Tabletting, one of the most essential processes in pharma manufacturing industry needs to undergo a metamorphosis to anticipate the changes coming its way and create capabilities to tackle opportunities and challenges. Experts unite and review the progress in this field and strategies for future growth
Pharma manufacturing has undergone a sea change in the past couple of decades. Rapid advances in technology and production processes have led to companies’ augmenting their efficiencies and output, both quantitatively and qualitatively. Enhanced maintenance and aftercare practices have also enabled pharma manufacturing facilities to attain an extended life and boost the benefits from their equipment and machinery.
Tabletting, one of the oldest and most widely used manufacturing techniques for solid dosage forms, has traversed a long journey. Tablets are a preferred choice insolid dosage forms for their ability to provide patient compliance, high-precision dosing, and manufacturing efficiency.
However, unprecedented shifts in drug discovery and the advent of next generation drugs which can also be administered through other dosage forms pose a threat to tabletting.
So, what are the measures needed for this field’s continued progress? How can tabletting reinvent itself to optimise its potential and eliminate its limitations? What is the way forward?
In an exclusive panel discussion, organised by Express Pharma, an eminent panel of pharma experts and veterans explored and examined answers to these queries. We present important lessons learnt from the five experts on the panel:
Begin with the basics: Dr Sanjit Singh Lamba, MD, Eisai Pharmaceuticals, India
Dr Sanjit Singh Lamba, MD, Eisai Pharmaceuticals, India urges the industry to get the basic and simple details right as they are very crucial when it comes to achieving success. He says, “The industry has graduated to automated, high-speed, rugged machines with high-compression forces and monitoring equipment.” Yet, often basic things get overlooked and this causes glitches in the tabletting process.
He provides a case in point by elaborating that while a lot of aspects are significant in tabletting, it all boils down to the quality of the punch. He states, “The quality of the punch and its infrastructure, both hardware and software are important.” Therefore, the success of the process also lies in how companies are studying and monitoring the functioning ability of the punches used.
Giving another example, he enlightens that even while machines have updated software and sophisticated features, small things like voltage fluctuation can cause a drop in productivity and quality. Therefore, companies should ensure that their machines are operating at optimal rates and maintain uninterrupted operations throughout the entire batch, especially as they expand their footprints and aims to compete with global players.
He stresses that despite automation, a lot of work and attention is needed in the back end to improve tabletting.
Dr Lamba also recounts instances of where Indian companies had all their products sent back within months of entering a new market because they didn’t meet the requirements, and emphasises that it is very important to get the processes right to get the perfect tablet, be it functionally or cosmetically. He points out that dissolution, compression, granulation, specifications, shine, etc. everything is important when it comes to tabletting.
He further informs that the Japanese market and other global markets come with very peculiar requirements, product-wise and in terms of regulations. Hence, his advice is that the players should carefully evaluate the availability, performance and quality of the tabletting equipment to gain optimal results.
It is all in the details: Dr Girish Jain, President, Research and Development, Alkem Laboratories
As a pharma scientist with decades of hands-on experience in tablet formulations, Dr Girish Jain, President, Research and Development, Alkem Laboratories emphasises on the need to pay attention to the smallest of details, when it comes to tabletting. Dr Jain points out that the success of tabletting, a seemingly simple operation, is dependent on several formulation and process-related parameters.
For instance, he explained the importance of the punch and coating in the development of a product. He also pointed out the significance of bisecting lines and informed that they are not just for cosmetic purposes. It often determines the divisibility of the dosage.
He called attention to the fact that throughput and efficiency can be hampered though several hitches in the tabletting process and hence even the smallest detail needs to be observed and evaluated thoroughly.
He explains that even small variations in formulations can have significant impact on tablets, be it on their solubility, compressibility or efficacy. He gave examples of bi-layer and tri-layer tablets to state his case.
Accentuating the importance of documenting each detail carefully, he says that it would be very beneficial for future reference and prove to be very crucial while applying for approvals in global markets. Dr Jain highlights the increasing stringency of global regulations and cites the approval process of the US FDA as an example.
He also recommends that a lot of controls need to be built into the processes, right from the R&D stage. This measure would go a long way in improving accuracy and precision, eliminating dosage variations, boosting the ruggedness of the product and creating better efficacies.
Get it right the first time: Sanjay Sharma, Head, Technology Transfer, Formulations (Sr General Manager), Lupin
Often companies in the pharma sector are faced with a scenario wherein a product has been developed and sent for manufacturing but they were forced to go back to R&D repeatedly because of some glitches. Frequently, due to these delays, the competition gets a march ahead.
Sanjay Sharma, Head, Technology Transfer, Formulations (Sr General Manager), Lupin informs that these glitches occur due to issues in tech transfer, especially during scale-up in tabletting.
For instance, the speed difference of making a product in a relatively slower R&D press and on high-speed production machines is considerable. Until it is accounted for properly, there will be challenges in the tech transfer stage, leading to capping, cracks, chipping etc. in the tablets manufactured.
Sharma also opines that pharma companies often do not do proper justice towards studying the impact of their complete blend. However, he urges the companies to take up this practice as apart from mitigating tech-transfer challenges, it will also aid in appeasing US FDA which insists on whole time data to understand the physical and chemical attributes of the tablet.
Underscoring that lack of a proper tech transfer strategy results in wastage of productivity, time, money and resources, he also states that as companies seek to build a robust tableting system, it is pivotal to tackle challenges in tech transfer without losing the products’ efficacy and equivalence.
He says that as equipment become more sophisticated, it is possible to study and examine even minute aspects of the process. He recommends that the companies should engage in these studies to get tech transfer right. He also urges scientists to rethink often implemented strategies to find better and simpler ways of product development. This will help in faster elimination of any anomalies in the product, thereby make tech transfer easier when it goes for manufacturing.
Befriend technology to accelerate progress: Ajit Kanetkar, Head-Process Technology & Training, ACG
As an expert with experience of working on both sides of the fence i.e. in pharma companies as well as with solution providers, Ajit Kanetkar, Head-Process Technology & Training, ACG, explains how technology is revolutionising tabletting. As automation touches every sphere of the process, he lays emphasis on choosing the right equipment when it comes to tabletting.
He says, “We see a lot of sophisticated machines but do not use all the features, especially in data compilation. Probably it is the fear of technology. There are so many features available in these machines, for isntance, it is very easy to pull out data from the last few batches and examine its findings.“
Giving a rundown on the characteristics of different types of tablets, he informs about the features that tablet manufacturers should look for to gain the best results in each technique.
Bi-layered and multi-layered tablets: These three factors are very important
- Re-circulation so that lack of layer thickness, probability of contamination is reduced.
- The machine should be capable of individual weight check to maintain the optimal layer thickness and ensure that it is not lost during the processes.
- Pre-compression is also important, compression forces on machine and granule characteristics is a result of the machine as well.
Mouth dissolving tablets: They have low-hardness and are high on friability. So the equipment should have excellent ejection.
OROS tablets: Choose an equipment which will prevent any surface damage to tablets as they get thrown in the air. It should also help achieve the right release profile.
MUPS: Two important things to be kept in mind while choosing a machine for these products are segregation and pre-corporation. Choose a single rotary and the feeder’s RPM should be less than the machine’s RPM to prevent segregation and crushing of beads.
Another insight from him was that we need to investigate not only faulty batches but also our best ones to gain knowledge of combinations which work very well for future use and reference.
He said that a batch which is not working properly only tells you what is wrong but a successful batch tells you how to replicate success.
Knowledge sharing is vital: Dr Vinay Nayak, Executive Director, Marksans Pharma
Dr Vinay Nayak, Executive Director, Marksans Pharma explains that tabletting has changed to incorporate several types of innovative tablets and recommends that innovation should be made a part of the whole process to stay at par with changing times.
He also emphasises on the very crucial need to peruse and document data whenever any tabletting technique is applied. Scanty data in the filings will adversely affect inspections. He said, “When there is a difference between what is written and what is practiced, a big gap in GMP is exposed. We should not only implement good designs and techniques but also adopt good practices in documentation.”
Dr Nayak explains that this would help in alleviating complex problems as data will enable the industry to predict potential issues and take proactive steps towards mitigating them. For instance, designing APIs with appropriate properties can help improve the tabletting process.
He affirms that the data can be also used to devise more effective and suitable tabletting machine settings. The learnings can also be shared so that the whole pharma community benefits and grows.
Dr Nayak also lauds Express Pharma for being a facilitator of such knowledge sharing platforms.
The way forward
The industry is adopting improved tabletting practices such as high-production rates and continuous production processes.
Every aspect of tabletting, be it the formula, excipients, production process or documentation, is getting automated with an aim to improve reproducibility, precision, and consistency in tabletting science. Adoption of the concept, ‘Quality by design’, is contributing significantly to the quality, safety and efficacy of drug products created through this process.
These advancements and patents in tablet technology have led to the creation of several modified release tablet formulations which are suited to current demands, including in-lay tablet, bi-layered tablet, medicated chewing gum, tablet tarts, pastilles, lollipop, tablet inserts, clinicaps, caplets, child ecstasy tablet and tablet in tablet etc.
However, as the pharma manufacturing industry undergoes a metamorphosis driven by market demands, tabletting will also have to continue anticipating the changes which would come its way and create capabilities to deal with the opportunities as well as challenges. Like any other scientific field, it will have to evolve to be more agile and responsive in a bid to stay relevant.