Granules Lecture 5 2024 PDF

Lecture 5 GRANULES Associate Professor Noha Alaa Definition: Granulation is the process in which primary powder particles adhere to form larger, multiparticle entities called granules. Size range Between 0.2 - 4.0 mm Used for the production of tablets or capsules Larger granules: Used as a do...

Lecture 5 GRANULES Associate Professor Noha Alaa Definition: Granulation is the process in which primary powder particles adhere to form larger, multiparticle entities called granules. Size range Between 0.2 - 4.0 mm Used for the production of tablets or capsules Larger granules: Used as a dosage form in their own  Reasons for Granulation 1. Prevent segregation of the constituents of the powder mix Segregation (= demixing) is due to: differences in size or density of components of the mix the smaller &/or denser the larger and / or less dense particles ones at the base of a container above them. 3  Ideal granulation Will contain all the constituents of the mix in the correct proportion in each granule, and Segregation of the ingredients will not occur.  Reasons for Granulation 2. Improve the flow properties ▪ Granules flow well compared to powders (granulated sugar versus powdered Sugar). ▪ Because of their flow properties, granulations are commonly used in tablet making to facilitate the free flow of material from the feeding container (or hopper) into the tablet presses. Many powders are cohesive ➔ Poor flow ➔ variable fill of tablet dies ➔ There is wide weight variation within the final product Granules will be larger and more isodiametric, ➔ improved flow properties. 5  Reasons for Granulation 3. Improve the compaction characteristics Some powders are difficult to compact even if a readily compactable adhesive is included in the mix, but granules of the same formulation are often more easily compacted and produce stronger tablets. This is associated with the distribution of the adhesive material within the granules and is a function of the method employed to produce the granules. 4- Reduce the hazard of toxic dust The granulation of toxic materials will reduce the hazard associated with generating toxic dust that may arise when handling powders.  Reasons for Granulation 5- Reduce the hazard of hygroscopic powder adhesion Slightly hygroscopic materials may adhere and form a cake if stored as a powder. Granulation may reduce this hazard, as the granules will be able to absorb some moisture and yet retain their flowability because of their size. 6- Increase stability Granules have a smaller surface area than a comparable volume of powders ➔ more stable physically and chemically. Granules are less likely to cake or harden upon standing than are powders. 7- More suitable for reconstitution Granules also are more easily wetted by liquids than certain light and fluffy powders (which tend to float on the surface). The granules are prepared to contain: ▪ medicinal agent ▪ other pharmaceutical ingredients (Additives) Additives Diluents to produce a unit dose weight of suitable size. which are added to aid the break-up of the Disintegrating granules when they reach a liquid medium, e.g. agents on ingestion by the patient. in the form of a dry powder may also be Adhesives added, particularly if dry granulation is employed. Wet Method Dry Method  Wet Method The general steps involved in a wet granulation process are: 1- Powders are mixed by geometric dilution. 2-The granulating solution or binder is prepared. 3- Powders and binder solution are kneaded (pressed) to the proper consistency. 4- Wet mass is forced through a screen to produce wet granules of desired size. 5- The granules are dried by air or under heat. 6- Granules are moved on the trays to prevent adhesion into a large mass. Granulating liquid Water, ethanol, and isopropanol, either alone or in combination. The granulating liquid must be volatile (removed by drying). It must be non-toxic. The granulation liquid may be used alone or as a solvent containing a dissolved adhesive (binder) for particle adhesion. Binding agents commonly used in wet granulation are:  Water as granulating liquid Water is commonly used as a solvent. Disadvantages Advantages Drug stability, and hydrolysis of susceptible products. Cheap solvent It needs a longer drying time Non-flammable than organic solvents. Non toxic This may affect stability because of the extended No expensive safety exposure to heat. precautions  Fluidized-bed granulation It is another method for wet granulation. The mixed powders are fluidized within a chamber by the action of a stream of air (temperature-controlled). Dispersed particles are sprayed with the granulation fluid (usually containing dissolved binder). The particles adhere to each other forming granules of defined particle size.  TIME LABOR EQUIPMENT Limitations of Wet Granulation LOSS OF ENERGY MATERIAL SPACE  Particle-particle interaction in wet granulation 1. Liquid bridges 2. Solid bridges Particle-particle interactions are facilitated by the formation of liquid bridges. The volume of the granulation medium contributes greatly to the granulation process. Liquid bridges are divided into four categories: 1- Pendular 2- Funicular 3- Capillary 4- Suspension Pendular state Funicular state Capillary state Slurry state  (Suspension)     Over-wetting Under-wetting (mixing and drying) problems. disintegrate individual granules excessive mass of the binder poor mechanical strength.  Particle-particle interaction in wet granulation Particle-particle interactions are facilitated by the formation of solid bridges. Solid bridges are formed following drying. Consisting predominantly of the polymeric binder. As drying progresses a polymeric network is formed (resembling the pendular structure). Contributes to the mechanical properties of the resultant granule.  Possible Problems 1- Over drying destruction of solid bridges 2- Crystallisation of binder on the surface of particles hardening effect 3- Crystallisation of drug on the surface of particles physicochemical properties  Dry granulation method Powder particles are aggregated under high pressure. Intermediate products are broken using a suitable milling technique to produce granular material. Slugging Roller compaction large tablet ('slug The Dry method is useful for drugs that: Do not compress well after wet granulation Are sensitive to moisture or heat. 21 Advantages Disadvantages Less No uniform equipment & color space distribution Eliminate need Process may of binder produce dust solution  Particle-particle interaction in dry granulation 1. Electrostatic forces 2. Van der Waals forces 3. Melting of components Electrostatic forces: may be important in causing powder cohesion and the initial formation of agglomerates, e.g. during mixing. In general, they do not contribute to the final strength of the granule. Van der Waals forces: are about four times greater than electrostatic forces and contribute to the strength of granules produced by dry granulation. The magnitude of these forces will increase as the distance between adjacent surfaces decreases. In dry granulation, this is achieved by using pressure to force the particles together. Melting of components: powders will be exposed to high shear stresses that may result in the partial melting of excipients (of low melting point). Upon cooling solidification of the excipients will occur, resulting in increased interactions between adjacent particles. This mechanism does not strongly contribute to particle- particle interactions in dry granulation.  ▪ Effervescent salts are granules or coarse to very coarse powders containing a medicinal agent in a dry EFFERVESCENT mixture. GRANULATED SALTS ▪ Composed of sodium bicarbonate, citric acid, and tartaric acid. When added to water, the acids and the base react to liberate carbon dioxide, resulting in effervescence. ▪ The resulting carbonated solution masks the undesirable taste of any medicinal agent. EFFERVESCENT GRANULES citric acid and tartaric acid The resulting carbonated solution masks undesirable taste of any medicinal agent.  The benefit of: Using granules rather than small Using a combination of citric powder particles and tartaric acids rather than either acid alone Decreases the rate of Tartaric acid alone: dissolution (formation of solution). the resulting granules readily lose Prevents violent and their firmness and crumble. uncontrollable effervescence. Citric acid alone: Sudden and rapid effervescence could overflow the glass. results in a sticky mixture difficult to granulate.  Preparation of effervescent granules (a) The fusion method The one molecule of water present in each molecule of citric acid (water of crystallization) acts as the binding agent for the powder mixture which released upon heating. (b) The wet method The source of the binding agent is not the water of crystallization from the citric acid but water added to alcohol as the moistening agent, forming the pliable mass for granulation. (c) The dry method THANK YOU