PharmChem 5 - PREBOARD REVIEW (Part 3 of 3) Compressed_compressed.pdf

Pharmaceutical Analysis 2 (INSTRUMENTATION METHOD OF ANALYSIS) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY...

Pharmaceutical Analysis 2 (INSTRUMENTATION METHOD OF ANALYSIS) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PART 1 PART 2 PART 3 Documents, Guidelines, Chromatography Spectroscopy Standards & Specifications UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PART 3 Documents, Guidelines, Standards & Specifications UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 1. What document contains a compiled step- by-step instructions to help workers carry out routine operations? A. SOP B. MSDS C. COA D. Monograph E. A&C UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 2. What document outlines a chemical's properties, including physical and chemical characteristics, as well as health, safety, fire, and environmental hazards? A. SOP B. MSDS C. COA D. Monograph UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 3. Temperature maintained for Disintegration Testing of tablets A. 37 ± 2 °C B. 37 ± 0.2 °C C. 37 ± 5 °C D. 37 ± 0.5 °C E. 35 ± 5 °C UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 4. The measure of the force required to break a tablet in a test apparatus that places the tablet under a tension or bending load. A. Hardness B. Friability C. Appearance D. Brittleness UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 5. A thin, water insoluble clear membrane of cross-linked protein on the inner or outer surface of the capsule that prevents the capsule fill from being released. A. Score B. Preservative C. Palpable core D. Pellicle UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez answers 1. What document contains a compiled step- by-step instructions to help workers carry out routine operations? A. SOP B. MSDS C. COA D. Monograph E. A&C UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 2. What document outlines a chemical's properties, including physical and chemical characteristics, as well as health, safety, fire, and environmental hazards? A. SOP B. MSDS C. COA D. Monograph UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 3. Temperature maintained for Disintegration Testing of tablets A. 37 ± 2 °C B. 37 ± 0.2 °C C. 37 ± 5 °C D. 37 ± 0.5 °C E. 35 ± 5 °C UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 4. The measure of the force required to break a tablet in a test apparatus that places the tablet under a tension or bending load. A. Hardness B. Friability C. Appearance D. Brittleness UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez 5A thin, water insoluble clear membrane of cross-linked protein on the inner or outer surface of the capsule that prevents the capsule fill from being released. A. Score B. Preservative C. Palpable core D. Pellicle UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DOCUMENTS IN QC MONOGRAPH It is a written document, or standard, that describes an item. USP-NF composed of 2 compendia: United States Pharmacopeia & National Formulary contains standards for medicines, dosage forms, drug substances, excipients, biologics, compounded preparations, medical devices, dietary supplements, and other therapeutics. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DOCUMENTS IN QC STANDARD OPERATING PROCEDURE It is a set of written instructions that documents a repetitive activity followed by an organization CERTIFICATE OF ANALYSIS It is a document issued by Quality Assurance that confirms that a regulated product meets its product specification. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DOCUMENTS IN QC MATERIAL SAFETY DATA SHEET It is a document that gives detailed information about the nature of a chemical, such as physical and chemical properties, health, safety, fire, and environmental hazards of a chemical product. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DRUG SPECIFICATION SPECIFICATION critical quality standards that are proposed and justified by the manufacturer and approved by the regulatory authorities as conditions of approval. It establishes the set of criteria to which a drug substance, drug product or materials at other stages of its manufacture should conform to be considered acceptable for its intended use. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING DRUG STABILITY the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, toxicological, protective and informational specifications UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING TYPES OF STABILITY TESTING PROCEDURES 1 LONG TERM STABILITY TESTING the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, toxicological, protective and informational specifications data is collected at an appropriate frequency such that a trend analysis is able to distinguish instability from day-to- day ambiguity STABILITY TEST CHAMBER UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING TYPES OF STABILITY TESTING PROCEDURES 2 ACCELERATED STABILITY TESTING product is stressed at several high (warmer than ambient) temperatures and the amount of heat input required to cause product failure is determined. done to subject the product to a condition that accelerates degradation, and is then projected to predict shelf life or used to compare the relative stability of alternative formulations. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING TYPES OF STABILITY TESTING PROCEDURES 2 ACCELERATED STABILITY TESTING The concept of accelerated stability testing is based upon the Arrhenius equation (1) and modified Arrhenius equation (2). UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING TYPES OF STABILITY TESTING PROCEDURES 3 RETAINED SAMPLE STABILITY TESTING usual practice for every marketed product for which stability data are required where stability samples, for retained storage for at least one batch a year are selected. more realistic since it challenges the product not just in the idealized retained sample storage conditions, but also in the actual marketplace UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING TYPES OF STABILITY TESTING PROCEDURES 4 CYCLIC TEMPERATURE STRESS TESTING not a routine testing method for marketed products designed on knowledge of the product so as to mimic likely conditions in market place storage period of cycle: 24 hours UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING CLIMATIC ZONES FOR STABILITY TESTING PHILIPPINES Zone IVB UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING EXPIRATION DATE/ SHELF LIFE An expiration date is the time up to which the product will remain stable when stored under recommended storage conditions. It is the date beyond which it is predicted that the product may no longer retain fitness for use. Shelf life is the time during which the product, if stored appropriately as per the manufacturer’s instructions, will retain fitness for use (>90% of label claim of potency) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez STABILITY TESTING STABILITY TEST EQUIPMENT The equipment used for stability testing is called stability chamber. These are specialized environmental chambers that can simulate the storage condition and enable evaluation of product stability based on real-time, accelerated and long-term protocols. They are available in both walk-in and reach-in styles. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: TABLETS Method 1 TITRIMETRIC It measures the Method 2 extent and rate of AZEOTROPIC solution formation from a dosage form, Method 3 such as tablet, GRAVIMETRIC capsule, ointment, etc. WATER It is important for its bioavailability and CONTENT therapeutic effectiveness. DISSOLUTION UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: TABLETS It is performed to measure their It is the measure of physical strength the force required to to ensure their break a tablet in a durability during test apparatus that transit. places the tablet under a tension or bending load. FRIABILITY HARDNESS ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: CAPSULES HARD GELATIN Brittleness refers to the property of breaking without DISSOLUTION much permanent distortion. Resistance to the applied force is made known. WATER CONTENT APPEARANCE + brittleness UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: CAPSULES HARD GELATIN Membrane Filtration Plate-count methods Pour-plate - the liquid sample is poured into the petri dish before the solidification of the agar medium. Then, colonies grow both inside and on the surface of the medium. MICROBIAL Surface spread - spreading a certain volume of the LIMITS sample over an appropriate solidified culture media. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: CAPSULES HARD GELATIN UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: CAPSULES SOFT GELATIN Leakage Test works on the principle DISSOLUTION of creating a negative pressure in a closed chamber which inflates dosage form due to pressure. Those who have leakage don’t inflate. LEAKAGE MICROBIAL LIMITS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: CAPSULES SOFT GELATIN A pellicle is a thin, water insoluble clear membrane of cross-linked protein on the inner or outer surface of the capsule that prevents the pH defined as the capsule fill from being value given by a released. suitable, properly calibrated, Cross-linking may result in the potentiometric formation of a pellicle on the sensor and internal or external surface of measuring the gelatin capsule shell. system. PELLICLE FORMATION pH UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: EMULSIONS pH Viscosity is the property of liquids that is closely related to the resistance to flow. VISCOSITY PRESERVATIVE CONTENT MICROBIAL LIMITS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: EMULSIONS (for lipid injectable emulsions) The size of the lipid droplets is critical: because of mechanical filtration, larger-size fat globules (>5 µm) can be trapped in the lungs. In particular, the amounts of fat globules comprising the large-diameter tail of the globule size distribution are especially important with respect to infusion safety. MEAN SIZE & DISTRIBUTION OF GLOBULES UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: ORAL SOLUTIONS & SUSPENSIONS Clarity of solution is the absence of any particles or in homogeneities in a solution results in a clear solution. A liquid is considered clear MEAN SIZE & VISCOSITY if its clarity is the same as DISTRIB OF that of water R or of the PARTICLES solvent used, or if its opalescence is not more pronounced than that of reference suspension. pH APPEARANCE + ppt formation, clarity of soln MICROBIAL LIMITS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: ORAL SOLUTIONS & SUSPENSIONS *ADDITIONAL FOR SUSPENSIONS Particles can be redispersed after settling or Rheology is the branch of physics that aggregation by studies how materials deform or flow in motion relative to the response to applied forces or stresses. fluid, which can be caused by oscillation The properties of materials that govern of the container or by the specific way in which these a rotating or deformation or flow behaviors occur oscillating stirrer are called rheological properties. within. REDISPERSIBILITY RHEOLOGICAL PROPERTIES UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez ASEAN GUIDELINES (DRUG STABILITY) TESTING PARAMETERS: ORAL POWDER FOR RECONSTITUTION RECONSTITUTION TIME WATER CONTENT Reconstitution is the process of adding a liquid diluent to a dry ingredient to make a specific concentration of liquid. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DISINTREGRATION & DISSOLUTION TESTING DISINTEGRATION TESTING The state in which any residue of the unit, except fragments of insoluble coating or capsule shell, remaining on the screen of the test apparatus is a soft mass having no palpably firm core. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DISINTREGRATION & DISSOLUTION TESTING DISSOLUTION TESTING Dissolution Dissolution is a process in which a solid substance solubilizes in a given solvent Dissolution Rate The amount of solute dissolved in a given solvent under standard conditions of temperature, pH, solvent composition and constant solid surface area. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DISINTREGRATION & DISSOLUTION TESTING DISSOLUTION TESTING FACTORS AFFECTING DRUG DISSOLUTION Drug substance Medium Particle size Volume & Concentration Polymorph pH & temperature Surface area Co-solvents Chemical stability in dissolution media Hydrodynamics Agitation rate Formulation of Drug Product Shape of dissolution vessel Excipients Placement of tablet in vessel Sinkers UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez DISINTREGRATION & DISSOLUTION TESTING DISSOLUTION TESTING USP APPARATUS (Dissolution Test) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  STAGES IN QC: RMQC RAW MATERIALS QUALITY CONTROL UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez IDENTIFICATION TESTS PURITY TESTS LIMIT TESTS PHYSICAL TESTS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  IDENTIFICATION TESTS Chemical Method It is the use of chemicals to confirm the identity of the sample. It is the confirmation of a complete reaction (precipitation, change in color, evolution of gas). UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  IDENTIFICATION TESTS Name of test For Reagent Positive Result Ninhydrin Test Free amino acids Ninhydrin Violet Biuret Test Peptide bonds Cupric sulfate in NaOH Violet Hopkin’s Cole Indole (AA: Trp) Glyoxylic acid in H2SO4 Violet ring Molisch Test Carbohydrates 10% alpha-naphthol in EtOH Violet ring Benedict’s Test Reducing sugars Cupric ions (acidic medium) Brick red Barfoed’s Reducing sugars Cupric ions (alk. medium) Brick red Wagner’s Test Alkaloids Iodine in KI Reddish brown Seliwanoff’s Test Ketoses Resorcinol in HCl Cherry red Dragendorff’s Test Alkaloids Potassium bismuth iodide Orange ppt UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  IDENTIFICATION TESTS TLC Analysis evaluates the composition of a sample, and the identity of a given compound. It works by chromatographic principles: a mobile phase (solvent or solvent mixtures) will climb up the plate material (stationary phase). SPRAY REAGENTS: allow visualization of the colorless components on a TLC plate; shows selectivity for a specific functional group or compound type. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez IDENTIFICATION TESTS Instrumental Method It is the use of calibrated instruments to confirm the identity of the sample. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  IDENTIFICATION TESTS HPLC Analysis HPLC separates compounds dissolved in a liquid sample and allows qualitative and quantitative analysis of what components and how much of each component are contained in the sample. HPLC Instrument UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  IDENTIFICATION TESTS UV-Vis Analysis It is an analytical technique that measures the amount of discrete wavelengths of UV or visible light that are absorbed by or transmitted through a sample in comparison to a reference or blank sample. UV-Vis Spectrometer UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez PURITY TESTS Assay: Titration Method It is the addition of a solution of known concentration to a solution of unknown concentration until equivalent amounts of both solutions have reacted, which is often indicated by a color change. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez PURITY TESTS N x ml x mEq wt %P = x 100 g (sample) (ml x N) - (ml x N) x mEq wt %P = x 100 g (sample) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PURITY TESTS Assay: Instrumental Method It is a method of determination that uses calibrated instruments to determine the purity of the sample. It can be spectral, electroanalytical, and separatory. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIMIT TESTS IMPURITIES They are critical quality attributes of drug substances and drug products because they have the potential to affect safety and efficacy of the product. LIMIT TEST It is a quantitative (or semi-quantitative) test designed to control small quantities of impurities which are likely to be present in a pharmaceutical substance. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIMIT TESTS Gross Impurity This includes insoluble matter and allowable dirt. Measures the number of particulate matter present in the sample, and often uses the ff tests: Light Obscuration Particle Count Test & Microscopic Particle Count Test UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIMIT TESTS What is Light Obscuration Particle Count Test? It uses a liquid particle counter machine that is based on the principle of light scattering; preferably used when examining injections and parenteral infusions for sub-visible particles. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIMIT TESTS What is Microscopic Particle Count Test? It uses a binocular microscope, a filter assembly for retaining particulate matter, & a membrane filter for sample examination. 2 Illuminators used: episcopic brightfield illuminator (internal) focusable auxiliary illuminator (external) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIMIT TESTS What is Microscopic Particle Count Test? It is preferably used for preparations having reduced clarity or increased viscosity (example: Emulsions, colloids, and liposomal preparations). UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez LIMIT TESTS Biological Impurity It results from living matter (like bacteria and fungi), endotoxins, and their by-products. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIMIT TESTS Endotoxin & Pyrogen Tests ENDOTOXINS come from the cell walls of gram-negative bacteria are molecules with fat (also known as lipid) and complex sugar components (also known as polysaccharides) considered pyrogens because they trigger the innate immune system & produce fever when released in the human body. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIMIT TESTS Endotoxin & Pyrogen Tests PYROGENS are molecules or substances that cause a feverous reaction when they enter the human body. Endogenous pyrogens are found naturally within the human body & trigger fever when naturally produced by the body. Exogenous pyrogens are molecules found outside of the body. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez LIMIT TESTS Chemical Impurity It is the presence of unwanted chemicals in a sample. It may include the following to name a few: chlorides, sulfates, Ca, Na. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PHYSICAL TESTS Specific Gravity It is the ratio of the density of any substance to the density of some other substance taken as a standard. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PHYSICAL TESTS pycnometer Mohr-westphal balance is traditionally a glass flask with a close-fitting a balance with unequal ground glass stopper arm length used to with a capillary tube measure the specific (fine hole) through it, so gravity (or density) of that a given volume can liquids, based on be accurately obtained. Archimedians principle. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PHYSICAL TESTS Solubility Tests These are tests performed to determine the ability of compounds to dissolve in a solvent, which is usually a liquid. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PHYSICAL TESTS Refractive Index It is a measure by how much the speed of light is reduced when it travels within specific solvents; measured using a refractometer. _s_i n = sin r_ n _ i _ UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PHYSICAL TESTS Optical Activity It is the ability of a substance to rotate the plane of polarization of a beam of light that is passed through it; measured by a polarimeter. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PHYSICAL TESTS POLARIMETRY TERMINOLOGIES OPTICAL ROTATION is the angle through which the plane of polarization is rotated when polarized light passes through a layer of a liquid. SPECIFIC ROTATION is a material constant. It is the optical rotation for a given number of optically active molecules in the light’s way through the sample. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  STAGES IN QC: IPQC IN-PROCESS QUALITY CONTROL UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez GRANULES & POWDERS TABLETS CAPSULES PARENTERALS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Uniformity of Mixtures The sample should contain 98 - 102% of the API (depending on the requirement in the USP-NF). Methods: 1. Coning and Quartering (1) 2. Thief Sampling 3. % Purity Determination (2) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Primary Moisture Content It counts for the moisture due to the starch which is used as binder. Acceptable limit: 31 - 35% Methods: 1. Karl Fischer Moisture Determination 2. Titration Karl Fischer Moisture Analyzer UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Moisture Content It refers to the weight of the water contained in a certain object or material. Acceptable limit: NLT 0.5% to NMT 1% Methods: 1. Gravimetric Method Ohaus Moisture Analyzer 2. Ohaus Moisture Analyzer UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez GRANULES & POWDERS Moisture Content Capping Chipping Lamination UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Particle Size Distribution It defines the relative amount (typically by mass) of particles present according to size; the sample should weigh about 25 grams Method: 1. Sieving/Sieve Analysis Sieve UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Angle of Repose It is the angle between the free surface of the powder body and the horizontal plane. It describes powder flowability. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Angle of Repose When the sample is smooth or rounded, the angle of repose is low. If the sample is very fine or is comprised of sticky materials, the angle of repose is high. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Bulk & Tapped Density Powder flowability can also be estimated from the bulk density of the powder using a tapped density measuring device. tapped density measuring device UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Bulk & Tapped Density The BULK DENSITY of a powder is the ratio of the mass of an untapped powder sample and its volume including the contribution of the interparticulate void volume. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Bulk & Tapped Density The TAPPED DENSITY is an increased bulk density attained after mechanically tapping a container containing the powder sample; is obtained by mechanically tapping a graduated cylinder containing the sample. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Compressibility Index & Hausner Ratio The Carr Compressibility Index and Hausner Ratio are 2 measures which can be used to predict the propensity of a given powder sample to be compressed. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GRANULES & POWDERS Compressibility Index & Hausner Ratio For free-flowing powders, interactions are less significant because tapped & bulk densities will be closer in value. For poorer flowing materials, a greater difference between bulk & tapped densities will be observed. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  TABLETS Tablet Hardness Stokes Monsanto Hardness Tester Tablet hardness (a.k.a. crushing strength) is the pressure force required to break a Strong Cobb tablet in a diametric compression test. Hardness Tester Hardness test in important to evaluate the tablet’s ability to withstand the shock of handling, packaging and shipping. Pfizer Hardness UNIVERSITY OF SAN AGUSTIN CPMT | DEPARTMENT OF PHARMACY PHARMACEUTICAL ANALYSIS 2 Prepared by MNG Nuñez Tester TABLETS Tablet Hardness If the tablet is too hard, it may not not meet dissolution specification. If the tablet is too soft, it will not withstand handling during subsequent processing, UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  TABLETS Tablet Thickness Tablet thickness can vary with no change in weight, due to the density of granulation & pressure Micrometer caliper applied to the tablets. Acceptable condition: Vernier caliper < or = to 5% Tablet Thickness tester UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  TABLETS Uniformity of Weight It is performed by individually weighing 20 tablets that are randomly selected from a tablet batch, and determining their individual weights. Coated tablets are exempted from this requirement, but must conform to content uniformity test. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  TABLETS Tablet Friability The friabilator is designed to evaluate the ability of the tablet to withstand abrasion in packaging, handling and shipping, Friabilator Tablets are weighed, placed inside the friabiliator. After a number of rotations, tablets are weighed, and % weight loss is determined. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  TABLETS Tablet Friability W1 - W2 Acceptable Criteria: % LOSS = x 100 NMT 1% weight loss; W1 NMT 0.8% weight loss for Where: new formulation W1 - weight before tumbling W2 - weight after tumbling UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez CAPSULES (& TABLETS) Disintegration Test Dissolution Test UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PARENTERALS Pyrogen Test Pyrogens are fever-inducing substances. Testing for pyrogens is a requirement for all parenteral products, including injectable vaccines, TEST: 1. Rabbit Pyrogen Test (RPT) UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez PARENTERALS Rabbit Pyrogen Test (RPT) It measures the raise in body temperature after injection of a drug. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PARENTERALS Endotoxin Test It can detect and quantify the endotoxins from gram-negative bacterial origin using amebocyte lysate from horseshoe crab (Limulus polyphemus). TEST: Horsehoe crab 1. LAL Test UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez PARENTERALS Limulus Amebocyte Lysate Test It measures the endotoxin-initiated clotting cascade in blood amebocytes (specific for gram-negative bacteria) POSITIVE RESULT: a firm gel forms upon inversion UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  PARENTERALS Test for Particulate Matter 2 METHODS: 1. Light Obscuration Particle Count Test 2. Membrane Filtration Particle Count Test UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  STAGES IN QUALITY CONTROL: FPQC & PMQC FINISHED PRODUCT QUALITY CONTROL PACKAGING MATERIAL QUALITY CONTROL UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez FPQC NON STERILE PRODUCTS LIQUID DOSAGE FORMS MICROBIAL ASSAY FOR ANTIBIOTICS BIOLOGICAL ASSAYS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez NON STERILE PRODUCTS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIQUID DOSAGE FORMS Dye Solubility Test for Emulsions Water-soluble dye will dissolve in the aqueous phase (methylene blue/amaranth). Oil-soluble dye will dissolve in the oil phase. O/W EMULSION W/O EMULSION UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez LIQUID DOSAGE FORMS Dilution Test for Emulsions O/W emulsion can be diluted with water. W/O emulsion can be diluted with oil. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez LIQUID DOSAGE FORMS Conductivity Test for Emulsions O/W emulsion will cause the lamp to glow. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIQUID DOSAGE FORMS Cobaltous Chloride in Filter Paper Test for Emulsions O/W emulsion will cause the Cobalt chloride filter paper to change in color from BLUE to PINK. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIQUID DOSAGE FORMS Sedimentation Volume for Suspensions Ratio of the height of sediment that settled after standard condition (Vf) and with the initial Vf height of the suspension (Vi). VS = Implications: Vi IDEAL if Vf = Vi; IDEAL if Vs = 1 NOT POSSIBLE if VF>Vi or Vs>1 UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  LIQUID DOSAGE FORMS Sedimentation Volume for Suspensions Flocculated high sedimentation rate easy redispersion of sediments Deflocculated low sedimentation rate difficult redispersion of sediments UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  MICROBIAL ASSAY FOR ANTIBIOTICS Cylinder Plate Method a.k.a. agar diffusion method or cup plate method Most widely employed method to estimate the potency and bioactive of antibiotics. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  MICROBIAL ASSAY FOR ANTIBIOTICS Turbidimetric Method turbidity = potency UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  BIOLOGICAL ASSAYS Bioassays are conducted by determining the amount of preparation of unknown potency required to produce a definite effect on suitable test animals or organs under standard conditions. UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  BIOLOGICAL ASSAYS TEST SUBJECTS: Intact animals Animal preparations Isolated living tissues and cells Microorganisms UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez BIOLOGICAL ASSAYS UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez PMQC GLASS CONTAINERS POWDERED GLASS TEST WATER ATTACK TEST UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GLASS CONTAINERS Glass is the very common packaging material used in pharmaceutical products. Its basic structural network is made of silicon oxide tetrahedron. Other migratory oxide may cause leaching. May hydrolyze to raise the pH of the solution May catalyze or enter into a reaction UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GLASS CONTAINERS 4 Types of Glass Test for each Glass Type UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GLASS CONTAINERS Powdered Glass Test Objectives: To evaluate the chemical resistance of glass formulations by measuring the amount of alkali released from the glass powder. Differentiate Type 1 from Type 2 Indicator: methyl red UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez  GLASS CONTAINERS Water Attack Test Objectives: To evaluate the hydrolytic stability of the container under more sever conditions. Amount of alkali released from the glass under 119 - 123 C Indicator: methyl red UNIVERSITY OF SAN AGUSTIN PHARMACEUTICAL ANALYSIS 2 CPMT | DEPARTMENT OF PHARMACY Prepared by MNG Nuñez