Advertorial
Next generation HPMC capsules
greatly expand pharmaceutical uses by Dominique Cadé, PhD
A powerful alternative for pharmaceutical dosage forms
Polymer choices in pharmaceutical dosage forms have always been a balancing act between performance and development time, and historically has been shaped by the interactions of gelatin. The first generation of HPMC capsules, which relied on a secondary gelling agent, were recognized by formulators as having issues with dissolution performance and product stability. Fortunately, new scientific discoveries in polymers and capsule manufacturing have resulted in the creation of the next generation of HPMC capsules – one that offers better performance and reduced development time compared to gelatin and first- generation HPMC capsules.
Capsugel, the market leader in research and development in this area, is now offering these second-generation HPMC capsules under the trade name, Vcaps® Plus capsules.
In a number of studies, Vcaps Plus capsules have been shown to deliver optimized compound stability and predictable in vitro dissolution while also helping to eliminate the complexity in formulation development. Known globally for their reliable and predictable performance, Vcaps Plus capsules are well suited for over-the-counter (OTC) or off-patent products as well as for new chemical entities (NCEs).
True pH and ionic media independent performance
Traditionally, HPMC capsules were created using secondary gelling agents and ionic gel promoters, which have been found to interact with dissolution media and delay compound release from the capsule. The activity of the gelling agent kappa-carrageenan, for example, is enhanced by potassium and calcium cations contained in many foods. The extent of the resulting delay in dissolution time was shown in an in vitro test in which caffeine-filled traditional HPMC capsules were dissolved in a number of dissolution media. In the simulated normal acidic environment of the stomach (pH 1.2 USP), 90% of the caffeine was dissolved within approximately 15 minutes (Figure 1). Adding 2 g/L of potassium chloride (KCl) to this medium resulted in no dissolution after 15 minutes and a caffeine dissolution between 70% and 80% after more than one hour. Increasing the KCl content to 9 g/L delayed caffeine release even further, with a dissolution rate of just over 10% in 45 minutes. Results with simulated milk fluid were equally disappointing. Similar delays in dissolution times were observed and attributed to carrageenan in an independent study (Ku et al., 2011). Of course, such long delays in capsule dissolution are unacceptable particularly for rapid-relief products.
Capsugel addressed this situation by developing a proprietary new thermal gelation manufacturing process for Vcaps
Plus capsules that eliminates the need for gelling systems all together and provides true pH and ionic media independence in disintegration. In vitro tests showed that these second-generation HPMC capsules had similar rates of dissolution at pH levels of 1.2 and 6.8 and with simulated milk fluid, achieving a nearly complete dissolution of the caffeine contents within approximately 30 minutes (Figure 2). Even adding 2 g/L or 9 g/L of KCl to the dissolution medium did not affect the performance of Vcaps Plus capsules, with dissolution of over 90% within 30 minutes, even under the most disadvantageous condition.
These findings were supported by an independent study that compared the dissolution performance of traditional and second-generation HPMC capsules (Ku et al., 2011), and underscores the superior performance of Vcaps Plus capsules.
Ideally suited for moisture sensitive compounds
While gelatin capsules have been effectively used for over a hundred years, due to their excellent flexibility and highly desirable dissolution properties, they are not typically the polymer choice for moisture sensitive compounds. Vcaps Plus capsules on the other hand have a three-fold lower moisture content than gelatin capsules and are less hygroscopic. That equates to fewer broken capsules due to brittleness and less of a chance of drug degradation compared to gelatin capsules.
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