Invitro dissolution

Invitro dissolution

• 1.
  Invitro dissolution ofdrugs M.SIMRANA FATHIMA M.PHARMACY (˘PHARMACEUTICS)
• 2.
  DEFINITION • DISSOLUTION RATE Thephysiochemical properties of most of the drugs that has greater influence on their absorption characteristics from the GIT. • INVITRO DISSOLUTION TEST Test used to qualitatively assure the biological availability of a drug from its formulation.
• 3.
  INTRODUCTION • Dissolution anddrug release tests are in-vitro test s that measure the rate and extent of dissolution or release of the drug substance from a drug prod uct, usually in an aqueous medium under specifie d conditions • The dissolution test is an important quality control procedure for the drug product and is often linked to product performance in vivo. • In-vitro drug dissolution studies are most often us ed for monitoring drug product stability and manu facturing process • Drug dissolution is important test used to evaluate drug release of solid and semisolid dosage forms. This test also quantifies the amount and extent of drug release from dosage forms.
• 4.
  • The valuesthat are obtained from the dissolution study can be quantitatively analyzed by using different mathematical formulae, Because qualitative and quantitative changes in a formulation may alter release of drug and in vivo performance • Thus mathematical models can be developed. This development requires the comprehension of all phenomena affecting drug release kinetics and this has a very important value in the formulation optimization. • Once a suitable function has been selected, the dissolution profiles are evaluated depending on the derived model parameters.
• 5.
  IMPORTANCE OF DISSOLUTION TESTING •As reliable predictor of in vivo dissolution performance of drug. • A rate limiting factor in determining the physiological availability of drug. • As quatity control tool for monitoring the uniformity and reproducibility of production batches. • As research tool in optimizing parameter and ingredients in new drug formulation. • It is widely accepted in animal experimentation.
• 6.
  WHY DISSOLUTION TESTING •Results from in-vitro dissolution rate experiments can be used to explain the observed differences in in-vivo availability. • Dissolution testing provides the means to evaluate critical parameters such as adequate bioavailability and provides information necessary to formulator in development of more efficacious and therapeutically optimal dosageforms. • Most sensitive and reliable predictors of in-vivo availability. • Dissolution analysis of pharmaceutical dosage forms has emerged as single most important test that will ensure quality of product.
• 7.
  • It canensure bioavailability of product between batches that meet dissolution criteria. • Ensure batch-to-batch quality equivalence both in-vitro and in-vivo, but also to screen formulations during product development to arrive at optimally effective products. • Physicochemical properties of model can be understood needed to mimic in-vivo environment. • Such models can be used to screen potential drug and their associated formulations for dissolution and absorption characteristics. • Serve as quality control procedures, once the form of drug and its formulation have been finalized
• 8.
  FACTORS FOR DESINGINGTHE DISSOLUTION TEST 1. FACTORS RELATING TO THE DISSOLUTION APPARATUS • the design • size of the container • shape of the container • nature of agitation • speed of agitation • performance precision of the apparatus 1. FACTORS RELATING TO THE DISSOLUTION FLUID • composition • viscosity • volume • temperature • maintainance of sink and non-sink condition 1. PROCESS PARAMETERS • introduction of dosage form • sampling technique 1. changing the dissolution fluid
• 9.
  IDEAL FEATURES OFA DISSOLUTION APPARATUS • simple in design, easy to operate and unstable under a variety of conditions. • provides an easy way of introducting the dosage form into the dissolution medium and once immersed, holding it in a regular and reliable fashion. • eliminates evaporation of the dissolution media and maintains it at a fixed temperature within a specific narrow range. (apparatus thermostatically controlled at 37˚C). • sensitive enough to reveal process changes and formulation differences but still yield repeatable results under identical condition.
• 10.
  COMMON DISSOLUTION MEDIA •purified water • diluted acid(0.1N Hcl) • buffered aqueous solution • simulated gastric fluid(with or without enzyme) • simulated intestinal fluid(with or without enzyme)
• 11.
  FACTORS AFFECTING SELECTIONOF DISSOLUTION MEDIA • DISSOLVED GASES - these sholud be removed prior dissolution testing dissolved gas can alter the ph of media distilled water ph : 6 deaerated water ph : 7.2 • COMPOSITION OF DISSOLUTION MEDIA - enzymes, surfactant etc ENZYMES : pancreatin, pepsin are added for degradation of gelatin which otherwise develop cross-links and with aging becomes insoluble in media slowing down the dissolution rate SURFACTANT NATURAL SURFACTANT : bile salt, phospholipids INTESTINAL SURFACTANT :fatty acid, monoglycerides.
• 12.
  • PH OFDISSOLUTION MEDIA ph of dissolution media should be greater than pka of drug for complete dissolution of drug. • VISCOSITY OF DISSOLUTION MEDIA dissolution rate decreases with increase in viscosity of dissolution media. • SURFACTANT the surfactant are added into dissolution media for improving the wetting characteristics of the drug Eg : tween80 • TEMPERATURE 37˚C for all dosage form except transdermal which is 32˚C
• 13.
  TYPES OF DISSOLUTIONAPPARATUS 1. CLOSED COMPARTMENT APPARATUS USP TYPE-I basket type USP TYPE-II paddle type 1. OPEN COMPARTMENT APPARATUS(continous flow through) USP TYPE-III reciprocating cylinder USP TYPE-IV flow through cell USP TYPE-V paddle over disk USP TYPE-VI rotating cylinder USP TYPE-VII reciprocating holder 3. DIALYSIS SYSTEM official or compendial methods
• 14.
  DISSOLUTION METHODS TWO METHOD •OFFICIAL METHODS  Rotating basket method  Paddle method   Flow-through method   Reciprocating cylinder method   Paddle over disk method   Rotating cylinder method   Reciprocating disk method • NON-OFFICIAL METHODS.  rotating static disk method  beaker method  flask stirrer method  peristalsis method  rotating bottle method  dialysis method  diffusion cell
• 16.
   Advantages • FullpH change during the test • Can be easily automated which is important for routine investigations.  Disadvantages • Basket screen is clogged with gummy particles. • Hydrodynamic „dead zone“ under the basket • Degassing is particularly important • Mesh gets corroded by HCl solution
• 18.
  Advantages • Easy touse • Robust • pH change possible • Can be easily automated which is important for routine investigations  Disadvantages • pH/media change is often difficult • Hydrodynamics are complex, they vary with site of the dosage form in the vessel (sticking,floating) and therefore may significantly affect drug dissolution • Sinkers for floating dosage forms
• 20.
  Advantages • Easy tochange the pH • pH-profiles • Hydrodynamics can be directly influenced by varying the dip rate Disadvantages • Small volume (max. 250 ml) • Little experience • Limited data
• 22.
  Advantages • easy tochange media pH • pH-profile possible • Sink conditions maintained. • different modes a) open system b) closed system Disadvantages • Deaeration necessary • high volumes of media • labor intensive
• 24.
  Advantages: • Easy tohandle • Sink conditions are maintained. • Membrane effect is minimum. i.e. drug is placed on a disc at the bottom. Disadvantages: • Disk assembly restricts the patch size • Borosilicate glass • 17 mesh is standard(others available) • Accommodates patches up to 90mm.
• 26.
  Advantages: • Equipment (apparatus1)available with the manufacturers can be used with modification as apparatus 6 Disadvantages: • Large volume of medium is required. • Drug gets diluted & causes difficulties in analysis • Difficult to clean the cylinder.
• 28.
  Advantages: • Convenient methodfor selecting the volume of the medium. • sink conditions can be maintained. -more sensitivity  Disadvantages: • Investment is high because the design is totally different from standard equipment already available in industry.
• 29.
  UNOFFICIAL METHOD 1.ROTATING/STATIC DISKMETHOD • Developed by late Eino nelson and described by Levy and Sahli. • In this method ,the drug is compressed in a non- disintegrating disc without excipients. • The disc is mounted in a holder so that only one face of the disc is exposed to the dissolution medium. • The holder and disc are immersed in medium and held in a fixed position as in static disc method and rotated at a given speed in rotating disc method. • Samples are collected at predetermined times. • Surface area of the drug through which dissolution occurs is kept constant –intrinsic dissolution rate
• 30.
  2.BEAKER METHOD: • Reportedby Levy and Hayes(1960). • Dissolution medium, 250ml of 0.1N HCl at 37°C placed in a 400ml beaker. • Agitation by three blade polyethylene stirrer,5cm diameter and rotates at 60 rpm. • Stirrer immersed to a depth of 2.7 cm in medium and in the center. • Tablets are placed in a beaker and test was carried out. • Samples are removed and assayed for the content. 3.FLASK STIRRER METHOD • Developed by Poole(1969).It includes RBF and a stirring element similar to that of beaker method. • RBF used to avoid the formation of moulds of particles in different positions on the flat bottom of a beaker.
• 31.
  4.PERISTALSIS METHOD: • Tostimulate hydrodynamic condition of GIT tract in an in- vitro dissolution device. • It consists of rigid plastic cylindrical tubing fitted with septum and rubber stopper at both ends. • Dissolution chamber consists of a space between septum and lower stopper. • Dissolution medium is pumped with peristaltic action through the dosage form. 5.ROTATING BOTTLE METHOD: • It consists of rotating rack to hold sample drug products in bottles and they are capped tightly & rotated in 37°C temperature bath. • Sample are decanted through a 40 mesh screen and residue are assayed.
• 32.
  6.DIALYSIS METHOD: • Cellconsist of 32mm inflated membrane. • Plugged at the lower end by tight fitting cylindrical perspex box. • Upper end of the tube held by thin perspex ring inserted into the tube and secured by an elastic band. • The cell suspended , from the arm of the tablet disintegration apparatus and containing the dosage form in 150ml of distilled water at 37°C. 7.DIFFUSION CELL : • Static or flow through diffusion cells are used to characterize invitro drug release and drug permeation kinetics from a topical drug product eg: Ointment, cream or transdermal drug product. • The Franz diffusion cell is static diffusion system used to characterize drug permeation through skin model. • The skin is mounted on the Franz diffusion cell and the drug product is placed on the skin surface.
• 33.
  CONCLUSION • By studyingvarious factors influencing the rate of dissolution, we can optimize the different properties of the formulation. • By conducting dissolution studies we can know the batch to batch reproducibility. • We can estimate the solubilty profiles of the drug. • The best available tool today which can atleast quantitatively assure about the biological availability of drug from its formulation is its invitro dissolution.
• 34.
  REFERENCE • Aulton M.E.Pharmaceutics “The Science of Dosage Form Design”, 2nd Ed.; Churchill Livingstone. • D.M.Brahmankar “Biopharmaceutics and Pharmacokinetics a Treatise” • Venkateshwarlu “Biopharmaceutics and Pharmaceutics”, 2nd Ed. • Leon Shargel “Applied Biopharmaceutics and Pharmacokinetics”,5th Edition. • The Science And Practice of Pharmacy by REMINGTON , 21 st Edition • C.V.S.Subrahmanyam “Biopharmaceutics and pharmacokinetics”, -concepts and applications.