How to improve patient compliance by Taste Making

Patient compliance

In 1979, the Johns Hopkins University defined patient compliance as related to “the extent to which a person’s behavior (in terms of taking medications, following diets, or executing lifestyle changes) coincides with medical or health advice.” [1]
Patient compliance is closely related to the acceptance of the medication. The pharmaceutical industry has seen the need to focus on the root causes of non-acceptance and to look deeply into finding improvements. Novel approaches like optimizing the physical aspects of oral solid dosage forms by reducing tablet size were explored. On the other hand, several studies were conducted to mask the taste or smell of challenging active ingredients. 

Bitter taste threat in pharmaceutical formulations

Medicinal products often have a bitter taste, leading to poor patient compliance, as patients can be reluctant to take the medicine or even refuse taking it altogether. Typical active pharmaceutical ingredients (APIs) known to have a bitter taste are macrolide antibiotics or penicillin, and anti-inflammatories like ibuprofen or quinine, as non-exhaustive examples.  For instant release formulations, drug products dissolve in the saliva in the mouth and the API particles bind to the taste receptors on the tongue. The bitter taste receptors are mostly found on the posterior part of the tongue, which can lead to a higher rate of rejection of the medicines.
This situation is particularly challenging for caregivers of the pediatric population, as children have a higher amount of taste buds than adults [2], thus having a stronger sensitivity to bitterness.
For that reason, masking the bitter taste of the drugs is a key consideration in new pharmaceutical developments for pediatric patients. 
 

Techniques to cover the bitter taste of APIs?

Several techniques have been developed to be used for concealing the unpleasant taste [2]. The most popular methods are the addition of sweeteners or flavors, or the use of amino acids or drug-resin complexes. Considering population diversity and the recent studies about the connection between taste and ethnicity or gender, it is challenging to find the right balance of sweeteners or flavors that would have universal appeal worldwide.  Furthermore, in cases of masking the taste of water-soluble drugs, the exclusive use of sweeteners even in combination with flavors isn’t sufficient because the OSD starts to disintegrate upon contact with saliva in the mouth, leading to a partial release of the bitter API.

Another way to cover up the bitter taste is to apply a coating layer, which can be easy to implement for different products. The coating formulation is very flexible as it can be applied on tablets, pellets and capsules by using a pan coater or a fluid bed. It provides a physical barrier, preventing the penetration of saliva and dissolution of the API in the mouth cavity.
 

How to formulate a coating with taste masking properties?

In a recent study, Shin-Etsu developed a coating formulation based on an enteric coating polymer with a higher pH solubility than the pH of saliva in the mouth (pH=6.2), and a pore former to allow  for disintegration in the acidic environment of the stomach. A typical enteric coating polymer dissolving at a pH higher than 6.2 is hypromellose acetate succinate, grade AS-H (Shin-Etsu AQOAT® AS-HG). Hypromellose 2910 with a viscosity of 6 mPas (PHARMACOAT® or TYLOPUR® 606) can be used as a pore former.
In table 1, three formulations based on those polymers are shown, whereas the ratio of enteric polymer and pore former were varied.
 

How to analyze the taste masking performance of the coating layer?

To assess the taste masking property of the taste masking coating formulations, a specific technique requiring a low volume (5 mL) of simulated saliva was used to mimic the amount of media present in the oral cavity.
The very bitter substance quinine was used as reference API threshold value. For successful taste masking, the amount of caffeine dissolved should be below the onset of taste perception of quinine (0.000008 M, 2.595 g/mL) measured by using UV detection (Erweka DT720 dissolution tester equipped with UV analysis,  = 275 nm) [3]. 
Therefore, one coated caffeine mini-tablet was put into an Ultra-Turrax tube drive vessel containing 5 mL simulated saliva. Mixing occured at 400 rpm for 5 min before a sample was drawn, and the sample was analyzed for caffeine content by UV spectroscopy (n=6 tablets).