[vc_row full_width=”stretch_row_content_no_spaces” css=”.vc_custom_1564596094827{padding-top: 300px !important;padding-bottom: 220px !important;background: #a3a3a3 url(http://br306.teste.website/~ferra863/steq/wp-content/uploads/2019/07/Img3.png?id=1050) !important;}”][vc_column][vc_column_text]
Challenges and Trends in Tablet Manufacturing
[/vc_column_text][vc_separator color=”sandy_brown” border_width=”3″ el_width=”10″][/vc_column][/vc_row][vc_row css=”.vc_custom_1564073259210{margin-top: 25px !important;margin-bottom: 25px !important;}”][vc_column width=”3/4″][vc_column_text]Flexibility and well-thought-out manufacturing approaches could help drug manufacturers cope with this growing pressure from the changing Bio/Pharma development landscape. Overall, oral solid dosage forms remain the most popular choice for drug manufacturers and patients, offering convenience, simplicity, cost-effectiveness, and higher compliance rates. Tablets have for some time held the lead in terms of popularity in dosing, but according to some reports, the growing trend in the development of more complex and specialized drugs is leading to the need for more flexible and sophisticated manufacturing approaches. In addition, growth in emerging markets has put pressure on solid dose manufacturers to accelerate production while keeping costs at an efficient level. To learn more about the challenges associated with tablets and these industry trends, Pharmaceutical Technology spoke with Michael Oxford, Research and Design Engineer at I HOLLAND.
Challenges faced by manufacturers
PharmTech: Could you highlight the main challenges that drug manufacturers face when trying to quickly and cost-effectively process solid dosage oral forms/tablets while maintaining high quality? Oxford (I Holland): To efficiently produce a quality tablet, design is key. Details such as the format, profile, and features, such as blended land, are just some of the factors that must be considered. Let’s first talk about the form. The round shape is the most common, as it is easier to produce. Non-rounded shapes are more complex and may require specialized manufacturing tooling capabilities. Once the basic shape has been decided, take some time to see the size. Note the type of compressor available for tablet production, as this may limit the size of the tablet. Also, if the production has to be fast, consider using multi-point tooling, which can also affect the size of the tooling. An important element of successful tablet design is ensuring that blended land works. If blended land is applied incorrectly, a number of problems can occur during compaction. For example, the edge of the tablet may be chipped at the outlet and the coating may eventually build up on the edge of the chipped tablet. Finding the right blended land will increase tablet strength and performance, resulting in larger volumes. It is important to remember that correctly selected and applied blended land provides benefits in terms of handling, loading, setup, tooling strength and the visual appearance of the tablet. Also consider the profile of the tablet. The profile is affected by several aspects, including the granule, engraving requirements, coating process, packaging, and the necessary visual identity. Also, think about the volume and whether it will be coated, as this can pose challenges to the tablet’s design. Successful coating depends on the profile. Because the core of a tablet has reduced hardness compared to the peripheral of the tablet, core erosion can occur during the coating process. Erosion is caused when it comes into contact with the lining container and other tablets, leading to wear. This weakness can be reduced by avoiding very deep concavities. An expert tooling designer will be able to design and add suitable strengthening features such as blended land and profile changes, resulting in a robust tablet that can be produced quickly and cost-effectively.
Dwell time and its impact
PharmTech: What about the dwell time and its impact on the compaction process? Oxford (I Holland): In a nutshell, dwell time is the time the punch head remains under full load when in contact with the compression roller. This will have a huge impact on production, as some tablet formulations are sensitive to morphology and therefore require longer compression. It is very important that the correct amount of force is used at the right time. Too much or too little can result in compaction problems. Excessive force or excess pressure on the punch can cause tooling failure and damage the compressor. For this reason, it is essential to understand how to properly optimize dwell time. Influences that can affect dwell time include the diameter of the flat head and shape, the use of pre-compression, and the revolutions per minute used during production. It is important to remember that dwell time plays a significant role in determining whether a tablet can be successfully produced, especially those that incorporate formulations that are difficult to compact. Not all formulations are sensitive, as some compress effectively at any speed; Most, however, are very susceptible to the slightest change. By understanding the dwell time required for a formulation, research into the characteristics of the formulation becomes essential – is it plastic or elastic? Does it have a high moisture content? All of these elements will affect the length of stay. Dwell time can also be an important factor in stopping common problems such as adhesion, capping or friability during manufacturing, for example, with specific tooling that can be used without slowing down the compressor, so production runs satisfactorily. Innovative new punches in the market enable tablet manufacturers to achieve higher compression speeds with challenging products and formulations without significant expenditure to acquire a new press.
[/vc_column_text][vc_single_image image=”1055″ img_size=”full” css=”.vc_custom_1564596422908{margin-top: 10px !important;margin-bottom: 10px !important;}”][vc_column_text]All formulation factors should be considered
PharmTech: You mentioned that the formulation of the drug can affect the length of stay. Does this have other implications for other aspects of the pill production process? Oxford (I Holland): The formulation can have a huge impact on the quality of the pill and the overall process. You must be attentive to all elements of the formulation; For example, does the formulation have a high moisture content? Does it have abrasive or corrosive ingredients? There are a whole series of factors to consider. The overall composition of the formulation must be studied so that the correct tooling can be utilized to reflect the formulation being compressed and ensure a final product free of quality defects. One of the main problems encountered is that of adherent or abrasive formulation. Looking at the last problem, some formulations contain unrefined, hard, and abrasive ingredients, which makes production challenging. Formulations with this composition, when compressed repeatedly, can scrape or penetrate the surface of the tooling. Abrasion can lead to erosion of the punch tip details, such as logo engraving and other identification specifications. Eventually, this wear and tear can lead to variation in weight, grip, and other problems, resulting in the puncture being discarded. Abrasion can be solved through the use of premium wear-resistant steel. It is important to fully understand the differences between steel selection, as they have a variety of advantages and disadvantages. One example is that some wear-resistant steels may be less prone to fractures in some applications, due to reduced toughness and tensile strength. If switching to a higher steel does not offer the extra wear resistance required, then a powder metallurgical steel will provide greater wear resistance. If selecting a wear-resistant steel is not enough, a tough coating can be applied to the tooling to offer more strength and extend its service life. The right coating not only adds wear resistance but also offers benefits in terms of corrosion protection and non-stick properties. There are coatings on the market that are about five times harder than normal tablet tooling steels. These coatings can increase the strength of tools compared to uncoated ones and can extend service life by more than 900%, following research and work examples from I HOLLAND.
Adherent tablet
PharmTech: As you pointed out earlier, the adherent tablet can be a common problem; What options are available to help overcome this problem? Oxford (I Holland): Adherence is the most common problem and one that we face daily. As it is a dominant issue in tablet production, I HOLLAND investigated the cause of adherent formulation and developed “TSAR Predict”. It is an algorithmic predictive model that calculates the optimal nonstick coating to apply to compression tooling based on the properties and characteristics of the formulation. We can identify the most suitable punch or die coating for adherent formulations, which can eliminate the need to perform field testing. There can be many reasons for adhesion, from Van der Walas forces to capillary action associated with high moisture content, or, conversely, adhesion due to static electricity generated in very dry conditions. Because the physical properties of any adherent formulation are unique, there is no single nonstick solution. Applying a purpose-built predictive tool to recognize the right punch or die coating solution for an adherent formulation is the answer that will save you a lot of time and money.
Tooling selection
PharmTech: What are some of your top tips and tricks for the best tooling selection? Oxford (I Holland): The correct choice of tool steel can have a huge impact on production and is one of the most important considerations. The tooling material must be balanced to provide optimal performance and durability. A good selection of steel will achieve the best possible balance of various properties, including abrasion and corrosion resistance, compressive strength, hardness and chipping and cracking resistance, clean structure, good machining, and moldability. Punches and dies are the main components to be interconnected with powders and granules, so they must be metallurgically robust. If the choice of tool steel is wrong, the compression of, for example, abrasive formulations, will result in various problems. To select the right tooling, consult with a tablet tooling expert and provide as much information as possible. With years of experience, they can offer advice on the most suitable tooling for the job.
Tablet trends
PharmTech: Have you seen any significant trends in tablet production in the last decade that have had a positive/negative impact on the industry? And what are your predictions for the next decade? Oxford (I Holland): Perhaps one of the most significant trends in the last 10 years is the use of multi-point tooling. The production of solid-dose oral drugs is increasing. To keep up with demand, manufacturers need to implement improvements in production processes to efficiently manufacture tablets. Multi-pronged tooling has transformed the way tablets are produced and is now considered one of the most productive ways in tablet manufacturing. Successful implementation of multi-tip tooling can reduce the need to invest in additional presses, thereby reducing overall capital expenditure. The number of tool set-ups per production batch can also be reduced and batches of products are completed quickly, decreasing the overall production time. It also benefits drugs that need to be compressed in a short time from the preparation of the formulation. Over the next decade, shorter lead times and cost implications will put pressure on manufacturers to invest in new technologies and processes. There are also strict quality requirements that the pharmaceutical industry must apply. These requirements are leading to the need to improve production through durable compression tooling and associated equipment maintenance. Implementing continuous manufacturing to increase volume will be a key trend in the future and one that will help reduce reaction time and time-to-market. At I HOLLAND, we have recently designed a product that aims to maximize uptime. XDF (eXtended Dwell Flat), the new patented elliptical head shape, is designed to increase the dwell time on existing presses without the need for modifications. As the importance of increased productivity continues to grow, adaptable solutions such as XDF will enable manufacturers to meet future industry demands and trends.
Reference: ISR Reports, “Oral Dosage Forms Market Overview and Outlook (2nd Edition),” ISRreports.com (April 2017), accessed March 9, 2019.
Quote: F.Thomas, “Under Pressure,” Solid Dosage Drug Development and Manufacturing Supplement (April 2019).
Original content: http://www.pharmtech.com/under-pressure-0?pageID=1
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