The latest taste-masking techniques can yield more palatable drugs
ISTOCKPHOTO.COM Taste is one of the most important organoleptic aspects determining the favorable acceptance of oral drugs. Because the majority of drugs taste unacceptable due to their functionalities, taste masking is essential to ensure patient compliance.
When they dissolve in saliva, molecules interact with taste receptors on the tongue to give a particular taste sensation. This sensation is the result of signal transduction from the receptor organs for taste, the taste buds. Two approaches that can be used to overcome a drug’s bad taste include reduction of drug solubility in saliva, which involves striving for a balance between reduced solubility and bioavailability, and alteration of the drug’s ability to interact with taste receptors.
An ideal taste-masking process should:
• involve the fewest pieces of equipment and processing steps possible;
• effectively mask taste with as few excipients as possible;
• have no adverse effect on drug dissolution and bioavailability;
• require excipients that are economical and easily available;
• be cost effective; and
• be scalable.
Flavor and Sweetener Profile
Flavoring and sweetening offer the simplest and most convenient way to mask taste. Flavors and sweeteners are chosen based on their specific taste and release profiles. Sweeteners like sodium saccharin, sucralose, and acesulfame potassium, for example, give instant sweetness, whereas sweeteners like monoammonium glycyrrhizate give lingering sweetness. These sweeteners are used either alone or in combination to give a desired sweetness profile.
Flavors are always a combination of various components that are formulated together to give a desired flavor profile. These components include base flavors, coolants, and desensitizers. Flavoring agents can be obtained from either natural or synthetic sources.Natural products include fruit juices, aromatic oils such as peppermint and lemon, herbs, spices, and distilled fractions of these. They are available as concentrated extracts in alcoholic or aqueous solutions such as syrups and spirits.
Many other compositions, such as alkaline earth oxide, alkaline earth hydroxide, and alkaline hydroxide, have also been found to improve flavor. Although these compositions offer the easiest technique to work with, it is generally not an effective method and can only mask the taste of mildly bitter low-dose drugs that have a low to moderate solubility.
Coating Drug Particles
Two approaches that can be used to overcome a drug’s bad taste include reduction of drug solubility in saliva and alteration of the drug’s ability to interact with taste receptors.Coating drugs with suitable polymer is an excellent way to provide a physical barrier around a drug, concealing it from the taste buds. Selecting the right type of coating material makes it possible to mask a drug’s bitter taste completely, without adversely affecting the intended drug release profile. The coating material can be selected from a range of hydrophobic and hydrophilic polymers, including polyvinylpyrollidone, polyvinyl alcohol, hydroxypropyl methyl cellulose, copovidone, ethyl cellulose, cellulose acetate and phthalates, metha acrylate, and shellac.
Drug particles can also be coated using spray congealing, microencapsulation, and fluidized bed coating. Of these, spray congealing and fluidized bed coating are the most effective taste masking techniques because they are cost effective, don’t require a solvent, and can produce a more dense film than other methods.
Another effective drug coating technique is microencapsulation, a process in which a relatively thin coating is applied to small particles of solid. Coating agents include gelatin, povidone, hydroxyprop-ylmethylcellulose (HPMC), ethyl cellulose, beeswax, carnauba wax, acrylics, and shellac. Bitter-tasting drugs can first be encapsulated to produce free-flowing microcapsules, which can then be blended with other excipients and compressed into tablets. Microencapsulation can be accomplished using a variety of methods including air suspension, coacervation, phase separation, spray drying and congealing, pan coating, solvent evaporation, and multiorifice centrifugation.
Although coating drug particles is the most efficient way to achieve near-to-complete taste masking, it is a complicated and time-consuming process that requires sophisticated equipment and can have a negative effect on dissolution rates.
Inclusion complexation is a process in which the guest molecule is included in the cavity of a host. The complexing agent masks the bitter taste of the drug either by decreasing its oral solubility on ingestion or decreasing the number of drug particles exposed to taste buds, thereby reducing the perception of bitter taste.
Cyclodextrins are the most widely used complexing agent for inclusion complex formation. Cyclodextrins are cyclic oligosaccharides containing either six, seven, or eight glucose units, categorized accordingly as alpha, beta, and gamma cyclodextrin. Beta cyclodextrin is the most commonly used cyclodextrin for inclusion complexation because its cavity size fits in the aromatic ring present in most drug molecules. Physical forces such as van der Waal’s forces and hydrophobic interactions stabilize the complex that is formed. The complex liberates the drug when diluted by a medium. In cases where the binary complex is not good enough to serve the purpose, ternary complexation, which involves the use of a third component in addition to the drug and cyclodextrin, is utilized for efficient taste masking. The third component is generally a low molecular weight hydrophilic polymer such as polyvinyl pyrollidone and HPMC.
Ion Exchange Resins
The adsorption of bitter drugs onto synthetic ion exchange resins to achieve taste coverage has been well documented. Synthetic ion exchange resin was used in pharmacy and medicine for taste masking or controlled drug release as early as 1950. Ion exchange resins are solid and suitably insoluble high molecular weight polyelectrolytes that can exchange their mobile ions of equal charge with the surrounding medium. The resulting ion exchange is reversible and stiochiometric, resulting in the displacement of one ionic species by another.
Drugs with ionizable functionalities form ion exchange complex with resin; this complex (resinate) is insoluble and prevents the drug’s exposure to the taste bud. On reaching the gastric lumen, the complex dissociates and releases the drug due to the exchange of drug with counterions. Because they are high molecular weight water-insoluble polymers, the resins are not absorbed by the body and are therefore inert.
Solid dispersion has been defined as dispersion of one or more active ingredients in an inert carrier or matrix at solid state prepared by melting (fusion) solvent or the melting solvent method. Carriers used in solid dispersion systems include povidone, polyethylene glycols of various molecular weights, HPMC, urea, mannitol, and ethyl cellulose. Though well documented and researched, this technique is not popular commercially because of difficulties with scalability at the industrial level.
Melt granulation is carried out at elevated temperatures (50-80°C) using low-melting lipids like glyceryl behenate and glyceryl palmitostearate as binders. This approach comes with its own drawbacks, however: It’s not suitable for drugs with heat sensitivity, it runs the risk of negatively affecting the dissolution rate, and it can create stability issues due to the susceptibility of lipids to oxidative degradation. Less commonly used techniques include:
Chemical modification: Using this technique, a drug is a chemically modified inert drug precursor that liberates the pharmacologically active parent drug upon biotransformation. This approach focuses on developing a salt or derivative form of the parent drug that tastes less bitter.
Wet granulation: This simple taste-masking method involves the use of hydrophobic solution or hydrophilic polymers as the binder for coating. This is a normal granulation process that requires no sophisticated equipment.
Anesthetizing/desensitizing agents: This technique involves the use of anesthetizing or desensitizing agents to temporarily numb the taste buds. The loss of sensation prevents perception of taste, which helps to mask the bitter taste.
Multiple emulsions: This is a novel technique for taste masking that employs multiple emulsions prepared by dissolving the drug in the inner aqueous phase of water-in-oil-in-water emulsion under conditions of good shelf stability. The formulation is designed to release the drug through the oil phase in the presence of gastrointestinal fluid.