Mucoadhesive Drug Delivery Systems Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM-590010,

Mucoadhesive Drug Delivery Systems

Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D

Department of Pharmaceutics

KLE University College of Pharmacy

BELGAUM-590010, Karnataka, India.

Cell No: 00919742431000

E-mail: [email protected]

7th December 2012 1KLE College of Pharmacy, Nipani.

CONTENTSCONTENTS• Introduction

• Definition

• Concepts

• Advantages

• Disadvantages

• Structure of oral mucosa

• Trans mucosal permeability

• Mimosa membrane

• Permeablity enhancers

• In-vitro and in-vivo methods for buccal absorption

• Nasal and Pulmonary drug delivery system and its applications


INTRODUCTIONINTRODUCTION

• Noninvasive systemic administration .Placing a drug or drug

delivery system in a particular region of body for extended

period of time

• Local targeting / systemic drug delivery

• Recent approaches : Bioadhesive polymers

• Mucoadhesive dosage forms : Wet adhesives

• Mucoadhesion is defined as the interaction between a mucin

surface and a synthetic or natural polymer7th December 2012 3KLE College of Pharmacy, Nipani.

BUCCAL CAVITY SITESBUCCAL CAVITY SITESSublingual / Buccal siteSublingual / Buccal site

DOSAGE FORMSDOSAGE FORMS TARGET SITESTARGET SITES

Adhesive tablets, gels, patches or Adhesive tablets, gels, patches or ointments, sprays, lozenges, insert formointments, sprays, lozenges, insert form

Eye, GIT, cervix, vagina, oral Eye, GIT, cervix, vagina, oral cavity, nasal cavitycavity, nasal cavity

YEARYEAR SCIENTISTSCIENTIST STUDYSTUDY

18471847 SobreroSobrero

(Nitroglycerin)(Nitroglycerin)

Absorption of drugs via the mucous Absorption of drugs via the mucous membranes of the oral cavitymembranes of the oral cavity

1935/19441935/1944 WaltonWalton Systemic studies of oral cavity Systemic studies of oral cavity absorptionabsorption

19551955 Kartz & Barr Kartz & Barr Reviews of the systemic studies of oral Reviews of the systemic studies of oral cavity absorptioncavity absorption19651965 GibaldiGibaldi

HISTORY


Concept of bioadhesion• Bioadhesion is the state in which two materials, (at

least one of which is biological in nature), are held together for a extended period of time by interfacial forces.

• The term bioadhesion implies attachment of drug-carrier system to specific biological location. This biological surface can be epithelial tissue or the mucous coat on the surface of tissue.

• If adhesive attachment is to mucous coat then phenomenon is referred as mucoadhesion.


• These drug delivery system utilize property of bioadhesion of certain water soluble polymers which become adhesive on hydration and hence can be used for targeting particular site.

• Definition:- Buccal delivery is the administration of the drug via buccal mucosa (lining of the cheek) to the systemic circulation.


Concept of bioadhesion

Advantages

• Ease of administration.

• Termination of therapy is possible.

• Permits localization of drug to the oral cavity for extended period of time.

• Avoids first pass metabolism.

• Significant reduction in dose can be achieved, thereby reducing dose dependent side effects.


• It allows local modification of tissue permeability, inhibition of protease activity or reduction in immunogenic response, thus selective use of therapeutic agents like peptides proteins and ionized species can be achieved.

• Drugs which are unstable in acidic environment of stomach or destroyed by the alkaline environment of intestine can be given by this route.

• Drugs which show poor bioavailability by oral route can be administered by this route.


Advantages

• It follows passive diffusion, and does not require any activation.

• The oral mucosa lacks prominent mucous secreting goblet cells and therefore there is no problem of diffusion limited mucous build up.

• The presence of saliva ensures large amount of water for dissolution of drug unlike in case of rectal and transdermal route.

• Drugs with short half life can be administered by this method. (2-8 hrs)

Eg. Nitroglycerine ( 2 hrs)

Isosorbide mononitrate ( 2-5 hrs)7th December 2012 9KLE College of Pharmacy, Nipani.

Advantages

• From the formulation point of view a thin mucin film exist on the surface of oral cavity provides opportunity to retain delivery system in contact with mucosa for prolonged period of time with the help of mucoadhesive compounds.

• The buccal membrane is sufficiently large to allow delivery system to be placed at different sites on the same membrane for different occasions, if the drug or other excepients cause reversible damage or irritate mucosa.


Advantages

DISADVANTAGESDISADVANTAGES

• Over hydration may lead to formation of slippery surface & structural integrity of the formulation may get disrupted by the swelling & hydration of the bioadhesive polymer.

• Eating and drinking may become restricted• There is possibility that Patient may swallow the tablet• The drug contained in swallowed saliva follows the per

oral route & advantages of buccal route is lost.• Only drug with small dose requirement can be

administered.


• Drug which irritate mucosa or have a bitter or unpleasant taste or an obnoxious odour cannot be administered by this route

• Drugs which are unstable at buccal pH cannot be administered by this route.

• Only those drugs which are absorbed by passive diffusion can be administered by this route


DISADVANTAGESDISADVANTAGES

HUMAN MUCOSAEHUMAN MUCOSAE

Physiological characteristic:-

Human nasal mucosa :- Ciliated columnar epithelium and squamous cutaneous epithelium

Human rectal mucosa :- Epithelium, lamina propria, double layer musclaris mocasae

Human vaginal mucosa :- Epithelium, lamina propria, tunica propria, muscularis mucosae, outer fibrous layer7th December 2012 13KLE College of Pharmacy, Nipani.

ANATOMY & PHYSIOLOGY OF ORAL MUCOSAANATOMY & PHYSIOLOGY OF ORAL MUCOSA

The oral cavity is lined by thick dense & multilayered mucous membrane of highly vascularized nature. Drug penetrating into the membrane passes through net of capillaries & arteries and reaches the systemic circulation.

There are mainly three functional zones of oral mucosa:-

Masticatory mucosa :- Covers gingiva/ hard palate regions, keratinized epithelium

Mucous secreting region :- Consist of soft palate, floor of mouth underside of tongue, labial & buccal mucosa. this region shows non-keratinized mucosa.

Specialized mucosa :- consist of lip border & dorsal surface of tongue with high selective keratinization


ORAL MUCOSAORAL MUCOSA

The oral mucosa consists of :- Stratified squamous epithelium Basement membrane Lamina propria and submucosa

Epithelium :-Epithelium :-

• Measure 100 cm2

• Protective surface layer

• Protective to deeper tissues

Important feature of oral mucosa is

rapid turnover of the cells(3 – 8 days)


Basement membraneBasement membrane :- :- Boundary between basal layer (epithelium) &

connective tissue (lamina propria & submucosa)

Submucosa layer :-Submucosa layer :-

• Adhesive interface

• Mucus : Secreted by goblet cells / special endocrine glands

• Connective tissue : Collagen, elastic fibers, cellular components.

RegionRegion Average epithelial thicknessAverage epithelial thickness

Skin (mammary region)Skin (mammary region) 100 - 120100 - 120

Hard palateHard palate 250250

Buccal mucosaBuccal mucosa 500 – 600500 – 600

Floor of mouthFloor of mouth 100 - 200100 - 200


The average thickness of various regions of the The average thickness of various regions of the human oral mucosa Epithelium human oral mucosa Epithelium

BIOCHEMICAL COMPOSITIONBIOCHEMICAL COMPOSITIONProtein :- Tonofilament (Keratinized & non – keratinised

epithelia)

Little known about lipid composition

Keratinized oral epithelium :- Neutral lipids (ceramides)

Non – keratinized epithelium :- Few neutral but polar lipids (cholesterol sulphate & glucosylceramides)

Oral epithelial cell :- Carbohydrate , protein complexes

Role of matrix :- Cell – cell adhesion, lubricant allowing cells to move relative to one another


• About 1.5 Liters of saliva is secreted daily• Chief secretions by : Parotid, sub maxillary,

sublingual glands• Minor salivary glands are situated in buccal, palatal

regions

The presence of saliva is more important for:-Drug dissolution Drug permeation (across mucous membrane).


SECRETION OF SALIVASECRETION OF SALIVA

VASCULAR SYSTEM OF VASCULAR SYSTEM OF THE ORAL MUCOSATHE ORAL MUCOSA

• Vascular system have been described by Stablein & Meyer (1984)

• Mucous membrane of buccal cavity is highly vascular

• Blood supply to mouth : External carotid artery

TISSUETISSUE BLOOD BLOOD FLOWFLOW

Ml/min/100 cmMl/min/100 cm22

BuccalBuccal 2.402.40

Sublingual Sublingual 3.143.14

Floor of mouthFloor of mouth 0.970.97

Ventral tongueVentral tongue 1.171.17

FrenulumFrenulum 1.001.00

Gingival(+)Gingival(+) 1.471.47

Palatal (-)Palatal (-) 0.890.89

Table:- Blood flow in the various regionsof the oral mucosa

Maxillary artery (Cheek, hard palate)

Lingual artery(Tongue, gingiva,

Mouth floor)

Facial artery(Lips, soft palate)


Function of oral mucosa.Function of oral mucosa. • Provide protection• Acts as a barrier• Provides adhesion• Keep the mucosal membrane moist

REGIONAL DIFFERENCES IN MUCOSALREGIONAL DIFFERENCES IN MUCOSALPERMEABILITYPERMEABILITY

Permeability : Intermediate between epidermis & intestinal mucosa

Galey (1976) estimated permeability of oral mucosa :sublingual > buccal > palatal

Pimlott & Addy (1985) measured the site dependent absorption of Isosorbide dinitrate tablets (Buccal, palatal, sublingual)

Palatal(keratnized), sublingual(thinner & immersed in saliva)7th December 2012 20KLE College of Pharmacy, Nipani.

TRANSPORT OF MATERIAL TRANSPORT OF MATERIAL ACROSS THE ORAL MUCOSA ACROSS THE ORAL MUCOSA

(TRASMUCOSAL PERMEABILITY)(TRASMUCOSAL PERMEABILITY)• Passive mechanism• Intercellular spaces & cytoplasm (permeability barriers)• Cell membrane ( liphophillic )

FACTORS TO BE CONSIDERED IN THE FACTORS TO BE CONSIDERED IN THE TRANSMUCOSAL PERMEABILITYTRANSMUCOSAL PERMEABILITY

Liphophilicity of drug Salivary secretion pH of saliva : Around 6 favours absorption Binding to oral mucosa Oral epithelium thicknessThere are two routes of drug transport :- Paracellular Transcellular 7th December 2012 21KLE College of Pharmacy, Nipani.

PARACELLULAR ROUTE :-PARACELLULAR ROUTE :- Primary route for hydrophilic drugs Intercellular spaces is the preferred route Disadvantage : Limited surface area

TRANSCELLULAR ROUTE :-TRANSCELLULAR ROUTE :- Route for lipophiollic compounds Lipophillic drugs passes through lipid

rich plasma membranes of the

epithelial cells.

MEMBRANE STORAGE DURING BUCCAL ABSORPTION MEMBRANE STORAGE DURING BUCCAL ABSORPTION

Solid drug powder/tablet

Dissolved drugIn buccal fluids

Drug removed from oral byswallowing

Dissolved drugIn buccal membrane

Drug in lymphatic circulation

Drug in blood circulation


The bioadhesion is mainly depends upon nature of bioadhesive.

First stage involves an intimate contact between a bioadhesive & a membrane.

second stage involves penetration of the bioadhesive into tissue.

At physiological pH the mucous network may carry negative charge because of presence of sialic acid & sulfate residue & this high charge density due to negative charge contributes significantly to bioadhesion


Mechanism of bioadhesion

MECHANISM OF ABSORPTION FROM A MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMMECHANISM OF ABSORPTION FROM A MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEM

AttachmentAttachment Bypasses firstBypasses first

pass metabolismpass metabolism

DRUG RELEASEDRUG RELEASE

Impermeable membrane (1)

Drug polymer layer (2)

Mucoadhesive polymer layer (3)

(1)

(2)

Mucous membrane saliva action Results in swelling

(1)

(2)

(3)

Internal jugular vein

Systemic circulation


IDEAL CANDIDATES FOR IDEAL CANDIDATES FOR BUCCAL DRUG DELIVERY SYSTEMSBUCCAL DRUG DELIVERY SYSTEMS

o Molecular size 75 – 100 Daltons

o Molecular weight 200 – 500

o Drugs should be hydrophilic / lipophilic in nature

o Drug should be stable at buccal pH ( 6.4 – 7.2 )

o Drug should be odourless

o Drugs which are absorbed only by passive diffusion should be used

TYPES OF BUCCAL DRUG DELIVERY SYSTEMS

Buccal drug delivery systems

Buccal tablets(a) Molded tablets

(b) Compressed tabletsBuccal adhesive tablets

Buccal patch /Buccal gels


It has been generally accepted that the biological membrane can be represented by the Fluid mosaic model. This model is proposed by Singer & Nicolson.

Fluid mosaic model is two dimentional model, which depicts a biological membrane composed of a fluid state lipid bilayer embeded with globular integral proteins.

The integral proteins are either embedded in a portion of lipoidal membrane or spanning throughout its entire thickness.


Mimosa membrane

The amphipathic protein molecules have been hypothesized to minimize the free energy required to for transmembrane permeation by maximizing both hydrophilic & lipophilic interaction in the membrane.

it is visualized that ionic & polar portion

of the protein molecule remain in contact with the aqueous environment on the membrane surface relatively nonpolar portions interact with the alkyl chains in the lipid bilayer


Mimosa membrane

The integral membrane protein may also exist as sub-unit aggregates, which span through entire thickness of the lipid bilayer to form a continuous water-filled channels.

Thus the mucosa as a biological membrane may be considered as composed of lipid rich regions interrupted aqueous channel pores form by subunit aggregates of membrane proteins.


Mimosa membrane

Fluid mosaic model



Fluid mosaic model

FUTURE SCOPE

• Management of illness

• Peptide based pharmaceuticals

• Among the non – oral routes available, i.e. the nasal, intraoral , vaginal & rectal. Major interested route is nasal mucosa (superior permeability)

• Peptides drugs ( insulin, oxytocin, protirelin, a vasopressin analog) can effectively permeate the buccal mucosa


FUTURE SCOPE

Various strategies are are being employed to achieve oral absorption of

Peptides:- Manipulation of formulation Maximizing retention of the delivery system Alteration of peptide Chemical & metabolic stability Maintain balance between lipophilicity & hydrogen

bonding potential


CONCLUSION

The buccal cavity provides a highly vascular mucous membrane

site for administration of drugs.

The main advantages of the buccal route of administration over

the traditional routes are that drug degradation in the stomach is

avoided, first pass metabolism is avoided & therapeutic drug

levels of drug can be achieved rapidly


Permeability Enhancers

• These are the Substances added to pharmaceutical formulation in order to increase the membrane permeation rate or absorption rate of co-administered drug.

• Categories of membrane permeation enhancers:-

A. Bile salts and there steroidal detergents- Sodium glycolate, sodium taurocholate, saponins,

etc.


B. Surfactants:-

i. Nonionic - Polysorbate 80,sucrose ester, etc.

ii. Cationic - Cetyltrimethyl ammonium bromide.

iii. Anionic - Sodium laurylsulfate,fatty acids.

C. Other enhancers:-

i. Azone, salisylates, chelating agents, sulfoxides.


Permeability Enhancers

Drug Enhancer Result

Insulin Glycocholate Absorption only in presence of enhancers

Calcitonin Saponins, Bile Salts, fatty acids, SLS

Increase pharmacological effect

Propranolol Methanol, lauric acid

Increases the permeation

Example of permeability enhancers


In Vitro Methods For Buccal Absorption

• Animals are sacrificed immediately before the start of an experiment.

• Buccal mucosa with underlying connective tissue is surgically removed from the oral cavity, the connective tissue is then carefully removed and the buccal mucosal membrane is isolated.


• The membranes are then placed and stored in ice-cold (4°c) buffers (usually Krebs buffer) until mounted between side-by-side diffusion cells for the in vitro permeation experiments.

• Preservation of dissected tissue is important, which will directly affect the results and conclusion of the studies.


In Vitro Methods For Buccal Absorption

In Vivo Methods for Buccal Absorption

• In vivo methods were first originated by Beckett and Triggs with the so-called buccal absorption test.

• Using this method, the kinetics of drug absorption were measured.


• The methodology involves the swirling of a 25 ml sample of the test solution for up to 15 minutes by human volunteers followed by the expulsion of the solution.

• The amount of drug remaining in the expelled volume is then determined in order to assess the amount of drug absorbed.


In Vivo Methods for Buccal Absorption

• It include those carried out using a small perfusion chamber attached to the upper lip of anesthetized dogs.

• The perfusion chamber is attached to the tissue.


Other in vivo methods

• The drug solution is circulated through the device for a predetermined period of time.

• Sample fractions are then collected from the perfusion chamber to determine the amount of drug remaining in the chamber and blood samples are drawn after 0 and 30 minutes to determine amount of drug absorbed across the mucosa.



• In-vivo method involve use of animals like dog, cat, rabbit, hamster to determine the oral mucosal absorption characteristics of drugs.



NASAL DRUG DELIVERY SYSTEM


INTRODUCTION

Anatomy of nose:-• The nasal cavity consists of

passage of a depth of approximately 12-14cm.

• The nasal passage runs from nasal vestibule to nasopharynx.


• The lining is ciliated, highly vascular and rich in mucus gland.

• Nasal secretions are secreted by goblet cells, nasal glands and transudate from plasma.

• It contains sodium, potassium, calcium, albumin, enzymes like leucine,CYP450,Transaminase,etc.

• The pH of nasal secretion is 5.5-6.5 in adults and 5.0-6.7 in infants.


INTRODUCTION

Advantages

• Large nasal mucosal surface area for dose absorption • Rapid drug absorption via highly-vascularized

mucosa

• Rapid onset of action

• Ease of administration, non-invasive

Contd..


• Avoidance of the gastrointestinal tract and first-pass metabolism

• Improved bioavailability

• Lower dose/reduced side effects

• Improved convenience and compliance

• Self-administration.


Advantages

Disadvantages• Nasal cavity provides smaller absorption surface

when compared to GIT.

• Relatively inconvenient to patients when compared to oral delivery since there is possibility of nasal irritation.

• The histological toxicity of absorption enhancers used in the nasal drug delivery system is not yet clearly established.


Factors affecting nasal absorption

1. Molecular weight :-

• The nasal absorption of drugs decreases as the molecular weight increases.

• Martin reported a sharp decline in drug absorption having molecular weight greater than 1000 daltons.


2. Lipophilicity :-

• Absorption of drug through nasal route is dependent on the lipophilicity of drugs.

• E.g. Alprenolol and Propranolol which are lipophilic, has greater absorption than that of hydrophilic Metoprolol.



3. pH of solution :-• pH should be optimum for maximum absorption.

• Nonionised lipophilic form crosses the nasal epithelial barriers via transcellular route and hydrophilic ionized form passes through the aqueous paracellular route.

• E.g. Decanoic acid shows maximum absorption at pH 4.5. Beyond this it decreases as solution becomes more acidic or basic.



4. Drug concentration :-

• The absorption of drug through nasal route is increased as concentration is increased.

• E.g. 1-tyrosine shows increased absorption at high concentration in rate.



Pathway

• In systemic absorption the drugs generally get diffused from epithelial cell into systemic circulation.

• It is reported that nasal cavity have alternative pathways of drugs absorption through olfactory epithelium to CNS and peripheral circulation.


Enhancement in absorption• Following approaches used for absorption

enhancement :- Use of absorption enhancers

Increase in residence time.

Administration of drug in the form of microspheres.

Use of physiological modifying agents


Use of absorption enhancers:-

Absorption enhancers work by increasing the rate at which the drug pass through the nasal mucosa.

Various enhancers used are surfactants, bile salts, chelaters, fatty acid salts, phospholipids, cyclodextrins, glycols etc.


Enhancement in absorption

Various mechanisms involved in absorption enhancements are:-

• Increased drug solubility

• Decreased mucosal viscosity

• Decrease enzymatic degradation

• Increased paracellular transport

• Increased transcellular transport


Increase in residence time:-• By increasing the residence time the increase in

the higher local drug concentration in the mucous lining of the nasal mucosa is obtained.

• Various mucoadhesive polymers like methylcellulose, carboxymethylcellulose or polyarcylic acid are used for increasing the residence time.


Administration of drug in the form of microspheres:-

• Microspheres have good bioadhesive property and they swell when in contact with mucosa.

• Microspheres provide two advantages-

a. Control the rate of clearance.

b. Protect drug from enzymatic degradation.

The microspheres of various materials showed increased half-life of clearance. E.g. starch, albumin, gelatin and dextran.


Use of physiological modifying agents:-

• These agents are vasoactive agents and exert their action by increasing the nasal blood flow.

• The example of such agents are histamine, leukotrienene D4, prostaglandin E1 and β-adrenergic agents like isoprenaline and terbutaline.


Nasal Delivery Systems

• They contain the drug in a liquid or powder formulation delivered by a pressurized or pump system.

• Various drug delivery systems are used for nasal drug delivery.


Liquid formulation :-

• These are usually aqueous solutions of the drug. The simplest way to give a liquid is by nose drops.

• They are simple to develop and manufacture compared to solid dosage forms but have a lower microbiological and chemical stability, requiring the use of various preservatives.



Squeezed bottles :-

• These are used for nasal decongestant and work by spraying a partially atomized jet of liquid into the nasal cavity.

• They give a better absorption of drug by directing the formulation into the anterior part of the cavity and covering a large part of nasal mucosa.



Metered-dose pump system :-

• They can deliver solutions, suspensions or emulsions with a predetermined volume between 25 and 200 μL, thus offering deposition over a large area.

• Particle size and dose volume are two important factors for controlling delivery from metered-dose systems.



• The optimum particle size for deposition in the nasal cavity is 10μm.

• The volume of formulation that can be delivered is limited by the size of the nasal cavity and larger volumes tend to be cleared faster despite covering a larger area.

• Better absorption is achieved by administering two doses, one in each nostril, rather than a single large dose.



Applications of Nasal Drug Delivery

A. Nasal delivery of organic based pharmaceuticals :-

• Various organic based pharmaceuticals have been investigated for nasal delivery which includes drug with extensive presystemic metabolism.

• E.g. Progesterone, Estradiol, Nitroglycerin, Propranolol, etc.


B. Nasal delivery of peptide based drugs :-• Nasal delivery of peptides and proteins is depend on: The structure and size of the molecule. Nasal residence time Formulation variables (pH, viscosity)

• E.g. Calcitonin, secretin, albumins, insulin, glucagon, etc.


Applications of nasal drug delivery

Pulmonary Drug Delivery System


• The lung is the organ of external respiration, in which oxygen and carbon dioxide are exchanged between blood and inhaled air.

• The structure of the airways prevent the entry of and promotes the removal of airborne foreign particles including microorganisms.

Contd..7th December 2012 69KLE College of Pharmacy, Nipani.

Introduction

• The respiratory tract consists of conducting regions (trachea, bronchi, bronchioles, terminal and respiratory bronchioles) and respiratory regions (respiratory bronchioles and alveolar regions).

• The upper respiratory tract comprises the nose, throat, pharynx and larynx; the lower tract comprises the trachea, bronchi, bronchioles and the alveolar regions.


Introduction


Anatomy of pulmonary system

• Trachea branches into two main bronchi- the right bronchus is wider and leaves the trachea at the smaller angle than the left.

• The conducting airways are lined with ciliated epithelial cells.


Anatomy of pulmonary system

Delivery systems

• Aerosols are used for the delivery of the drug by this route of administration.

• The aerosols are defined as pressurized dosage from containing one or more active ingredients which upon actuation emit a fine dispersion of liquid or solid materials in gaseous medium.


• There are three main types of aerosols generating devices:-

i. Pressurized metered dose inhalers.

ii. Dry powder inhalers.

iii. Nebulizers.


Delivery systems

i. Pressurized metered dose inhalers:

• In pMDI’s, drug is either

dissolved or suspended in

liquid propellants together with other excipients and presented in pressurized canister fitted with metering valve.

• The predetermined dose is released as a spray on actuation of the metering valve.


Delivery systems

• Containers:- Aerosol container must withstand pressure as high as 140-180 psig at 130°F.

• Pharmaceutical aerosols are packaged in tin-plated steel, plastic coated glass or aluminium containers.

• Aluminium is relatively inert and used uncoated where there is no chemical instability between containers and contents.

• Alternatively aluminium containers with an internal coating of chemically resistant organic material such as epoxy-resin or polytetrafluorine can be used


Delivery systems

• Propellants: These are liquified gases like chlorofluorocarbons and hydrofluoroalkanes.

• These develop proper pressure within the container & it expels the product when valve is opened.

• At room temperature and pressure, these are gases but they are readily liquified by decreasing the temperature or increasing pressure.

• The vapour pressure of the mixture of propellants is given by Raoult’s law,

Contd…7th December 2012 77KLE College of Pharmacy, Nipani.

Delivery systems

i.e. vapour pressure of the mixed system is equal to the sum of the mole fraction of each component multiplied by it’s vapour pressure.

p = pa + pb

where p = total vapour pressure of the system,

pa & pb = partial vapour pressures of the components a & b.

Contd…


Delivery systems

• Metering valves:

It permits the reproducible delivery of small volumes of product.

Depression of the valve stem allows the contents of the metering chamber to be discharged through the orifice in the valve stem and made available to the patient.

After actuation the metering chamber refills with liquid from the bulk and is ready to dispense the next dose.


Delivery systems

ii. Dry powder inhalers:

In this system drug is inhaled as a cloud of fine particles.

DPI formulations are propellant free and do not contain any excipients.

They are breath activated avoiding the problems of inhalation/actuation coordination encountered with pMDI’s.


Delivery systems

iii. Nebulizers:

It delivers relatively large volume of drug solutions and suspensions.

They are used for drugs that cannot be formulated into pMDI’s or DPI’s.

There are three categories :-

a. Jet nebulizers

b. Ultrasonic nebulizers

c. Vibrating-mesh nebulizers7th December 2012 81KLE College of Pharmacy, Nipani.

Delivery systems

a. Jet nebulizers:-

They are also called as air-jet or air-blast nebulizers using compressed gas.

The jet of high velocity gas is passed tangentially or coaxially through a narrow venturi nozzle typically 0.3 to 0.7 mm in diameter.

e.g. Pari LC nebulizer.


Delivery systems

b. Ultrasonic nebulizers:

In this the energy necessary to atomize liquids come from the piezoelectric crystal vibrating at high frequency.

c. Vibrating-mesh nebulizers:

In this device aerosols are generated by passing liquids through a vibrating mesh or plate with multiple apertures.


Delivery systems

Applications • Smaller doses can be administered locally.

• Reduce the potential incidence of adverse systemic effect.

• It used when a drug is poorly absorbed orally, e.g. Na cromoglicate.

• It is used when drug is rapidly metabolized orally, e.g. isoprenaline


REFERENCES

Y.W. Chein , Novel Drug Delivery Systems, 2 nd edition, revised and expanded , Marcel Dekker , Inc. New York , 1992(pg. no. 195 – 224)

N.K. Jain , Controlled and Novel drug delivery , CBS Publishers & Distributors, New Delhi, First edition 1997(reprint in 2001)

S.P. Vyas and R.K.Khar, Controlled Drug Delivery, CBS Publishers & Distributors, New Delhi, First edition 1997.

Indian Journal of Pharmaceutical science, January 1998.


THANK YOU


Cell No: 00919742431000E-mail: [email protected]

Documents

Mucoadhesive Drug Delivery Systems Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM-590010,