Oral Liquid Pharmaceutical Dosage Forms

 

Oral Liquid Pharmaceutical Dosage Forms

by Tapamoy Chakraborty

 

Oral Liquid Dosage Forms in Pharmaceuticals including Syrup, Oral Suspension, Oral Solution, Oral Drop, Oral Emulsion, Mixture, Linctuse and Elixir.

Oral liquids are homogeneous liquid preparations, usually contains a solution, an emulsion or a suspension of one or more active ingredients in a suitable liquid base. They are prepared for oral administration either as such or after dilution. They may contain other substances such as suitable dispersing, solubilizing, wetting, emulsifying, stabilizing, suspending, thickening agents and antimicrobial substances for preservation. They may also contain suitable sweetening agents, flavoring agents and permitted coloring agents. If sodium saccharin or potassium saccharin is used for sweetening, then its concentration in pediatric preparations should not be more than 5 mg per kg of body weight. During manufacturing, packaging, storage and distribution process of oral liquids, microbial quality should be maintained and microbial count should be within the acceptance criteria. Oral Liquids should not be diluted and stored after dilution unless the individual monograph directs for dilution. Diluted oral liquids may not be stable for long period physically and chemically so it should be diluted freshly or should be used within the period as stated on the label.

Types of oral liquids:

1. Syrup

2. Oral Suspension

3. Oral Solution

4. Oral Drop

5. Oral Emulsion

6. Mixture

7. Linctus

8. Elixir

1. Syrup: The syrup is a vicious oral liquid that contains one or more active ingredients in solution. The base generally contains large amounts of sucrose or other sugars to which sorbitol may be added to inhibit crystallization or to modify solubilization, taste and other base properties. Sugarless syrups may contain other sweetening agents as saccharin and thickening agents. Syrups may contain ethanol (95%) as a preservative or as a solvent for flavors. Antimicrobial agents may also be added to syrups to maintain the microbial quality of preparation.

2. Oral Suspension: Oral Suspension is an oral liquid that contains one or more active ingredients suspended in a suitable base. Suspended solids may separate a time period on keeping but are easily re-dispersed on shaking. In the manufacturing of oral suspensions containing suspended particles, it should be ensured that particle size should be controlled with regard to the intended use of the preparation.

3. Oral Solution: Oral Solution is an oral liquid that contains one or more active ingredients dissolved in a suitable base.

4. Oral Drop: Oral Drop is an oral liquid that is prepared to take in small quantity with the help of a suitable measuring device such as a dropper.

5. Oral Emulsion: Oral Emulsion is an oral liquid that contains one or more active ingredients that are unstable in the water phase and is stabilized oil-in-water dispersions; either or both phases of the preparation may contain dissolved solids. Both phases of the preparation may separate but are easily mixed by shaking. The preparation is fully stable to give a homogeneous dose when taken after proper shaking.

6. Mixtures: The mixture is an oral liquid containing one or more active ingredients suspended or dispersed in a suitable base. Suspended solids may separate on keeping for a time period but are easily re-suspended on shaking.

7. Linctus: Linctus is a vicious oral liquid that contains one or more active ingredients dissolved in a suitable base that generally contains a higher concentration of sucrose or other sugars. Linctuses are generally prepared for treatment of a cough and these are taken without the addition of water.

8. Elixir: This is a clear, flavored oral liquid containing one or more active ingredients dissolved in a suitable base that contains a high proportion of sucrose and may also contain ethanol (95 percent) or a diluted ethanol.

Drug solubility In pharmaceutical solutions both the therapeutic agent and the excipients are legally required to be present in solution over the shelf-life of the formulated product. As a result pharmaceutical solutions are termed homogeneous. One of the major challenges to the pharmaceutical scientist is the attainment of homogeneity in the formulation, due primarily to, in many cases, the limited aqueous solubility of the therapeutic agent.

Initially there are possible scenarios regarding the formulation of pharmaceutical solutions of a therapeutic agent for oral administration:

■ The aqueous solubility of the therapeutic agent is high at the selected pH of the formulation. Under these circumstances the therapeutic agent may be readily incorporated into the vehicle and formulated as an oral solution.

■ The aqueous solubility of the therapeutic agent is moderate at the selected pH of the formulation, i.e. the aqueous solubility is less than the requested concentration of therapeutic agent.

■ The aqueous solubility of the therapeutic agent is low at the selected pH of the formulation. The difference between the aqueous solubility of the therapeutic agent and the required concentration is too great to be bridged by the use of co-solvents and related methods or the concentration of cosolvents or surfactants in the solubilised formulation may be toxic when administered orally. The drug may therefore be formulated as an alternative-dosage form, e.g. a suspension. Prior to discussing the solubility of therapeutic agents and formulation strategies to modify this property, it is worth considering the process of drug dissolution.

The dissolution of a therapeutic agent in water involves several key molecular steps: the removal of a molecule of the drug from the solid state, the formation of a cavity within the solvent and the accommodation of the drug molecule into the formed cavity. This process involves the breakage of solute–solute and solvent–solvent bonds (endothermic processes) and the formation of a bond between the solute and the solvent (with the subsequent liberation of energy). Dissolution occurs whenever the Gibb’s free energy  of the process is negative and involves a balance between the enthalpy of dissolution  and the associated entropy  at the temperature of dissolution (T), as defined below:

Factors affecting the solubility of therapeutic agents The solubility properties of drug molecules in a particular solvent system are sometimes difficult to predict and have been reported to be dependent, at least in part, on several physicochemical properties, including molecular weight, volume, radius of gyration, density, number of rotatable bonds, hydrogen bond donors and hydrogen bond acceptors. Furthermore, the properties of the solid state, e.g. crystal habit, crystalline/amorphous properties, will also affect the solubility of the therapeutic agent.

There are some empirical relationships between the physicochemical properties and the solubility of therapeutic agents that influence formulation strategies, as follows:

■ The solubilities of a chemically related series of therapeutic agent are inversely related to their melting points. Therefore, as the melting point of the therapeutic agent is increased, the solubility would be expected to decrease.

■ The solubility of a therapeutic agent is directly affected by both the type of chemical substituent groups and the substituent position. The solubility of therapeutic agents Oral pharmaceutical solutions containing hydrophilic groups (e.g. OH, COO, ammonium ion) will accordingly be greater than those containing lipophilic substituent groups, e.g. methyl, ethyl, ethoxy or chlorine groups.

■ The solubilities of therapeutic agents that are either acids or bases (representing the vast majority of drug substances) are pH-dependent. The solubility of acids and bases increases as the degree of ionisation increases and may be easily calculated using the following equation (where S refers to the solubility of the drug and So is the intrinsic solubility, i.e. the solubility of the unionised form of the drug). pK  pKa  log S  So for acids ( So ) pH pKa log So for bases (S  So) From these equations two invaluable conclusions may be drawn: – At pH values above the pKa, the solubility of acidic drugs increases. – At pH values below the pKa, the solubility of basic drugs increases. In simple terms the solubility of acidic compounds increases as the pH of the solution is increased (above the pKa) and the solubility of basic compounds increases as the pH is lowered below the pKa. Determination of the solubility properties of zwitterionic compounds, i.e. those that exhibit both acidic and basic properties, is more complicated than for simple acids or bases. However, in common with simple acids and bases, the solubility of zwitterionic therapeutic agents is affected by pH. At basic pH values the therapeutic agent behaves primarily as an acid whereas at low pH values the molecule behaves as a base. The pH range at which the therapeutic agent exhibits minimal solubility lies between the pKa values of the acidic and basic groups. Formulation methods to enhance/optimise the solubility of therapeutic agents The information described below may be employed to optimise the formulation of pharmaceutical solutions, remembering that the prerequisite for pharmaceutical solutions is the exclusive presence of dissolved therapeutic agent.

 Appropriate selection of drug salt The reader will be aware that the majority of therapeutic agents are commercially available to the pharmaceutical scientist in a range of salt forms, each form exhibiting a different aqueous solubility. The differences in solubility may be accredited, at least in part, to the crystal properties of the salt, which, in turn, affect the energy required to dissociate solute–solute bonds. Therefore, unless a specific salt form is specified or in the absence of a pharmaceutical approved salt of a therapeutic agent, the formulation scientist should select the salt that provides the required solubility in the dosage form. Optimisation of the pH of the formulation As mentioned above, the solubility of an ionised therapeutic agent is a function of both the pKa of the compound and the pH of the formulation. Importantly, the acceptable pH range of solutions for oral administration is large, ranging from circa 5 to 8 pH units. Therefore, a common formulation strategy involves the selection of a pH value for the formulation that optimises the ionisation and hence solubility of the therapeutic agent. Control of the pH in the formulation is achieved using a buffer that does not adversely affect the solubility of the therapeutic agent. Use of co-solvents Co-solvents are primarily liquid components that are incorporated into a formulation to enhance the solubility of poorly soluble drugs to the required level. In the formulation of pharmaceutical solutions for oral administration, aqueous solutions are preferred due to the lack of toxicity of water as the vehicle. However, if the solubility of the therapeutic agent renders this approach inappropriate, the incorporation of co-solvents within the formulation offers a pharmaceutically acceptable approach. Commonly employed co-solvents include glycerol, propylene glycol, ethanol and poly(ethylene glycol), details of which are provided in subsequent sections. Prediction of the solubility of therapeutic agents in mixed solvent systems (the vehicle, water and the chosen co-solvent) is difficult, due to the effects of many variables on the solubility (as described previously). In practice the pharmaceutical scientist should measure the solubility of the chosen therapeutic agent in a series of mixed solvents to determine the most suitable solvent system for the given purpose.

The final choice of the co-solvent system for a particular formulation involves consideration of the solubility of the therapeutic agent in the vehicle, the toxicity of the vehicle and the cost of the formulation. Indeed, it should be noted that the range of concentrations of each co-solvent used in oral formulations is primarily limited by concerns regarding toxicity.

Excipients used in pharmaceutical solutions for oral administration Excipients in pharmaceutical formulations are physiologically inert compounds that are included in the formulation to facilitate the administration of the dosage form, e.g. pourability, palatability, to protect the formulation from issues regarding physical and chemical stability and to enhance the solubility of the therapeutic agent. Pharmaceutical solutions commonly contain a wide range of excipients, the details of which are provided below.

The vehicle The preferred and most commonly used vehicle in solutions for oral administration is Purified Water USP, due to the low cost and low toxicity of this ingredient. Under normal circumstances tap (drinking) water should not be used due to the possibility of chemical imcompatibities within the formulation.

The main features of Purified Water USP are as follows:

■ It is prepared by distillation, ion exchange methods or by reverse osmosis.

■ The solid residue (obtained after evaporation) is less than 1 mg per 100 ml of evaporated sample.

■ It must not be used for the preparation of parenteral formulations.

In the case of parenteral formulations Water for Injections BP must be used, the specifications, co-solvents are employed to increase the solubility of the therapeutic agent within the formulation. The main co-solvents that are used in the formulation of oral solutions are detailed below.

Glycerol  (also termed glycerin) is an odorless, sweet liquid that is miscible with water and whose co-solvency properties are due to the presence of three hydroxyl groups (termed a triol. It has similar co-solvency properties to ethanol.

Alcohol USP (CH3CH2OH) Alcohol USP contains between 94.9 and 96.0% v/v ethyl alcohol (ethanol) and is commonly used as a co-solvent, both as a single co-solvent and with other co-solvents, e.g. glycerol. The known pharmacological and toxicological effects of this co-solvent have compromised the use of alcohol in pharmaceutical preparations. As a result there are both labelling requirements for preparations that contain alcohol and upper limits with respect to the concentration of alcohol that may be used in formulations.

Propylene Glycol USP is an odourless, colourless, viscous liquid diol that contains two hydroxyl groups.It is used in pharmaceutical preparations as a co-solvent, generally as a replacement for glycerin.

Poly(ethylene glycol) (PEG) PEG is a polymer composed of repeating units of the monomer ethylene oxide (in parenthesis). The physical state of the polymer is dependent on the number of repeat units (n) and hence on the molecular weight. Lower-molecular-weight grades (PEG 200, PEG 400) are preferred as co-solvents in pharmaceutical solutions. Miscellaneous agents used to enhance the solubility of therapeutic agents In addition to the use of co-solvents, other pharmaceutical strategies are available to the pharmaceutical scientist to increase the solubility of therapeutic agents in the chosen vehicle.

Surface-active agents are chemicals that possess both hydrophilic (water-liking) and hydrophobic (water-disliking) regions. At dilute concentrations surface-active agents will orient at the interface between two phases (e.g. water/oil, water/air), with the hydrophilic and hydrophobic regions of the molecule being positioned to the hydrophilic and hydrophobic phases, respectively. As the concentration is increased, the interface will become saturated with surface-active agent and the molecules that are present in the bulk aqueous phase will orient themselves in an attempt to shield the hydrophobic regions of the surface-active agent. This orientation is referred to as a micelle and the concentration of surface-active agent at this occurs is termed the critical micelle concentration (CMC). The use of surface-active agents for the solubilisation of poorly soluble drugs occurs exclusively in the presence of micelles and hence at concentrations of surface-active agents in excess of the CMC. In this the core of the micelle represents a hydrophobic region into which the poorly water-soluble drugs may partition. The location in the micelle is related to the chemical structure of the drug. For example, if the therapeutic agent is poorly soluble the molecule will locate exclusively within the micelle, whereas if the drug is water-insoluble but contains polar groups, the molecule will orient within the micelle, with the polar groups at the surface of the micelle and the hydrophobic region of the molecule located within the hydrophobic core of the micelle. In so doing the drug is solubilised within the colloidal micelles; due to their small size, the resulting solution appears homogeneous to the naked eye. Complexation Complexation refers to the interaction of a poorly soluble therapeutic agent with an organic molecule, e.g. surface-active agents, hydrophilic polymers to generate a soluble intermolecular complex. One particular concern regarding the use of solution of drug complexes is the ability of the complex to dissociate following administration. This is particularly important in situations where the complexing agent is a hydrophilic polymer, as the high molecular weight of the 8 Pharmaceutics: Dosage Form and Design As the reader will have observed, there are several methods that may be used for the solubilisation of therapeutic agents.

Drug–polymer complex would prevent drug absorption across biological membranes. Common excipients in pharmaceutical solutions There are several excipients that are commonly employed in the formulation of pharmaceutical solutions. These include:

(1) buffers;

(2) sweetening agents; and

(3) viscosity-enhancing agents.

Buffers are employed within pharmaceutical solutions to control the pH of the formulated product and, in so doing, optimise the physicochemical performance of the product.

Typically pH control is performed:

■ to maintain the solubility of the therapeutic agent in the formulated product. The solubility of the vast number of currently available drugs is pH-dependent and, therefore, the solubility of the therapeutic agent in the formulation may be compromised by small changes in pH

■ to enhance the stability of products in which the chemical stability of the active agent is pH-dependent. The concentration (and hence buffer capacity) of buffer salts employed in the formulation of oral solutions should be selected to offer sufficient control of the pH of the formulation but yet should be overcome by biological fluids following administration. This latter property is particularly appropriate for parenteral formulations to ensure that there is no irritation or damage following injection.

Examples of buffer salts used in pharmaceutical solutions include:

■ acetates (acetic acid and sodium acetate): circa 1–2%

■ citrates (citric acid and sodium citrate): circa 1–5%

■ phosphates (sodium phosphate and disodium phosphate): circa 0.8–2%.

It must be remembered that the buffer system used in solution formulations should not adversely affect the solubility of the therapeutic agent, e.g. the solubility of drugs may be affected in the presence of phosphate salts. Sweetening agents Sweetening agents are employed in liquid formulations designed for oral administration specifically to increase the palatability of the therapeutic agent. The main sweetening agents employed in oral preparations are sucrose, liquid glucose, glycerol, sorbitol, saccharin sodium and aspartame.

Saccharin sodium is used either as the sole sweetening agent or in combination with sugars or sorbitol to reduce the sugar concentration in the formulation. The use of sugars in oral formulations for children and patients with diabetes mellitus is to be avoided.

Viscosity-enhancing agents The administration of oral solutions to patients is usually performed using a syringe, a small-metered cup or a traditional 5-ml spoon. The viscosity of the formulation must be sufficiently controlled in order to ensure the accurate measurement of the volume to be dispensed. Furthermore, increasing the viscosity of some formulations may increase the palatability. Accordingly there is a viscosity range that the formulation should exhibit to facilitate this operation. Certain liquid formulations do not require the specific addition of viscosity-enhancing agents, e.g. syrups, due to their inherent viscosity. The viscosity of pharmaceutical solutions may be easily increased (and controlled) by the addition of non-ionic or ionic hydrophilic polymers. Examples of both of these categories are shown below:

■ non-ionic (neutral) polymers – cellulose derivatives, e.g.: ● methylcellulose ● hydroxyethylcellulose ● hydroxypropylcellulose – polyvinylpyrrolidone

■ ionic polymers – sodium carboxymethylcellulose (anionic) – sodium alginate (anionic). Full details of the physicochemical properties of these polymers are provided in later chapters. Antioxidants Antioxidants are included in pharmaceutical solutions to enhance the stability of therapeutic agents that are susceptible to chemical degradation by oxidation.

Typically antioxidants are molecules that are redox systems that exhibit higher oxidative potential than the therapeutic agent or, alternatively, are compounds that inhibit free radical-induced drug decomposition. Typically in aqueous solution antioxidants are oxidised (and hence degraded) in preference to the therapeutic agent, thereby protecting the drug from decomposition. Both water-soluble and water-insoluble antioxidants are commercially available, the choice of these being performed according to the nature of the formulation,sodium sulphite, sodium metabisulphite, sodium formaldehyde sulphoxylate and ascorbic acid. Examples of antioxidants that may be used in oil-based solutions include: butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) and propyl gallate. Typically antioxidants are employed in low concentrations (0.2% w/w) and it is usual for the concentration of antioxidant in the finished product to be markedly less than the initial concentration, due to oxidative degradation during manufacture of the dosage form. Antioxidants may also be employed in conjunction with chelating agents, e.g. ethylenediamine tetraacetic acid, citric acid, that act to form complexes with heavy-metal ions, ions that are normally involved in oxidative degradation of therapeutic agents.

Preservatives are included in pharmaceutical solutions to control the microbial bioburden of the formulation. Ideally, preservatives should exhibit the following properties:

■ possess a broad spectrum of antimicrobial activity encompassing Gram-positive and Gram-negative bacteria and fungi

■ be chemically and physically stable over the shelf-life of the product

■ have low toxicity. A wide range of preservatives is available for use in pharmaceutical solutions for oral use, including the following (values in parentheses relate to the typical concentration range used in oral solutions):

■ benzoic acid and salts (0.1–0.3%)

■ sorbic acid and its salts (0.05–0.2%)

■ alkyl esters of parahydroxybenzoic acid (0.001–0.2%).

Usually a combination of two members of this series is employed in pharmaceutical solutions, typically methyl and propyl parahydroxybenzoates (in a ratio of 9:1). The combination of these two preservatives enhances the antimicrobial spectrum. Factors affecting preservative efficacy in oral solutions The activity of a preservative is dependent on the correct form of the preservative being available in the formulation at the required concentration to inhibit microbial growth (termed the minimum inhibitory concentration: MIC). Unfortunately, in many solution formulations, the concentration of preservative within the formulation may be affected by the presence of other excipients and by formulation pH. Factors that directly affect the efficacy of Oral pharmaceutical solutions preservatives in oral solutions include: (1) the pH of the formulation; (2) the presence of micelles; and (3) the presence of hydrophilic polymers. The pH of the formulation. In some aqueous formulations the use of acidic preservatives, e.g. benzoic acid, sorbic acid, may be problematic.

 

Flavours. These are employed whenever the unpalatable taste of a therapeutic agent is apparent, even in the presence of the sweetening agents. The flavours may be of natural origin (e.g. peppermint, lemon, herbs and spices) and are available as oils, extracts, spirits or aqueous solutions. Alternatively, a wide range of synthetic flavours are available that offer advantages over their natural counterparts in terms of purity, availability, stability and solubility. Certain flavours are also associated with a (mild) therapeutic activity. For example, many antacids contain mint due to the carminative properties of this ingredient. Alternatively other flavours offer a taste-masking effect by eliciting a mild local anaesthetic effect on the taste receptors. Examples of flavours in this category include peppermint oil, chloroform and menthol. The concentration of flavour in oral syrups is that which is required to provide the required degree of taste-masking effectively.

 Colours These are generally natural or synthetic watersoluble, photo-stable ingredients that are selected according to the flavour of the preparation. For example, mint-flavoured formulations are commonly a green colour, whereas in banana-flavoured solutions a yellow colour is commonly employed. Such ingredients must not chemically or physically interact with the other components of the formulation.

An elixir is a clear, hydroalcoholic solution that is formulated for oral use. The concentration of alcohol required in the elixir is unique to each formulation and is sufficient to ensure that all of the other components within the formulation remain in solution. For this purpose other polyol co-solvents may be incorporated into the formulation. The presence of alcohol in elixirs presents a possible problem in paediatric formulations and, indeed, for those adults who wish to avoid alcohol. The typical components of an elixir are as follows:

■ Purified water.

■ Alcohol. This is employed as a co-solvent to ensure solubility of all ingredients. As highlighted above, the concentration of alcohol varies depending on the formulation. Generally the concentration of alcohol is greater than 10% v/v; however, in some preparations, the concentration of alcohol may be greater than 40% v/v.

■ Polyol co-solvents. Polyol co-solvents, e.g. propylene glycol, glycerol, may be employed in pharmaceutical elixirs to enhance the solubility of the therapeutic agent and associated excipients. The inclusion of these ingredients enables the  concentration of alcohol to be reduced. As before, the concentration of co-solvents employed is dependent on the concentration of alcohol present, the type of co-solvent used and the solubility of the other ingredients in the alcohol/co-solvent blend. The reader is directed to the pharmacopoeial monographs to observe the concentration of co-solvents in specific examples of the pharmaceutical elixirs. Two examples in the USP that illustrate the range of concentrations of co-solvents are Phenobarbital Elixir and Theophylline Elixir .

■ Sweetening agents. The concentration of sucrose in elixirs is less than that in syrups and accordingly elixirs require the addition of sweetening agents. The types of sweetening agents used are similar to those used in syrups, namely syrup, sorbitol solution and artificial sweeteners such as saccharin sodium (Figure 1.8). It should be noted, however, that the high concentration of alcohol prohibits the incorporation of high concentrations of sucrose due to the limited solubility of this sweetening agent in the elixir vehicle. To obviate this problem, saccharin Oral pharmaceutical solutions

Phenobarbital Elixir Phenobarbital (therapeutic agent) 0.4% w/v Orange oil (flavour) 0.025% v/v Propylene glycol (co-solvent) 10% v/v Alcohol 20% v/v Sorbitol solution (sweetener) 60% v/v Colour As required Purified water ad 100%

Theophylline Elixir Theophylline (therapeutic agent) 0.53% w/v Citric acid (pH regulation) 1.0% w/v Liquid glucose (sweetening agent) 4.4% w/v Syrup (sweetening agent) 13.2% v/v Saccharin sodium (sweetening agent) 0.5% w/v Glycerin (co-solvent) 5.0% v/v Sorbitol solution (co-solvent) 32.4% v/v Alcohol 20% v/v Lemon oil (flavour) 0.01% w/v FDC yellow no. 5 (colour) 0.01% w/v Purified water ad 100% sodium, an agent which is used in small quantities and which exhibits the required solubility profile in the elixir, is employed.

■ Flavours and colours. All pharmaceutical elixirs contain flavours and colours to increase the palatability and enhance the aesthetic qualities of the formulation. The presence of alcohol in the formulation allows the pharmaceutical scientist to use flavours and colours that may perhaps exhibit inappropriate solubility in aqueous solution. For example, it may be observed that in the two formulations cited above, essential oils were used as the flavouring agents. As before, the selected colour should optimally match the chosen flavour.

■ Ancillary comments – Preservatives are not required in pharmaceutical elixirs that contain greater than circa 12% v/v alcohol, due to the antimicrobial properties of this co-solvent. – Due to the volatile nature of some of the components of elixirs, elixirs should be packaged in tight containers and not stored at high temperatures. – The addition of viscosity-enhancing agents, e.g. hydrophilic polymers, may be required to optimise the rheological properties of elixirs. Miscellaneous oral solutions In addition to conventional solutions, syrups and elixirs, there are other solution-based dosage forms that are administered orally, in particular linctuses and mouthwashes/ gargles. These two subcategories are briefly described below.

Linctuses are viscous preparations that contain the therapeutic agent dissolved in a vehicle composed of a high percentage of sucrose and, if required, other sweetening agents. These formulations are administered: Dosage Form and Design The choice of liquid type for oral administration (solution, elixir or linctus) is often dependent on the physicochemical properties of the therapeutic agent. For example, if the drug has a bitter taste, linctuses are often used. It should be noted that linctuses are now commonly formulated as sugarfree preparations. The use of elixirs is not common.

For the treatment of cough, due to their soothing actions on the inflamed mucous membranes. Linctuses may also be formulated as sugar-free alternatives in which sucrose is replaced by sorbitol and the required concentration of sweetening agent. Mouthwashes and gargles Mouthwashes/gargles are designed for the treatment of infection and inflammation of the oral cavity. Formulations designed for this purpose employ water as the vehicle, although a co-solvent, e.g. alcohol, may be employed to solubilise the active agent. The use of alcohol as a co-solvent may act to enhance the antimicrobial properties of the therapeutic agent. Other formulation components are frequently required to enhance the palatability and acceptability of the preparation. These include preservatives, colours, flavouring agents and non-cariogenic sweetening agents. Usually by softening the faeces or by increasing the amount of water in the large bowel (osmotic laxatives). It may be aqueous or oil-based solutions and, in some formulations, the vehicle is the agent that promotes bowel evacuation, e.g. arachis oil retention enema. Aqueous formulations usually contain salts (e.g. phosphates) to alter the osmolality within the rectum, thereby increasing the movement of fluid to the rectal contents. Viscosity-enhancing agents, e.g. glycerol, may be included to aid retention of the formulation within the rectum and to reduce the incidence of seepage.

 

Quality control requirements for liquid preparations

Tests include:

1.    Evaluation for visual appearance, colour, taste, odour, labelling, and homogeneity,

2.    Assay of active ingredients and of degradation products.

3.    Pourability

4.    Viscosity

5.    Isotonicity

6.    Particle size agglomeration and particle size distribution

7.    Clarity

8.    Crystallization and precipitation

9.    Gas evolution

10. Relative density

11. pH

12. Surface tension

13. Microbial limit tests

14. Stability of the active ingredient(s), and identification tests

15. Light stability

16. Container and closure compatibility

17. Redispersibility

18. Suspensibility

19. Storage condition

For liquid products to be used as injections, eye drops or vaccines sterility, apyrogenicity test and particulate matter testing are necessary as additional tests.