Powders and Granules.pdf

Powders and Granules BST 31433- Pharmaceutics-I 28/06/2024 Intended Learning Outcomes: By the end of this lecture, you will be able to; ✓ Know the definition of pharmaceutical powders ✓ Identify bulk properties of powders ✓ Describe particle size reduction of powders...

Powders and Granules BST 31433- Pharmaceutics-I 28/06/2024 Intended Learning Outcomes: By the end of this lecture, you will be able to; ✓ Know the definition of pharmaceutical powders ✓ Identify bulk properties of powders ✓ Describe particle size reduction of powders ✓ Identify manufacturing methods of powders and granules ✓ Explain types of powder dosage form 2 Introduction to Pharmaceutical Powders Powder applications are very common in pharmaceutical industry. Majority of active pharmaceutical ingredients (APIs) in the form of powders are incorporated to the dosage forms. Not only the APIs, majority of excipients related to solid dosage forms are taken into the formulation as powders. Powder is defined as a dry, solid substance, consisting of a large number of finely divided particles and typically obtained by crushing, grinding, or comminuting. 3 Granules Granules are prepared from powdered substances, the particles which are made up of powders aggregate with the help of solvent or binder. Granules are prepared agglomerates of smaller particles. The process of preparing granules is commonly called granulation. Granulation of powders is frequently carried out during pharmaceutical manufacturing to improve the bulk properties of the starting materials. 4 Properties of Powders Particle Size Particle Density Particle Shape 5 Particle Size Particle size is a basic property of a powder, which is essential to powder technology and dosage form design. Particles with different size and size distributions exhibit different behaviors. Specific surface area Physical stability Bulk density Porosity Flowability Solubility Particle size, typically expressed as particle diameter, is essential to characterizing powders. 6 Particle size distribution Power bed is consist of number of particles, the size and shape of these particles vary greatly. Therefore, expressing particle size is difficult and generally mean diameter and particle size distribution is used for this. Mean diameter represents the average size of a collection of particles and it is more practical and representative than a single particle diameter. 7 Particle size distribution cont. Particle size distribution can be expressed as the frequency distribution. Histograms represent the particle size distribution, and the percentage of particles having a given diameter can be determined from the histogram. 8 Particle size distribution cont. Symmetrical distribution presented is a normally distributed histogram, where the particle size is distributed uniformly around a mean value. However, most pharmaceutical powder particles will not exhibit a normal distribution. Their curves are usually skewed to one side of the histogram, depending on which size range occupies a larger portion of the powder solids, the smaller particles or the larger particles. 9 Particle Density Density is a physical property of powders, is the ratio of mass to volume (mass/volume). To obtain the density of particles or powders, it is necessary to determine the volume first. For nonporous solids, the estimation of the exact volume is straight forward. However, for powders with rough surfaces, cracks, and pores, the determination of volume is extremely complicated. According to different powder volume representations, the density for particles and powder can be classified. 10 Powder Density True Density- refers to the ratio of the mass of the particle to its actual volume, excluding pore volume and the volume of the gap between particles. Bulk Density–refers to the ratio of powder bed mass to volume of that powder bed, including both the pores and gap volume. Tapped density - represents the settled or packed volume of a given mass of particles under well-defined rate and extent of agitation. Particle Density–defined as the ratio of particle mass to the particle volume, including the pores within the particle, but still excluding the gaps between particles. 11 Particle Shape US Pharmacopoeia has given various particle descriptors e.g.- Acicular (slender, needle-like particle of similar width and thickness), Columnar (long, thin particle with a width and thickness that are greater than those of the acicular particle). The shape of powder particles in pharmaceutical applications is very complex, due to the method of particle formation and the milling method used to reduce the size of the particles. Therefore, the particle shape is often irregular and surface is very rough, making it difficult to use appropriate descriptor terms to describe the shape of these irregular powder particles. Microscopic methods are often used to characterize particle shapes. 12 13 Bulk Properties of Powder ✓ Specific surface area ✓ Porosity ✓ Powder flowability ✓ Crystallization and amorphous states 14 Specific surface area Total surface area available in a powder sample is a function of both its particle size and porosity. Porosity of the particles refers to air filled solvent accessible channels inside particles. Thus, porosity contributes to the surface area of the particles without impacting particle size or shape. A higher porosity particle of the same size and shape as a lower porosity particle will have greater surface area. Surface area is commonly measured by the adsorption of an inert gas on a solid surface. It is commonly expressed as specific surface area, which is the surface area per unit weight of the powder. High-specific surface area of APIs is often desired to increase their dissolution rate 15 from the dosage forms. Porosity Porosity of powder particles refers to the ratio of the volume of the pore interior and the space between particles to the total volume of the powder. Powder porosity is affected by many factors, such as particle shape, size, and surface properties. When granules and tablets are made from fine powders, they tend to be porous, and the porosity of tablets has a great impact on the disintegration time. For tablets with higher porosity, water can penetrate the tablets, more readily resulting in a rapid disintegration. 16 Powder flowability Flowability of a powder refers to its rate of passage, mass per unit time, through an aperture of given dimensions. Powder flowability is an essential property, which has a great impact on many unit operation. Blending, Transfer, Mixing, and Compression Poor flowability of granules lead to weight variation in compressed tablets and the accuracy of hard gelatin capsule filling also directly influenced by the flow property (content uniformity and weight variation ). Particle Size, Particle Shape, Porosity, and Density are main factors affecting flowability. 17 Powder flowability cont. A typical flow test consists of passing a predetermined mass of powder through a small hopper, or funnel, with an aperture of known diameter and quantifying the time it takes for the powder to pass through the aperture with or without any agitation of the powder bed in the hopper. The angle of repose is the angle of the slope of a cone of powder, from the horizontal base, when the powder is made to fall on a horizontal surface in a uniform stream and allowed to settle undisturbed. When particle size increases, the angle of repose decreases, so the powder has better flowability. 18 Powder flowability cont. Particles with irregular shape and rough surface has poor flowability since more work must be done to overcome the frictional force. Cohesive forces between powder particles are related to water content in powder. Within a certain range, flowability decreases due to increasing cohesive forces. Once water content is further increases, gaps between particles get filled with water and produce lubrication effect and increases the flowability. 19 Affect of Lubricants and Glidants on Flowability Lubricants and glidants are powders consisting of very fine particles. When adding lubricants and glidants to a powder with rough surfaces, the fine particles of lubricants and glidants can fill the hollow parts on the powder surfaces. The surface properties are improved, and particles are separated from each other, leading to a reduction of frictional forces between particles and, thus, enhancing powder flowability. If too much lubricants and glidants are added to the powder, there are too many fine particles in the powder, and the powder flowability decreases instead. 20 Crystallization and Amorphous States of Powder A powder is either in a crystalline or an amorphous state. Crystalline powders have a well-defined and repeating, long-range order of the arrangement of molecules due to intermolecular interactions in the solid state. In a crystalline material, the arrangement of molecules with respect to each other is well defined and not random. Crystalline solids exhibit a melting point (An amorphous solid does not have a melting point). The formation of crystals contributes greatly to powder production technology. The internal packing of molecules in a substance is important to its properties. Properties of the powder will change based on the internal packing of molecules, as 21 well as the crystal habit (crystal habit is defined as the outer appearance of a crystal).  The terms used to describe the crystal habit include sphere, cube, and needle. Different crystal habits may have different surface properties, which leads to differences in powder properties, such as dissolution rate and powder flowability. Amorphous powders do not have a well-defined and repeating, long range order of the arrangement of molecules. The molecules of an amorphous solid may show intermolecular interactions, but these interactions may not repeat consistently over several molecules. Therefore, in an amorphous material, the orientation of molecules with respect to each other is largely random. 22 23 Polymorphism Polymorphism refers to crystals with different packing orders. Polymorphic forms are obtained by changing the crystallization conditions, for example, by changing to a different solvent or changing the stirring method. There are numerous examples of organic materials, including drugs and excipients that exhibit polymorphism. For a particular compound, only one form is most stable, and other polymorphic forms will, eventually, convert to the more stable form. The most stable polymorphic form has the highest melting point and lowest dissolution rate. All of the other polymorphic forms are referred to as metastable, meaning they may exist for a certain period time, varying from seconds to months, based on the storage conditions. Since metastable polymorphic forms have a relatively high dissolution rate, they might be a candidate for enhancing the bioavailability of poorly water soluble drugs. However, stabilization of the metastable form must be addressed. E.g.- Chloramphenicol palmitate, 24 Celecoxib. Solubility and Dissolution Rate of Powders Solubility and dissolution rate are extremely important properties as they greatly influence bioavailability. Dissolution is a phenomenon, where molecules or ions are transferred from solid into solution. The extent of dissolved substance is known as the solubility of the solute in the solvent. Solubility of a substance is defined as the amount of substance in the solution at a specific temperature, when equilibrium is achieved between the dissolved and non-dissolved substance. 25 Improvement of solubility and dissolution rate of powders in pharmaceutical applications ✓ Particle size reduction ✓ Increasing porosity of powders ✓ Addition of wetting agents ✓ Cosolvents ✓ Surfactants 26 Particle Size Reduction Comminution is defined as a process that breaks larger particles of solid into smaller particles of appropriate size, by application of mechanical forces. Importance of Particle Size Reduction Reduction of drug particle size, increasing surface area, improve bioavailability. To improve powder flow, mixing efficiency of different drugs and reduce segregation. Acceleration of dissolution rate of powder. 27 Comminution Cont. Mechanism of particle size reduction is by employment of external mechanical forces to decrease the cohesion forces between the powder particles leading to size reduction and surface area enhancement. Hence particle size reduction process involves transfer of mechanical energy to surface energy. Comminution consists of a variety of operations, such as cutting, chopping, crushing, grinding, and milling, and is dependent on the type of equipment used. Different methods of comminution are dry comminution, wet comminution, and comminution at low temperature. 28 Comminution Equipment Coarse crushers -feed materials ranging from 1.5 to 60 inches. E.g. jaw, gyratory, roll, and impact crushers Intermediate grinders E.g.- rotary cutters, disk, hammer, roller, and chaser mills Fine grinding mills E.g.- ball, rod, hammer, colloid, and fluid-energy mills 29 Fundamental Actions Involved in Comminution Attrition—breaking down of the material by a rubbing action of two surfaces. Rolling—uses heavy rolling to crush and pulverize the material. Impact—the operation of hammers at high-speed impacts the lumps of material and breaks large particles to smaller ones, until the desired size is achieved. 30 Preparation of powders 1. Particle size reduction / milling 2. Particle size measurement and classification Techniques used – microscopy, sieving, sedimentation rate, permeability 3. Mixing Large scale mixing – rotating shell mixers, fixed shell mixer, vertical impeller mixer Small scale mixing – motar and pestle, spatulation, sieving 4. Packaging 5. Storage 31 Manufacturing methods of granules Following methods are employed for the preparation of granules, Dry method -Powder material is passed through a roll compactor -Granulating machine -Densified sheets or flakes -The compacted powder is then granulated to uniform particle size by passing through a mechanical granulator Wet method -Moistening the desired powder -Passing paste like mass through sieve no 4-14 -Tray dry/oven dry/vacuum dry -Packed and labeled 32 Types of powder dosage forms Oral powders in unit dose sachets Powders containing drugs intended for children, such as antibiotics, are commonly made available in powder-filled unit-dose sachets. These powders are intended for administration after premixing with a food product, such a yogurt or juice. The powder blend is required to have a sweet taste, pleasant flavor, appealing color, and an acceptable mouthfeel. Powders for oral solution or suspension Powders for reconstitution into an oral solution or suspension are commonly dispensed to the patient in multidose bottles. The pharmacist reconstitutes the powder using water, and the patient is instructed to consume a defined dose, by volume, of the resulting suspension. This mode of drug dispensing is intended to minimize the effects of physical instability of the suspension and/or the chemical instability of the drug compound on storage. 33 Bulk Powders Mixed ingredients are packed into a suitable bulk container, such as a wide-mouthed glass jar. Herbal medicines, such as laxatives, are commonly dispensed in bulk powder containers for dose dispensing and administration by the patient. Divided powders Are similar formulations to bulk powders but individual doses are separately wrapped. Bulk granules Granules are packed into a suitable bulk container. Divided Granules Granulated products in which sufficient for one dose in individually wrapped. Dry powder inhalers Dry powder inhalers (DPIs) are devices that deliver medication to the lungs using an inhalation device in the form of a dry powder. 34 Dusting powders Dusting powders are intended for external, local application. Contain ingredients used for therapeutic, prophylactic or lubricant purposes. Only sterile dusting powders should be applied to open wounds Dusting powders for lubricant purposes or superficial skin conditions should be free from pathogenic organism. Normally dispensed in glass or metal containers with a perforated lid. Store in a dry place. Insufflations Medicated powders which are blown into various body tracts and cavities using an insufflator. E.g. ear, nose, vagina, throat Particle size should be very small. 35 Effervescent granules Effervescent granules are sold as bulk powders intended for dispensing of a unit dose and reconstitution with water to form a solution by the patient immediately before administration. Generally contain acid substances and carbonates or hydrogen carbonates which react rapidly in the presence of water to release CO2. Effervescent granules must be kept in dry state to prevent this reaction before reconstitution by the patient. 36 Self studies List the advantages and disadvantages of powders and granules. 37 Thank You! 38