TABLE 24.4 REQUIREMENTS OF PHARMACEUTICAL SOLUTIONS WITH RESPECT TO THEIR ROUTE OF ADMINISTRATION

Oral solutions

swallowed, in which case the drug may exert a local effect on the gastrointestinal tract or be absorbed into the blood and exert a systemic action

Oral solutions

• REQUIREMENTS OF THE SOLUTION WITH RESPECT TO THE ROUTE OF ADMINISTRATION

• Aqueous solutions

• Must be palatable = flavoring, coloring, and sweetening agents are added to enhance their appearance and taste

• pH is usually 7 but 2-9 can be tolerated

• The dose is usually in multiples of 5 mL. If smaller volumes are required, oral syringes are used.

• Has a higher viscosity than water = viscosity must be appropriate for platability and pourabilit

ORAL CAVITY

• mouthwash & gargles

• gingival solutions

Mouthwashes and gargles

are used to treat local infection and inflammation in the oral cavity. 

Gingival solutions

are applied to the gingivae. These are not intended to be swallowed and the drug exerts a local effect in the mouth.

ORAL CAVITY

• REQUIREMENTS OF THE SOLUTION WITH RESPECT TO THE ROUTE OF ADMINISTRATION

• Aqueous formulations

• Must be palatable and acceptable = Flavouring, colouring and sweetening agents are often added

• As far as possible, the pH should be around neutral.

TOPICAL SKIN/NAIL/HAIR

• Solutions are applied to the skin for local and/or systemic effect.

• Solutions are also applied to the nails or hair for local effect.

TOPICAL SKIN/NAIL/HAIR

• REQUIREMENTS OF THE SOLUTION WITH RESPECT TO THE ROUTE OF ADMINISTRATION

• Vehicles may be aqueous or nonaqueous

• Must be acceptable to the patient. 

• Formulations which are easy to transfer from the container and will spread easily and smoothly are preferred.

• Must adhere to the site of application, without being tacky or difficult to remove.

Lotion

- aqueous-based, and is intended for application without friction.

Liniment

- alcoholic or oily solution (or emulsion) designed to be rubbed into the skin.

Paints and tinctures

- concentrated aqueous or alcoholic antimicrobial solutions.

Collodion

- solution of a polymer, usually pyroxylin, in a volatile organic solvent system (a mixture of ethanol and ether). Following application to the skin, the solvents evaporate, leaving a polymeric film on the skin.

Nail solutions

- applied to the nail to treat nail diseases.

OTIC (EAR, AURAL)

Solutions are instilled in the outer ear to exert a local effect. They are used to remove ear wax or to deliver anti- infective, anti-inflammatory and analgesic drugs.

OTIC (EAR, AURAL)

• REQUIREMENTS OF THE SOLUTION WITH RESPECT TO THE ROUTE OF ADMINISTRATION

• May be aqueous or nonaqueous solutions. 

  • Water, glycerol, propylene glycol and oils may be used as solvents. 

  • Nonaqueous vehicles are used when ear wax removal is desired as ear wax can dissolve in them. 

• Increase in viscosity = Prolonged stay in the ear

  • Viscosity can be increased by the use of polymers. 

    • Propylene glycol and glycerol solutions are naturally viscous = increase the residence time. 

• Solutions do not need to be isotonic as they are external preparations

OCULAR

Eye drops are used to treat local disorders of the eye, e.g. infection. Ocular solutions may also be used to treat intraocular disorders, such as glaucoma.

Eye lotions

are solutions for rinsing or bathing the eye, or for impregnating eye dressings.

OCULAR

• REQUIREMENTS OF THE SOLUTION WITH RESPECT TO THE ROUTE OF ADMINISTRATION

• Most are aqueous solutions

• Must be manufactured sterile due to the sensitivity of the tissues they contact

• Multidose ocular products must contain antimicrobial preservatives to remain free from viable microorganisms once opened and during the period of use.

• The solution pH should ideally be close to the physiological pH of tears (pH 7.4) or slightly more alkaline to reduce lacrimation, irritation, and discomfort.

  • The eye can tolerate solutions with a pH as low as 3.5 and as high as 9

• Ocular solutions should ideally be isotonic with tears to minimize irritation and discomfort.

  • Small volumes = fine to deviate from normal isotonicity as it is diluted by tears quickly

  • Large volumes = required to be isotonic

• Most products have a viscosity of 15 mPa s to 25 mPa s (for comparison, the viscosity of water is 1 mPa s). 

Increase in viscosity = prolonged stay in the eye

NASAL

Nose drops and nasal sprays, used for local, e.g. decongestant, effect, or for systemic drug delivery.

NASAL

REQUIREMENTS OF THE SOLUTION WITH RESPECT TO THE ROUTE OF ADMINISTRATION

• Aqueous formulations.

• Solution pH is in the normal pH range of nasal fluids (pH 5.5–6.5).

• Usually isotonic to nasal fluids.

• Solution viscosity is similar to that of nasal mucus (which is higher than that of water).

• Flavouring or sweetening agents are sometimes used to mask taste, as a small proportion of nasal solution may be swallowed following nasal administration.

• Multidose solutions require preservatives.

PULMONARY

• Inhaled solutions are administered by pressurized metered-dose inhalers or by nebulizers for local or systemic effect.

PULMONARY

• Solutions of drug and excipients dissolved in liquefied propellants, such as trifluoromonofluoroethane, are used in pressurized metered-dose inhalers.

• Solutions used in nebulizers are aqueous formulations. 

  • Must be isotonic and have a pH not lower than 3 and not higher than 10.

• Multidose preparations containing preservatives are available, although generally, sterile, single-unit doses without a preservative are used.

RECTAL

• Solution enemas are usually administered for local or systemic drug action.

Enemas

- can be aqueous or oily solutions

Micro enemas

- have a volume of 1 mL to 20 mL

Macro enemas

• - have volumes of 50 mL or more.

• should be warmed to body temperature before administration.

VAGINAL

• Vaginal solutions are administered for local effect, for irrigation or for diagnostic purposes.

VAGINAL

• Aqueous solutions

• Excipients to adjust the pH may be included.

PARENTERAL

• ‘Parenteral’ refers to the injectable routes of administration. Drugs are most commonly injected into the veins (intravenous), into the muscles (intramuscular) and into (intradermal) and under (subcutaneous) the skin, although they can also be injected into arteries, joints, joint fluid areas, the spinal column, spinal fluid and the heart.

PARENTERAL

•  must be sterile and pyrogen-free.

• Preservatives, such as benzyl alcohol, are included under certain conditions such as in multidose products

• must be isotonic when large volumes are administered = wider range of tonicity can be tolerated when smaller volumes are used because dilution with body fluids occurs quickly

Intravenous

– the solution must be aqueous, as oil droplets can occlude the pulmonary microcirculation.

Intramuscular and subcutaneous

– the solution can be aqueous or nonaqueous.

Aqueous parenteral solutions

should have a pH close to physiological pH (7.4) to prevent pain, phlebitis, and tissue necrosis.

A pH of 7.4 may not be optimal for drug solubility and product stability

= most licensed parenteral solutions have a pH between 3 and 9.

This wide range is tolerated because the administered solution is diluted on administration, particularly with the intravenous route.