Formulation liquid dosage forms
Compared to conventional tablets and capsules, oral liquid dosage forms including solutions, syrups, suspensions, elixirs, and concentrates offer
unique advantages to many patients. For example, liquids may provide better patient compliance for those with swallowing difficulties and better
dosage control versus a fixed tablet dose. However, there are also a number of “challenges” surrounding the formulation and development
of these forms. Hence, liquid dosage forms are generally formulated for use in geriatric and pediatric patients. But, this section of patients have
been regarded as a small fraction of the overall population, pharmaceutical companies often develop oral liquid formulations out of
necessity rather than responding to a patient need. However, there are potential advantages of oral liquid dosage forms, such as no dissolution
time and rapid absorption from the stomach/intestines compared to tablets, which may be an important factor for pain-relieving drugs.
Inherent in this benefit is the risk of reaching peak plasma levels too fast, which could be harmful. Finally, as the excipient technology advances,
a controlled release profile in liquid dosage forms will likely become readily available.
FORMULATIONS OF LIQUIDS
Oral liquids are formulated as solutions, suspensions and emulsions depending on the nature of the active ingredient particularly solubility
and stability. They are also designed as ready to use liquids and powders for reconstitution into liquid orals like syrups, solutions, suspensions
and emulsions. Liquid formulation needs various excipients including vehicle, solubilizer, stabilizer, and viscosity builder, preservative and off
course sweeteners, colour and flavour. The selection of these excipients is of major concern to design stable, effective and palatable oral liquid
formulation.
Formulation liquid dosage forms
Selection of Excipients
Characteristics of active drug are of major concern in developing an oral liquid dosage formulation. The major challenges in developing oral liquid
dosage forms are:
(i) The stability of a drug in solution,
(ii) The solubility of a drug at the required level, and
(iii) An acceptable taste.
It is the effective use of excipients, which allows formulators overcome these challenges. Additionally, an excipient’s compatibility with a drug
in the solid state cannot infer the same compatibility in solution. However, if the mechanism of degradation of the drug is understood, the process
of selecting suitable excipients to use in a solution will be much easier.
Finally, some knowledge of the drug’s physical and chemical characteristics such as the solubility, pH stability, and pKa value (s) of
reactive functional groups is essential in order to choose the proper excipients, effectively.
Ideally, the pH at which the drug is most stable would also be close enough to the solubility for delivering the desired dose in a tea spoon
(approximately 5 mL). Requiring patients to take more than two tea spoon full at a time may not be advisable because of lower patient
compliance. In such conditions, a simple oral solution or syrup formulation may be developed. However, if the pH at which the drug
is most stable is not one at which there is enough solubility, a suspension formulation may be required.
A quick means to identify whether or not a drug may be more suitable for solution or suspension is to overlap the pH-stability profile
with the pH-solubility profile. This overlap creates a window, which may suggest which dosage form might be most desirable and
subsequently the type of excipients needed. The overlapped figures below demonstrate for aspirin (which is a weak acid) that the pH of greatest
stability is also the pH at which there is low solubility.
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Formulation liquid dosage forms
The decision to develop a solution, syrup or a suspension of a drug is influenced by many factors like solubility and the desired release
profile of the drug and properties of the base vehicle like surface tension, viscosity, boiling point, and specific heat of solution, all of which may be
affected in various ways. In case of clear liquids, lack of solubility of the drug in the base vehicle may demand the need for miscible co-solvents.
Similarly, a miscible solvent may be needed to decrease the solubility of the drug in a primary vehicle in formulating a suspension. Another
approach to increasing the solubility of a drug in solution is to use a complexing agent such as a cyclodextrin. Currently in the United States,
only hydroxypropyl-β-cyclodextrin has been used in an oral liquid formulation. However, many other cyclodextrins are widely used outside
the United States in both oral and parenteral formulations. Surfactants are also used to increase aqueous solubility of the drugs.
Excipients for Oral Liquid Formulations
Oral liquid formulation needs a meticulous blend of ingredients to perform various functions like wetting and solubilisation, stabilization
and to impart suitable colour, taste and viscosity. The blend should be compatible, non reactive and stable. The common excipients generally
required for any liquid formulation are vehicles (base), viscosity builders, stabilizers, preservatives, colours and flavours. In addition, solubilizers
are required in case of clear liquids, suspending agents are needed for suspensions and emulsifying agents for emulsions.
Oral liquid dosage – forms includes solutions, syrups, suspensions, elixirs, and concentrates that offer better patient compliance for those with swallowing difficulties and better dosage control versus a fixed tablet dose. However, there are also a number of “challenges” in the formulation and development of these dosage forms.
It is the effective use of excipients, which allows formulators overcome these challenges.
Formulation liquid dosage forms
