seds.et.al

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DEPARTMENT OF PHARMACY NUTRITION AND DIECTETICS

BIOPHARMACEUTICS

4TH YEAR BACHELOR PHARMACY DEGREE

STUDENTS IDENTIFICATION NUMBER……………………………….00001/2012

STUDENTS NAME ………………SEDRICK M PHIRI

LECTURER ……………………………….MRMWILA PHARMACIST

DUE DATE ………………………………..28/10/14

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TASK……………………………….ROUTES OF DRUG ADMINISTRATION

CONTENTS

1.1 .....................INTRAVENEOUS DRUG DELIVELY

1.2 .....................INTRAMUSCULAR DRUG DELIVELY

1.3 .....................SUBCUTANEOUS DRUG DELIVALY

1.4 .....................RECTAL DRUG DELIVELY

1.5 ......................INTRA OCULAR

1.6 .....................INTRA NASAL DRUG DELIVELY

1.7 .....................INTRAVAGINAL AND INTERUTERIN

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1.1 INTRAVENOUS DRUG DELIVERY SYSTEM

There are a various ways by which drugs are delivered into the blood systemand produce local effects, in fact the route of administration tends to dictateto a larger extent the amount that is required to impact a pharmacologicaleffect on a particular organism with respect to time.The route ofadministration (ROA) that is chosen may have a profound effect upon thespeed and efficiency with which the drug acts.

Routes of administration can be classified as ENTERAL and PARENTERAL.Enteral means to do with the GI tract and includes oral, buccal, and rectal.Parenteral means not through the alimentary canal and commonly refers toinjections such as intravenous, intra muscular, and Subcutaneous but couldalso include topical and inhalation. We can also distinguish intravenous fromthe rest.

As with all others at least one membrane must be crossed, thus an

absorption process is involved in the administration and the

pharmacokinetics

Intravenous route is among the most important routes of Parenteral drug

delivery. This route involves the direct injection of the formulation into the

venous circulation. Intravenous route may be used to correct electrolyte

imbalances, deliver medications, blood transfusion, in fluid replacement

therapy, chemotherapy, provide Parenteral nutrition, provide a platform for

dialysis and hemodynamic monitoring.

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MERITS

i. Drugs administered directly into the vein goes directly into the heart

and carried to the tissues before passing on the liver where they are

metabolized,Drugs administered through intravenous route prevents

degradation of drugs through the first pass metabolism by the liver.

FIGURE 0.

ii. Rapid of action because drugs are delivered directly to the circulation

without the need for them to overcome such barriers as release from

formulation, absorption through the membrane.

iii. Response to drug therapy is much more predictable following

intravenous administration as compared to other routes of

administration because the pharmacokinetic profiles are simple and the

only parameters considered are elimination profiles.

Figure con.1Typical Plot of plasma concentration versus Time afterIV Bolus

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Figure con.2 Typical Plot of plasma concentration versusTime during an IV Infusion administration

(vi)Peptides that are degraded in the stomach as well as amphortericin B

which is unabsorbed in the stomach due to its size, molecular properties

and its insolubility with irritancy may prompt intravenous administration

(vii)Unco-operative and patients unable to swallow orally may find this route

to be appropriate

(viii)Compared to the enteral route of administration, this route provides the

maximum concentration of the drug that is required, that is to say that about

100% of the drug shall be available to impact a pharmacological effect.

DEMERITS

i. Suitable veinIt may be difficult to find a suitable vein. Tissue damage can occur due to theleakage of the injection from the vein into the surrounding tissue.

ii. Maybe toxicBecause of the rapid response, toxicity can be a problem with rapid drugadministrations, could then give as an infusion, monitoring for toxicity.It is the most dangerous route of administration because it bypasses most of

the body’s natural defenses exposing the people to health problems such as

hepatitis, abscesses, infections and undissolved particles or additives and

unwanted materials.

When irritant formulations are injected too rapidly, thrombosis my occur.

iii. Requires trained personnel

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Trained personnel are required to give intravenous injections, if propercare is not taken while injecting, potentially fatal air bubbles may beintroduced into the vascular pool and occlude the flow of blood.

iv. ExpensiveSterility, pyrogen testing and larger volume of solvent means greater cost for

preparation, transport and storage the cost of injection is higher than tablets,capsules or other oral dosage forms.

Vi .Abuse potential

For drug abusers that wish to have a drive faster, they tend to inject

themselves using this route.

Vii. Inconvenience

Maintaining a therapeutic effective concentration of the drug requires

frequent injections which ultimately lead to patient discomfort. Canulating is

distressing especially in children and neonates.

INTRAVENEOUS FORMULATION CONSIDERATIONS

a) PERCENTAGE PURITY

Percentage purity of a particular intravenous preparation should near a

100%, especially that a drug is administered directly into the vascular pool.

Percentage purity in this instance harnesses the issue of any detectable

impurities.

As much as possible intravenous preparations should be free of contaminants

in order not to have infections introduced into the blood.

A number of sterilization procedures are available on the market that

includes;

1.Filtration and preparation under septic conditions

2.Autocaving

3.Gamma radiations

b)PH

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This defines the log to the base 10 of the Hydrogen ion concentration.The PH

of the solution should be in line with the PH of the plasma in order to

maintain its intergrity.

Small volume parenterals below 100ml in volume can be formulated at the PH

of 4-10, while larger volume should should be matched to plasma

constituents that is to say 6-8. c)SOLUBILITY AND SOLVENTS

Solubility of a drug to a larger extent describes the bioavailability of the

drug, drugs that have poor solubility, solvents or co solvents to be used

should be compatible with biological systems and not be able to cause

unwanted effects upon administration such as, pain and tissue damage at

the injection site.

DEVICES AND TECHNOLOGY

Drug administration might be such a strenuous activity. Technology has

since developed device to aid in the handling as well as administration and

delivery of a particular dosage form.

FIGURE 3.

The following devices may aid in drug administration;

A .INFECTION PREVENTION

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1) Sterile disposable canulae,

2) Catheters

3) Needles

B .NON IRRITANT POLYMERIC MATERIAL

1) Teflon,

2) polyethylene,

3) silicones

4) polyurethane.

5) Polyvinylchloride

C.MECHANICAL PUMPS

i. Implantable pumps for long term administration of small volumes

ii. Packaging systems such as prepacks minibags, premixed drugs in

intravenous fluids, frozen premixes have been developed to reduce on

the cost.

1.2 .INTRAMUSCULAR DRUG DELIVERY SYSTEM

FIGURE SED.4

Drug delivery involves the injection of a substance directly into a muscle

depending on the chemical properties of the drug; the medication may either

be absorbed fairly quickly or more gradually.

Intramuscular injections are often given in the deltoid, vastus lateralis, Vento

glutei and dorso gluteal muscles. Though the vastus lateralis muscles have

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fewer major blood vessels into which the injection might be accidentally

placed, deltoid muscle is the most preferred one because of greater perfusion

rate compared to the other muscles.

Care must be taken with deep muscular injection to avoid hitting the nerve,

artery and vein.

In adults, intramuscular injections are given on the upper, outer potion of the

gluteus maximus the large muscle on either side of the buttocks.

Figure.sed 5. Possible sights of intramuscular administration

MERITS

i. Excellent absorption with drugs that have low oral

bioavailability.

ii. Compared to enteral route, this route tends to have a quick onset

in as much as response is concerned.

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Figure .sed. 6 Typical plot of plasma concentration after intramuscular

injection.

iii.Based on the formulation characterization this route may provide depot

kind of drug release, providing a long duration of action.Typical example are

medroxylprogesteron and benzathine penicillin that may be administered

intramuscularly.

iv.Patients suffering from diarrhea and vomitous illnesses including those

that are not co operative may find this route to be very user friendly.

v. The route does favor drugs that are liable to be destroyed by hydrolysis

and gastric enzymes

DEMERITS OF INTRAMUSCULAR ADMINISTRATION

I. Dosage withdrawal upon administration maybe almost impossible

II. Self medication is not attainable as it requires skilled labour.

III. Pyrogen and other contaminants can enter the vascular pool.

IV. Poor peripheral perfusion may lead to unpredictable absorption.

V. Pain may actually lead to non patient compliance,

VI. Improper use of the injectables may lead to formation of boils at the

site of injection.

VII. A possibility nerve damage if administration is done by unskilled

worker.

Factors affecting drug bioavailability

Low perfusion of the muscle by the blood If cardiac failure has occurred, absorption will be extremely low since

the muscle Perfusion rate will be small. For this reason intramusculardelivery is contra-indicated if cardiac function is poor

If the drug is extremely hydrophobic it will not dissolve in theIntracellular Fluid

Strongly ionized or extremely water soluble it will not be able to crossthe capillary membrane.

Drugs which are strongly protein-bound will also be slowly absorbedsince their activity in solution will be reduced

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Affinity of the tissue for the drug. Affirnity for the tissue is in two forms that is passive or active.

Passive affinity is simply the partitioning of the drug such aspartitioning of lipophilic drug into adipose tissues results in high drugconcentrations in that tissue, although this is achieved slowly due tothe poor perfusion of the adipose tissue.

While active partitioning occurs if the drug is taken up by the tissue bya specific transport mechanism

a patient's posture can alter the time course and extent of drugabsorption

CONSIDERATIONS DURING FORMULATIONS

It is important to consider the fact that highly hydrophobic drugs will not be

dissolved in plasma fluids and so are highly ionized molecules. For drugs

which are highly hydrophilic, they tend to fail to permeate the capillary walls.

A number of drugs are administered using this method of administration and

include the following;

1. AQUEOUS PREPARATIONSi. Solutions

ii. Suspensions

iii. Oleic solutions

iv. Oil in water emulsions

v. Water in oil emulsions

vi. Water in oil in water emulsions

vii. Oil in water in oil emulsions

DEVICES AND TECHNOLOGIES

That the skin is involved, it is obvious that disposable needles and syringes

are used.

This is equally important to reduce on infections.

1.3SUBCATENEOUS DRUG DELIVERLY

SUBCUTANEOUS

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Figure 6This involves administration of the drug dose just under the skin.

IMPLANT :a tablet or porous capsule is inserted into the loose tissues byincision of the

skin, which is then stiched up,example certain hormonal drugs

Advantages:1. Can be iven by patient, e.g. in the case of insulin2. Absorption slow but usually complete. Improved by massage or heat.

Vasoconstrictor may be added to reduce the absorption of a localanaesthetic agent, thereby prolonging its effect at the site of interest.

Disadvantages:1. Can be painful2. Irritant drugs can cause local tissue damage3. Maximum of 2 ml injection thus often small doses limit use.

Figure 7 Typical Plot of Cp versusTime after Subcutaneous

AdministrationIMPLANT: a tablet or porous capsule is inserted into the loose tissues byincision of the skin, which is then stitched up.Example: certain hormonal

Factors affecting bioavailability1.Slow Perfusion rate into the tissue

FORMULATION CONSIDERATION

Subcutaneous route allows for administration of a wide range of drugs in

that the formulation does not have to be hydrophilic.

Materials used this way are;

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a) aqueous solutions,

b) aqueous suspensions,

c) oily solutions,

d) oil in water emulsions,

e) water in oil emulsions,

f) oily suspensions, Dispersions in polymer or solid implants.

DEVICES AND TECHNOLOGIES.

Needles and syringes are employed to deliver the drugs.

CONCLUSION ON PARENTERAL DRUG ADMINISTRATION

Parenteral route of drug administration is quite a sensitive means ofdrug delivery, it should be realized that if a drug has to be deliveredappropriately, a number of considerations that include thephysicochemical parameters of a drug, sterility, and microbiologicalconsiderations.

A pharmacists role shall be to ensure actual information is given tothe administrators and that suitable means of delivery systems areused..

1.4 .RECTAL DRUG DELIVELY

The delivery of drugs via the use of anal canal. It capitalises on the fact thatthe anal membranes are endowed with the vasculature rich in blood.

FIGURESED 8

Most commonly by suppository or enema. Some drugs given by this routeinclude;

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I. aspirin,II. theophylline,

III. chlorpromazine andIV. some barbiturates

FIGURE CON. 9

Typical Plot of plasma concentration versus Time after Rectal Administration

Advantages:

1. By pass liverWhilst some of the veins draining the rectum lead directly to the generalcirculation, thus by passing the liver. Reduced first pass effect.

2. This route may be most useful for patients unable to take drugs orally orwith younger children.

Disadvantages:1. Erratic absorption

Absorption is often incomplete and erratic. However for some drugs it isquite useful. There is research being conducted to look at methods ofimproving the extent and variability of rectal administration.

2. Not well accepted.

FORMULATION CONSIDERATIONSTo ensure improved bioavailability, putative absorption enhancers have

been included in the formulation and these help in the opening of tight

junctions and allow for both paracellular and transcellular routes.

Such agents include;

a) enamine derivatives

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b) salicylates,

c) calmodulin inhibitors,

d) surfactants,

e) chelating agents

f) fatty acids

g) lectins.

Patients must be advised to remove the suppository from its package, insert a

small tapered end first with index finger, as shown in the figure above in the

full length of the finger and the area may need to be lubricated with a water-

soluble gel to ease insertion e,g k-y jelly.

1.5 NASAL DRUG DELIVERYThis route is essential in the delivery of drugs that are active at low doses andhardly shows minimal oral bioavailability.Available delivery systems for nasal drug delivery take the following forms;

1.Low molecular weight and hydrophobic drugs for the treatment of the nasal

mucosa and sinus allergy including ;

I. decongestants,

II. topical steroids,

III. antibiotics and

IV. other over the counter products.

2.The second class encompasses a few drugs, which have sufficient nasal

absorption for displaying systemic effects and include;

I. Xylometazoline

II. Oxymetazoline

ADVANTAGES OF NASAL DRUG DELIVERY1.8 MERITS

a) Rapid absorption,

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b) by passing the liverc) Absorption of gases is relatively efficient,d) Self medication is so very much possible.e) Drugs which are unstable in the stomach may use this form.f) Easy to work around with e.g if need arises to enhance absorption,

the enhancers may be used.DEMERITS

a) solids and liquids are excluded if larger than 20 micron and even thenonly 10 % of the dose may be absorbed.

b) Cromolyn is taken as a powder with 50 % of the particles within therange of 2 to 6 micron.

c) If Larger than 20 micron the particles impact in the mouth and throat.d) When smaller than 0.5 micron they are not retained.e) There is a risk of local side effects and irreversible damage of the cilia

on the nasal mucosa, both from the substance and from constituentsadded to the dosage form.

f) Some portions of the drug may be swallowed

g) Surfactants used as chemical enhancers may disrupt and even

dissolve membrane in high concentration.

h) Risk of local side effects and irreversible damage of the cilia on the

nasal mucosa, both from the substance and from constituents added to

the dosage form,

FACTORS AFFECTING NASAL DRUG DELIVERY

A.PHYSIOLOGICAL FACTORSI. VENOUS AND ARTERIAL DRAINAGE

The rich supply of blood and a large surface area make the nasal mucosa an

optimal location for drug absorption.

Nasal absorption of drugs is influenced by blood flow rate, as it increases the

amount of drug that passes through the membrane and hence reaching the

general circulation.

Vasoconstriction decreases nasal drug absorption by diminishing the blood

flow.

I.MUCOCILLIARY ACTIVITY

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Mucociliary clearance is the self‐clearing mechanism that defends the

respiratory tract by preventing the lungs from foreign substances, pathogens

and particles carried by inhaled air and influences significantly the nasal

drug absorption.

II. TRANSPORTERS AND EFFLUX MECHANISMS

Multidrug resistance transporters which are involved in the transportation of

hydrophobic and amphiphilic drugs are found in the apical area of ciliated

epithelial cells and sub mucosal vessels of the human olfactory region plays

an important role in the influx of drugs from nasal

III. ENZYMATIC DEGRADATION

Nasal drug administration avoids gastrointestinal and hepatic first‐pass

effect. Drugs may be metabolized in lumen of nasal cavity due to the presence

of a broad range of metabolic enzymes in nasal tissues. Some examples of

enzyme which may play role in enzymatic degradation of drugs are;

I. carboxyl esterase,

II. aldehyde

III. dehydrogenases,

IV. epoxide hydrolases,

V. glutathione S‐transferases and

VI. Cytochrome P450 isoenzymes

VII. Others.

B.THE PHYSICOCHEMICAL PROPERTIES OF A DRUG

Physicochemical properties of drugs can influence nasal drug absorption.

Factors such as molecular weight,

I. Lipophilicity

II. Stability

III. Solubility

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IV. pKa

A. Drug dissolution is a pre‐requisite for drug absorption because

molecularly disperse form of a drug may cross the

membranes.Enhancing drug solubility using various techniques may

help to resolve issues of drug solubility.

B. If lipophilicity is too high, the drug permeation through the wall may be

reduced because drug does not dissolve easily in the aqueous

environment of nasal cavity.

C. Biological stability of nasally administered drugs may reduce due to the

metabolism of drugs by defensive enzymatic mechanisms by nasal

cavity. If this is to be overcome, varieties of strategies such as the use

of prodrugs and enzymatic inhibitors have been used.

D. Extent of nasal absorption of lipophilic drugs bigger than 1 kDa is

significantly reduced. Rate and degree of nasal absorption of polar

drugs is low and highly dependent of the molecular weight.

E. Drugs are absorbed quickly and efficiently across the nasal membrane

via transcellular mechanisms. This is true for lipophilic compounds

having molecular weight lower than 1 kilo Daltons.

F. Drugs that are polar may not make through the membrane.

G. Drug molecules such as propranolol, progesterone and fentanyl are

well absorbed from the nasal cavity because they are lipophilic,

exhibiting pharmacokinetic profiles similar to those obtained after

intravenous administration.

DRUG FORMULATION EFFECTS

A. Higher viscosity formulation has a better contact time thus increases

the absorption. At the same time, high viscosity enhances the

permeability of drugs.

B. pKa of drug and pH at the absorption site plays important role in

absorption of drug through nasal route. Stability can be achieved by

proper selection of pH of formulation. However, the pH of formulation

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should be near on human nasal mucosa of 5.0‐6.5 to prevent the

sneezing.

C. Nasal drops are the simplest and the most convenient nasal

pharmaceutical dosage form, but the exact amount of drug delivered is

not easily quantified and often results in overdose. Moreover rapid

nasal drainage can occur when using this dosage form.

D. Instilled powder ,spray solution and suspension sprays are preferred

because powder spray may cause nasal mucosa irritation.

E. Nasal gels have been developed for accurate drug delivery. This

increases the nasal absorption by enhancing the drug residence time

and diminishing mucocilliary clearance.

F. With nasal formulations pharmaceutical excipients are selected

according to their functions. The most commonly used excipients are

Solubilizers, buffer components, antioxidants, preservatives,

humectants, and gelling or viscosifying agents.


A. NASAL DISPENSERS and SYRINGES with NEEDLES have been used

deliver drugs to the nasal cavity.

B. Depending on the nature of the disease, local application may be

suitable.

Systemically, drugs may also employ the use of nasal cavity, this includesdrugs that can affect the central nervous system.

Other devices include;

i. Insufflatorsii. Squeezed bottleiii.Metered dose pump spraysiv. Compressed air nebulizersv. Instillater and rhinyle cathetervi. Dry powder inhalersvii. Pressurized metered dose inhaler

CONCLUSION

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The nasal delivery system of drugs may be of altmost importance when it

comes to drug delivery. It in fact is an alternative means by which drugs

can be administered into the body.

1.6 OCULAR DRUG DELIVERY SYSTEM

FIGURE 10

This is the delivery of a medicament in the eyes. This is primarily

concerned with the need to treat ophthalmic diseases.

Major classes of drugs used are;

A. Miotics, through the use of cholinergic agents.

B. Mydriatics, Atropine, anticholinegic.

C. Diclofenac eye preparation as an anti-inflammatory

D. Anti- infectives

E. Surgical adjuvants

F. Diagonostics

It should be noted that these drugs are designed for local effects and not

systemic effects.

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PICTORIAL ANATOMY OF THE HUMAN EYE

FIGURE.11

MECHANISM OF OCULAR ABSORPTION

A. Non-Corneal Absorption

Penetration across Sclera & Conjuctiva into Intra Ocular tissues,it is non-Productive because penetrated drug is absorbed by general circulation.

B. Corneal Absorption

The Outer Epithelium is the rate limiting barrier, with pore size 60å, Onlyaccess to small ionic and lipophilic molecules.

Trans cellular transport system between corneal epithelium and stroma is themost common transport mechanism.

FACTORS AFFECTING DRUG BIOAVAILABILITY

Factors that affect drug bioavailability towards ocular drug administrationare as follows;

A .Pre-cornealB .CornealC .Interior of the eye

I. Inflow and out flow of lacrimal fluidsII. Efficient nasal-lacrimal drainage

III. Interaction of a drug with proteins embedded in the eyes.IV. Dilution of the drug with the tears.V. Physicochemical properties of the drug

VI. Corneal barriersVII. Active ion transport in the corneal

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FORMULATION CONSIDERATIONS

For ophthalmic preparations, it is important to understand their sterility asthey are to be applied topically to the cornea and or instilled in the spacebetween the eyeball and lower eyelid.

CONVERSIONAL OCULAR FORMULATIONS AND DRUGDELIVELY SYSTEM

1. Solutions

2. Suspensions

3. Ointments

4. Gels

5. Emulsions

Solution

Dilute with tear and wash away through lacrimal apparatus.

Usually do not interfere with vision of patient.

To be Administered at frequent intervals.

Suspension

Longer contact time.

Irritation potential due to the particle size of the drug.

Ointment

Longer contact time and greater storage stability.

Producing film over the eye and blurring vision.

Interfere with the attachment of new corneal epithelial cells to theirnormal base.

CLASSIFICATION OF OPHTHALMIC PREPARATION

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A) Based on Root of Administration

1.Topical Solution:

Multiple Dose container With Preservatives.

2. Intra-ocular Solution:

For Surgery, Single dose, Without preservative.

3.Ophthalmic Solution Injections:

Intra-ocular injection, given in eye tissues, without preservative.

B) Based on Physical Form

1. Aqueous Solution.

2. Suspension.

3. Ointments.

4. Gels.

5. Eye Lotions.

6. Solid Inserts.

FACTORS AFFECTING DRUG BIOAVAILABILITY

I. Interaction of drug with proteins of lacrimal fluid

II. Conjuctival drainage which is the major site for drainage

III. Solution drainage such as nasal lacrimal drainage which is the major

site for drainage

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IV. Several pre cornea constraints are responsible for poor ocular

bioavailability and these include

V. Tears circulating may decrease absorption by diluting the drugs

VI. Other factors include metabolism of drugs in pre corneal area, PH,

tonicity of dosage form

APPROACHES TO IMPROVING BIO AVAILABILITY

1. To prolong the contact time of drug with corneal surface

2. To enhance corneal permeability either by mild or transient structuralalteration of corneal epithelium or modification of chemical structure ofdrug molecules.

Recent trends:

1. Polymeric solutions

2. Phase transition systems

3. Mucoadhesive/ bioadhesive dosage forms

4. Collagen shields

5. Pseudolatices

6. Ocular penetration enhancers

7. Ocular Iontophoresis

MERITS OF OCULAR DRUG DELIVERY SYSTEM

I. Absorption is rapid and quick onset of action because of large

absorption surface area and higher vascularisation.

II. Ocular administration would act as an alternative to other routes of

drug administration

III. Improved patient compliance due to easy mode of application plus

needle free.

IV. Good penetration of hydrophilic, low molecular weight drugs can be

obtained through the eye.

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DEMERITS

I. An administered portion of a dose drains into the lacrimal duct

and thus can cause unwanted systemic side effects.

II. Physiological restriction is the limited permeability of cornea

resulting into low absorption of ophthalmic drugs.

III. Rapid elimination of the drug through the eye blinking and tear

flow results in a short duration of the therapeutic effect resulting

in a frequent dosing.

DESIRED CRITERIA FOR CONTROLLED RELEASE FOR OCULARINSERTS

I. Comfort

II. Ease of handling

III. Reproducibility of release kinetics

IV. Sterility

V. Stability

VI. Ease of manufacturing.


1. Matrix type Drug Delivery System – Hydrophilic soft contact lens

2. Capsule type Drug Delivery System – ocusert

3. Implantable Drug Delivery pumps – osmotic mini pumps

4. Other devices – lacrisert

a) minidisk ocular therapeutic

b) The new ophthalmic delivery system

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5. Particulate systems – microspheres & Nanoparticles

6. Vesicular system – liposomes

niosomes

TYPES OF OCULAR CONTROL RELEASE SYSTEMS

A) NON-ERODIBLE Ocusert

Contact lenses

Diffusional inserts

B) ERODIBLE Lacrisert

Minidisc

C) Nanoparticle

D) HVBLiposomes

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niosomes



Contact lenses

Diffusional inserts


Minidisc

C) Nanoparticle

D) HVBLiposomes

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niosomes



Contact lenses

Diffusional inserts


Minidisc

C) Nanoparticle

D) HVBLiposomes

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FIGURE SHOWING OCCUSET

2. CONTACT LENS

• Presoaked Hydrophilic lens.

• Drug Release is within first 30 Min.

• Alternate approach, incorporate drug either as solution or suspensionof solid monomer mixture.

• Release rate is up to 180 hr.

3. Diffusional Inserts : Central reservoir of drug enclosed in Semi permeable or micro

porous membrane for diffusion of drug. Diffusion is controlled by Lacrimal Fluid penetrating through it. It prevents continues decrease in release rate due to barrier. Release follows Zero Order Kinetics.

B.ERODIBLE INSERTS

1.Lacrisert:

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• Sterile, Rod Shaped device.

• Composition: HPC without preservative.

• Weight:5mg,

• Dimension:Diameter:12.5mm, Length:3.5mm

• Use:-Dry eye treatment, Keratitis Sicca.

2.SODI:

Soluble Ocular Drug Insert.

• Small water soluble developed for Cosmonauts who could not use theireye drop in liquid condition.

• Composition : Acryl amide, Vinyl Pyrolidone, Ethylacrylate.

• Weight 15-16 mg.

• In 10-15 sec Softens;

• In 10-15 min. turns in Viscous Liquids;

• After 30-60min. Becomes Polymeric Solution.

ADVANTAGES OF SODI

Single SODI application :replaces 4-12 eye drops Instillation or 3-6application of Ointments.

Once a day treatment of Glaucoma and Trachoma

3)Minidisc:

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• It is made up of counter disc with Convex front & Concave back surfacein contact with eye ball.

• 4-5mm in diameter.

• Composition : Silicon based pre polymer.

• Hydrophilic or Hydrophobic.

• Drug release from 170 hr.

C.NANOPARTICLES

I. For water soluble drugs.II. Size:10-1000nm

III. Drug is Dispersed, Encapsulated, or AbsorbedIV. Produced by Emulsion PolymerizationV. Polymerization is carried out by

VI. Chemical initiation, Gamma irradiation, Visible light.VII. Emulsifier stabilizes polymer particle

VIII. Polymer used are Biodegradable.IX. E.g. :- Nanoparticle of Pilocarpine enhances Mitotic response by

20-23%.

D.LIPOSOMES

a) Biodegradable, Non-toxic in nature.b) Vesicle composed of lipid membrane enclosed in an

aqueous volume.c) Formed when matrix of phospholipids is agitated in

aqueous medium to disperse two phase.d) Phospholipids used aree) Phophotidylcholine

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f) Phophotidic acid,g) Sphingomyline,h) Phosphotidyleserine,i) Cardiolipine

CONCLUSION

Ocular drug delivery has to overcome unique barriers development ofophthalmic drug delivery systems at present include polymeric gels, colloidalsystems, cyclodextrins, collagen shields. Activated gel-forming systems arepreferred to hydro gels while Colloidal systems have convenience inmaintaining drug activity at the site of action & is suitable for poorly solubledrugs.

New tendency of research in ophthalmic drug delivery system is directedtowards combination of several drug delivery technologies.

1.7 VAGINAL AND INTER UTERINE

I. VAGINAL AND INTER UTERINE DRUG DELIVERY : Refers to thedelivery of drugs within or through the vaginal mucosa for local orsystemic pharmacological action. The rate and extent of drugabsorption after intravaginal administration may vary depending onvaginal physiology, age of the patient, stage in the menstrual cycle,pathological conditions and formulation factors.

MERITS;

a) Preferred in cases of nausea and vomiting, the act of takingmedication orally may induce emesis so that the drug isvomiting before it is absorbed.

b) The area has relatively low enzymatic activities causingreduction in drug metabolism and degradation

c) The vaginal cavity is also an effective site for the uterinetargeting of various therapeutic

d) Reduces side effects due to avoidance of repeatedadministration of the drug.

e) The area has relatively low enzymatic activities causingreduction in drug metabolism and degradation

f) The vaginal cavity is also an effective site for the uterinetargeting of various therapeutic

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g) The area has relatively low enzymatic activities causingreduction in drug metabolism and degradation

h) The vaginal cavity is also an effective site for the uterinetargeting of various therapeutic agents such as terbutaline,progesterone and danazol.

i) It permits continuous and prolonged residence of thedosage form at the site of application.

j) The area has relatively low enzymatic activities causingreduction in drug metabolism and degradation

k) The vaginal cavity is also an effective site for the uterinetargeting of various therapeutic agents such as terbutaline,progesterone and danazol.

l) It permits continuous and prolonged residence of thedosage form at the site of application.

m) Convenient for the patients, especially for those on long-term therapy, when compared with parenteral medication.

n) The vaginal bioavailability of smaller drug molecules isgood.

o) The bioavailability of larger drug molecules can beimproved by means of absorption enhancer or otherapproach.

p) Self-medication is possible.DEMERITS;

a) Sometimes leakage of drugs from vagina and wetting of undergarments may make patients feel uncomfortable

b) Local irritation of some drugs may occurc) Some of the drugs are sensitive at the vaginal pH.d) Personal hygienee) Gender specificity

VAGINAL DRUG DELIVELY SYSTEM

a) This route of drug administration is useful for vaginal immunization.

b) Multi-cycle administration of vaginal contraceptive rings.

c) Effective route for the treatment of HIV infection.

d) Effective route for the treatment of local fungal infection.

e) Effective for the delivery of hormones

FACTORS AFFECTING THE VAGINAL ABSORPTION

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Unlike Parenteral drug administration, the mucosal route of administration,

drugs via the vaginal route are absorbed transcellularly via concentration

dependent diffusion through the cells, paracellularly mediated by tight

junctions and vesicular or receptor mediated transport.

Absorption of drugs from vaginal delivery systems occurs in two main steps;

drug dissolution in vaginal lumen and membrane penetration. Any

biological or formulation factor that affects the drug dissolution and

membrane transport could potentially affect the absorption profile from

vaginal drug delivery systems.

Overall, many factors and processes are involved in drug absorption

from the vaginal route.

A.PHYSIOLOGICAL FACTORSa) The absorption of a drug that is poorly water-soluble may be

increased when the fluid volume is higher. However, the presence

of overly viscous cervical mucus may present a barrier to drug

absorption and increased fluid volume may remove the drug from

vaginal cavity and subsequently reduce absorption.

b) Since many drugs are weak electrolytes, the pH may change their

degree of ionization and affect the absorption of the drug

c) The presence of cervical mucus could also serve as a permeability

barrier to drug absorption

d) The volume, viscosity and pH of vaginal fluid may have

eithernegative or positive impact on vaginal drug absorption.

e) Cyclic changes in thickness of the vaginal epithelium, fluid

volume and composition, pH and sexual arousal could potentially

affect drug release from intravaginal delivery systems.

B.PHYSICOCHEMICAL PROPERTIES

a) Low molecular weight lipophilic drugs are likely to be absorbed more

than large molecular weight lipophilic or hydrophilic drugs.

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b) Physicochemical properties such as molecular weight, lipophilicity,

ionization, surface charge, chemical nature can influence vaginal drug

absorption.

c) Vaginal permeability is much greater to lipophilic steroid such as

progesterone and estrogens than to hydrophilic steroid such as

hydrocortisone and testosterone.

VAGINAL DRUG ABSOPTION

1. The absorption of drugs, targeted for local action in the vagina, is not

desirable.

2. The external cell layers and the basal cell layers of the vagina retain most

ofthe enzyme activity Among the enzymes present, proteases are likely to

be the prominent barrier for the absorption of intact peptide and protein

drugs into the vagina.

3. The physiological factors e.g. cyclic changes in the thickness and porosity

of the epithelium, volume, viscosity and pH of the vaginal fluid and

physicochemical properties of drug.

4. Drugs are transported across the vaginal membrane by the transcellular

route, intracellular route or vesicular and receptor mediated transport

mechanisms.

DELIVERY SYSTEMS FOR VAGINA AND INTRAUTERINECREAMS AND GELS

Figure 11 Candid v gel.

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Creams and gels are used for topical delivery of contraceptives and

antibacterial drugs. These vaginal dosage forms are uncomfortable and

sometimes embarrassing when they leak into the undergarments.

Further, creams and gels may not provide an exact dose because of non-

uniform distribution and leakage. The desirable properties of vaginally

administered cream or gel against microbicides are acceptability and

feasibility.

They must be easy to use, non-toxic and non irritating to the mucus

membrane. In the treatment of bacterial vaginosis, metronidazole and

clindamycin vaginal cream are found to be nearly as effective as orally

administered drugs.

VAGINAL TABLETS AND SUPPOSITORIESA large number of vaginal medications are available in the form of tablets or

suppositories. These vaginal formulations are designed to melt in the vaginal

cavity and release the drug for several hours.

Suppository systems are now most commonly used to administer drugs for

cervical ripening prior to childbirth and local delivery of drugs.

Drugs that are administered as suppository include miconazole for vaginal

candidiasis and progesterone for hormonal replacement therapy.

Mucoadhesive polymers are sometimes used in vaginal tablet formulation to

increase vaginal residence time. Drugs that are administered as vaginal

tablets include itraconazole, clotrimazole and prostaglandins.

Presence of hydrophobic and release retarding materials may decrease the

absorption of a drug from a vaginal formulation

VAGINAL RINGSRings are circular ring type drug delivery devices designed to release the

drug in a controlled manner after insertion into the vagina.

Advantages of vaginal ring are that it is user controlled, does not interfere

with caution, does not require a daily intake of pills and allows continuous

delivery of low dose steroids.

CONCLUSION:

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Among the drug delivery systems available for this route, intravaginal gels for

labor induction have been found to be potential vaginal drug delivery systems

mainly because of their bearing on childbirths. Bioadhesive vaginal

formulations are likely to emerge as new vaginal formulations for both local

and systemic delivery.Vaginal rings have shown significant promise and are

well accepted within female population.

It is obvious that among the routes of drug delivery, the Vagina still remains

an area which has not been fully explored, in as much as only the local effect

is employed, it is imperative that the systemic bioavailability may employ this

route.

REFERENCES

1) Single‐dose pharmacokinetics of sublingual versus oraladministration of micronized 17 beta‐estradiol. Obstet Gynecol1997; 89: 340‐45.

2) A. D. Woolfson, R.K. Malcolm, R.Gallagher, Drug delivery by the

intravaginal route, 17th edition. (2000) pages 509– 555

3) R.P Walton Absorption of drugs through the oral mucosa. IIIFat‐water solubility coefficient of alkaloids. Proc Soc Exp Bio Med1935; 32: 1488..

4) Regional variation in oral mucosal drug absorption permeabilityand degree of keratinization in hamster oral cavity. Pharm Res1991; 8: 1297‐1301.

5) V. manimaran lecturer department of pharmaceutics SRM college of

pharmacy Ocular Drug Delivery System. Unit V11. Slide 2-16

6) Komal R. Nikam et al. /international journal of pharmacy and

technology novel trends in parenteral drug delivery system:

review.22-05-2013

7) Encyclopedia of pharmaceutical technology -third edition edited by

James Swarbrick volume-4 Microsphere Technology and

Applications by Diane J. Burgess and Anthony J. Hickey

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8) Microneedles : The option for painless delivery by Geeta M Patel.

9) Dosage form definations from the FDA10) Applied Biopharmaceutics and Pharmacokinetics 4th edition

Appleton and lange,Stamford,CT pp108-109,pp154-1611) Biopharmaceutics and clinical pharmacokinetics,3rd ed,lea and

Febiger chapters 3-7

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