Oral Solution Dosage Forms (w7) Flashcards
Define what pharmaceutical solutions are …
- Pharmaceutical solutions = liquid preparations in which the therapeutic agent and the various excipients are dissolved in the chosen solvent system
What can limit the rate of absorption ?
Precipitation
What are the advantages of pharmaceutical products as solutions?
- 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 gastrointestinal tract - Taste-masking of bitter therapeutic agents
What are the disadvantages of pharmaceutical products as solutions ?
- 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
Give some examples of Co-solvent excipients ….
- ethanol
- glycerol
- propylene glycol
Give some examples of antioxidants excipients …
- sodium meta bisulphite
- ascorbic acid
Give some examples of antimicrobial preservatives excipients …
- Benzalkonium chloride
- parabens
- potassium sorbate
How is water purified to make pharmaceutical solutions?
ap 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
How is homogeneity attained in a formulation ?
- attainment of homogeneity in the formulation, due to limited aqueous solubility of the therapeutic agent
What three stages does the dissolution of a therapeutic agent in water involve ?
1) Removal of a molecule of the drug from the solid state
2) Formation of a cavity within the solvent
3) Accommodation of the drug molecule into the formed cavity.
What are the factors affecting the solubility of therapeutic agents ?
Physicochemical properties
-Molecular weight
-Particle size
-Solubility ∝ “1” /”melting point”
-Number of hydrogen bonds
-Hydrophilic groups (OH-, COO-, NH4+) > lipophilic groups (methyl, ethyl)
-Crystalline/amorphous properties
What are some factors that need to be considered during the conversion of a weak acid to a salt ?
-chemical stability
- hygroscopicity
- manufacturability
- crystallinity may preclude the choice of a particular salt
What are co-solvents ?
Co-solvents = liquid components (miscible in both phases) incorporated into a formulation to enhance the solubility of poorly soluble drugs
What are some commonly employed co-solvents ?
-Glycerol
-Ethanol
-Propylene glycol
-Poly(ethylene glycol)
I where can Micellar solubilization increase the solubility of drugs ?
In the GI tract
(Drugs can be incorporated into or onto Micelles )
What are cyclodextrins ?
Enzymatically modified starches composed of glucopyranose units which form a ring of either six (α-cyclodextrin), seven (β-cyclodextrin) or eight (γ-cyclodextrin) units
-normally one drug molecule will associate with one cyclodextrin molecule to form reversible complexes.
What are the main purposes of excipients ?
Purposes:
- To facilitate the administration of the dosage form, e.g. pourability, palatability
- To protect the formulation from issues regarding physical and chemical stability and to enhance the solubility of the therapeutic agent
What do buffers do as excipients and give some examples …
- To control the pH of the formulated product
- To maintain the solubility of the therapeutic agent in the formulated product
- To enhance the stability of products in which the chemical stability of the active agent is pH-dependent
Examples:
Acetates (acetic acid and sodium acetate)
Citrates (citric acid and sodium citrate)
Phosphates (sodium phosphate and disodium phosphate)
When should sweetening agents as excipients be avoided ?
Avoid in oral formulations for children and patients with diabetes mellitus
Why are sweetening agent excipients used in formulation ?
To increase the palatability of the therapeutic agent
How are formulations containing viscosity-enhancing agents administered ?
-syringe
-small-metered cup
-traditional 5-ml spoon
(Viscosity-enhancing agents help it pour)
What don’t require the specific addition of viscosity-enhancing agents ?
Syrups due to the inherit viscosity
What do antioxidants excipients do for a formulation ?
They enhance the stability of the therapeutic agents that are susceptible to chemical degradation by oxidation.
What are antioxidants and give an example …
- Molecules that exhibit higher oxidative potential than the therapeutic agent, to inhibit free radical-induced drug decomposition
Example ;
-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 do chelating agents do in a formulation ?
They form complexes with the heavy metal ions involved in oxidative degradation of the therapeutic agent.
What do preservative excipients do and what are some examples ?
They control the microbial bio burden of the formulation.
Examples:
Benzoic acid and salts
Sorbic acid and its salts
Alkyl esters of parahydroxybenzoic acid
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What are the principle types of solution formulations administered orally ?
- Oral solutions
- Oral syrups
- Oral elixirs
- Linctus
- mouthwashes or gargles (for local effect)
What is Lactulose oral solution used to treat and what does it consist of and produce ?
Treats ; Lactulose is indicated for use as a laxative in the treatment of chronic constipation in adults and geriatric patients.
Consists of ;A synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose
Produces ; an osmotic diarrhoea because it is unabsorbed
What are the excipients in lactulose oral solution ?
Excipient: Purified water (lactulose is water-soluble)
What are the major components of an oral syrup ?
Major components:
- Purified water
- Sugar (sucrose) or sorbitol (non-sucrose base) or sugar substitutes (artificial sweeteners)
- sweetening agents
- viscosity-modifying agents
- preservatives
What is an issue with cherry and orange flavoured oral syrups ?
- They are acidic
- This mean the solubility of these acidic drugs may be lowered causing precipitation.
- this reduces the chemical stability for acid-Kabila therapeutic agents.
Who are medicated sugar-free syrups administered to ?
- children and diabetic patients.
-Sugar-free due to glycogenetic and cariogenic properties of sucrose.
-Syrup substitutes must provide equivalent sweetness, viscosity and preservation to the original syrups
-To achieve these properties ;
-Artificial sweeteners (typically saccharin sodium, aspartame)
-Non-glycogenetic viscosity modifiers (e.g. methylcellulose, hydroxyethylcellulose)
-Preservatives (e.g. sodium benzoate, benzoic acid and parahydroxybenzoate esters) are included.
Give an example of an artificial sweetener …
Aspartame or saccharin sodium
Give an example of a non-glycogenetic viscosity modifier ..
Methylcellulose or hydroxyethylcellulose
Give an example of a preservative …
Sodium benzoate, benzoin acid and parahydroxybenzoate esters
What is Bronchostop cough syrup traditionally used to treat ?
- traditional herbal medicinal product used for the relief of coughs ( chesty and dry )
- is sugar-free
Give an example of an antioxidant (buffering agent) …
Citric acid monohydrate or ascorbic acid
Give an example of a viscosity excipient …
Xanthan gum, acacia or Maltodextrin.
What is an oral elixir and what is required to make sure all its components remain in solution ?
1) An elixir is a clear, hydroalcoholic solution for oral use
2) [Alcohol] required is sufficient to ensure all components remain in solution
Other polyol co-solvents may be incorporated
What is a possible problem with an oral elixir when considering patient administration ?
A possible problem in paediatric formulations and adults who wish to avoid alcohol
What are the typical components of oral elixirs ?
- purified water
- alcohol (co-solvent to ensure stability)
- polygon co-solvents (enables alcohol to be reduced and enhances stability)
- sweetening agents (high alcohol conc prohibits incorporation of high sucrose due to limiting solubility in this elixir vehicle)
- flavours and colours.
What does a phenergan elixir contain and what does it treat ?
What does it treat for short term use ?
1) Contains ; promethazine (antihistamine)
2) Treatment: As symptomatic treatment for allergic conditions of the upper respiratory tract and skin including allergic rhinitis, urticaria and anaphylactic reactions to drugs and foreign proteins
(As an antiemetic)
3) For short term use ;
- Treatment of insomnia in adults
- Paediatric sedative
(An alcohol-free, sugar-free antihistamine formulation designed for use by children)
Give an example of a sweetening agent …
Maltitol liquid and acesulfame potassium
What is a linctuses and what is it primarily employed for the treatment of ?
1) Viscous preparations that contain the therapeutic agent dissolved in a vehicle composed of a high percentage of sucrose and, if required, other sweetening agents.
2) Primarily employed for the treatment of cough, due to their soothing actions on the inflamed mucous membranes
(Can also be sugar-free)
What is codeine linctus used to treat ?
- Indicated in adults for relief of the symptoms of dry or irritating coughs
What is an example of a colourant flavouring …
- colourant = quinoline yellow, yellow dye sunset, caramel
- flavouring = lemon oil terpeneless, orange juice
What are mouthwashes and gargles used to treat and what acts as the vehicle ?
1) treatment ; of infection and inflammation of the oral cavity
2 ) Water = vehicle
(Co-solvent may be employed to solubilise the active agent)
