Some powders require the addition of only small amounts. How to scaleup a wet granulation end point scientifically. Recommended citation ghanta, sambasiva rao, an investigation of the effect of some formulation and manufacturing variables on the wet granulation process 1985. In addition, many of the scaleup problems associated with batch granulation processes can be avoided by applying a continuous granulation process. The particle size can be adjusted by changing the working level in the granulator. An investigation of the material and process variables in. The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required. Closedloop feedback control of a continuous pharmaceutical. The mechanism of granulation formation and methods. Assessing the use of twin screw wet granulation in a multi. The manufacturing process is independent of extensive critical process parameters as seen in wet granulation process. Wet granulation process overview in wet granulation, powders are bound together using adhesives rather than by compacting as in the dry granulation process.
The fluid should be nontoxic and may include water, isopropanol, ethanol and methylene. Enhance the uniformity of drug substance in the final dosage form increase the density of blend. However, this route is still operated in batch mode with little if any usage of an automatic control system. The fluid contains a solvent which can be removed by drying, and should be nontoxic. The aim of the present study was to investigate and compare granule and tablet properties of granules prepared by wet granulation in a rotary processor or a conventional fluid bed. Moreover, scaleup of high shear granulators is still difficult to perform. The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, to name a few. Typical solvents include water, ethanol and isopropanol and methylene chloride either alone or in combination. Pharmaceutical granulation processes, mechanism, and the use of binders 271 where g is the surface tension of the liquid, q the contact angle, and r is the radius of the capillary. The binding liquid must also contain the binding agent as well as a solvent, such as water or alcohol. Wet granulation involving wet massing wet granulation involves the massing of a mix of dry primary powder particles using a granulating. In the traditional wet granulation method the wet mass is forced through a sieve to produce wet granules which are subsequently dried. The present research mainly focuses on the high shear wet granulation of pharmaceutical powders. For example, in wet granulation, screw speed, feed rate, and water content all contribute to the physical properties of the granules.
The granulation liquid may be used alone or, more usually, as a solvent containing a dissolved. Wet granulation process overview lfa tablet presses. The study also used pept data to assess motion within the tsg. Therefore, when optimizing a granulation process, it stands to reason to include, alongside the endpoint factor, the tableting processing parameters, such as compression force or tablet press speed. The process of wet granulation includes the massing of mix dry powders with granulating fluid. The fluid contains solvent, which can easily be removed when dried. An investigation of the effect of some formulation and. The first model relates the crushing strength cs, disintegration time dt and ejection force ef of the tablets with process variables from both the wet granulation and tableting steps and the. Wet and hot melt granulation for producing granules. Wet granulation is the process by which powders are converted to granules with the desired properties to ensure good tablet production. Handbook of pharmaceutical wet granulation 1st edition. May, 2014 understanding continuous granulation process variables real time process understanding via inline particle characterization. How to scaleup a wet granulation end point scientifically provides a singlesource devoted to all relevant information on the scaleup of a wet granulation end point contents include a general description, problem identification, and theoretical background with supporting literature, case studies, potential solutions, and more.
Screening study for wet granulation initial risk assessment wet granulation potential impact on cqas of appearance, degradation products, dissolution, content uniformity, and physical form 20 experiment design including material attributes and process parameters on commercial scale equipment. The mechanisms of the effect of process parameters on primary properties of granules manufactured by wet granulation size and density, bulk performance indicating properties flow, compaction properties, and final tablet quality attribute dissolution are discussed based on studies performed on active and placebo formulations. The adhesive usually called a binder is incorporated in the form of a solution or suspension in a suitable liquid. Particularly, this research aims at closing the gap in understanding the role of. Theory and practice in a quality by design paradigm offers a single and comprehensive reference dedicated to all aspects of pharmaceutical wet granulation, taking a holistic approach by combining introductory principles with practical solutions. How to scaleup a wet granulation end point scientifically provides a singlesource devoted to all relevant information on the scaleup of a wet granulation end point.
With the development of dry granulation approach for quetiapine extendedrelease tablets using hpmc k4m as a rate controlling polymer, found to be innovative and much suitable than wet granulation. Wet granulation advantages and disadvantages biology essay. The whole wet granulation process takes place in a few seconds with only a few grams of product in process at a given time, resulting in faster startup and no losses. The effects of changes in the granulation process were not statically relevant on the final tablet for the process set up. In the course of wet granulation small andor irregular shaped particles e. Wet granulation using a twin screw extruder is a promising continuous processing technique for granulation of pharmaceutical formulations. Wet granulation in a vertical granulator is the classical method for building up granulates from powder. Subramanian g 2015 process analytical technology for high shear wet granulation.
Formulation design of granules prepared by wet granulation. Like any other manufacturing process, wet granulation technology has both advantages and disadvantages. Quality by design qbd for the continuous manufacturing of. Servolift provides a variety of granulation equipment such as. Granulation is the process in which primary powdergranulation is the process in which primary powder particles are made to adhere to form larger,particles are made to adhere to form larger, multiparticle entities called granules. The process can be very simple or very complex depending on the characteristics of the powders, the final objective of tablet making, and the equipment that is available. Pdf pharmaceutical granulation processes, mechanism and. Pat for high shear wet granulation monitoring and control. Tablet manufacturing via wet granulation, integrated with onlineinline real.
Typical liquids include water, ethanol and isopropanol, either alone or in. In the traditional wet granulation method, the wet mass is forced through a sieve to produce wet granules that are subsequently dried. Melt granulation is an appropriate alternative to other wet granulation techniques which are used for water sensitive materials. Understanding continuous granulation process variables. Pharmaceutical products are processed all over the world using the directcompressing, wetgranulation, or dry granulation methods. Wet granulation, the process of adding a liquid solution to powders, is one of the most common ways to granulate. An investigation of the material and process variables in pharmaceutical wet granulation george sienkiewicz university of rhode island follow this and additional works at. The aims of the study were to evaluate the effect of high shear mixer hsm granulation process parameters and scaleup on wet mass consistency and granulation characteristics. Endpoint detection in a wet granulation process request pdf. The process of adding a liquid solution to powders involves the massing of a mix of dry primary powder particles using a granulating fluid. The fluid contains a solvent that must be volatile, so that it can be removed by drying, and be nontoxic. Consequently, impeller speed and wet massing time affect the granule size.
The liquid should be nontoxic and is preferably water, although. Formulation design of granules prepared by wet granulation method using a multifunctional singlepunch tablet press to avoid tableting failures. Manufacturing variables on the wet granulation process sambasiva rao ghanta university of rhode island follow this and additional works at. Process variables higher degree of densification of the granules results due to higher impeller speed as well as longer wet massing time. Nov 18, 2015 for the love of physics walter lewin may 16, 2011 duration. Wet granulation is fundamentally a batch process, which can be divided into two types. Feb 18, 2015 granulation process can be divided into two types. Understanding continuous granulation process variables real time process understanding via inline particle characterization.
The process can be very simple or very complex depending on the characteristics of the powders and the available equipment. Wet granulation is defined to be a process in which a liquid solution is added to powders and involves the use of a granulating fluid in massing a mix of primary particles that are dry dhenge et al. Diosna high shear granulators p 100 and p 150 are designed for efficient mixing and wet granulation of tablet masses. Overview of the spheronizationextrusion process wet granulation. In summary, wet granulation process involves 4 main stages preparing material, wetting powder, nucleation and drying. Next, lets have a quick overview of the advantages and disadvantages of the wet granulation process. The final goal of any granulation process is a solid dosage form, such as tablets. The wet granulation process is the traditional method of manufacture and is frequently used in the pharmaceutical industry.
Measurement control corporation east hanover, new jersey, usa scaleup basics once you determine an acceptable endpoint of granulation in terms of process and product parameters, the task of its scaleup should include. Successful integration of a continuous wet granulation process, therefore, relies on understanding how to manipulate these variables to produce granules that will reliably deliver high quality tablets. For wet granulation in highshear mixers, specific methods based on the liquid saturation and the consistency of the wet mass are described. For the love of physics walter lewin may 16, 2011 duration. Chapters are written by international experts across industry, academic and regulatory settings, and cover. The wet granulation route of tablet manufacturing in a pharmaceutical manufacturing process is very common due to its numerous processing advantages such as enhanced powder flow and decreased segregation. The first investigation utilized rsm methods with a centralcomposite experimental design to study two process variables using a doublepaddle planetary mixer. For this purpose the working range of selected process variables was determined and a factorial study with 3 factors equipment type, filler type, and liquid addition rate and 1 covariate fluidizing air flow rate. In wet granulation, powders are bound together using adhesives rather than by compacting as in the dry granulation process. Formulation design of granules prepared by wet granulation method using a multifunctional singlepunch tablet press to avoid tableting failures author links open overlay panel takashi osamura a b yoshiko takeuchi a risako onodera a masahiro kitamura b yoshiteru takahashi b kohei tahara a hirofumi takeuchi a. Wet and hot melt granulation for producing granules engineering essay. The effects of process and formulation variables on pharmaceutical wet granulation processes using various mixerprocessors were studied.
Wet granulation involves the mixing of dry active ingredients and excipients using a fluid, which must be safe and volatile enough to be dried in a subsequent drying step. The role of powder characterization in continuous manufacturing. Coupling science and engineering practices it covers differing length scales from the subgranule level through behaviour through single granules, to bulk granule behaviour and equipment design. Expertise in wet granulation is widely available, as in the required equipment. Wet granulation in the vertical granulator in this process, powder is fed to a product container and then moistened or sprayed with molten material in. Fundamentals of granule growth, granulation methods and equipments, granulation variables, scalingup and endpoint control. Recommended citation sienkiewicz, george, an investigation of the material and process variables in pharmaceutical wet. Wet granulation involves the massing of a mix of dry primary powder particles using a granulating fluid. Typical liquids include water, ethanol and isopropanol, either alone or in combination. Pdf pharmaceutical granulation processes, mechanism and the. The granulation liquid may be used alone or, more usually, as a solvent containing a. Wet granulation wet granulation process simply involves wet massing 815 of the powder blend with a granulating liquid, wet sizing and drying. The most widely used process of agglomeration 17 in pharmaceutical industry is wet granulation.
Handbook of pharmaceutical wet granulation sciencedirect. Sep 25, 20 while wet granulation is used for a large number of pharmaceutical drugs, it does have the drawback of being a highenergy process, because drying is necessary once the wet granulation process is complete, notes dejan djuric, manager of scientific operations at lb bohle. Wet granulation methods utilize a liquid in the process whilst dry granulation methods do not use. Although granulating with more consistency than a traditional high shear batch mixer,1 the understanding of the granulation mechanisms in twin screw granulation is still not complete. If liquid saturation increases tendency of agglomeration may occurs. The purpose of wet granulation can be, but is not limited to. The process improves flow and cohesion reduces dust and cross contamination and permits the handling of powder blends without loss of homogeneity. Contents include a general description, problem identification, and theoretical background with supporting literature, case studies, potential solutions, and more. Granulation is a typical unit operation of particle enlargement carried out by the pharmaceutical industry to produce pharmaceutical dosage forms like tablets and capsules for over 70 years parikh, 2009. From here on there has been numerous research done on the process variables and optimisation of the material formulation. Which method is chosen depends on the ingredients individual characteristics and ability to properly flow, compresses. At 6% binder level, hardness values were essentially equivalent for all binder materials, although lowshear granulation processes tended to. While wet granulation is used for a large number of pharmaceutical drugs, it does have the drawback of being a highenergy process, because drying is necessary once the wet granulation process is complete, notes dejan djuric, manager of scientific operations at lb bohle.
822 15 872 862 360 1214 794 1230 1040 929 1303 562 292 19 1418 370 478 545 199 198 610 974 706 478 1337 1456 706 749 1034