Taste Masking of Bitter Drugs in Pharmaceutical Suspension: A Review

 

Kishan Pal Singh1*, Santosh Dighe2

1Research Scholar Bhagwant University, Ajmer, Rajasthan.

2Department of Pharmacology, Pravara Rural College of Pharmacy, Loni.

*Corresponding Author E-mail: sbdigheprcop@gmail.com

 

ABSTRACT:

One of the most vital factors in the formulation of medications for children, the elderly, immobile patients, and uncooperative patients is taste, which is mainly controlled by taste buds in the tongue. The biggest challenge for the compounding scientists is to mask the unpleasant and bitter tastes of the pharmaceuticals, which prevent patients from obtaining the full therapeutic benefit of their prescription. In order to increase patient compliance, which ultimately determines the product's economic success, it may be possible to mask the bitter taste of medications. Inclusion complexation, the use of ion exchange resin, mass extrusion, solid dispersions, coating granulation, spray drying, microencapsulation, liposomes, emulsions, and gel formation effervescence are current methods of flavour masking. Active pharmaceutical ingredient (API) taste masking is an area that is constantly developing because of unusual excipients and a variety of techniques.

 

KEYWORDS: Oral dosage Form, Pharmaceutical Suspension, Bitter drug, Taste Masking.

 

 


INTRODUCTION:

The primary concern is the oral delivery of bitter medications with a sufficient level of palatability. For medical professionals, especially those who treat children. In earlier times, it was thought that giving medications orally with a bitter taste would be more effective and curable1. In a biological sense, taste is defined as a chemical reaction that results from mouth-based sensory trigger signals that are delivered to the brain, where a particular taste experience is acknowledged as a reaction from the four basic taste perceptions: salt, sour, bitter, and sweet. Taste is the body's capacity to discern the flavour of various substances, including food, medications, and other things. Humans have between 9000 and 10000 taste buds, and under foetal settings, one cell can have between 55 and 105 taste buds. People typically acquire appetites for flavours or meals that they once considered unpleasant as youngsters.

 

The majority of pharmaceutical active ingredients have a disagreeable taste, which can range in intensity from mild to strong and can taste like a lingering chemical flavour or a sharp bitterness. Including liquid forms such as solutions, emulsions, or suspensions with solid forms such as capsules and tablets presents a difficulty for pharmaceutical makers since these forms have the highest potential to expose the drug in the mouth, leading to an unpleasant taste and low compliance2,3. The liquid composition uses a reverse enteric coating, which is relatively insoluble at the non-acidic pH of the mouth but soluble in the stomach's acid pH, which is typically between 1-4. In the case of liquid dosage forms, the coating allows for the drug's fast release and absorption, which is normally preferred4.

 

 

Two methods are frequently employed, among many others, to lessen the harsh taste of medications5.

1.     By lowering the drug's solubility in saliva, which has a pH between 5.5 and 6.9.

2.     By changing the drug's affinity and makeup, which will affect how it interacts with the taste receptor.

 

The attributes that follow should be included in the ideal taste-masking formulations:

·       Fast and simple preparation.

·       There are no adverse effects on drug bioavailability.

·       Can be done in a warm environment.

·       Lowest manufacturing expenses.

·       Request a minimal amount of excipients in an optimum formulation.

·       Request for inexpensive, widely accessible excipients.

 

Pharmaceutical Suspension:

For poorly soluble medications with a variety of therapeutic goals, suspensions are one of the most significant pharmaceutical dose forms. They are designed to be used in the production of oral, ophthalmic, tropical, and parental dosage forms6. In heterogeneous systems with uniform dispersion, suspensions are made up of minimally soluble solid drug particles that are kept suspended within the medium.

 

 

Figure 1. Classification of Pharmaceutical Suspension:

 

Classification of Pharmaceutical Suspension:7

Pharmaceutical Suspension Formulation:

A discussion of multiple issues is necessary for formulating a suspension. A suspension that provides content homogeneity is desirable. Important issues with particle size distribution, particular surface area, preventing crystal development, and changes in the polymorphic form must be dealt with by the formulator.

 

Table 1. Formulation additives

Sr.

No

Ingredients

Purpose

Examples

1

Liquid vehicle

To construct the structure of the final suspension

Water and oily vehicles

2

Flocculating agents

To form loose aggregates of the dispersed phase

Gums, polacrylamides. gelatin, alginates, and chitosan

3

Colouring agents

To impart the desired colour to suspension and improve elegance.

Amaranth, saffron, sunflower yellow, caramel, and madder plants

4

Antioxidant

To prevent the degradation of drugs by oxidation and to improve stability.

Ascorbic acid, tocopherols,

sodium metabisulphite

5

Buffers and pH-adjusting agents

To stabilise the suspension to a desired pH range.

Salts of weak acids such as citrate, phosphate, and carbonate

6

Preservatives

To prevent microbial growth.

Sodium benzoate, methyl paraben, and benzoic acid

7

Anticaking agent

Prevents hard cake formation and forms an easily redispersible suspension.

Colloidal silicon dioxide

(Aerosil 200), talc.

8

Flavouring agent

To improve product elegance.

Ginger, cherry syrup, orange oil, nutmeg oil, Peppermint oil, and pineapple

9

Suspending agent (thickener)

To increase the viscosity of the suspension.

Methyl cellulose, CMC, tragacanth, and xanthan gum

10

Wetting agents

To disperse solids in a continuous liquid phase.

Surfactants, polysorbate 80

 

The formulator must make sure that these and other qualities remain unchanged over time and have no adverse effects on suspension applications. Some of the most important variables that must be regulated during formulation are the choice of pH, particle size, viscosity, flocculation, taste, colour, and aroma.

 

Advantage:7,8

·       Safe for both paediatric and elderly patients

·       Medicines that are insoluble and suspended are simple to consume.

·       Improve bioavailability

 

Disadvantage:7,8

·       The preparation must be shaken prior to measuring a dose.

 

Taste Masking:9

To increase patient compliance, particularly in the paediatric and geriatric population, taste masking becomes essential for bitter drugs. A chemical stimulus to the taste receptors of the tongue causes a sensory response known as taste, according to biology. A substance's flavour is determined by its taste, appearance, smell, and other characteristics like mouth feel. Taste is a sense that arises from the activation of taste buds that are located on the tongue's surface. Sourness, saltiness, sweetness, bitterness, and umami (savoury) are the five taste sensations that humans are able to differentiate between10. On the apical membrane of the taste receptor cells (TRC) found in the taste buds, bitter chemicals bind to a G protein-coupled receptor type T2R. There are over 25 distinct T2Rs known to exist in humans. There are also a number of identified genes and around 100 distinct phenotypes in humans. TRC is an expert in a certain flavour quality.

 

One TRC expresses more than one T2R type for the bitter modality, but not in every variety. However, it is now recognised that a single bitter substance may bind to many T2R subtypes with varying degrees of affinity and that at least certain bitter receptor proteins, such as hT2R47, are extensively tailored for a variety of bitter molecule structural classes. As a result, the cells experience a bitter taste pattern similar to olfaction; nevertheless, the final signal to the brain is mostly "negative" or "bitter."

 

Multiple techniques are considered to be effective in reducing a drug's bitter or unpleasant taste, as follows10:

 

Figure 2.Taste masking techniques

 

 

 

A.   Taste masking by Microencapsulation:11

The active moiety (solid or liquid droplets) is covered with a polymeric substance or film during the microencapsulation process.

Types of microencapsulation include:

·       Spray drying.

·       Spray congealing

·       Air suspension coating

·       Coacervation phase separation

·       Solvent evaporation

·       Pan coating

·       Interfacial polymerization, etc.

 

The first four of these procedures are typically used as methods for disguising tastes. Three processes, including the production of three immiscible phases, the application of the coating, and the regasification of the coating, are involved in the process of microencapsulation by coacervation phase separation.

 

Table 2. Taste masking of bitter drugs by microencapsulation

Technique

Drug

Coatingagent

Dosage form

Spray drying

Roxithromycin, Nizatidine  

Sodium CMC, Eudragit E100

Suspension, Powders, and sprinkles

Solvent Evaporation

Metronidazole

Eudragit E., Fattibase

Dry Suspension

Top spray fluid bed coating

Sildenafil citrate, Chlorpheniramine maleate, and dextromethorphan hydrobromide

Eudragit NE30D, E100

Dry suspension, mouth-melting tablet

 

B.    Taste masking by Coating:12

One of the most effective and widely used techniques in taste masking technology is coating. Lipids, polymers, and sugars are the different types of coating materials. To cover up the taste of the bitter medications, these compounds can be employed singly or in combination, as a single layer or many layers of coating. To disguise the taste of bitter medications, hydrophobic polymers have been used more frequently than hydrophilic polymers. To improve flavour masking, sweeteners can also be added to the coating solution. To overcome coating flaws that might ordinarily result in a reduction in taste masking performance, especially with drugs with a strong bitterness, multilayer coating has been done. Polymers are one of the many types of coating materials that are currently available. Lymers are further classified into water-soluble, water-insoluble, and Before making a decision, the following factors must be considered:

·       The particle size of the drug

·       Flow characteristics of the drug.

·       Long-term stability

·       Moisture sensitivity

·       Temperature of processing and most important

·       Method of delivery of the active drug molecule

C.   Taste masking by gelation:12

For taste masking, a water-insoluble gel can be applied to the surface of a bitter medicine tablet. When dual metal ions are present, sodium alginate can lead to water-insoluble gelation. Amiprolose hydrochloride tablets have been coated with calcium gluconate on top and sodium alginate underneath to hide their flavour. A water-insoluble gel is created when sodium alginate and bivalent calcium interact in the presence of saliva, disguising its taste.

 

D.   Taste masking by gel formation:

For taste masking, a water-insoluble gel can be applied to the surface of a bitter medicine. When bivalent metal ions are present, sodium alginate can lead to water-insoluble gelation. Amiprolose hydrochloride tablets have been coated with calcium gluconate on top and sodium alginate underneath to hide their taste. By forming a water-insoluble gel in the presence of saliva, sodium alginate and bivalent calcium cover up the taste of mixes.

 

E.    Taste masking by Adsorption:

A less saliva-soluble form of bitter-tasting drugs is known as an adsorbate. Adsorbents for bitter drugs are created using this technology. In this procedure, insoluble substances like silica gel, bentonite, veegum, etc. are used to adsorb the medication solution. The dried adsorbate (resultant powder) is used to create the final dosage forms.

 

F.    Taste masking by Granulation:

The granulation technique has a tendency to cover up a drug's unpleasant taste. Granulation is a significant and frequent step in the manufacture of pharmaceuticals. In this method, the binding agents employed to make the suspension are saliva-insoluble polymers. The bitter taste of the drugs can be covered up since these polymers are insoluble in saliva. The taste-masked granules can also be made into chewable medications that dissolve quickly.

 

G.   Taste masking by flavors and sweeteners:

Sweeteners are often used to mask the flavour of medications. These are frequently used with other taste-masking innovations. These can be used with bitter medications to enhance the flavour of the main ingredient. Based on where they come from, sweeteners are divided into natural and synthetic categories. As opposed to natural sweeteners, artificial sweeteners like sucralose, aspartame, and saccharin are more prominent in taste masking. To lessen the aftertaste they impart, these sweeteners are combined with sugar alcohols such as lactitol, maltitol, and sorbitol. Acids and sucrose can be combined.

 

Examples:

·       Artificial sweetener: saccharin, saccharin sodium aspartame

·       Nutritive: Sucrose, Fructose, and Glucose Polyols: Mannitol, Sorbitol, Xylitol, Erythritol, and Maltitol

·       Natural Sweeteners: Sucrose, glucose, fructose, sorbitol, mannitol, glycerol, Honey, and liquorice

·       Non-Nutritive: Aspartame, sucrose, Neotame, and saccharine

·       Novel sweeteners: trehalose and tagatose

 

Evaluation Techniques:

Sensory evaluation To be straight forward, taste is a highly personal experience. The perceived taste can vary to varying degrees among people. The ability to precisely and consistently assess taste thresholds depends on the design of the experiment.

 

To quantitatively evaluate taste sensation, the following methods have been reported in the literature:

1.     Panel testing (human subjects)

2.     Spectrophotometric evaluation/D30’s value

3.     measurement of frog taste nerve responses

4.     Multichannel taste sensor/magic tongue.

 

1.     Panel Testing:

The panel test evaluates the gustatory stimuli psychophysically. In this procedure, reference solutions varying in taste from tasteless to extremely bitter are used to teach a group of 5–10 human volunteers to rate their taste. These levels of bitterness are then given numerical numbers. The test solution is then tasted and graded using the same scale to determine how bitter it is14,15.

 

2.     Spectrophotometric Method:

By spinning the syringe from end to end five times in the space of 30 seconds, a known amount of the taste-masked formulation is combined with 10 ml of distilled water in a 10 ml bottle. The test medium is then passed through a membrane filter, and the concentration of the drug in the filtrate is subsequently determined spectrophotometrically. It may be taken into consideration that the bitter taste would be covered up in vivo if this concentration was lower than the threshold concentration.16,17

 

3.     Measurement of Frog Taste Nerve Responses:

This technique involves anaesthetizing adult bull frogs intraperitoneally, identifying the glossopharyngeal nerve, separating it from the surrounding tissue, and cutting it proximally. The nerve impulses are enhanced and combined, respectively, using an ace-amplifier and an electronic integrator. The amplitude of the reaction is then determined by the integrated response's peak height18, 19.

4.     Multichannel Taste Sensor/Magic Tongue:

This is a machine that automatically assesses taste to determine how bitter a drug substance is. The device is a transducer that is made up of several lipid or polymer membrane types with various properties that can detect taste in a way that is similar to the human gustatory sense. The receptor part's membrane potentials are used to translate the taste reaction into an electric signal pattern. For drugs providing various taste characteristics, distinct reaction electric potential patterns are obtained20.

 

CONCLUSION:

The scientific community is divided on whether bitter drugs may be masked by taste. Taste-masked medicinal research is becoming increasingly significant and economically successful for improving the quality of treatment provided to unwell patients, particularly children. We attempted to clarify a range of strategies that may be effective for hiding the taste of bitter drugs by developing the way the drug interacts with taste receptors. There are several technologies that can successfully mask the disagreeable taste of pharmaceuticals, but they must be utilised carefully to avoid interfering with drug absorption. Implementing these tactics and appropriately measuring the taste-masking influence can significantly boost product popularity. The two more recent advances are an improvement in coating technique through the use of multiple or spacer layers and a switch to an aqueous-based coating of hydrophobic polymers.

 

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21    Takagi S, Toka K. Detection of suppression of bitterness by sweet substance using a multichannel taste sensor. J Pharm Sci. 1998; 87: 552‐555.

 

 

 

 

 

Received on 28.06.2023         Modified on 20.09.2023

Accepted on 17.11.2023   ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech. 2023; 13(4):270-274.

DOI: 10.52711/2231-5713.2023.00048