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Editor of Pharmaceutical Technology Europe
OSD forms are popular within the industry due to the various advantages they offer, but there are specific considerations required to get the best OSD form possible.
According to market research, the global oral solid dosage (OSD) formulation market is projected to experience growth, potentially reaching $926.3 billion by the end of 2027 (1). As the most common form of pharmaceutical dose used in the world, not only do OSDs offer a cost-effective option for manufacture but they also provide advantages in terms of ease of packaging and transportation, compared with other dosage forms.
To discuss some of the key considerations, potential issues, available techniques and solutions, and best practices that formulators and manufacturers should keep in mind when approaching OSDs and tableting, Pharmaceutical Technology spoke with Rob Blanchard, research, development and quality systems manager, I Holland; John McQuaid, vice-president of technical operations, Almac Pharma Services; and Michael Wilkins, head of formulation and process development, Almac Pharma Services.
PharmTech: What are some of the key considerations for formulating a robust OSD drug?
Wilkins (Almac): For formulators and developers, it is essential to have information about a compound’s solubility and permeability. Knowing the position of the drug in the Developability Classification System (DCS) helps determine an appropriate formulation strategy for an OSD form. In addition, understanding the compounds’ degradation pathway and sensitivities to environmental conditions maintains focus on the stability of the drug product. Together, these considerations direct the formulator to develop a robust drug product with optimal release profile and shelf-life.
Standard functional excipients are incorporated into OSD forms. These can include diluents, disintegrants, binders, glidants, preservatives, and lubricants to name a few. They should be biologically inert, but they play a role in the performance of the drug product and impact on the robustness of the manufacturing process. They should not negatively impact the stability of the product, and so selection of different materials and grades is important to produce the ideal formulation.
PharmTech: Are there techniques that can be used to improve the solid dosage formulation for specific patient populations?
McQuaid (Almac): It is imperative that dosages are designed with the particular patient population in mind-for example, specific formulations for pediatrics or other patient populations who may have difficulty swallowing conventional solid dosage forms such as capsules or tablets. Common techniques that are employed to help with the challenges of these specific patient requirements include modifying release formulations to improve patient convenience/compliance, taste masking, and changes to the dosage form itself.
In particular, age-appropriate formulations, especially for pediatrics, is an area that requires much consideration. Industry is witnessing significant growth in multi-particulate formulations, such as mini-tablets that are filled into unit dose stick packs or proprietary dispensing devices where the dose can be adjusted at the point of pharmacy dispensing to suit the bodyweight of the patient. An alternative approach is powder-in-bottle or powder-in-sachet formulations, which are also growing strongly.
PharmTech: From your experience, what are some of the main aspects of a pharmaceutical formulation that could cause issues when compacting/compressing into an OSD form?
Blanchard (I Holland): Sticking is one of the most common problems to affect tablet production and occurs when granule builds-up on the punch tip face. Sticking has huge implications on production, causing tablet press downtime and reduced tablet output. Pinpointing the root cause of sticking is very challenging, but the main causes include:
PharmTech: What process solutions are available to help overcome challenging formulations in tableting?
Blanchard (I Holland): There are a number of solutions, and it is really dependent on the problem; however, tool coating selection can have a fundamental impact. With the correct specialized coating or treatment applied, some of the biggest challenges that can delay production, such as corrosion, wear, and sticking issues, can be avoided. What is crucial, when it comes to choosing a tool coating, is understanding the product being compressed. Match the properties of the formulation to the coating, so for example, if the formulation is particularly abrasive, use an anti-wear coating that will improve the hardness of the tooling.
Correctly matched coatings allow for better tableting efficiency and output by reducing the requirement for tools to be taken out of production for additional cleaning and maintenance work to remove problematic residue. There is a tool coating to suit every requirement, whether that is preventing sticking, reducing wear, or withstanding corrosive properties.
PharmTech: Are there any best practices you could share with drug formulators to achieve optimal tablet production?
Blanchard (I Holland): For optimal tablet production, improve workplace skills. It’s all very well investing in the latest high-speed tablet press and innovative tooling, but this can be compromised without a trained and knowledgeable team in place who understands how to use and maintain the equipment correctly. Improving and recording levels of workplace skills is critical to the success of efficient modern manufacturing.
Investing in learning and development provides several benefits, such as reduced downtime, increased productivity, and increased profit. Effective, planned training will not only save on labor by anticipating problems that could halt production before they occur, but ultimately, will also create a better educated workforce.
Another best practice to optimize production is through a tool management system (TMS). The efficient and accurate management of punches and dies is vital to optimize output and profitability. Through computer-based monitoring systems, productivity per punch can be maximized more effectively to meet with high-capacity manufacturing requirements. Any problems within tool inventory management can have serious implications on the bottom line. Crucially, manufacturers should have a complete audit trail covering tooling usage and maintenance, which a TMS can fulfill. This is not only good practice, but an important regulatory requirement in the majority of pharmaceutical environments.
PharmTech: What trends do you foresee happening in the field of solid dosage formulations and tableting over the coming 5–10 years?
McQuaid (Almac): As well as an increasing use of appropriate technologies to address issues related to poorly soluble drugs, we also foresee an increase in the requirement or technologies to safely handle the development and manufacture of more potent drugs. We also see a trend of batch sizes decreasing as medicines are targeted towards smaller patient population in line with the growing trend in orphan and ultra-orphan indications.
Blanchard (I Holland): The mass appeal of tablets and rising competition from emerging markets is pushing manufacturers to find quick, efficient, and cost-effective methods of producing high-quality tablets. To accomplish this goal, the implementation of continuous manufacturing (CM) will be an important trend in the future of tablet manufacture.
For CM to be successful, manufacturers must utilize innovative solutions and technology, including the correct tool steel and coating choices, for example, or appropriate tablet design. The use of specialized tooling that helps to achieve higher press speeds with challenging products and formulations will also be highly important to minimize manual intervention such as tool cleaning or replacement and maximize the benefits of CM.
To take these different elements of CM into account and lead the way to cost-effective and efficient processes, manufacturers should seek expert advice from tooling manufacturers so the appropriate adaption and updates can be made to current production processes and designs.
1. Future Market Insights, “Oral Solid Dosage Formulation Market,” futuremarketinsights.com, Market Report, July 18, 2017.
Supplement: Solid Dosage Drug Development and Manufacturing
When referring to this article, please cite it as F. Thomas, “In Top Tablet Form,” Solid Dosage Drug Development and Manufacturing Supplement (April 2020).