Presentation on theme: "Mucoadhesive Drug Delivery Systems Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM-590010,"— Presentation transcript:
Mucoadhesive Drug Delivery Systems Dr. Basavaraj K. Nanjwade M. Pharm., Ph. D Department of Pharmaceutics KLE University College of Pharmacy BELGAUM , Karnataka, India. Cell No: th December 20121KLE College of Pharmacy, Nipani.
CONTENTS 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 7th December 20122KLE College of Pharmacy, Nipani.
INTRODUCTION 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 polymer 7th December 20123KLE College of Pharmacy, Nipani.
BUCCAL CAVITY SITES Sublingual / Buccal site DOSAGE FORMS TARGET SITES Adhesive tablets, gels, patches or ointments, sprays, lozenges, insert form Eye, GIT, cervix, vagina, oral cavity, nasal cavity YEARSCIENTISTSTUDY1847Sobrero(Nitroglycerin) Absorption of drugs via the mucous membranes of the oral cavity 1935/1944Walton Systemic studies of oral cavity absorption 1955 Kartz & Barr Reviews of the systemic studies of oral cavity absorption 1965Gibaldi HISTORY 7th December KLE College of Pharmacy, Nipani.
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. 7th December 20125KLE College of Pharmacy, Nipani.
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. 7th December 20126KLE College of Pharmacy, Nipani. 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. 7th December 20127KLE College of Pharmacy, Nipani.
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. 7th December 20128KLE College of Pharmacy, Nipani. 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 20129KLE 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. 7th December KLE College of Pharmacy, Nipani. Advantages
DISADVANTAGES 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. 7th December KLE College of Pharmacy, Nipani.
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 7th December KLE College of Pharmacy, Nipani.DISADVANTAGES
HUMAN 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 layer 7th December KLE College of Pharmacy, Nipani.
ANATOMY & 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 7th December KLE College of Pharmacy, Nipani.
ORAL MUCOSA The oral mucosa consists of :- Stratified squamous epithelium Basement membrane Lamina propria and submucosa Epithelium :- Measure 100 cm 2 Protective surface layer Protective to deeper tissues Important feature of oral mucosa is rapid turnover of the cells(3 – 8 days) 7th December KLE College of Pharmacy, Nipani.
Basement membrane :- Basement membrane :- Boundary between basal layer (epithelium) & connective tissue (lamina propria & submucosa) Submucosa layer :- Adhesive interface Mucus : Secreted by goblet cells / special endocrine glands Connective tissue : Collagen, elastic fibers, cellular components. Region Average epithelial thickness Skin (mammary region) Hard palate 250 Buccal mucosa 500 – 600 Floor of mouth th December KLE College of Pharmacy, Nipani. The average thickness of various regions of the human oral mucosa Epithelium
BIOCHEMICAL COMPOSITION Protein :- 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 7th December KLE College of Pharmacy, Nipani.
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). 7th December KLE College of Pharmacy, Nipani. SECRETION OF SALIVA
VASCULAR SYSTEM OF THE 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 TISSUE BLOOD FLOW Ml/min/100 cm 2 Buccal2.40 Sublingual3.14 Floor of mouth 0.97 Ventral tongue 1.17 Frenulum1.00 Gingival(+)1.47 Palatal (-) 0.89 Table:- Blood flow in the various regions of the oral mucosa Maxillary artery (Cheek, hard palate) Lingual artery (Tongue, gingiva, Mouth floor) Facial artery (Lips, soft palate) 7th December KLE College of Pharmacy, Nipani.
Function of oral mucosa. Provide protection Acts as a barrier Provides adhesion Keep the mucosal membrane moist REGIONAL DIFFERENCES IN MUCOSAL PERMEABILITY 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 KLE College of Pharmacy, Nipani.
TRANSPORT OF MATERIAL ACROSS THE ORAL MUCOSA (TRASMUCOSAL PERMEABILITY) Passive mechanism Intercellular spaces & cytoplasm (permeability barriers) Cell membrane ( liphophillic ) FACTORS TO BE CONSIDERED IN THE TRANSMUCOSAL PERMEABILITY Liphophilicity of drug Salivary secretion pH of saliva : Around 6 favours absorption Binding to oral mucosa Oral epithelium thickness There are two routes of drug transport :- Paracellular Transcellular 7th December KLE College of Pharmacy, Nipani.
PARACELLULAR ROUTE :- Primary route for hydrophilic drugs Intercellular spaces is the preferred route Disadvantage : Limited surface area TRANSCELLULAR ROUTE :- Route for lipophiollic compounds Lipophillic drugs passes through lipid rich plasma membranes of the epithelial cells. MEMBRANE STORAGE DURING BUCCAL ABSORPTION Solid drug powder/ tablet Dissolved drug In buccal fluids Drug removed from oral by swallowing Dissolved drug In buccal membrane Drug in lymphatic circulation Drug in blood circulation 7th December KLE College of Pharmacy, Nipani.
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 7th December KLE College of Pharmacy, Nipani. Mechanism of bioadhesion
MECHANISM OF ABSORPTION FROM A MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEM Attachment Bypasses first pass metabolism pass metabolism DRUG 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 7th December KLE College of Pharmacy, Nipani.
IDEAL CANDIDATES FOR BUCCAL DRUG DELIVERY SYSTEMS oMolecular size 75 – 100 Daltons oMolecular weight 200 – 500 oDrugs should be hydrophilic / lipophilic in nature oDrug should be stable at buccal pH ( 6.4 – 7.2 ) oDrug should be odourless oDrugs 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 tablets Buccal adhesive tablets Buccal patch / Buccal gels 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. 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 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. Mimosa membrane
Fluid mosaic model 7th December KLE College of Pharmacy, Nipani.
7th December KLE College of Pharmacy, Nipani. 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 7th December KLE College of Pharmacy, Nipani.
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 7th December KLE College of Pharmacy, Nipani.
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 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. Permeability Enhancers
DrugEnhancerResult InsulinGlycocholateAbsorption only in presence of enhancers CalcitoninSaponins, Bile Salts, fatty acids, SLS Increase pharmacological effect PropranololMethanol, lauric acid Increases the permeation Example of permeability enhancers 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. Other in vivo methods
In-vivo method involve use of animals like dog, cat, rabbit, hamster to determine the oral mucosal absorption characteristics of drugs. 7th December KLE College of Pharmacy, Nipani. Other in vivo methods
NASAL DRUG DELIVERY SYSTEM 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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,CYP 450, Transaminase,etc. The pH of nasal secretion is in adults and in infants. 7th December KLE College of Pharmacy, Nipani. 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.. 7th December KLE College of Pharmacy, Nipani.
Avoidance of the gastrointestinal tract and first-pass metabolism Improved bioavailability Lower dose/reduced side effects Improved convenience and compliance Self-administration. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. Factors affecting nasal absorption
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. 7th December KLE College of Pharmacy, Nipani. Factors affecting nasal absorption
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. 7th December KLE College of Pharmacy, Nipani. Factors affecting nasal absorption
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. 7th December KLE College of Pharmacy, Nipani.
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 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. 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 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. Nasal Delivery Systems
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. 7th December KLE College of Pharmacy, Nipani. Nasal Delivery Systems
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. 7th December KLE College of Pharmacy, Nipani. Nasal Delivery 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. 7th December KLE College of Pharmacy, Nipani. Nasal Delivery Systems
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. 7th December KLE College of Pharmacy, Nipani.
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. 7th December KLE College of Pharmacy, Nipani. Applications of nasal drug delivery
Pulmonary Drug Delivery System 7th December KLE College of Pharmacy, Nipani.
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 KLE 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. Contd.. 7th December KLE College of Pharmacy, Nipani. Introduction
Contd.. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani.
There are three main types of aerosols generating devices:- i.Pressurized metered dose inhalers. ii.Dry powder inhalers. iii.Nebulizers. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. Delivery systems
Containers:- Aerosol container must withstand pressure as high as 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 7th December KLE College of Pharmacy, Nipani. 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 KLE 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 = p a + p b where p = total vapour pressure of the system, p a & p b = partial vapour pressures of the components a & b. Contd… 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. 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 nebul izers 7th December KLE 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. 7th December KLE College of Pharmacy, Nipani. 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. 7th December KLE College of Pharmacy, Nipani. 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 7th December KLE College of Pharmacy, Nipani.
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 Indian Journal of Pharmaceutical science, January th December KLE College of Pharmacy, Nipani.
THANK YOU 7th December KLE College of Pharmacy, Nipani. Cell No: