W7 Oral Solution: Dosage Forms l Flashcards
What are some examples of pharmaceutical solutions?
Injections, eye and ear drops, enemas, vaginal douches, topical solutions, nebulisers.
Definition of a pharmaceutical solution
Pharmaceutical solutions = liquid preparations in which the therapeutic agent and the various excipients are dissolved in the chosen solvent system
What is the advantage of liquid oral dosage forms?
(solution)
Absorption from is often
- Rapid and complete
- Greater bioavailability
Advantages and Disadvantages of pharmaceutical products as solutions
Advantages
- Easily administered for individuals who have difficulty in swallowing, e.g. elderly patients, infants
- The therapeutic agent is dissolved in the formulation and is therefore immediately available for absorption (Provided the drug does not precipitate within the GI tract)
- Taste-masking of bitter therapeutic agents
Disadvantages
- Unsuitable for therapeutic agents that are chemically unstable in the presence of water
- The poor solubility of certain therapeutic agents may prohibit their formulation as pharmaceutical solutions
- Expensive to ship and are bulky for the patient to carry
Excipients in solution
How is Water used in pharmaceutical solutions?
- Tap drinking water not normally used for the manufacture of pharmaceutical solutions / extemporaneous compounding
- Purified by distillation, ion exchange, or reverse osmosis non-parenteral solutions
- Further purified to remove pyrogens (fever-producing compounds) water for injections
When a drug is ionised (charged) it is….
More water soluble
Drug solubility
When a drug solubility is high, medium, low what changes if any are made?
Solubility at selected pH of formulation
High
Readily incorporated into the vehicle and formulated as an oral solution
Moderate
Solubility enhanced using co-solvents or by related methods (changing pH, salt conversion)
Low
Formulated as an alternative-dosage form, e.g. a suspension
What is the pH range for oral administration
The acceptable pH range of solutions for oral administration is large, ranging from 5 to 8 pH units
Co-solvent definition
Liquid components (miscible in both phases) incorporated into a formulation to enhance the solubility of poorly soluble drugs.
Approaches to help with drug solubilisation? (5)
Complexation such as;
1.Change pH
2.Add co solvent, 3.Change to a salt, 4.Make it into a disperse phase, 5.Make it more amorphous (so more water soluble)
How to increase pourability and palatability
Decrease viscosity and add sweetners
Qualitative vs Quantitative
pH paper is qualitative and a pH meter is quantitative
Why are sweeteners added?
What are the main sweetening agents?
To increase the palatability of the therapeutic agent
Sucrose, liquid glucose, glycerol, sorbitol
To mask the taste of the drug substance
Salty: butterscotch, apricot, peach, vanilla, wintergreen mint
Bitter: cherry, mint, anise
Sweet: vanilla, fruit, berry
Sour: citrus, raspberry
Viscosity-enhancing agents:
How is viscosity increaser?
Increased (and controlled) by the addition of non-ionic or ionic hydrophilic polymers
Non-ionic (neutral) polymers:
Cellulose derivatives
Methylcellulose
Hydroxyethylcellulose
Hydroxypropylcellulose
Polyvinylpyrrolidone
Ionic polymers:
Sodium carboxymethylcellulose (anionic)
Sodium alginate (anionic)
Antioxidants
To enhance the stability of therapeutic agents that are susceptible to chemical degradation by oxidation
Antioxidants = Molecules that exhibit higher oxidative potential than the therapeutic agent, to inhibit free radical-induced drug decomposition
Examples:
Aqueous solutions
Sodium sulphite, sodium metabisulphite, sodium formaldehyde sulphoxylate and ascorbic acid
Oil-based solutions
Butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA) and propyl gallate.
What are present in pharmaceutical oral solutions?
Active ingredient, water, buffer, co-solvent (vehicle), excipients, flavouring agents, sweeteners, preservatives, antioxidants, chelating agents, viscosity-modifying agents
Preservatives
To control the microbial bioburden of the formulation
Ideal properties:
Broad antimicrobial spectrum (gram-positive, gram-negative bacteria and fungi)
Chemically and physically stable over the shelf-life of the product
Low toxicity
Examples:
Benzoic acid and salts
Sorbic acid and its salts
Alkyl esters of parahydroxybenzoic acid
A combination of two members enhances the antimicrobial spectrum
Typically methyl and propyl parahydroxybenzoates (in a ratio of 9:1)
Chelating agents
To form complexes with heavy-metal ions involved in oxidative degradation of therapeutic agents
Ethylenediamine tetraacetic acid (EDTA)
Citric acid
Employed in conjunction with antioxidants
Colourants
Give examples of co-solvents?
Ethanol, glycerol, propylene glycol
Antioxidant examples
Sodium metabisulphite, ascorbic acid
Antimicrobial preservatives examples
Benzalkonium chloride, parabens, potassium sorbate
pH adjusters examples
Citric acid, potassium phosphate
Isotonicity adjusters
Sodium chloride, glucose
Viscosity enhancers examples
Hydroxymethylcellulose
Chelating agents examples
EDTA
Flavours
Taste masking
Sweeteners examples
Sucrose, sorbitol, mannitol, aspartame, sucralose
Colouring agents example:
Dyes
