In the author’s experience, dissolution testing can be used as a surrogate test for taste by evaluating the drug release from the taste-masked beads at earlier time points. The FIP/AAPS (Federation International Pharmaceutique/American Association of Pharmaceutical Scientists) guideline recommends multi-point dissolution testing within early points of analysis (eg, ≤ 5 min) as a means to address the taste-masking properties of the formulation. 8 Data collected at these early time points may be used for in vitro evaluation of the taste-masking efficiency. Figure 2 shows the release comparison of Niravam tablets containing layer-coated taste-masked drug beads vs. A multi-point profile in neutral pH medium with early single point specification (NMT X% released at 5 or 10 min) is applied to determine the taste-masking efficiency.
Hot-Melt Extrusion Hot-melt extrusion (HME) offers a relatively newer approach to taste-masking and provides advantages such as absence of organic solvents in the process, fewer processing steps, continuous operation, and scale-up capabilities. 9 For the purpose of taste-masking, the bitter active is mixed with other ingredients in a dry state. The mixture is filled in a hopper, conveyed, mixed, and melted by an extruder. The process subjects the materials to a heating process under intense mixing to obtain the taste-masked extrudates. The extrudate can then be milled or micronized to obtain taste-masked granules or particles, which are then incorporated into a suitable dosage form. Twin screw extruders (Figure 3) are one of the most popular extruders and provide advantages such as short transit time, convenient material feed, high shear kneading, and less over-heating. Microencapsulation Microencapsulation is a technology with a long history in the pharmaceutical industry, and taste-masking represents an expanded area of its application. In principle, microencapsulation provides the opportunity to encapsulate the bitter active and thus prevent its contact with taste buds.
Microcaps ® is one such well-recognized technology that applies coacervation/phase separation to produce different encapsulated polymeric membranes. The process primarily consists of formation of three immiscible phases, formation of the coat, and deposition of the coat. The formation of the three immiscible phases is accomplished by dispersing the core particles in a polymer solution. A phase separation is then induced by change in the temperature of polymer solution; change in the pH, addition of a salt, non-solvent, or by inducing a polymer-polymer interaction. This leads to deposition of the polymer coat on the core material under constant stirring. The core particles coated by the polymer are then separated from the liquid phase by thermal, crosslinking, or desolvation techniques leading to rigidization of the coat. 10 Microcaps are used in conjunction with Advatab ® compressed ODT technology. Complexation Cyclodextrins have been extensively used for taste-masking bitter drugs by forming inclusion complexes with the drug molecule. Cyclodextrins are unique bucket-shaped cyclic oligosaccharides containing at least six D-(+)-glucopyranose units attached by alpha-(1,4)-glucosidic bonds with a molecular structure of hydrophobic cavity and hydrophilic exterior. The formation of inclusion complexes and its type depends on several factors like drug properties, processes involved, the equilibrium kinetics, formulation excipients, and the desired final dosage form and delivery system. Taste-masking is achieved by the interaction of cyclodextrins with proteins of the taste buds or by inhibiting the contact of bitter drug molecules with taste buds. Ion exchange resins provide an alternative to cyclodextrins to achieve taste-masking by complexation. 11 Ion exchange resins are high molecular weight polymers with cationic and anionic functional groups. The preparation of the taste-masked complex involves suspending the resin in a solvent in which the drug is dissolved. The drug-resin complex formed is referred to as drug-resinate, which prevents direct contact of the drug with taste buds, thus providing taste-masking during administration. Upon ingestion, the resin exchanges the drug with the counter ion in the gastrointestinal tract, and the drug is released to be absorbed. Commercially available ion exchange resins that may be used for taste-masking are based on methacrylic acid – divinyl benzene polymer and styrene – divinyl benzene polymer. Spray-Drying Spray-drying provides an alternate approach to taste-masking by applying a physical barrier coating. The bitter drug is either dissolved or dispersed along with the polymer in a suitable solvent followed by spray-drying. The process usually consists of three different steps: (1) atomization of feed into a spray, (2) spray-air contact (mixing and flow) followed by drying, and (3) separation of dried product from the air. The process provides the option of using aqueous and non-aqueous solvents. The dried product often includes granules or beads containing taste-masked encapsulated drug. The amount of polymer coat can sometimes retard the drug release, and therefore requires careful polymer selection and process design to afford taste-masking. Also, the formulation and processing can affect whether or not the polymer is “coated” on the surface or dispersed.
The quality of taste-masking depends on providing a coat, not a dispersion.
Some of the advantages of spray-drying include (a) less processing time being a single step process, (b) scale-up capability, and (c) wide variety in the choice of solvent and polymer. In summary, a variety of taste-masking technologies are available and used in the pharmaceutical industry today with new platforms being researched and developed constantly.