactions by secreting bioactive mediators such as histamine.

Skin surface

The skin surface has a population of microorganisms. They can contribute to the skin enzymology.

Their diversity and abundance can vary considerabely among individuals and body sites. They can

also effect skin surface lipid composition via hydrolysis of secreted sebum.

Absorption through skin:16-18

Two principal absorption route are identified:

Transepidermal absorption

It is now generally believed that the transepidermal pathway is principally responsible for diffusion

across the skin. The resistance encountered along this pathway arises in the stratum corneum.

Permeation by the transepidermal route first involves partitioning into the stratum corneum.

Diffusion then takes place across this tissue. The current popular belief is that most substancesdiffuse across the stratum corneum via the intercellular lipoidal route. This is a tortuous pathway of

limited fractional volume and even more limited productive fractional area in the plane of diffusion.

However, there appears to be another microscopic path through the stratum corneum for extremely

polar compounds and ions. Otherwise, these would not permeate at rates that are measurable

considering their o/w distributing tendencies. When a permeating drug exits at the stratum corneum,

it enters the wet cell mass of the epidermis and since the epidermis has no direct blood supply, the

drug is forced to diffuse across it to reach the vasculature immediately beneath. The viable epidermis

is considered as a single field of diffusion in models. The epidermal cell membranes are tightly joined

and there is little to no intercellular space for ions and polar nonelectrolyte molecules to diffusionallysqueeze through. Thus, permeation requires frequent crossings of cell membranes, each crossing


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being a thermodynamically prohibitive event for such water-soluble species. Extremely lipophilic

molecules on the other hand, are thermodynamically constrained from dissolving in the watery

regime of the cell (cytoplasm). Thus the viable tissue is rate determining when nonpolar compounds

are involved.

Passage through the dermal region represents a final hurdle to systemic entry. This is so regardless of

whether permeation is transepidermal or by a shunt route. Permeation through the dermis is

through the interlocking channels of the ground substance. Diffusion through the dermis is facile and

without molecular selectivity since gaps between the collagen fibers are far too wide to filter large

molecules. Since the viable epidermis and dermis lack measure physiochemical distinction, they are

generally considered as a single field of diffusion, except when penetrants of extreme polarity are

involved, as the epidermis offers measurable resistance to such species.

Transfollicular (shunt pathway) absorption

The skins appendages offer only secondary avenues for permeation. Sebaceous and eccrine glandsare the only appendages, which are seriously considered as shunts bypassing the stratum corneam

since these are distributed over the entire body. Though eccrine glands are numerous, their orifices

are tiny and add up to a miniscule fraction of the bodys surface. Moreover, they are either

evacuated or so profusely active that molecules cannot diffuse inwardly against the glands output.

For these reasons, they are not considered as a serious route for percutaneous absorption. However,

the follicular route remains an important avenue for percutaneous absorption since the opening of

the follicular pore, where the hair shaft exits the skin, is relatively large and sebum aids in diffusion of

penetrants. Partitioning into sebum, followed by diffusion through the sebum to the depths of the

epidermis is the envisioned mechanism of permeation by this route. Vasculature sub serving the hairfollicle located in the dermis is the likely point of systemic entry. Absorption across a membrane, the

current or flux is and terms of matter or molecules rather then electrons, and the driving force is a

concentration gradient (technically, a chemical potential gradient) rather then a voltage drop. A

membranes act as a diffusional resistor. Resistance is proportional to thickness (h), inversely

proportional to the diffusive mobility of matter within the membrane or to the diffusion coefficient

(D), inversely proportional to the fractional area of a route where there is more than one (F), and

inversely proportional to the carrying capacity of a phase.

R = h/FDK

R =Resistance of diffusion resistor

F = Fractional area

H = Thickness

D = diffusivity

K = Relative capacity

Basic principle of permeation:9


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In the initial transient diffusion stage, drugs molecules may penetrate the skin along the hair follicles

or sweat ducts and then be absorbed through the follicular epithelium and sebaceous glands. When

a steady state has been reached diffusion through stratum corneam becomes the dominant pathway.

The membrane-limited flux (J) under steady condition is described by expression.

DAKO/W r C

J = ---------------------

h

Where:

J = Amount of drug passing through the membrane system per unit area, per unit area per unit time.

D= Diffusion coefficient

A= Area of the membrane

C= Concentration gradient

Ko/w= Membranes / vehicle partition coefficient

h= Thickness of the membrane.


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Kinetics of permeation:16-18

Knowledge of skin permeation is vital to the successful development of topical formulation.

Permeation of a drug involves the following steps,

Sorption by stratum corneum, Penetration of drug though viable epidermis, Uptake of the drug by the capillary network in the dermal papillary layer.

This permeation can be possible only if the drug possesses certain physicochemical properties. The

rate of permeation across the skin (dQ/dt) is given by:

dQ

----- = Ps(cd-cr)

dt


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Where Cd and Cr are, the concentrations of skin penetrant in the donor compartment (e. g., on the

surface of stratum corneum) and in the receptor compartment (e.g., body) respectively. Ps is the

overall permeability coefficient of the skin tissues to the penetrant. This permeability coefficient is

given by the relationship:

Ks Dss

Ps = --------------

Hs

Where Ks is the partition coefficient for the interfacial Partitioning of the penetrant molecule form a

solution medium on to the stratum corneum, Dss is the apparent diffusivity for the steady state

diffusion of the penetrant molecule through a thickness of skin tissues and hs is the overall thickness

ofskin tissues. As Ks, Dss and hs are constant under given conditions, the permeability coefficient (Ps)

for a skin penetrant can be considered to be constant.

From equation (1) it is clear that a constant rate of drug permeation can be obtain when Cd >> Cr i.e.,

the drug concentration at the surface of the stratum corneam (Cd) is consistently and substantially

greater than the drug concentration in the body (Cr). The equation (1) becomes:

And the rate of skin permeation (dQ/dt) is constant provide the magnitude of Cd remains fairly

constant throughout the course of skin permeation. For keeping Cd constant, the drug should be

released from the device at a rate (Rr) that is either constant or greater than the rate of skin uptake

(Ra) i.e., Rr >> Ra.

Factor affecting topical permeation:

Physicochemical properties of drug substances19-20

Partition coefficient pH-condition Drug solubility Concentration Particle size Polymorphism Molecular weight

Penetration enhancer21-26

Percutaneous absorption can be enhancing in two ways either by chemical enhancer or by physical

method.

Chemical penetration enhancer: By definition, a chemical skin penetration enhancer increase skin

permeability by reversibly damaging or by altering the physicochemical nature of the stratum

corneam to reduce its diffusional resistance. Among the alterations are increased hydration of

stratum corneam and / or a change in the structure of the lipids and lipoproteins in the intercellular

channels through solvent action or denaturation. These may conveniently be classified under the

following main heading:


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Solvents: These compounds increase penetration possibly by swelling the polar pathwayand/or by fluidizing lipids. Examples include water, alcohols, methanol and ethanol; alkyl methyl

sulfoxide, dimethyl sulfoxide, alkyl homologs of methyl sulfoxide, dimethyl acetamide and

dimethylformamide; pyrrolidones- 2 -pyrrolidone, N-methyl, 2- pyrrolidone; laurocapram

(Azone), miseellancous solvents- propnylene glycol, glyeerol, silicone fluids, isopropyl palmitate.

Surfactant: These compounds are proposed to enhance polar pathway transport, especially ofhydrophilic drugs. The ability of the surfactant to alter penetration is a function of polar head

group and the hydrocarbon chain length. Commonly used surfactant are as follow

Anionic surfactant: can penetrant and interact strongly with skin. Examples include are Dioctyl

sulphosuccinate, Sodium lauryl sulphate, Decodecylmethyl sulphoxide etc.

Cationic surfactant: Cationic surfactants are reportedly more irritating than anionic surfactants and

they have not been widely studied as skin permeation enhancer.

Nonionic surfactant: Nonionic surfactants have least potential for irritation. Example includes are

Pluronic F127, Pluronic F68 etc.

Bile salts: Sodium taurocholate, Sodium deoxycholate, and Sodium tauroglycocholate. Binary system: These systems apparently open the heterogeneous multilaminated pathway

as well as the continuous pathways. Examples include are Prolylene glycol -oleic acid and 1,4-

butane diol- linoleic acid.

Miscellaneous chemicals: These includes urea, N,N-dimethyl-m-toluamide, calciumthioglycolate etc.

Physical method of topical drug delivery

Intophorosis: Intophorosis is a process or a technique involving the transport of ionic orcharged molecules into a tissue by the passage of direct or periodic electric current through an

electrolyte solution containing the ionic molecules to be delivered using an appropriate

electrode polarity.

Electroporation: The process involves the application of transient high voltage electrical pulseto cause rapid dissociation of the stratum corneam through which large and small peptides,

oligonucleotides and other drugs can pass in significant amounts. Electroporation or elecro-

permeabilization involves changes in membrane cells due to application of large

transmembrane voltage. The change in the membrane involves structural arrangement and

conductance leading to temporary loss of semi-permeability of cell membranes suggesting

formation of pores.

Sonophoresis: Sonophoresis involves the usage of the frequency ultrasound waves. Theultrasound application has resulted in permeation of low frequency ultrasound was shown to

increase the permeability of human skin to many drugs including high molecular weight protein

by several orders of magnitude.


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Phonophoresis: The movement of drugs through living intact skin and into soft tissues underthe ultrasound perturbation is called phonophoresis. The technique involves placing an

ultrasound-coupling agent on the skin over the area to be treated and massaging the area with

an ultrasound source.

Vesicular concept: Drug enclosed vesicle made from phospholipids and nonionic surfactants areused for transport of drug into and across the skin. The various vesicles used for this purpose

are liposomes, niosomes and transferosome. The lipid vesicle serve as a rate limiting membrane

barrier for system absorption of drug, non-toxic penetration enhancers for drug, organic

solvents for solubilization of poorly soluble drugs and can incorporate both hydrophillc and

lipophillic drugs.

Microfabricated microneedles technology: This technology employed micron-sized needalesmade silicon. These microneedles after insertion into the skin create conduits for transfer of

drug through the stratum corneum. The drug after crossing stratum corneum diffuses rapidly

through deeper tissues and taken up by capillaries for systemic adminitration.

Physicochemical properties of topicals15

Release characteristics: The mechanism of drug release depends on Whether the drugmolecules are dissolved or suspended in the delivery system. The interfacial partition

coefficient of drug from delivery systems to the skin pH of the vehicle

Composition of drug delivery system: Example polyethylene glycols of low molecular weightdecrease permeation.

Nature of vehicle : Liphophilic vehicle increase permeation where as lipophobic vehicledecrease permeation.

Physiological and Pathological Condition of Skin27-30

Reservoir effect of horny layer: The horny layer, depot and modify the transdermal permeationcharacteristics of some drugs. The reservoir effect is due to irreversible binding of a part of the

applied drug with the skin. This binding can be reduced by pretreatment of skin surface with

anionic surfactants.

Lipid film: The lipid film on the skin surface acts a protective layer to prevent the removal ofmoisture from the skin and helps in maintaining the barrier function of the stratumcorneum.

Skin hydration: Hydration of stratum corneum can enhance transdermal permeability. Coveringor occluding the skin with plastic sheet leading to sweet and condensed water vapor can

achieve skin hydration.

Skin temperature: Raising skin temperature results in an increase in rate of skin permeation.This may be due to.

Thermal energy required diffusivity.

Solubility of drug in skin tissues.

Increased vasodilatation of skin vessels.


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Regional Variation: Differences in the nature and thickness of barrier layer of skin causesvariation in permeability. Rate of permeation increase in an atomic order: Plantar anterior fore

arm, scalp, ventral thigh, scrotum and posterior auricular area.

Pathologic injuries to the skin: Injuries that disrupt the continuity of stratum corneum increasepermeability

Cutaneous Drug Metabolism: Catabolic Enzymes present in the viable epidermis may render adrug inactive by metabolism and thus affect topical bioavailability of the drug. Example.

Testosteron is 95% metabolized.

Common Topical Ingredients

Vehicle:1,3,11

Hydrophobic vehicle

Hydrocarbons:Liquid petrolatum (mineral oil, liquid paraffin, paraffin oil)

White petrolatum (petroleum jelly, Vaseline)

Yellow petrolatum (petroleum jelly)

Squalane (perhydrosqualene, spinacane)

Silicones:Liquid polydimethylsiloxanes (dimethicone, silastic, medical grade silicone oil)

Alcohols:Lauryl alcohols (1-dodecanol, dodecyl alcohols)

Myristyl alcohols (tetradecanol, tetradecyl alcohols)

Cetyl alcohols (hexadecanol, ethal, palmityl alcohols)

Stearyl alcohols (stenol, cetosteryl alcohols)

Oleyl alcohols (ocenol)

Sterols; sterol esters:Lanolin (hydrous wool fat, lanum)

Anhydrous lanolin (wool fat, anhydrous lanum, agnin)

Semi synthetic lanolins

Carboxylic acids:Lauric acid, Myristic acid, palmitic acid, stearic acid, oleic acid

Esters; polyesters:Cholesterol esters (stearate), Ethylene glycol monoesters, Propylene glycol monoesters, Glycerylmonoesters, Glyceryl monostearate, Sorbitol monoesters, Sorbitain monoesters, Sorbitol diesters,


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Sorbitan polyesters (spans, arlacels), Glyceryl tristearate, Lard, Almond oil, Corn oil, Caster oil,

Cottonseed oil, Olive oil,Soyabean oil,Hydrogenated oils, Sulfated oils, Isopropyl myristate, Isopropyl

palmitate.

Ethers; polyethers:Polyethylene-polypropylene glycols (pluronics)

Water-miscible vehicle, co solvent

Polyols; polyglycols:Propylene glycol (1,2-propanediol)

Glycerin (glycerol)

Liquid polyethylene glycol

Solid polyethylene glycol (hard macrogol, carbowax)

1,2,Phenols-hexanetriol, Sorbitol solution 70%

Esters; polyesters:Polyoxyethylene sorbitain monoesters (stearate- tweens)

Polyoxy ethylene sorbitan polyesters (tweens)

Ethers; polyethers:Polyethylene glycol monocetyl ether (cetomacrogol 1000)

Polyethylene-polypropylene glycols (pluronics)

Structural matrix former:11

Hydrocarbons

White petrolatum (petroleum jelly, vaseline)

Yellow petrolatum (petroleum jelly)

Paraffin (paraffin wax, hard paraffin)

Microcrystalline wax

Ceresin (mineral wax, purified ozokerite)

Silicones

Fumed silica (cab-O-sil)

Bentonite (colloidal aluminum silicate)

Veegum (colloidal magnesium aluminum silicate)

Polyols, polyglycols

Solid polyethylene glycol (hard macrogol, carbowax)


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Alcohols

Cetyl alcohols (hexadecanol, ethal, palmityl alcohols)

Stearyl alcohols (stenol, cetosteryl alcohols)

Sterols; sterol esters

Cholesterol (cholesterin)

Lanolin (hydrous wool fat, lanum)



Carboxylic acids

Lauric acid, Myristic acid, palmitic acid, stearic acid, oleic acid

Esters; polyesters

Bees wax, White bees wax (bleached bees wax), Carnauba wax,

Myricin, Cholesterol esters (stearate), Polyoxyethylene sorbitain

Monoesters (stearate- tweens), Lard, Hydrogenated oils.

Suspending, jelling, or viscosity inducing agents:31-34

Silicones

Fumed silica (cab-O-sil)

Bentonite (colloidal aluminium silicate)

Veegum (colloidal magnesium aluminium silicate)

Polycarboxylates; polysulfates; polysaccharides

Agar, Alginates, Carragen, Acacia, Tragacanth, Methylcellulose, Carboxy methylcellulose, Hydroxy

ethyl cellulose, Carboxy vinyl polymer, gelatin, pectin, xanthan, polyacrylic acid.

Others

Ethanolamin, Triethanolamin.

Water-in-oil(w/o) emulsifier:15,34-36

Sterols; sterol esters

Cholesterol (cholesterin)

Lanolin (hydrous wool fat, lanum)



Carboxylic acids


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Na+, K+, ethanolamin salts of Lauric acid, Myristic acid, palmitic acid, stearic acid, oleic acid.

Ethers; polyethers


Oil-in-water (o/w) emulsifier:15,34-37

Esters;polyesters

Polyoxyethylene sorbitain monoesters (stearate- tweens)

Polyoxy ethylene esters (stearate-polyethylene glycol monoesters, Myrj).

Polyoxy ethylene sorbitan polyesters (tweens)

Ethers; polyethers

Polyethylene glycol monocetyl ether (cetomacrogol 1000)


Others

Sodium lauryl sulfate, Borax (sodium borate), Ethanolamine, Triethanolamine.

Preservative:1,27

Antimicrobial

Benzalkonium chloride, Benzoic acid, Benzyl alcohol, Bronopol, Chlorhexidine,

Chlorocresol, Imidazolidinyl urea, Paraben esters, Phenol, Phenoxyethanol, Potassium sorbate,Sorbic acid

Antioxidants

a-Tocopherol, Ascorbic acid, Ascorbyl palmitate, Butylated hydroxyanisole, sodium ascorbate,

sodium metabisulfite

Chelating agents, Citric acid, Edetic acid

Buffer:1

Citric acid and salts, Phosphoric acid and salts, H3PO4 / NaH2PO4, Glycine, Acetic acid,

Triethanolamine, Boric acid.

Humectant:15,35

Glycerin (glycerol),propylene glycol(E1520),glyceryl

triacetate(E1518),sorbitol(E420),xylitolandmaltitol(E965),polydextrose(E1200),quillaia(E999),lac

tic acid,urea, lithium Chloride.

Sequestering antioxidant:38, 39

Citric acid and salts

Ethylenediaminetetraacetic acid (Versene, EDTA)L
http://en.wikipedia.org/wiki/Propylene_glycolhttp://en.wikipedia.org/wiki/Propylene_glycolhttp://en.wikipedia.org/wiki/Propylene_glycolhttp://en.wikipedia.org/wiki/E_numberhttp://en.wikipedia.org/wiki/E_numberhttp://en.wikipedia.org/wiki/E_numberhttp://en.wikipedia.org/wiki/Glyceryl_triacetatehttp://en.wikipedia.org/wiki/Glyceryl_triacetatehttp://en.wikipedia.org/wiki/Glyceryl_triacetatehttp://en.wikipedia.org/wiki/Glyceryl_triacetatehttp://en.wikipedia.org/wiki/Sorbitolhttp://en.wikipedia.org/wiki/Sorbitolhttp://en.wikipedia.org/wiki/Sorbitolhttp://en.wikipedia.org/wiki/Xylitolhttp://en.wikipedia.org/wiki/Xylitolhttp://en.wikipedia.org/wiki/Xylitolhttp://en.wikipedia.org/wiki/Maltitolhttp://en.wikipedia.org/wiki/Maltitolhttp://en.wikipedia.org/wiki/Maltitolhttp://en.wikipedia.org/wiki/Polydextrosehttp://en.wikipedia.org/wiki/Polydextrosehttp://en.wikipedia.org/wiki/Polydextrosehttp://en.wikipedia.org/wiki/Quillaiahttp://en.wikipedia.org/wiki/Quillaiahttp://en.wikipedia.org/wiki/Quillaiahttp://en.wikipedia.org/wiki/Lactic_acidhttp://en.wikipedia.org/wiki/Lactic_acidhttp://en.wikipedia.org/wiki/Lactic_acidhttp://en.wikipedia.org/wiki/Lactic_acidhttp://en.wikipedia.org/wiki/Ureahttp://en.wikipedia.org/wiki/Ureahttp://en.wikipedia.org/wiki/Ureahttp://en.wikipedia.org/wiki/Ureahttp://en.wikipedia.org/wiki/Lactic_acidhttp://en.wikipedia.org/wiki/Lactic_acidhttp://en.wikipedia.org/wiki/Quillaiahttp://en.wikipedia.org/wiki/Polydextrosehttp://en.wikipedia.org/wiki/Maltitolhttp://en.wikipedia.org/wiki/Xylitolhttp://en.wikipedia.org/wiki/Sorbitolhttp://en.wikipedia.org/wiki/Glyceryl_triacetatehttp://en.wikipedia.org/wiki/Glyceryl_triacetatehttp://en.wikipedia.org/wiki/E_numberhttp://en.wikipedia.org/wiki/Propylene_glycol


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Topical Dosage Form

Ointment:1,3,11,40

Definition

Ointments are semisolid preparation intended for external application to the skin or mucousmembranes. Typical ointments are based on petrolatum. An ointment does not contain sufficient

water to separate into a second phase at room temperature. Water-soluble ointments may be

formulated with polyethylene glycol. Ointments are ideal emollients with good skin penetration and

adherence to surfaces. We prepare ointments of smooth consistency, non-grittiness, and

pharmaceutical elegance. We use geometric dilution when manually compounding with a spatula or

mortar and pestle. For larger quantities, a mixer is utilized. The final procedure involves a brass mill

to reduce particle size and to produce a non-irritating ointment. Ointments are packaged in

convenient containers such as tubes or jars.

Ointment bases

Ointment bases are classified by theUSPinto four general groups

(a)Hydrocarbon bases: Hydrocarbon bases are also termed oleaginous bases. On application to the

skin, have an emollient effect, as occlusive dressing, can remain on the skin for prolonged periods of

time without drying out.

Petrolatum,USP

White petrolatum, USP

Yellow petrolatum, USP

White petrolatum, USP

(b)Absorption bases: Absorption bases are of two types:

(1) Those that permit the incorporation of aqueous solutions resulting in the

formation of water-in-oil emulsions

Hydrophilic Petrolatum

(2) Those that are water-in-oil emulsions (syn: emulsion bases) and permit the

incorporation of additional quantities of aqueous solutions

Lanolin

(c)Water-removable Bases: Water-removable bases are oil-in-water emulsions resembling creams in

appearance. Because the external phase of the emulsion is aqueous, they are easily washed from

skin and are often called water-washable bases.

Hydrophilic Ointment,USP

(d)Water-soluble Bases: Water- soluble bases do not contain oleaginous components. They are

completely water-washable and often referred to as greaseless Because they soften greatly with
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the addition of water, large amounts of aqueous solutions are not effectively incorporated into these

bases. They mostly are used for the incorporation of solid substances.

Polyethylene Glycol Ointment, NF

Cream :15,16

Definition

Creams consist of medicaments dissolved or suspended in water removable or emollient bases.

Creams are classified as water-in-oil or oil-in-water. Therefore, combining immiscible compounds is

possible by mechanical agitation or heat. The wet gum, dry gum, bottle, and beaker methods are

employed. More recently, the term has been restricted to products consisting of oil-in-water

emulsions or aqueous microcrystalline dispersions of long chain fatty acids or alcohols that are water

washable and more cosmetically and aesthetically acceptable.

Types

Most commonly available creams classified on the basis of their function.

Cleansing & cold cream or lotion

Vanishing & Foundation cream

Night & massage cream

Hand &body cream

All purpose cream

Moisturizing cream

Cream bases

(a) Cream base, w/o (rose water ointment, MF 14)

Oleaginous phase

Spermaceti12.5%

White wax12.0%

Almond oil..55.58%

Aqueous phase

Sodium borate..0.5%

Stronger rose water, NF...2.5%

Purified water, USP..16.5%

Aromatic

Rose oil, NF.0.02%

(b) Cream base, o/w (general prototype)


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Oleaginous phase

Steryl alcohol15%

Beeswax.8%

Sorbitan monooleate.1.25%

Aqueous phase

Sorbitol solution, 70% USP7.5%

Polysorbate 80.3.75%

Methyl paraben.0.025%

Purified water, qs.100%

(c) Cream base, o/w (vanishing cream)

Oleaginous phase

Stearic acid.13%

Stearyl alcohol..1%

Cetyl alcohol.1%

Aqueous phase

Glycerin..10%

Methyl paraben..0.1%

Propyl paraben.0.05%

Potassium hydroxide.0.9%

Purified water, qs.100%

Paste:41,42,48

Pastes are basically ointments into which a high percentage of insoluble solids have been added-as

much as 50% by weight in some instances. They much stiffer then ointment due to presence of

solids, which contribute a particulate matrix over and above the ointment structure already present.

Ingredients such as starch, zinc oxide, calcium carbonate, and talc are used as the solid phase. Paste

make particularly good protective barrier on skin, for in addition to the formation of an unbroken

film, the high-surface area they contain absorb noxious chemicals before they reach the skin. This

explains their use in diaper rash, as they absorb irritating ammonia formed by bacterial action on

urea. Like ointment, paste form an unbroken, relatively water impermeable film on the skin surface;

unlike ointment the film is opaque and therefore an effective sun filter. Thus pastes are often by

skiers around the nose and lips, for the solids block out the suns rays and formed film prevent

excessive wind dehydration (windburn). Pastes are less greasy than ointments by reason of the fact

that much of the fluid hydrocarbon fraction is molecularly associated with the particulates.

Gels:31,34,44-48


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Definition

Gels are semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid

vehicle rendering jelly-like through the addition of gelling agent. Among the gelling agents used are:

Synthetic macromolecules: Carbomer 934

Cellulosederivatives:Carboxymethylcellulose, Hydroxypropylmethyl-cellulose

Gels are compatible with many substances and may contain penetration enhancers for anti-

inflammatory and anti-nauseant medications.

Types

Single phase gels: Gels in which the macromolecules are uniformly distributed throughout a liquid

with no apparent boundaries between the dispersed macromolecules and the liquid.

Double phase gels: Gel mass consists of floccules of small distinct particles, often referred to as a

magmas. Milk of magnesia (or magnesia magmas)

Jelly:48

Jellies are water-soluble bases prepared from natural gums such as tragacanth, pectin, alginate, and

boroglycerin. Or from synthetic derivatives of natural substance such as methylcellulose and

carboxymethylcellulose.

Lotion:15

Definition

The lotions are clear solution containing 25-50% alcohol. Additionally they may contain antiseptic,

emollient, and haemostypic substance. Also they may contain extract of witchhazel, menthol,

glycerin, boric acid, alum, potassium oxyquinoline sulfate & chloro form. Most of the lotions are used

as after-shave preparation. Lotions are not rubbed when applied.

Types

Hand lotion

Face lotion

Body lotion

After shave lotion

Antiperspirants lotion

Liniment: 15

Liniments are same as lotion but they are rubbed when applied.

Suppository:48

Suppositories are solid dosage forms intended to deliver medicine into the rectal, vaginal, or urethral

orifice. Suppositories may prepare by the cold compression or fusion technique. An appropriate base


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is selected for its compatibility, stability, melting point, and esthetics. Commonly used bases are

cocoa butter, glycerin, hydrogenated vegetable oils, and polyethylene glycol.

Powder:15,48

Powder differs from liquid skin care preparation in their physical characteristics. Very fine particle

size produces large surface area per unit weight, which covers a large surface area of the body &

result in strong light dispersion. There are body powders, which are also known as dusting powder or

talcum powder, face powder and compact. Medicated powders are used for prickly heat or

preventing microbial growth on skin.

Solution:3,49

Solutions are liquid preparations of soluble chemicals dissolved in solvents such as water, alcohol, or

propylene glycol.

Aromatic waters

Tinctures

Tincture of iodine

Sterile Indian ink for surgical procedures

Emulsion:35,36,48,50

Emulsions are two-phase preparations in which one phase (the dispersed or internal phase) is finely

dispersed in the other (continuous or external phase). The dispersed phase can have either a

hydrophobic-based (oil-in-water), or be aqueous based (water-in-oil). Because there are two

incompatible phases in close conjunction, the physical stabilizing system. In most pharmaceutical

emulsions, the stabilizing system comprises surfactant (ionic or nonionic), polymers (nonionic

polymers, polyelectrolytes, or biopolymers), or mixtures of these.

Types

Water-in-oil emulsion

Oil-in-water emulsion

Water-in-oil-in-water emulsion

Oil-in-water-in-oil emulsion

Suspension:31-34,48

Suspensions are heterogeneous system consisting of two phases. The continuous or external phase is

generally a liquid or semisolid and the disperse or internal phase is made up of particulate matter

that is essentially insoluble in, but dispersed throughout, the continuous phase; the insoluble matter

may be intended for physiologic absorption or for internal or external coating function. The dispersed

phase may consist of discrete particle, or it may be a network of particles resulting from particle-

particle interactions. Almost all suspension system separated on standing. The formulators main

concern, there fore, is not necessarily to try to eliminate separation, but rather to decrease the rate

of settling and to permit easy resuspendability of any settled particulate matter. A satisfactory


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suspension must remain sufficiently homogenous for at least the period of time necessary to remove

and administered the required dose after shaking its container.

Types

Flocculated suspension

Deflocculated suspension

Aerosol:48

A system that depends on the power of compressed or liquefied gas to expel the contents from the

container. The propellants responsible for developing the proper pressure within the container, and

it expel the product when the valve is opened and aids in the atomization or foam production of the

products. Topical pharmaceuticals aerosols utilize hydrocarbon (propane, butane, and isobutene)

and compressed gases such as nitrogen, carbon dioxide, and nitrous oxide.

Evaluation Of Topical Dosage Form

Evalution of patch:27

21-day cumulative irritancy patch test:

In this test the test compound is applied daily to the same on the back or volar forearm. Test

materials are applied under occlusive tape, and scores are read daily. The test application and scoring

are repeated daily for 21 days or until irritation produces a predetermined maximum score. Typical

erythema scores range from 0 (no visible reaction) to 4 (intense erythema with edema and vesicular

erosion). Usually, 24 subjects are used in this test

Draize-shelanski repeat-insult patch test

This test is designed to measure the potential to cause sensitization. The test also provides a

measure of irritancy potential. In the usual procedure the test material or a suitable dilution is

applied under occlusion a 7-day rest period, the test material is applied again to a fresh site for 24

hours. The challenge sites are read on removal of the patch and again 24 hours later. The 0-4

erythema scale is used. A test panel of 100 individuals is common.

Kligman maximization test

This test is used to detect the contact sensitizing potential of a product or material. The test material

is applied under occlusion to the same site for 48-hr periods. Prior to each exposure the site may be

pretreated with a solution of sodium lauryl sulfate under occlusion. Following a 10-day interval the

test material again is applied to a different site for 48 hours under occlusion. The challenge site may

be treated briefly with a sodium lauryl sulfate solution. The maximization test is of shorter duration

and makes use of fewer test subjects than the Draize-Shelanski test.

Evaluation of ointments:3,48

Penetration

For assessing the penetration some very simple experiments have been suggested. Weighed

quantities of the ointments are rubbed over definite areas of the skin for a given length of time.


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Thereafter the unabsorbed ointment is collected from the skin and weighed. The difference between

the two weights roughly represents the amount absorbed.

Rate of release of medicaments

To assess the rate of release of a medicament small amount of the ointment can be placed on the

surface of nutrient agar contained in a petry dish or alternately in a small cup cut in the agar surface.

If the medicament is bactericidal the agar plate is previously seeded with a suitable organism like S.

aureus. After a suitable period of incubation the zero of inhibition is measured and correlated with

the rate of release. Another method for finding out release rate is to smear internal surface of test

tubes with thin layers of ointment, fill the tubes with saline or serum and after a gap of time

estimating the amount of drug present in the serum/saline.

Absorption of medicaments into blood stream

The diadermatic ointments should be evaluated for the rate of absorption of drug into the blood

stream. This test can be in vivo only. Definite amounts of ointments should be rubbed the skin under

standard conditions and medicaments estimated in the blood plasma or urine.

Irritant effect

In general no ointment should possess irritant effect on the skin or the skin or mucous membranes.

The tests for irritancy can be carried out on the skin and eyes of rabbits or the skin in rats. Reactions

are noted at intervals of 24, 48, 72 and 96 hours. Lesions on cornea, iris, conjunctiva are used for

judging the irritancy to the eyes. Presence of patches on the skin within 2 weeks indicate irritancy to

skin.

Evaluation of cream:15

Rheology

Rheology is very important as these creams are marketed in tubes or containers. The rheology or

viscosity should remain constant. As these products are normally non-newtonian in nature, the

viscosity can be measured using viscometers used for such liquids.

Sensitivity

As various types of ingredients are used with occasional use of antiseptic, hormones. etc., there is a

possibility of sensitization or photosensitization of the skin. This should be tested beforehand. This

test is normally done by patch test on skin and can be either open or occlusive. The test sample is

applied along with a standard market product at different places and effect is compared after a

period of time.

Biological testing

This is particularly essential for products containing antiseptics, hormones, vitamins, etc.

Evaluation of emulsions:35,36,48

Phase separation

The rate and degree of phase separation in an emulsion can be easily determined by keeping a

certain amount in a graduated cylinder and measuring the volume of separated phase after definite


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time intervals. The phase separation may result from creaming or coalescence of globules. The phase

separation test can be accelerated by centrifugation at low/moderate speeds. One can at best expect

a mixture of creamed and coalesced particles and in such a situation it may be difficult to make

correct interpretations.

Globule size

Growth in the globule size after the preparation of an emulsion is an indication of its physical

instability. The globule size is measured by microscopic methods or by electronic devices such as

coulter counter. In either of these two techniques the original product has to be suitable diluted

before estimation. The dilution may introduce errors because of incomplete deflocculation or new

patterns of flocculation.

Rheological properties

The rheological characteristics of an emulsion system depend upon globule size, emulsifier and its

concentration, phase volume ration etc. Use of a heliapath attachment with Brookfield viscometer

helps in detection of creaming tendency and hence it is advisable to study rheological properties over

extended periods of time, which can help in prediction of their long-term behaviour. Many emulsion

show change in consistency with time which follows linear relationship when plotted on a log-log

scale over a number of ten fold time intervals.

Effect of thermal stresses

It is usual to evaluate thew stability of an emulsion by subjecting it too high and low temperatures in

alternating cycles. The samples are first exposed to 60 C for a few hours and then to o to 40 C. Such

exposures are repeated a number of times and emulsion stability assessed after each cycle.

Evaluation of paste:15,41,42

Abrasiveness

The teeth were mechanically brushed with pastes or powders and then the effects were studied by

observation, mechanical or other means. Abrasive character normally depended on the particle size

Particle size

This can be determined by microscopic study of the particles or other means.

Cleansing property

This is studied by measuring the change in the reflectance character of a lacquer coating on a

polyester film caused by brushing with a tooth cleanser (paste or power). Also an in vivo test has

been suggested in which teeth were brushed for 2 weeks and condition of teeth was assessed before

and after use with the help of photographs.

Consistency

It is important that the product, paste, should maintain the consistency to enable the product press

out from the container. Study of viscosity is essential for these powders from the container.

pH of the product


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pH of the dispersion of 10% of the product i9n water is determined by pH meter.

Foaming character

This test is specially required for foam-forming tooth pastes or tooth pastes or tooth powers.

Especially amount of product can be mixed with specific amount of and water to be shaken. The

foam thus formed is studies for its nature, stability, washability.

Limit test for arsenic and lead

This is very important, as these are highly toxic metals. Specific tests are there to estimate these two

metals. However, if the raw materials are tested for the limit of these two metals, products

may not have excess of such metals.

Volatile matters and moisture

A specific amount of the product required to be taken in a dish and drying is to be done till constant

weigh. Loss of weigh will indicate percentage of moisture and volatile matters.

Effect of special ingredients

Special tests should be done for the special ingredients if any like antiseptic, enzymes, etc. For each

one special and specific test are to be done.

Evaluation of powder:15

Shade control and lighting

This is to control and determine the variation of color shade from batch to batch and with the

stander, Proper test is to be done to prevent in shades. One such method is comparison of the

appearance of the body of the power with a standard when it is spread out and flattened on a white

paper background. The other method of evaluation is comparison of the sample with the standard by

skin tone or undertone. Powers should be applied by the same puff that is to be used for finished

pack. This is the final judgement for the shade test. Artificial lighting is used for color evaluation.

Dispersion of color

Color should be homogeneously distributed in the power base. There should not be segregation or

bleeding of color. This can be tested by spreading the power on a white paper and checking if with a

magnifying glass.

Pressure testing

Pressure applied to compact powder should be uniform to the hardness can be tested by

penetrometer. Reading on hardness is checked at various points of compact tablet to see the

uniformity of hardness.

Breakage test

This is carried out by dropping the compact tablet of powder on a wooden surface several times from

a height of 8 to 10 inches and checking the breakage or clipping of the resistance against travel and

normal handling.

Flow property


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This is very important, particularly for body powders, as they should come out easily from the

container for easy application. This can be studied by measuring angle of repose of powder product

by allowing to fall on a plate from a funnel and measuring the height and radius of heap formed.

Particle size and abrasiveness

Particle size can be determined by microscope, sieve analysis or by using sophisticated instrument

and techniques. Abrasiveness can be studied by rubbing the powers on a smooth surface and then

studying the effect on the surface using microscope.

Moisture content and limits for color

These can be estimated by using suitable analytical methods.

Evaluation suspension:48

Sedimentation volume

Measurement of the sedimentation volume and its ease of redispersion from of the most common

basic evaluative procedures. The concept of sedimentation volume is simple. In short, it

considers the ratio of the ultimate height (Hu) of the sediment to the initial height (Ho) of the total

suspension as the suspension settles in a cylinder under standard conditions. The larger this fraction,

the better is the suspendability. First obtain the Hu /Ho ratios and plot them as ordinates with time as

the abscissa. Note that although the height at any particular time. The plot just described will at time

zero start at 1.0, with the curve then being either horizontal or gradually sloping downward to the

right as time goes on. One can compare different formulation and choose the best by observing the

lines, the better formulations obviously producing lines that are more horizontal and/or less steep.

The evaluation of redispersibility is also important. To help quantitate this parameter to some extent,

a mechanical shaking device may be used. It simulates human arm motion during the shaking process

and can give reproducible results when used under controlled conditions.

Rheologic methods

Rheologic methods can be used to help determine the setting behavior and the arrangement of the

vehicle and particle structural features for purpose of comparison. A practical rheologic method

involves the use of the Brookfield viscometer mounted on a helipath stand. The T-bar spindle is made

to descend slowly into the suspension, and the dial reading on the viscometer is then a measure of

the resistance the spindle meets at various levels in a sediment. In this technique, the T-bar is

continually changing position and measures undisturbed samples as it advances down into the

suspension. This technique also indicates in which level of the suspension the structure is greater,

owing to particle agglomeration, because the T-bar descends as it rotates, and the bar is continually

entering new and essentially undisturbed material.

Electrokinetic techniques

Instrumentation permitted measurement of the migration velocity of the particles with respect to

the surface electric charge or the familiar zeta potential; the latter has units of viscosity times

electrophoretic mobility, or more familiarly, volts.


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Particle size changes

The freeze-thaw cycling technique is particularly application to stressing suspension suspension for

stability testing purposes. This treatment promotes particle growth and may indicate the probable

future state of affairs after long storage at room temperature. Thus, it is of prime importance to be

alert for changes in absolute particle size, particle size distribution, and crystal habit. Particle size

distribution is sometimes determined by microscopic means. This method of necessity requires dilute

suspensions that are counted with the aid of an ocular grid. In some instances, photomicrographs

may to take for permanent records.

Evaluation of aerosol:48

Flame projection

This test indicates the effect of an aerosol formulation on the extension at an open flame. The

project is sprayed for about 4 sec into a flame. Depending on the nature of the formulation, the

flame is extended, the exact exact length being measured with a ruler.

Flash point

This is determined by use of the standard Tag Open Cup apparatus. The aerosol product is chilled to a

temperature of about -250

F and transferred to the test apparatus. The test liquid is allowed to

increase slowly in temperature, and the temperature at which the vapors ignite is taken as the flash

point obtained is usually the flash point of the most flammable component, which in the case of

topical pharmaceuticals is the hydrocarbon propellant.

Vapor pressure

The pressure can be measured simply with a pressure gauge or elaborately through use of a water

bath, test gauges, and special equipment. Methods are available for aerosols packaged in both metal

and glass containers.

Density

The density of an aerosol system may be accurately determined through the use of a hydrometer or

a pycnometer. These methods, which have been modified to accommodate, liquefied gas

preparations. A pressure tube is fitted with metal flanges and a Hoke valve, which allow for the

introduction of liquids under pressure. The hydrometer is placed into the glass pressure tube.

Sufficient sample is introduced through the valve to cause the hydrometer to rise halfway up the

length of the tube. The density can be read directly. Specific gravity can be determined through the

use of a high-pressure cylinder of about 500-ml capacity.

Moisture

Many methods have proven useful for this purpose. The Karl Fischer method has been accepted to a

great extent. Gas chromatography has also been used.

Aerosol valve discharge rate


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This is determined by taking an aerosol product of known weight and discharging the contents for a

given period of time using standard apparatus. By reweighing the container after the time limit has

expired, the discharge rate, which can then be expressed as grams per second.

Spray patterns

The method is based on the impingement of the spray on a piece of paper that has been treated with

a dye-talc mixture. Depending on the nature of the aerosol, an oil-soluble or water-soluble dye is

used. The particles that strike the paper cause the dye to go into solution and to be absorbed onto

the paper. This gives a record of the spray, which can then be used for comparison purposes. To

control the amount of material coming into contact with the paper, the paper is attached to a

rotating disk that has an adjustable slit.

Dosage with metered valves

Method that can be used involves accurate weighing of filled container followed by dispensing of

several doses. The container can then be reweighed, and the difference in weigh divided by the

number of doses dispensed gives the average dose. This must then be repeated and the results

compared. Determination of the does received by a patient is a rather difficult procedure, since all of

the respiratory system has been developed and is satisfactory for this purpose.

Net contents

The tared cans that have been placed onto the filling line are reweighed, and the difference inweigh is equal to the vet contents.

Method is a destructive method and consists of weighing a full container and then weighed,with provision being made for the amount retained in the container.

Opening the container and removing as much of the produce as possible. These tests are notindicated in determining the actual net weight of each container as related to the amount that

can actually be dispensed.

Foam stability

The life of a foam can range from a few seconds (for some quick breaking foams) to one hour or

more depending on the formulation. Several methods have been used, which include a visual

evaluation, time for a given rod that is inserted into the foam to fall, and the use of rotational

viscometers.

Particle size determination

Cascade impactor and light scatter decay. The cascade impactor operates on the principle that in a

stream of particles projected through a series of nozzles and glass slides at high velocity, the larger

particles become impacted first on the lower velocity stages, and the smaller particles pass on and

are collected at higher velocity stages. Light scatter decay method as the aerosol settles under

turbulent conditions, the change in light intensity of a Tyndall beam is measured.

Evaluation of lotion:15

Antiseptic property


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As these preparations contain antiseptics, it is necessary to evaluate antiseptic property by in-vitro

test.

Determination of alcohol content

This can be determining by any suitable method as these preparations contain alcohol it is necessary

to estimate the alcohol content.

Evaluation of gel:44-48

Drug content

1gm of gel was accurately weighed in a 50ml of volumetric flask to which 20ml purified water was

added with continuous shaking. Volume was adjusted with a mixture of 10% methanol in water. Plain

bases were also treated in similar manner for blank determination. Absorbance of the solution with

the blank was measured at 360nm using UV-spectrophotometer.

Homogeneity of drug content

For homogeneity of drug contents, six tubes weretaken randomly and assayed for the drug content

as stated above. Studies were performed in triplicate and mean values were used for the analysis of

data.

Measurement of pH

The pH ofcarbopolgels ofTN were determined by digital pH meter. One gram of gel was dissolved in

100ml of distilled water and stored at 4C for two hours. The measurement of pH of each

formulation was in triplicate and the average values are presented.

Viscosity

Brookfield synchrolectric viscometer model RVT attached with spindle D was used for determination

of viscosity. Gels were filled in jar andspindle was lowered perpendicularly taking care that spindle do

not touch bottom of the jar. The spindle was rotated in the gel at increasing shear rates 0.5, 1, 2.5

and 5rpm. At each speed, the corresponding dial reading was noted. The reverse reading were also

noted and average was taken for these two readings.The viscosity of the gel was obtained by the

multiplication of the dial readings with the factors given in the Brookfield viscometer catalogues.

Spreadability

A modified apparatus consisting of two glass slides containing gel in between with the lower slidefixed to a wooden plate and the upper one attached to a balance by a hook was used to determine

spreadability.

Extrudability

A simple method was adopted for determination of extrudability in terms of weight in grams

required to extrude a 0.5cm ribbon of gel in 10 seconds from the collapsible tube.

Evaluation of suppository:48-54

Melting range test
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This test is also called the macro melting range test and is a measure of the time it takes for the

entire suppository to melt when immersed in a constant-temperature (37C) water bath.

Liquefaction or softening time test

It consists of a U-tube partially submersed in a constant temperature water bath. A constriction on

one side holds the suppository in place in tube. A glass rod is placed on top of the suppository, and

the time for the rod to pass through to the constriction is recorded as the softening time.

Breaking test

The apparatus used for the test consists of a double-wall chamber in which the test suppository is

placed. Water at 37C is pumped through the double walls of the chamber, and the suppository,

contained in the dry inner chamber, supports a disc to which a rod is attached. The other end of the

rod consists of another disc to which weights are applied. The test is conducted by placing 600 g on

the platform. At 1-min intervals, 200-g weights are added, and the weight at which the suppository

collapses is the breaking point, or the force that determines the fragility or brittleness characteristics

of the suppository

Dissolutiontest

Testing for the rate of in vitro release of drug substances from suppositories has always posed a

difficult problem, owing to melting, deformation. and dispersion in thedissolutionmedium. Early

testing was carried out by simple placement in a beaker containing a medium. In an effort to control

the variation in mass/ medium interface, various means have been employed, including a wire mesh

basket, or a membrane, to separate the sample chamber from the reservoir. Samples sealed in

dialysis tubing or natural membranes have also been studied. Flow cell apparatus have been used,holding the sample in place with cotton, wire screening, and most recently with glass beads.

Summary And Conclusion

Topical delivery can be defined as the application of a drug containing formulation to the skin to

directly treat cutaneous disorders (e.g. acne) or the cutaneous manifestations of a general disease.

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

intravenous therapy and of the varied conditions of absorption, like pH changes, presence of

enzymes, gastric emptying time are other advantage of topical preprations.

The topical drug delivery system is generally used where the others system of drug administration

fails or it is mainly used in pain management, contraception, and urinary incontinence. Iontophoresis,

Electroporation, Sonophoresis, Phonophoresis, Vesicular concept and Microfabricated microneedles

technology are some advanced technique which are widely 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 even medicated adhesive systems are in use.

References:
http://www.pharmainfo.net/tablet-evaluation-tests/dissolutionhttp://www.pharmainfo.net/tablet-evaluation-tests/dissolutionhttp://www.pharmainfo.net/tablet-evaluation-tests/dissolutionhttp://www.pharmainfo.net/tablet-evaluation-tests/dissolutionhttp://www.pharmainfo.net/tablet-evaluation-tests/dissolutionhttp://www.pharmainfo.net/tablet-evaluation-tests/dissolutionhttp://www.pharmainfo.net/tablet-evaluation-tests/dissolution


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