Liquid orals
Liquid orals are homogeneous liquid formulations that contain one or more active ingredients with or without additives that dissolves in the suitable vehicle which is to be meant for oral administration.Liquid orals generally contain solutions, suspensions as well as emulsions.
For any liquid oral preparations, the vehicle that is to be chosen is depending upon the nature of the active ingredients and the organoleptic characteristics of the liquid preparations.
The oral liquids may also contain antioxidants, antimicrobials, preservatives, and a few other excipients like emulsifying agents, suspending agents, thickening agents, dispersing agents, buffering agents, wetting agents, flavoring and sweetening agents.
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a) Monophasic liquid dosage forms
b) Biphasic liquid dosage forms
Examples - Syrups, Elixirs, Mixtures, draughts, Linctuses, drops, etc.
Examples - Suspensions, Emulsions
Classification of Liquid Orals
Liquid oral dosage forms are classified into two types.a) Monophasic liquid dosage forms
b) Biphasic liquid dosage forms
a) Monophasic liquid dosage forms
The monophasic liquid dosage forms contain only one phase.Examples - Syrups, Elixirs, Mixtures, draughts, Linctuses, drops, etc.
b) Biphasic liquid dosage forms
The biphasic liquid dosage forms contain two phases.Examples - Suspensions, Emulsions
Advantages of Liquid Orals
1) liquid oral preparations are generally preferred for children as well as elderly patients who are not able to take solid dosage forms like tablets or capsules. Read More - Solid oral dosage Forms (Tablet or Capsules)
2) Few drugs may cause gastric irritation if taken in the form of tablets or capsules. This can be minimized by giving the drugs in liquid form as the drug gets diluted.
3) The shaking of the container is not required because the drug is distributed uniformly.
4) By adding suitable colors, flavors, and sweeteners the liquid oral dosage forms can be made more pleasant. If there is required then to increase the viscosity, viscolizers can be added to the formulations.
5) For some diseases, sometimes patients expect that the drug is in liquid dosage forms such as antacids and cough syrups.
6) Liquid oral dosage forms are very convenient for prescribing and dispensing the substances of the dose that are in a very small fraction.
7) The bioavailability of liquid oral preparation is more as compared to the solid oral dosage forms.
8) Few compounds can only be obtained in the form of liquid or solutions.
9) Sometimes liquid oral dosage forms are more stable and convenient dosage forms than solid dosage forms.
10) In solutions or liquid dosage forms the substance is formed by chemical interaction.
11) Liquid oral dosage forms are the most preferred dosage forms, especially for infants, children, and geriatric patients.
12) Liquid orals provide beneficial physiological effects and also these dosage forms are very attractive.
13) Liquid oral dosage forms are absorbed very quickly.
2) Few drugs may cause gastric irritation if taken in the form of tablets or capsules. This can be minimized by giving the drugs in liquid form as the drug gets diluted.
3) The shaking of the container is not required because the drug is distributed uniformly.
4) By adding suitable colors, flavors, and sweeteners the liquid oral dosage forms can be made more pleasant. If there is required then to increase the viscosity, viscolizers can be added to the formulations.
5) For some diseases, sometimes patients expect that the drug is in liquid dosage forms such as antacids and cough syrups.
6) Liquid oral dosage forms are very convenient for prescribing and dispensing the substances of the dose that are in a very small fraction.
7) The bioavailability of liquid oral preparation is more as compared to the solid oral dosage forms.
8) Few compounds can only be obtained in the form of liquid or solutions.
9) Sometimes liquid oral dosage forms are more stable and convenient dosage forms than solid dosage forms.
10) In solutions or liquid dosage forms the substance is formed by chemical interaction.
11) Liquid oral dosage forms are the most preferred dosage forms, especially for infants, children, and geriatric patients.
12) Liquid orals provide beneficial physiological effects and also these dosage forms are very attractive.
13) Liquid oral dosage forms are absorbed very quickly.
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Disadvantages of Liquid Orals
1) Many drugs undergo reactions such as oxidation, and hydrolysis. These reactions are very severe in liquid oral dosage forms.2) The overdosage may be happened due to the pleasant taste of the liquid oral dosage forms. This can especially happen with children.
3) Liquids are more susceptible to bacterial contamination.
4) Dose measurement depends upon the patients. So, the accuracy of dose measurements is very important.
5) The drug content is at risk if the breakage of the container may occur.
6) The weight as well as the bulk of liquid oral dosage forms are very high.
7) In liquid orals, it is difficult to mask the unpleasant flavors.
8) The containers may also create problems in which liquid oral preparation is stored such as air permeability, and leaching.
9) Sometimes manufacturing of liquid orals contains many steps as compared to the solid oral dosage forms.
10) Many drugs may create problems while solubilizing these drugs into the given solvent. So, a special method should be Pursued to dissolve the poorly soluble drugs.
11) Liquid orals have less stable as compared to solid oral dosage forms.
12) As liquids are bulky so, it is very tough to transport them as well as store them.
13) Accidental conditions may cause the breakage and complete loss of liquid oral dosage forms.
Preformulation of Liquid Orals
An ideal liquid oral dosage form is designed to assure the stability, appearance as well as therapeutic effectiveness of the medicaments. To solve manufacturing problems it is very important to be aware of the factors that influence the formulation of liquid orals.Solubility
While formulating the liquid orals the drug is dissolved in the solvent which is intended to be used. The dissolution of drugs is depending upon a few factors;- Nature of solute
- Nature of solvents
- Solute and solvent interactions
- The intensity of the forces that present in solute-solvent
- Electronic factors and steric factors
Determination of Solubility
The solubilities of any drug component must be determined before initiating the manufacturing of liquid orals.This can be performed by putting the finely divided drugs with the solvent into a tightly closed container.
Now, agitated this tightly closed container at a constant temperature bath for 72 hours.
Finally, the samples are withdrawn and with the help of suitable analytical techniques, the solubility of the drug is determined.
Factors Influencing Solubility
pH
Several drugs are either weak acids or weak bases. These drugs are either slightly soluble or insoluble in water although their salts are soluble. The solubility of these drugs is enhanced by the pH of their environment.The pH environment of the drugs should be fixed by keeping a few points such as;
1) The stability of the drug product should not be decreased due to the pH.
2) The drug concentration is required in the formulation.
3) The physiological compatibility should be boosted by the pH.
While formulating the solutions of acidic as well as basic drugs, there are a few factors that must be observed;
1) The therapeutic efficacy of the drug should be considered.
2) The solubility of ionized and unionized forms of the drug should be considered.
3) The buffer component and chemical stability of the drug substance as functions of the pH should be considered.
The type of buffer and the pH of the buffer should be selected to maintain a proper balance between them.
Buffers
Although the pH of the liquid oral formulations is fixed. But in some cases, there is a possibility of a change in the pH of the formulations.To avoid these issues of changes in pH, a suitable buffer must be added to the formulations.
The selection of buffer as per the following basis;
1) The buffer should not have any harmful effect on the stability of the final product.
2) The buffer that is intended to be used must be biologically safe.
3) The buffer must have enough capacity in the acceptable pH range.
4) The buffer should allow acceptable flavoring as well as coloring to the formulation.
5) The pka value of the acid that is used in the buffer should be near the required pH of the final liquid oral dosage forms.
Cosolvency
Certain drugs are not soluble in water. To overcome this, the solubility is increased by using water-miscible solvents in which the drugs are soluble. This process is called cosolvency and the solvent used for this purpose is known as cosolvent.Examples - Commonly used cosolvents in liquid orals are ethanol, polyethylene glycol (PEGs), sorbitol, glycerin, syrups, propylene glycol, etc.
Ethanol is also used as a cosolvent but the amount of ethanol that is to be used is kept minimum due to the burning taste in high concentration, pharmacological effect, and high cost.
Dielectric Constant
The dielectric constant is the measurement of the polarity of a molecule.As per their dielectric constant, the compounds are classified that is either they are polar or non-polar.
| Polarity | Dielectric constant |
|---|---|
| Non-polar | 1-20 |
| Semi-polar | 20-50 |
| Polar | >50 |
The dielectric constant of water decreases as the temperature of water decreases. Although, the solubility of many compounds increases as the temperature increases.
The dielectric constant of a solvent provides a rough estimate of the solvent properties as well as the degree of solubility of polar and nonpolar compounds.
Solubilization
For increasing the solubility of poorly water-soluble drugs solubilization is another method..Solubilization is the process through which poorly water-soluble drugs are dissolved into an aqueous solution of soap, in which a thermodynamically stable solution is formed.
If surfactants are added into the liquid at lower concentrations they tend to position at the air-liquid interface and if added at higher concentrations, it forms micelles. The surfactant concentration at which it occurs is known as the critical micelle concentration (CMC).
Example - For liquid oral preparations polysorbates are used as surfactants.
Complexation
In the solution, the organic compounds are generally related to each other and each substance at a given temperature has its specific solubility.Any differences in the solubility may be due to the formation of complexes in the solution.
To form a soluble complex insoluble compounds interact with soluble ingredients.
Example - Preparation of iodine solution
Hydrotrophy
Term hrdrotrophy denotes the increase in the solubility of many substances in the water due to the presence of a specific quantity of additives.Example - Sodium benzoate increases the solubility of benzoic acid and Sodium benzoate increases the solubility of caffeine.
Chemical Modification of the Drug
With the help of chemical modification of the drugs, the solubility of poorly soluble drugs can be increased.Example - Betamethasone alcohol in water, the solubility is 5.8 mg/100 ml at 25°C.
Temperature
As the temperature increases the solubility of most of the drugs got increases.Salting-out
Adding a large amount of highly soluble salts to the aqueous solutions of organic compounds may cause precipitation or separation. This phenomenon is called salting-out.Salting-in
In this process by the addition of salts, there is an increase in the solubility of an organic compound.Example - Salting of proteins in water in the presence of salts.
Particle Size
As the particle size decreases the solubility increases at submicron levels. This occurs because of the large surface free energy which is associated with small particles.Molecular Size of Solvent Molecules
Water shows a good solvent property because of the small size of its molecules. Any other liquids that are similar to the water in polarity, hydrogen bonding, as well as dielectric constant, may be poor solvents for the ionic compounds because of the larger size of the liquid molecules as compared to water molecules.Molecular Shape of Solute Molecules
The solubility is influenced due to the shape of the solute molecules. The solubility of ammonia in water is high because of the shape of solute molecules.Macromolecules
Macromolecules are those compounds that have molecular weights ranging from 10,000 to millions.The solubility of macromolecules depends upon shape, pH, temperature, ionic character as well as molecular weight.
Examples - Enzymes, Proteins, Plasma, cellulose derivatives, and natural polysaccharides.
I hope that you have liked the article about liquid orals. In this article, i have tried to give all the basic information regarding the liquid oral dosage forms. If you have any questions feel free to ask in the comments.
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