60 %
40 %
Information about dnyanesh

Published on September 30, 2011

Author: dnyaneshwalunj

Source: authorstream.com

DESIGNING OF SUSTAINED RELEASE DOSAGE FORMS : DESIGNING OF SUSTAINED RELEASE DOSAGE FORMS Presented by- Walunj Dnyanesh R. M’Pharm II nd SEM Pharmaceutics Dept . S.N.D College of Pharmacy 1 IDEAL DRUG DELIVERY SYSTEM: IDEAL DRUG DELIVERY SYSTEM Drug delivery systems refer to the technology utilized to present the drug to the desired body site for drug release and absorption. First, it should deliver drug at a rate dictated by the needs of the body over the period of the treatment. Second it should channel the active entity solely to the site of action. This is achieved by development of new various modified drug release dosage forms, like- >Control release dosage forms >Time release dosage forms >Sustained release dosage forms >Site specific or targeted drug delivery systems etc 2 Slide 3: SUSTAINED RELEASE DRUG DELIVERY : Any of the dosage form that maintains the therapeutic blood or tissue levels of drug by continuous release of medication for a prolonged period of time, after administration of a single dose. In case of injectable dosage forms it may vary from days to months. SITE SPECIFIC AND RECEPTOR TARGETING : Targeting a drug directly to a certain biological location .For site specific release the target is the adjacent to or in the diseased organ or tissue, for receptor release the target is the particular drug receptor within an organ or tissue. CONTROLLED RELEASE DRUG DELIVERY :Delivery of the drug at a predetermined rate and /or to a location according to the needs of the body and disease states for a definite period of time. 3 Sustained release dosage forms (SRDF’S): Sustained release dosage forms (SRDF’S) 4 Introduction: Introduction Sustained release describes the release of drug substance from a dosage form or delivery system over an extended period of time. Also referred to as prolonged-release (PR), slow release (SR), sustained action (SA), prolonged action (PA) or extended-release (ER). 5 Advantages of SRDF: Advantages of SRDF Reduction in blood level fluctuations of drug, thus better management of the disease. Reduction in dosing frequency. Enhanced patient convenience and compliance. Reduction in health care costs. Improved efficiency of treatment. Reduces nursing and hospitalizing time. Maximum bioavailability with a minimum dose. 6 Contd..: Contd.. Make use of special effects, e.g. sustained-release aspirin for morning relief of arthritis by dosing before bedtime. Constant blood levels achieve desired effect and this effect is maintained for an intended period of time . Disadvantages of SRDF:: Disadvantages of SRDF: Immediate changes in the drug if needed during therapy when significant adverse effects are noted cannot be accommodated. The physician has less flexibility in adjusting dosage regimen, as it is fixed by dosage form design. More costly process and equipment are involved in manufacturing many sustained release dosage forms . Dose dumping : It is phenomenon where relative large quantity of drug is released introducing potential toxicity. This is related to manufacturing process. 8 Contd..: Contd.. Need additional patient education.(such as not to chew or crush the dosage form before swallowing) Drugs having very short half life or very long half life are poor candidates for sustained release dosage forms. For Ex: diazepam. Delayed onset of action, hence sometimes not useful in acute conditions Characteristics of Drugs Unsuitable for oral SRDF: Characteristics of Drugs Unsuitable for oral SRDF Those which are not effectively absorbed in the lower intestine. Ex- riboflavin,ferrous salts. Those which are absorbed and excreted rapidly; short biological half life(<1 hr). Ex- penicillin G , furosemide . Those with long biologic half life(>12 hrs). Ex- Diazepam, Phenytoin . For those which require large doses(>1 gm). Ex- sulfonamides. Extensive binding of drugs to plasma proteins will have long elimination half life and such drugs generally do not require to be formulated to SRD F. 10 Slide 11: Design of SRDF: 11 Design of SRDF:: Design of SRDF: The objective in designing a sustained release forms is to deliver drug at a rate necessary to achieve and maintain a constant drug blood level. This is usually accomplished by attempting to obtain zero order release from dosage forms. Zero order release constitutes drug release from dosage form that is independent of the amount of drug in the delivery system. Generally sustain release system do not attain this type of release and try to mimic zero order release by providing drug in slow first order fashion as shown by following equation. Rate in = Rate out = K.Cd.Vd Where, Cd = Desired drug level Vd = Volume of distribution K = elimination rate constant. 12 FORMULATION APPROACHES: FORMULATION APPROACHES Methods for formulating SRDF include: Increasing particle size of drug and/or the dosage form Embedding drug in a matrix Coating the drug or dosage form containing the drug (micro-encapsulation) Forming complexes of the drug with material such as ion exchange resins 13 I) Increasing of particle size of drug or dosage form: I) Increasing of particle size of drug or dosage form Increase of particle size of drug or dosage form Aim is to decrease surface area exposed to dissolution fluid thus decrease rate of drug availability . Increase in particle or crystal size. Tablets with reduced porosity . 14 II. Embedding drug in a matrix: Drug dispersed uniformly in polymer matrix Time = 0 Drug still present in polymer Polymer without drug Time= t II. Embedding drug in a matrix 15 Types of Matrix System: Types of Matrix System Two types Slowly eroding matrix Inert plastic matrix 16 1. Slowly eroding matrix: 1. Slowly eroding matrix Consists of using materials or polymers which erode over a period of time such as waxes, glycerides, stearic acid, cellulosic materials etc. 17 Method: Method Portion of drug intended to have sustained action is combined with lipid or cellulosic material and then granulated. Untreated drug granulated Both mixed 18 Examples: Examples Quindex - Quinidine sulphate by Robins Extended release is by hydrophilic matrix which swells and slowly erodes Used as antiarrhytmic Oromorph SR-Morphine sulphate by Roxane HPMC based Used in severe pain 19 2. Embedding drug in Inert plastic matrix: Inert insoluble polymers such as polyethylene, polyvinyl acetate, polystyrene, polyamide or polymethacrylate(eudragits). 2. Embedding drug in Inert plastic matrix 20 Examples: Examples Procanbid ( procainamide Hcl ) tablets by Parke Davis – antiarrhythmic Extended- release tablet with core tablet of non- erodible wax material with cellulosic polymer 21 III)Micro-encapsulation: III)Micro-encapsulation Defined as a means of applying relatively thin coatings to small particles of solid or droplets of liquids and dispersions Provides a means of converting liquids to solids , of altering colloidal and surface properties , of providing environmental protection , of controlling release characteristics or availability of coated material. 22 Methods of micro-encapsulation: Methods of micro-encapsulation Pan coating Air suspension coating Coacervation-phase separation Spray drying and congealing Multi-orifice centrifugal In-situ-polymerization 23 Applications: Applications Sustained release Taste masking chewable tablet Powders and suspensions Single layered tablets containing chemically incompatible ingredients New formulation concepts for creams, ointments, aerosols, dressings, plasters, suppositories and injectables 24 Example: Example Aspirin encapsulated for Taste-masking Sustained release Reduced gastric irritation Separation in case of incompatibilities-such as CPM 25 Materials Used in Coating of Sustained Release Dosage Forms(encapsulation): Materials Used in Coating of Sustained Release Dosage Forms(encapsulation) Ø Mixtures of waxes [bees wax, carnauba wax, etc] with glyceryl monostearate , stearic acid , glyceryl mono palmitate and cetyl alcohol.These provide coatings that are dissolved slowly or broken down in the GIT. Ø Shellac and zein Ø Ethyl cellulose , which provides a membrane around the dosage form and remains intact throughout the GIT. However, it does permit water to permeate the film, dissolve the drug , and diffuse out again. Ø Acrylic resins , which behave similarly to ethyl cellulose as a diffusion controlled drug release coating material. Ø Cellulose acetate [ di acetate and tri acetate] Ø Silicone elastomers . 26 Slide 27: Principle Is based on preparation of totally insoluble ionic material Resins are insoluble in acidic and alkaline media Structurally made up of a stable acrylic polymer of styrene- divinyl benzene copolymer They contain ionizable groups which can be exchanged for drug molecules Thus IER are capable of exchanging positively or negatively charged drug molecules to form insoluble poly salt resinates . IV)Ion Exchange Resin (IER) method 27 Slide 28: These resinates are administered orally 2 hrs in stomach in contact with acidic fluid at pH 1.2 Intestinal fluid, remain in contact with slightly basic pH for 6hrs. Drug can be slowly liberated by exchange with ions present in G.I.T. 28 Physicochemical properties of drug candidate:: Physicochemical properties of drug candidate: 29 Biological properties of drug candidates:: Biological properties of drug candidates: Margin of safety Dosage form index (DI) Side effect Elimination half life Metabolism Distribution Absorption Biological properties 30 Physicochemical properties: 1) Aqueous solubility : Physicochemical properties: 1) Aqueous solubility A drug with good aqueous solubility, especially if pH independent, serves as a good candidates Drug to be absorbed it first must dissolve in the aqueous phase surrounding the site of administration and then partition into absorbing membrane. 31 2) Partition coefficient : 2) Partition coefficient Between the time a drug is administered and is eliminated from the body, it must diffuse through a variety of biological membranes . The ability of drug particles to penetrate through these membranes is given by Partition coefficient. 32 3) Drug stability : 3) Drug stability Drog for sustain release should not have a high degradation rate in GI track. drugs with stability problems are poor candidates. Localized delivery can be attained by bioadhesive drug delivery systems and can act as reservoir of drugs, thus enhancing their bioavailability. 33 4) Protein binding : 4) Protein binding Most part of the blood protein are re- circulated and are not eliminated, drug-protein binding can serve as a depot . In general charged compounds have a greater tendency to bind a protein . Ex: 95% PPB drugs are Diazepam, Dicoumarol , Novobiocin . 34 6) Dose size : 6) Dose size For oral dosage form a dose size of 0.5 to 1.0 gm is considered maximum . Higher doses have to be given as liquids. Drugs with low therapeutic index needs to given additional core if dose size is high. 35 Biological properties : 1) Absorption : Biological properties : 1) Absorption The rate-limiting step in drug delivery from a sustained release product is release, from the dosage form rather than absorption. A high absorption rate is advantageous for sustain drug release. The rate, extent and uniformity of absorption is an important factor, as here Kr<<<Ka. 36 2) Distribution : 2) Distribution It not only lowers the concentration of circulating drug but it also can be rate limiting in its equilibration with blood and extracellular fluid . The V d and the ratio of drug in tissue to that of plasma at steady state is an important parameters to be considered in determining the release rate. 37 3) Metabolism : 3) Metabolism Metabolism to other active form can also be considered as sustained effect. The extent of metabolism should be identical and predictable when the drug is administered by different routes. If a drug, upon chronic administration, is capable of either inducing or inhibiting enzyme synthesis, it will be poor candidate. 38 4) Elimination half life : 4) Elimination half life Smaller the t ½, larger the amount of drug to be incorporated in the sustained release dosage form. Drug with the half life in the range of 2 to 4 hours make good candidate for such a system. e.g. Propranolol. Drugs with long half-life need not be presented in such a formulation e.g. Amlodipine. 39 5) Side effect: 5) Side effect The incident of side effects can be minimized by controlling the concentration at which the drug exists in plasma at any given time. Hence sustained release formulation appear to offer a solution to this problem. 40 Routs for Administrations: Routs for Administrations Parenteral rout 1.Intravenous 2. Intramuscular Oral rout TRANSDERMAL 41 References:: References: Lachman L, Lieberman HA, and Kanig JL, The Theory and Practice of Industrial Pharmacy, Bombay: Varghese Publishing House, 3 rd edition. 1990, 293,430. Y.W.Chien , Novel Drug Delivery System, published by Marcel Dekkar , inc., New York ,Pg no. 17-36 & 57-111 3 Vyas SP, Khar RK, Controlled Drug Delivery Concept and Advances, New Delhi: Vallabh Prakashan, 1 st edition 2001, 54,155,196. 4 Jain NK, Controlled and Novel Drug Delivery, New Delhi, CBS Publisher and Distributors, 1 st edition 2004, 256. 5 Robinson JR, Lee VHL, Controlled Drug Delivery: Fundamentals and Applications, New York: Marcel Dekker, Inc.2 nd edition. 1978, 373. Remington. The Science and Practice of Pharmacy, lippincot william and wilkines publication, 21 st edition, Vol-1;Pg:1047 . 42 Slide 43: Thank you 43

Add a comment

Related presentations

Related pages

Dnyanesh Maharao - Wikipedia

Dnyanesh Maharao; Born: Dnyanesh Ramkrishna Maharao (1960-06-11) 11 June 1960 (age 56) Mumbai, Maharashtra, India: Occupation: Journalist, Editor: Years active
Read more

Suchergebnis auf Amazon.de für: Dnyanesh Deo: Musik-Downloads

Online-Shopping mit großer Auswahl im Musik-Downloads Shop.
Read more

HsH - Fakultät III - Personen - Limaye, Dnyanesh, Dr. (WM)

Dr. Dnyanesh Limaye Expo Plaza 12 30539 Hannover Gebäude: EP 12 Raum: 3.51 Tel: +49 511 9296 2585 E-Mail: dnyanesh.limaye hs-hannover.de
Read more

Dnyanesh Gangamwar - CEO - Amazatic Solutions | XING

XING ist Deutschlands größtes berufliches Netzwerk: Mit XING finden Sie Ihren Traumjob, knüpfen wertvolle Kontakte, tauschen Wissen aus – und haben ...
Read more

Dnyanesh Golatkar - Partner - Nature Knights | XING

Honest friends; Swiss Knife & Maglite; Visit to Egypt; People intrested in adventure sports as a hobby turned profession
Read more

Dnyanesh Tipre | LinkedIn

Dnyanesh Tipre. Founder and Chairman, United Translational Molecular Imaging Center. Location New York, New York Industry Pharmaceuticals
Read more

Dnyanesh Mhatre - YouTube

Dnyanesh Mhatre - YouTube
Read more

Dnyanesh Dengale | LinkedIn

View Dnyanesh Dengale’s professional profile on LinkedIn. LinkedIn is the world's largest business network, helping professionals like Dnyanesh Dengale ...
Read more

Dnyanesh Mankar (@dnyaneshmankar) | Twitter

The latest Tweets from Dnyanesh Mankar (@dnyaneshmankar). Tech & aviation enthusiast, UI designer at @mysmartprice, Blogger at @RedmondTimes. BOM/HYD
Read more

Dnyanesh M (@dnyanesh115) | Twitter

The latest Tweets from Dnyanesh M (@dnyanesh115). Kid, Weird, an Avid Reader, Coffee & Badminton Lover, Tennis Aficionado, Mechanical Engineer and a QUANT ...
Read more