NANOSUSPENSION A novel approach in drug delivery: NANOSUSPENSION A novel approach in drug delivery Seminar by: Shivraj P. Jadhav M. Pharm. 1 st semester (Pharmaceutics) Amrutvahini college of pharmacy, sangamner. 1 Slide content: Slide content Introduction Need Preparation methods Evaluation parameters Applications Marketed preparations Conclusion References 2 Introduction: Introduction 3 Nanosuspension can be defined as a biphasic system consisting of pure drug particles dispersed in a aqueous vehicle in which the diameter of the suspended particle is less than 1μm in size. Nanosuspension consist of the poorly water soluble compound without any matrix material suspended in dispersion Need for Nanosuspension: Need for Nanosuspension Most of the drugs coming from high-screening are poorly water soluble. Formulation of poorly water soluble drug is always being a challenge. One of the major problem associated with them is low bioavailability due to less absorption. This problem can be overcome by using nanosuspension . 4 Slide 5: 5 Bottom up Technology: Bottom up Technology In Bottom up technology the drug is dissolved in a solvent, which is then added to non‐solvent that causes precipitation of the fine drug particles. Simple and low expenditure. In this technique, the drug needs to be soluble in at least one solvent which is miscible with nonsolvent. 6 Media milling: Media milling In this method the nanosusensions are produced using high‐shear media mills or pearl mills. Milling chamber consist of Milling chamber Milling shaft Recirculation chamber Process is done under controlled temperature. 7 Slide 8: Advantages Disadvantages Media milling is applicable to the drugs that are poorly soluble in both aqueous and organic media. Very dilute as well as highly concentrated nanosuspensions can be prepared by handling 1mg/ml to 400mg/ml drug quantity. Nanosuspensions contaminated with materials eroded from balls may be problematic when it is used for long therapy. The media milling technique is time consuming. Some fractions of particles are in the micrometer range. Scale up is not easy due to mill size and weight 8 Media milling Homogenization: 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. 9 Homogenization: Homogenization Advantages Disadvantages 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. Preprocessing like micronization of drug is required. High cost instruments are required that increases the cost of dosage form 10 Examples of Commercial homogenizers : Examples of Commercial homogenizers APV micron LAB 40 (APV Deutschland GmbH, Lubeck, Germany) Piston‐gap homogenizers from Avestin (Avestin Inc., Ottawa, Canada) Stansted (Stansted Fluid Power Ltd, Stansted, UK) 11 Nanoedge: 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. 12 Evaluation Parameters: 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 In-vivo Evaluation 13 Mean particle size and Size Distribution: 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: Photon correlation spectroscopy (PCS), Laser diffraction (LD), Coulter counter multisizer. 14 Zeta Potential (particle charge): 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. 15 Crystalline state and Particle Morphology: Crystalline state and Particle Morphology X‐ray diffraction analysis, DSC, SEM are used to determine Nanosuspension can undergo a change in the crystalline structure, which may be to an amorphous form or to other polymorphic forms because of high pressure homogenization. 16 Saturation solubility and Dissolution rate: 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. 17 Applications : Applications Bioavailability enhancement Ocular administration Mucoadhesion of the nanoparticles Parenteral purpose 18 Potential benefits : Potential benefits Route of administration Potential benefits Oral Rapid onset Improved bioavailability Intravenous Rapid dissolution Tissue targeting Ocular Higher bioavailability More consistent dosing Inhalation Higher bioavailability More consistent dosing Subcutaneous/ intramuscular Higher bioavailability Rapid onset Reduced tissue irritation 19 Formulations : Formulations Drug Indications Route Status Paclitaxel Anticancer i.v. Phase IV Rapamuane Immunosupperesant Oral Marketed Emend Antiemetic Oral Marketed Budesonide Antiasthamatic Pulmonary Phase I Busulfan Anticancer Intrathecal Phase I Fenofibrate Hypolidemic Oral Phase I Thymectacin Anticancer I.V. Phase I/II Insulin Antidiabetic Oral Phase I Calcium Phosphate Mucosal vaccine adjuvant for Herpes Oral ------ Silver Eczema, atopic dermatitis Topical Phase I Cytokine Inhibitor Crohn’s disease Oral Phase II 20 Conclusion: Conclusion Nanosuspension solved poor bioavailability problem of hydrophobic drugs and drugs which are poorly soluble in aqueous and organic solutions. Nanotechnique is simple, less requirements of excipients, increased dissolution velocity and saturation solubility many poor bioavailability drugs are formulated in nanosuspension form. 21 References: References 1. Nagarjun . P*, Krishnacharya . K., Srinivas V. D. N. and Padma . S. N. ,”Nanosuspension-a promosing drug delivery”, International journal of pharmaceutical sciences and nanotechnology, vol. 2, issue 4, Jan-Mar 2010, 680-684. 2. Elaine Merisko‐Liversidge , Gary G. Liversidge , Eugene R.Cooper . Nanosizing : a formulation approach for poorly water‐soluble compounds. Eur.J.Pharm.Sci.2003; 18:113‐120. 3. Dubey R. Impact of nanosuspension technology on drug discovery and development. Drug Deliv Technol 2006;6 :65–7. 4. Amidon GL, Lennerna¨s H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability . Pharm Res 1995;12 :413–420. 22 References: References 5. Jadhav KR,Shaikh IM,Ambade KW, Kadam VJ. Applications of microemulsion based drug delivery system. Cur Dr del 2006;3(3) :267‐273. 6. Lawrence MJ, Rees GD. Microemulsion‐based media as novel drug delivery systems. Adv Drug Deliv Rev 2000;45 :89–121. 7. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000;50(1) :47‐60. 8. Hemant NJ, Ravindra WT, Martha D, Vaishali PS, Mohammed J, Mohinder SB, Sailesh AV, Abu Serajuddin TM. Bioavailability enhancement of a poorly water‐soluble drug by solid dispersion in polyethylene glycol–polysorbate 80 mixture: Int J Pharm 2004;269 :251‐258. 9. Stella VJ, Rajewski RA. Cyclodextrins: their future in drug formulation and delivery. Pharm Res 1997;14:556–567. 23 Slide 24: 24 Thank You !