Nano Suspensions

Information about Nano Suspensions

Published on July 17, 2014

Author: amballa.sridivya



PowerPoint Presentation: SUSPENSIONS PowerPoint Presentation: NANO SUSPENSIONS BY A. SRI DIVYA PowerPoint Presentation: SUSPENSIONS: Definition: Suspensions is heterogeneous system consisting of two phases. The continous or external phase is generally liquid or semi solid and the dispersed phase is made up of particulate matter that is essentially insoluble in but disperssed throught out the disperssed phase. ADVANTAGES: Suspensions can improve chemical stability of certain drugs. eg : Procaine pencillin –G Duration and onset of action can be controlled. eg : Protamine Zinc-Insulin suspension. Suspension can mask the unpleasent or bitter taste of drug. eg : Chloramphenicol PowerPoint Presentation: DISADVANTAGES : Physical stability , sedimentation and compaction can cause problems. It is bulky, sufficient care must be taken during handling and transport. It is difficult to formulate. Uniform and accurate dose cannot be achieved unless suspension are packed in unit dosage form. PowerPoint Presentation: CLASSIFICATION OF PHARMACEUTICAL SUSPENSIONS : Based on Route of administration Based on size of solid particles Based on electro kinetic nature of solid particles Based on proportion of solid particles Oral suspensions Colloidal suspensions (<1µ) Flocculated suspensions Dilute suspensions (2 to 140./.w/v solid. Externally applied suspension Coarse suspensions (>1µ) Deflocculated suspension Concentrated suspension (50./. w/v solid). Parenteral suspensions PowerPoint Presentation: FORMULATIONS OF SUSPENSIONS: The formulator should encounter important problems regarding particle size distribution, specific surface area, inhibition of crystal growth and changes in polymorphic form. The formulator must ensure that these and other properties should not change lon term storage and do not adversely effect the performance of suspension. MEDICAMENTS: 2 Types Diffusible 2. Indiffusible 3.Poorly soluble solids Diffusuble : These are poorly soluble in water and uniformly distributed in water. Eg : Caco 3, Mgco 3, Mg trisilicate . 2. Indiffusible : These are poorly soluble in water and not unifomly didtributed in water. uniformly distribution is obtained by increasing viscosity of suspension by using viscosity increasing agents. Eg : Calamine, Zno , Aspirin. PowerPoint Presentation: Poorly soluble solids: These are insoluble in water solubility can be increased by using surfactants. Eg : Charcoal. FLOCCULATING AGENT: These are the agents used to prevent aggregation of suspended particles.. It includes surfactants, electrolytes, hydrophilic polymers THICKENNING AGENTS: These are agents used to prevent rapid sedimentation of disperssed particles. Classified into 3 types: Polysaccharides a) Natural Eg : Acacia, Tragacanth , Strach b) Semisynthetic Eg : Cellulose, Methyl cellulose Inorganic Agents: Eg : clay. Al(OH) 2 Synthetic Compounds: Eg : Carbomer , Collidal silica dioxide. PowerPoint Presentation: WETTING AGENTS : It is an absorption process in which solubility of poorly soluble drugs can be increased by lowering interphascial tension and surface intension between immiscible phases. It is of 3 types: Surfactants Eg : Sodium lauyrl sulphate Hydrophillic polymers. Eg : Accacia , Bentonite . Hydrophillic liquids . Eg : 90./. Alcohol, Glycerin STABILIZERS: These are the agents used to stabilize the preparations from microbial growth change in P H and oxidative degradation. PRESERVATIVES: Liquid dosage forms are more suspectible to microbial growth due to various sources like rawmaterial source, equipment source, process environment and packaging for prevention of micro organisms Preservative is an substance used to prevent growth of micro organisms PowerPoint Presentation: Type Preservatives Strength Acids Phenol, Chlorophenicol , Benzoic acid salts, Boric acid 0.5-0.5./. 0.5-1./. 0.2-0.3./. 0.5-1./. Neutrals Butanol , Benzyl alcohol, Phenyl Ethyl alcohol. 0.5 1 1 Mercurals Phenyl mercuric acetate nitrate 0.0005-0.005 Quarternary ammonium compounds Benzolkonium chloride 0.0002-0.002 PowerPoint Presentation: ANTIOXIDANTS: Liquid dosage forms are easily oxidised in presence of heavy metals, it can be prevent completing agent. Eg : EDTA, Ascorbic acids, Sodium sulphitw , Sodium thio sulphate FLAVOURING AGENTS: It is used to mask the unpleasent taste of preparations Taste Flavour Salt Butter scotch, vanilla Bitter Chocolate, Cherry Sweet Strawberry, Vanilla Sour Citrus fruit flavour SWEEETING AGENTS: These are used to mask the unpleasent taste preparations Eg : Sucrose, Saccharin, Liquid glucose. PowerPoint Presentation: EMULSIFYING AGENTS: These are substances used to lower the interficial tension between two immiscible liquids and make them miscible with each other to produce stableemulsion PowerPoint Presentation: PREPARATIONS OF SUSPENSIONS: Insoluble and large solid substances are finely powdered in a motar . Generally, this process is known as trituration or grinding ( in caser of ointments it is known as levigation ) This finely powdered substance is titurated with a sufficient vehicle. This leads to formation of a smooth cream. Then, add more quantity of vehicle to dissolve the soluble drugs which makes the suspension pourable. This suspension is then taken into a container. Rinse the motar thorougly with the remaining vehicle and transfer it into the container so as to make final volume of the suspension. PowerPoint Presentation: EVALUTION TESTS: Sedimentation volume: The suspension formulation (50 mL ) was poured separately into100 mL measuring cylinders and sedimentation volume was readafter 1, 2, 3 and 7 days, and thereafter at weekly intervals for 12 weeks. Sedimentation volume was calculated according to the equation F = Vu/Vo Where, F = sedimentation volume, Vu= ultimate height of sedimentand Vo= initial height of total suspension PowerPoint Presentation: Rheological method: Brookfield viscometer is used to study the viscosity of the suspension . It is mounted on heli path stand and using T-bar spindle. T-bar spindle is made to descend slowly into the suspension and the dial reading on the viscometer is then a measure of the resistance the spindle meets at various level . This technique also indicates at which level of the suspension the structure is greater owing to particle agglomeration. The dial reading is plotted against the number of turns of the spindle. The better suspension show a lesser rate of increase of dial reading with spindle turns, i.e. the curve is horizontal for long period. PowerPoint Presentation: Micromeritic method : The stability of suspension depends on the particle size of the dispersed phase. Change in the particle size with reference to time will provide useful information regarding the stability of a suspension. A change in particle size distribution and crystal habit studied by microscopy coulter counter method FREEZE- THAW TEST Freeze-Thaw test conducted by placing the sample in a freezer for 18 hours followed by thawing at room temperature for 4 to 6 hours. Repeat the Freeze-Thaw cycle for up to 10 times. This test is conducted to determine the tendency to crystallize or cloud. PowerPoint Presentation: DISSOLUTION STUDY OF SUSPENSIONS It is known as paddle method. The apparatus consists of a cylindrical 1000- ml round bottom flask in a multiple – spindle dissolution drive apparatus and immersed in a controlled temperature bath. determined at 37°C in 900 ml of pH 7.2 phosphate buffer using the FDA paddle method at 25 RPM The suspension is to be introduced carefully into the flask at the bottom using a 10- ml glass syringe with an attachment 19-cm needle. Withdraw 5 ml of dissolution medium (and replace with an equal volume of drug –free buffer) in a 5 ml glass syringe. Immediately filter through a 0.2 µm membrane and analyze. PowerPoint Presentation: NANO SUSPENSIONS PowerPoint Presentation: INTRODUCTION: Solubility is an important for drug formulation and their effectiveness One of the problem of new molecular enitities as the drug formulation is poor solubility. Nanosuspension technology can be used to improve the stability as well as the bioavailability of poor solubility of drugs. WHAT ARE NANO SUSPENSIONS: Nanosuspensions are the biphasic colloidal dispersions of nanosized drug particles stabilized by surfactants. Size of the drug particles is less than 1mm. Average particle size range from 200-600nm. PowerPoint Presentation: Route of administration action Action Oral route Rapid onset of action, improved bioavailability Intravenous Rapid dissolution, 100./. Tissue targeting Occular High bioavailability, more consistent dosing Inhalation High bioavailability, more consistent dosing Sub- cutaneous Rapid onset of action, reduced tissue irritation. PowerPoint Presentation: METHOD OF PREPARATION BOTTOM UP TECHNOLOGY NANOEDGE TOP DOWN TECHNALOGY MEDIA MILLING HIGH PRESSURE HOMOGINIZER IN WATER i.e is DISSUBES HIGH PRESURE HOMOGINIZER IN NONAQUEOUS SOLVENTS i.e , NANOPORE PowerPoint Presentation: PREPARATIONS OF NANO SUSPENSIONS: MEDIAMILLING : Nano particles are produced using high shear media mills or pear mills. Size obtained is < 200nm. Milling chamber consists of Milling chamber 2) Milling shaft 3) Recirculation chamber ADVANTAGES: Narrow size particles are obtained. Flexibility in handling of drug is seen i.e from 1 to 400mg/ml. DISADVANTAGES : Residues may occur due to corrosion. PowerPoint Presentation: Homogenization: Homogenization involves the forcing of the suspension under pressure through a valve having a narrow aperture. Most of the cases require multiple passes or cycles through the homogenizer. Advantages : It does not cause the erosion of processed materials Very dilute as well as highly concentrated nanosuspensions can be prepared by handling 1mg/ml to 400mg/ml drug quantity . It is applicable to the drugs that are poorly soluble in both aqueous and organic media. It allows  aseptic production  of nanosuspensions for parentral administration DISANVANTAGES: Preprocessing like micronization of drug is required. High cost instruments are required that increases the cost of dosage form PowerPoint Presentation: Nanoedge : Principle: same that of the precipitation and homogenization techniques. In this technique the precipitated suspension is further homogenized to get smaller particle size and to avoid crystal growth. NON-solvent, such as methanol, ethanol, and isopropanol added. PowerPoint Presentation: CHARECTERSTICS OF NANOSUSPENSIONS: Size and distribution Particle charge Crystalline status. Dissolution velocity Saturation solubility Based on invitro behaviour properties to be included are: Adhesion properties( in case of mucoa dhesive particles) Surface hydrophilicity Interactin with body proteins PowerPoint Presentation: ACTION OF NANO PARTICLES: The nano particles bind with opsions ( immunoglobulins ) and from the opsonised particles. Recognition by cytoplasmic membrane receptors. Entry into pseudopod extension on membrane. Release of phagosome into cytoplasam . Formation of phaglycosome by binding with lysosomes . Release of nano particle into extracellular region. PowerPoint Presentation: USES OF NANOSUSPENSIONS: Anticancer Antiinfective Anti- Emetic Antiasthmatic agent Immuno suppresants Lipid lowering substances PowerPoint Presentation: Evaluation Parameters: :  In-vitro Evaluation : 1. Particle size and size distribution 2. Zeta potential 3. Crystalline state and morphology 4. Saturation solubility and dissolution velocity Mean particle size and Size Distribution: The most important characterization parameter Governs the physicochemical properties like saturation solubility, dissolution velocity, physical stability and even biological performance. Methods for determining particle size distribution are Photon correlation spectroscopy (PCS), Laser diffraction (LD), Coulter counter multisizer . Zeta Potential (particle charge): Determines the physical stability of nanosuspension . In order to obtain a nanosuspension exhibiting good stability, for an electrostatically stabilized nanosuspension a minimum zeta potential of ± 30mv is required. PowerPoint Presentation: Crystalline state and Particle Morphology: The X-Ray Diffraction (XRD) is also used for determining change in physical state and extent of amorphous drug . Differential Scanning Calorimetry (DSC) determines the crystalline structure. When nanosuspensions are prepared drug particles get converted to amorphous form hence it is essential to measure the extent of amorphous drug generated during the production of nanosuspensions Saturation solubility and Dissolution rate: Nanosuspension increases the dissolution velocity and saturation solubility . An increase in solubility that occurs with relatively low particle size reduction may be mainly due to a change in surface tension leading to increased saturation solubility . Depend upon temperature and properties of dissolution medium PowerPoint Presentation: CONCLUSION: This technology is gaining significane as the number of molecules solublility and bioavailability problems are increasing day by day. Thus NANOSUSPENSION technology play a vital role in drug discovery program as well as increasing the bioavailability of poorly soluble drugs. PowerPoint Presentation: REFERENCES: www. author

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