Pharmaceutical solutions dosage form
Solutions are homogeneous mixtures of one or more solutes molecularly dispersed in a suitable solvent or a mixture of mutually miscible solvents. A solution composed of only two substances is a binary solution. The components making up a binary solution are termed the solute and the solvent depending on their relative proportions (component in lower proportion is termed solute).
Pharmaceutical solutions are used for many routes of administration, including oral, rectal, vaginal, ophthalmic, parenteral, and otic. The most common solution dosage form is the oral liquid, which includes aqueous solutions, syrups, and elixirs. The physicochemical (e.g., solubility) and stability characteristics of the active drug determine whether an oral solution dosage form can be prepared.
The required solubility of a drug and its solubility in water and biocompatible water-miscible solvents help decide the dosage form composition. For example, if the drug is water soluble, a simple aqueous solution can be prepared. However, if it is soluble in a water–alcohol–glycerin co-solvent system, an elixir is appropriate.
Saturated solutions are solutions which, at a given temperature and pressure, contain the maximum amount of solute that can be dissolved in the solvent.
Buffer solutions contain a combination of weak acid and its salt with a strong base or a weak base and its salt with a strong acid. These solutions resist changes in pH upon the addition of small quantities of acid or base. Solubility and stability of most ionic drugs change with pH. Therefore, most pharmaceutical solutions are pH controlled using an appropriate buffer.
Isotonic solutions have similar tonicity as biological fluids. These solutions cause no swelling or contraction of the tissues with which they come in contact and produce no discomfort when instilled in the eye, nasal tract, blood, or other body tissues.
Parenteral solutions or solutions for direct administration to mucosal tissues should be isotonic or hypotonic to avoid local tissue stress and pain upon administration. Tonicity is usually adjusted using dextrose or sodium chloride. Isotonic sodium chloride is a 0.9% w/v concentration of NaCl in water and is also called normal saline. A 5% w/w dextrose, also known as glucose, solution in water is also isotonic. These are commonly used infusion fluids for intravenous administration.
Types of solutions
Syrup is a saturated sugar solution. Thus, aqueous solutions containing sugar at or close to its saturation concentration of 67% w/w are called syrups. In special circumstances, it may be replaced in whole or in part by other sugars (e.g., glucose/dextrose) or non-sugars (e.g., sorbitol, glycerin, and propylene glycol). Syrups containing flavoring agents but no drugs are called non-medicated syrups. Syrups provide a pleasant means of administering a liquid form of a disagreeable tasting drug. Syrups are appropriate for water-soluble drugs. Cold and cough syrups are the most common examples of medicated syrups.
Sweetened hydroalcoholic (combinations of water and ethanol) solutions are termed elixirs. Compared to syrup, elixirs are usually less sweet and less viscous, because they contain a lower proportion of sugar and are consequently less effective than syrups in masking the taste of drugs. In contrast to aqueous syrups, elixirs are better able to maintain both water-soluble and alcohol-soluble components in solution due to their hydroalcoholic properties. These solubility characteristics often make elixirs preferable to syrups.
All elixirs contain flavoring and coloring agents to enhance their palatability and appearance. Each elixir requires a specific proportion of alcohol and water to maintain all of the components in solution. Elixirs containing over 10%–12% alcohol are usually self-preserving and do not require the addition of antimicrobial agents for preservation.
Examples of some commonly used elixirs include dexamethasone elixir USP, phenobarbital elixir, pentobarbital elixir USP, diphenhydramine HCl elixir, and digoxin elixir.
Tinctures are alcoholic or hydroalcoholic solutions of chemical or soluble constituents of vegetable drugs. Most tinctures are prepared by the extraction process. Depending on the preparation, tinctures contain alcohol in amounts ranging from approximately 15% to 80%.
Simple liquid preparations intended for oral use containing dissolved medicaments may be described as oral solutions or mixtures, although the term ‘mixture’ may also be applied to a suspension.
A draught is an older term used to describe a liquid preparation formulated as a single dose, in a volume which is larger than generally utilized in traditional mixture formulations. Each draught was usually supplied in a 50mL unit dose container.
Spirits are solutions containing one or more active medicaments dissolved in either absolute or dilute ethanol.
These are an oral liquid formulation of potent drugs usually in solution, intended for administration to paediatric patients, though they may be useful in other patients with swallowing difficulties. The formulation is designed to have very small dose volumes which must be administered with a calibrated dropper.
Gargles and mouthwashes
Gargles and mouthwashes are aqueous solutions that are intended for treatment of the throat (gargles) and mouth (mouthwashes) and are generally formulated in a concentrated form.
Enemas and douches
These liquid preparations are often formulated as solutions (though they may be presented as an emulsion or suspension) and are intended for instillation into the rectum (enema) or other orifice, such as the vagina or nasal cavity (douche).The volumes of these preparations may vary from 5mL to much larger volumes. When the larger volumes are used it is important that the liquid is warmed to body temperature before administration.
Lotions are solutions, but may also be suspensions or emulsions, that are intended to be applied to the skin without friction on a carrier fabric such as lint and covered with a waterproof dressing. In some cases lotions are applied to the scalp, where the vehicle for the medication is alcohol based, allowing for rapid drying of the hair and thus making the product more acceptable to the patient(e.g.SalicylicAcidLotion2% BPC). In these cases, problems of flammability are addressed by suitable labelling.
A liniment is a liquid preparation intended to be rubbed with friction and massaged onto the skin to obtain analgesic, rubefacient or generally stimulating effects. Liniments should not be used on broken skin. They are usually solutions of oils, alcohols or soaps, but may be formulated as emulsions.
Applications are solutions, though they may also be suspensions or emulsions, intended to be applied without friction to the skin and to be used without any dressing or covering material.
These are principally solutions of pyroxylin in a vehicle of ether and alcohol that are intended to be painted onto the skin and left to dry. When dry, the collodion leaves a flexible film of cellulose on the skin which may be used to seal minor injuries or retain a dissolved drug in contact with the skin for an extended period. Collodions are highly volatile and highly flammable and care should be taken to label any preparation appropriately.
The advantages of solutions as pharmaceutical products are that:
* The drug is immediately available for absorption. When solid dosage forms are taken orally, the drug needs to dissolve before absorption into the body can take place. By providing the drug in a solution, the dissolution phase of the absorption process can be bypassed, providing quicker absorption.
* Flexible dosing is possible. The active ingredient within the solution will be present in a certain concentration per unit volume. If alterations to the quantity of active ingredient to be administered are required, a simple alteration to the quantity of solution to be taken is all that is required.
* They may be designed for any route of absorption. Although when discussing solutions the oral route of administration is often considered, solutions can be administered via a number of other routes. Parenteral preparations (injections), enemas for rectal use, topical (for use on the skin) preparations and ophthalmic preparations can all be solutions.
* There is no need to shake the container. Unlike some liquid preparations (e.g. suspensions), as the active ingredient is dissolved within the vehicle there is no need to shake the container to ensure a uniform dose is measured.
* They facilitate swallowing in difficult cases. Some patients may find it hard to swallow traditional solid dosage forms (e.g. infants or the elderly). In these situations, it may be easier for the patient to take a liquid dosage form.
The disadvantages of solutions as pharmaceutical products are that:
* Drug stability is often reduced in solution by solvolysis, hydrolysis or oxidation. The stability of the active ingredient needs to be taken into consideration when formulating a solution. For this reason, it is common for solutions to attract a shorter expiry date than equivalent solid dosage forms.
* It is difficult to mask unpleasant tastes. Although liquid dosage forms may be ideal for small children who are unable to swallow solid dosage forms, many drugs taste unpleasant when formulated into a solution. It is possible to attempt to mask any unpleasant tastes by the addition of a flavoring, but this will not always be successful.
* They are bulky, difficult to transport and prone to breakages. A major disadvantage of all liquid dosage forms is that they are always much larger and more bulky than their comparable solid formulation. This makes them heavier and more difficult to transport. Coupled with this is the fact that, traditionally, pharmaceutical liquids are packed in glass bottles. These are obviously prone to breakage which can be hazardous and cause the loss of the preparation.
* Technical accuracy is needed to measure the dose on administration. Although the dose can be titrated without the need to produce additional preparations (see point 2 from the advantages above), patient accuracy in measuring a dose is required. It is accepted that patients’ abilities to measure an accurate dose can vary considerably and this needs to be taken into consideration when preparing a liquid preparation. This is especially important when the volume of liquid to be administered is very small, where small changes in the volume administered may result in large increases or decreases in dose.
* Some drugs are poorly soluble. The solubility of a drug needs to be taken into consideration when preparing a solution to ensure that the final volume produced is not excessive. In some cases it may be necessary to alter the vehicle or drug form (for example the free alkaloid or its salt) in order to be able to formulate a convenient preparation.
* A measuring device is needed for administration. Although not a major disadvantage, it must be borne in mind that a measuring device will need to be supplied to the patient in order for them to be able to measure an accurate dose (this will have cost implications), and in addition the patient will need counselling on the use of the measuring device.