Pharmaceutical Technology III PPT 539: Pharmaceutical Quality Control PDF

Pharmaceutical Technology III PPT 539 Pharmaceutical Quality Control Dr. Rawan Bafail Dr. Marey Almaghrabi Dr. Amani Abdelaziz 1446 /...

Pharmaceutical Technology III PPT 539 Pharmaceutical Quality Control Dr. Rawan Bafail Dr. Marey Almaghrabi Dr. Amani Abdelaziz 1446 / 2024  Course Objectives 1. Explain various methods used for the quality control of raw materials, in- process materials and different pharmaceutical dosage forms. 2. Identify different pharmacopeial standards and limits of official quality control tests. 3. Correlate the data obtained from different quality control tests with pharmacopeial standards. 2 Content Quality Control of Solid Dosage Suppositories Liquid Parenteral Aerosols form Dosage form Products Dosage form 3 Steps of Manufacturing Any Dosage Form 1 Raw Materials 2 Manufacturing 3 Packing 4 Final Products Serious Error can occur at any time from the receipt of raw materials, through the different steps of manufacturing and packaging to the final acceptance of a product. 4 Quality control can be defined as the day-to- day control of: 1 Quality of Raw Materials including the acceptance or rejection of the incoming raw materials (active ingredients and additives). 2 In-process Test inspections during the different manufacturing processes. 3 Quality of Final Product including the acceptance or rejection of completed dosage forms. 5 Physical Properties of Powder 6 Physical Properties of Powder Powder Density 01 Powder flow properties 02 03 Particle size 04 Loss on drying 7 1. Powder Density Definition: üThe average spatial distribution of mass in a material. üThe density of solids is typically expressed in g per cm3. m r = V 8  Powder Density High Density Low Density 9 Powder Density Density of a solid particle can assume different values depending on the method used to measure the volume of the particle : 1. True Density 2. Pycnometric Density 3. Granular Density 10  1. Powder True Density Definition Properties Is the average mass per It is a property of a unit volume, exclusive of particular material, and all voids that are not a hence should be fundamental part of the independent of the molecular packing method of determination. arrangement. Determination The true density of a perfect crystal can be determined from the size and composition of the unit cell. 11  2. Powder Pycnometric Density Definition Measuring Is a convenient density Gas pycnometer, the volume measurement for occupied by a known mass of pharmaceutical powders. powder is determined by measuring the volume of gas displaced by the powder. The measure of the mass and volume is the pycnometric density. 12 Powder Density Pycnometric True Density = Density Unless the material contains impenetrable voids, or sealed pores, that are inaccessible to the gas used in the pycnometer. 13  3. Powder Granular Density Definition Measuring The granular density Mercury porosimetry, where the includes contributions to limiting pore size depends upon particle volume from open the maximum intrusion pores smaller than some pressure. limiting size. The size limit depends on the method of measurement. m r = Because of the additional contribution from pore volume, V the granular density will never be greater than the true density. 14 Powder Density The pycnometric density and the true density are both referred to as density. True Density Density Pycnometric Density 15 Powder Density The density of a material depends on the molecular packing. Solid It will vary with the crystal structure and degree of crystallinity. The density will depend only Liquid on temperature and and Gas pressure. 16 Powder Density If the solids are amorphous, the density may further depend upon the history of preparation and treatment. Therefore, unlike fluids, the densities of two chemically equivalent solids may be different, and this difference reflects a difference in solid- state structure. 17 Bulk and Tapped Density 02 03 04 18  Bulk Density ü The bulk density often is the bulk density of the powder “as poured” or as passively filled into a measuring vessel. ü It is often very 02difficult to measure 03 since the 04 slightest disturbance of the bed may result in a new bulk density. ü The bulk density of a powder includes the contribution of inter-particulate void volume. 19 Bulk Density 02 Envelope 03 Envelope 04 Volume Apparent Volume True Volume 20  Bulk Density ü Bulk density depends on both: 1. Density of powder particles. 2. Packing of powder particles. ü Bulking properties 02 of a powder 03 are dependent 04 on the “history” of the powder (e.g., how it was handled), and that it can be packed to have a range of bulk densities. ü Thus, it is essential in reporting bulk density to specify how the determination was made. 21 Tapped Density ü Tapped density is a limiting density attained after “tapping down” usually in a device that lifts and drops a volumetric measuring cylinder containing the powder at fixed distance. 02 03 04 22 Bulk and Tapped Density 02 03 04 Bulk Density Tapped Density 23  Bulk and Tapped Density ü Because the inter-particulate interactions that influence the bulking properties of a powder are also the interactions that interfere with powder flow à a comparison of the bulk and tapped densities can give a measure of 02 the relative 03importance of04 these interactions in a given powder. ü Such a comparison is often used as an index of the ability of the powder to flow. 24  Powder Compressibility ü The Compressibility Index and Hausner Ratio are measures of the propensity of a powder to be compressed. ü As such, they are measures of the relative importance of inter- particulate interactions. ü Compressibility is indirectly related to the relative flow rate, and particle size of a powder. ü A compressible material will be less flowable, & powders with compressibility values greater than 20-21% have been found to exhibit poor flow properties. 25  Powder Compressibility 01 Calculation Compressibility Index æ V 0 - Vf ö Compressibility Index = 100 ´ ç ÷ 02 03 è V 0 04ø Hausner Ratio V0 Hausner Ratio = Vf V0 = Bulk volume Vf = Tapped volume 26 Powder Compressibility Free-flowing Powder 01 Such interactions are Poorer flowing generally less significant, Powder and the bulk and tapped 02 densities will be closer in value. There are frequently greater interparticle interactions, and a greater difference between the bulk and tapped densities will be observed. These differences are reflected in the Compressibility Index and the Hausner Ratio 27 Applications of Density Density measurements have been correlated to several physical properties: A The crystallinity and purity of powders have been investigated using density measurements. B Particle shape has been shown to influence bulk and tap densities. 28  Applications of Density ü Several controlled release applications have used density to estimate the porosity of materials such as microcapsules and microsponges. ü Density was used to calculate the wall thickness of the microcapsules, and it was found that the decreased porosity could be correlated to a greater wall thickness. ü Investigations of hollow microspheres for use as a floating controlled drug delivery system in the stomach also extensively employed density measurements for porosity and wall thickness calculations. 29 Applications of Density The study showed that the floatability of the hollow microspheres was dependent on the bulk density. The larger-diameter spheres result in a lower density and better floating behavior. Tap density of the material was used to investigate the packing properties of the microspheres in gelatin capsules. 30 Applications of Density For prolonged release microsponges , the internal porosity was found to be easily controlled by changing the concentration of the drug and the polymer. The porous internal structure resulted in stronger tablets and was correlated to the drug release rate for the materials. Porosity calculations from density measurements have also been applied to granulations prepared using different processes. 31 Applications of Density 32 Applications of Density The method of granulation, such as the type of adjuvant used or the amount of granulation liquid, was found to change the bulk density and porosity of the material. Consequently, the compression and flow properties of the materials were also different. 33 Applications of Density During the granulation of micronized active drugs à the granules with the highest bulk density resulted in the best flow rate. In a study on the lubrication properties of magnesium stearate, it was concluded that à low bulk densities of the granules resulted in poor flow properties, which impeded the formation of a lubricant film during mixing. 34