Fernando Diez, business development manager of Qualicaps, explains the advantages of the hard capsule dosage form in protecting drugs from light radiation
The problem
A drug substance or drug product can be exposed to natural or artificial light during production, storage, administration and use. The great majority of drug substances and pharmaceutical excipients absorb UV and visible radiation. Absorption is a first indication that a compound may participate in a photochemical process, i.e. be photoreactive, which can result in its own decomposition or that of other components of the formulation in vitro.
It is well known that optical radiation can change the properties of various materials and products. This is often manifested as discoloration of colourless products or bleaching of coloured compounds. The number of drugs identified as photo chemically unstable is steadily increasing. Some examples include ketoprofen (nonsteroidal anti-inflammatory drug), fenofibric acid (hypolipidemic drug) and tiaprofenic acid (nonsteroidal anti-inflammatory agent).
Absorption of optical radiation may result in the formation of free radicals and/or reactive oxygen species, which are identified as the reactive species in the process. Following photoexcitation, the substrate will dissipate the excess energy in a chemical or physical process. Competition between photochemical and photo physical events ultimately determines to what extent given excited state will undergo chemical reactions, or deactivate either radiatively or by heat dissipation.
Hard shell capsules
Capsules, along with tablets, are the most common form of dosage for the oral administration of solid-state pharmaceuticals and nutraceuticals. One of the main advantages of the capsule as dosage form is the time-to-market. In standard conditions, the time needed to develop the drug is shorter if the capsule is the option chosen. This is the reason why lately there is a growing demand for this dosage form.
Patented in the 19th century, two-piece capsules have played a prominent role in the pharmaceutical sector. For much of that period, gelatin capsules, which contain fillings such as active pharmaceutical ingredients (APIs) and excipients, dominated as the market standard. However, in recent years, there has been a shift, with hydroxypropyl methyl cellulose (HPMC) capsules rising to the fore.
The switch has come on the back of substantial pharmaceutical research revealing that while gelatin allows for an overall decent powder release from the capsule shell, as a protein derived from animals, it also has the potential to become chemically unstable and carries the risk of transmissible spongiform encephalopathy, a group of neurodegenerative conditions.
Subsequently, HPMC, known for its chemical inactivity, lack of crosslinking and low moisture content, not to mention excellent microbiological qualities, has emerged as the market’s most viable alternative to gelatin in the manufacture of capsules.
Both capsule types have a low refractive index, 1.24 for gelatin and 1.34 for HPMC. Once a pigment with a high refractive index such as titanium dioxide (2.27—2.71) is added, a structure with high radiation barrier is formed.
When a ray of light passes from a substance of low refractive index to a substance of high refractive index, light is reflected at the boundary; the amount of light scattered is higher, and the difference between their respective refractive indices is greater. As a portion of the light reflects at the surface of each pigment particle, changes in the speed of light as it enters the pigment particle causes it to bend or refract. This part of the light is then impeded from passing through the particles, changing its path at the surface and thus reflecting out. This scattering of light by the many pigment particles is what causes opacity and ultimately creates a protective barrier to harmful radiation.
Without these changes in the refractive index between the pigment and the medium, light passes through it practically unaffected. The system is transparent.
In Figure 2 an UV/VIS spectra for gelatin and HPMC capsules is shown. The light transmission is very low for TiO2 concentrations over 3.5%. Protection is higher in the UV area (200–400 nm).
It is remarkable that protection can be obtained with low concentrations of TiO2. Adding a pigment to a system can affect mechanical properties such as stiffness and tensile and impact strength or rheology. Therefore, the use of higher quantities of this additive must be avoided.
Conclusion
There is a growing interest on developing drug products in capsules in the pharmaceutical marketplace. Apart from all the advantages: reduced time-to-market, possibility of filling liquids, inhalation platform, etc., this oral dosage form provides light radiation protection of the drug substance when a low concentration of pigment is added to the capsule shell.