The escalating demand for cancer and hormonal therapy has generated high interest and significant attention towards cytotoxic and/or highly potent active pharmaceutical ingredients (HPAPI). Nearly a quarter of pharmaceutical products currently in the development pipeline have HPAPIs. However, the HPAPI market, although lucrative, brings with it several challenges. According to QY Research, the global HPAPI market which stood at an estimated USD 16 600 in 2018 is expected to grow at a CAGR of 8.7% between 2019 and 2025 and reach USD 32 200 million by the end of 2025.
Challenges of manufacturing highly potent drug products
Due to their high potency, the quantities in which HPAPIs are required to formulate drug products are relatively small. Therefore, mmanufacturing these substances and their drug products require great care and attention to ensure the safety of the personnel involved in handling the materials. However, the handling of potent drug substances is not the only challenge associated with developing and manufacturing these products – producing a homogeneous batch of products with unit doses containing very small quantities of drug can be quite difficult.
Benefits of liquid filled hard capsules
One of the best formulation strategies to deal with highly potent drugs is liquid or semisolid encapsulation using two-piece hard-shell capsules. This approach incorporates the drug in a liquid vehicle which facilitates its dissolution offering it the best opportunity for homogenous distribution. In case of manufacturing other solid dosage forms that utilise solid blending steps, achieving the intended content uniformity at low doses is extremely tough. Further, with the filling of liquids into capsules, a high degree of accuracy and control over fill weight can also be achieved.
Once the drug substances are dissolved in the liquid vehicle to form suspensions or solutions, the formulation can be processed through the further stages of capsule filling and sealing which pose a reduced risk of contamination to the operators and the manufacturing environment, minimising the chances of airborne contamination. The operator is at highest risk while dispensing the drug and adding it to the vehicle which, however, can be minimised by performing it in a containment hood or isolator. The production environment of liquid filled hard capsules makes containment easy so that the necessary operations can be carried out with lower safety risk compared with powder filling or tablet manufacture that typically generate dust particles. The finished product also has a reduced risk of surface contamination which can help the personnel to safely carry out the processing and packaging of the products with minimal risk of exposure.
The manufacturing process employed for liquid encapsulation starting with dispensing, followed by mixing, filling, and banding (or sealing) are well-defined, known and validated unit operations. The minimal number of processing steps helps cut down product development time substantially and aids further in rapid scale-up compared to other solid oral manufacturing techniques. Moreover, the technology now available for filling liquids into hard shell capsules makes it even more convenient than softgel capsules that require a specialised equipment and an intricate integrated manufacturing process.
Takeaway
As a cost-effective and time-saving solution for poorly soluble drug candidates and high-potency drugs, liquid filled hard capsule technology offers several advantages for product development and manufacturing of oral solid dosage forms. It can significantly help fasten the speed-to-market.
