Oral solution dosage forms Flashcards
What are some common forms of pharmaceutical solutions?
Injections, eye and ear drops, enemas, vaginal douches, topical
solutions, nebulisers.
What are two downsides to pharmaceutical solutions?
- Rate of absorption can be limited by precipitation
- Chemical stability is lowest in solutions
What is a pharmaceutical solution?
liquid preparations in which the
therapeutic agent and the various excipients are dissolved in
the chosen solvent system
What are some common liquid oral solution forms? + why so used?
- Drugs are commonly given in solution
- in cough/cold remedies
- for the young and elderly (people with Parkinson’s)
- Absorption from an oral solution is often rapid and complete, skip one step compared to tablets, greater bioavailability compared to other oral dosage forms
What are the advantages to pharmaceutical oral 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 to pharmaceutical oral 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
What are some examples of co-solvent excipients?
Ethanol, glycerol, propylene glycol
What are some examples of antioxidants excipients?
Sodium metabisulphite, ascorbic acid
What are some examples of antimicrobial preservatives excipients?
Benzalkonium chloride, parabens, potassium sorbate
What are some examples of pH adjusters excipients?
Citric acid, potassium phosphate
What are some examples of Isotonicity adjusters excipients?
Sodium chloride, glucose
What are some examples of viscosity enhancers excipients?
Hydroxymethylcellulose
What are some examples of chelating agents excipients?
EDTA
What are some examples of flavours excipients?
Taste masking
What are some examples of sweeteners excipients?
Sucrose, sorbitol, mannitol, aspartame, sucralose
What are some examples of colouring agents excipients?
Dyes
What type of water is used in pharm sols?
Tap drinking water not normally used for the manufacture of pharmaceutical solutions /extemporaneous compounding
If tap water is used/ water what type of processes must it go through to be used?
- Purified by distillation, ion exchange, or reverse
osmosis → non-parenteral solutions - Further purified to remove pyrogens (fever-
producing compounds) → water for injections
What is a challenge in drug solubility?
- Challenge: attainment of homogeneity in the formulation, due to limited aqueous solubility of the therapeutic agent
What happens when drug solubility high?
- Readily incorporated into the vehicle and formulated as an oral solution
What happens when drug solubility is moderate?
- Solubility enhanced using co-solvents or by related methods (changing pH, salt conversion)
What happens when drug solubility is low?
- Formulated as an alternative-dosage form, e.g. a suspension, emulsion biphasic
What needs to happen in drug dissolution between therapeutic agent and water?
- Removal of a molecule of the drug from the solid state
- Formation of a cavity within the solvent
- Accommodation of the drug molecule into the formed cavity.
What factors affect the solubility of therapeutic agents?
*physicochemical properties
*big molecular weight (not likely to dissolve)
*big particle size (not likely to dissolve)
* solubility ∞1/melting point
*number of hydrogen bonds
*not many hydrophilic groups (not likely to dissolve)
* mostly crystalline (not likely to dissolve) / amorphous properties
pH and pka in terms of solubility for acids and bases?
acids: pH > pKa = solubility increases
bases: pH < pKa = solubility increases
What is the acceptable range for pH in oral solutions?
pH 5 - 8
cannot go below or above + can be adjusted using a buffer as long as its in the safe pH
What is another way to increase pH?
converting weak acids into a salt
Why can we not always change weak acids into salts?
*chemical stability, hygroscopicity,
manufacturability and crystallinity may preclude the choice of a
particular salt
*The sodium salt of aspirin, sodium acetylsalicylate, is much more
prone to hydrolysis (phenolic ester bond) than aspirin (acetylsalicylic
acid)
What is a co-solvent?
liquid components (miscible in both phases) incorporated into a formulation to enhance the solubility of poorly soluble drugs
What are commonly used co-solvents?
- Glycerol
- Ethanol
- Propylene glycol
- Poly(ethylene glycol)
What are some properties of glycerol and propylene glycol?
- Odourless, sweet, viscous
What are some properties of ethanol?
- Known pharmacological and
toxicological effects have
compromised use
What are some properties of PEG?
- Lower-molecular-weight grades
(PEG 200, PEG 400) are
preferred
What is a cyclodextrin?
Enzymatically modified starches composed of
glucopyranose units which form a ring of either six (α-
cyclodextrin), seven (β-cyclodextrin) or eight (γ-cyclodextrin)
units
Why are cyclodectrin used?
- The ring of β-cyclodextrin is the correct size for most drug
molecules, and normally one drug molecule will associate with
one cyclodextrin molecule to form reversible complexes
What are the purposes of excipients?
- 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
*physiologically inert
What is the purpose of buffers?
- 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
What are some examples of buffers?
- Acetates (acetic acid and sodium acetate)
- Citrates (citric acid and sodium citrate)
- Phosphates (sodium phosphate and disodium phosphate)
What is the purpose of sweetening agents?
- To increase the palatability of the therapeutic agent
- Main sweetening agents
- Sucrose, liquid glucose, glycerol, sorbitol
- Artificial sweetening agents is increasing in use
*avoid in oral formulations for children and patients with diabetes mellitus
What is the purpose of flavouring agents? +examples of flavours
- 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
- Usually a combination to achieve the optimal
taste-masking
What else is in flavouring agents?
*methanol, chloroform to numb your taste buds to stop you from tasting the drugs
What is the purpose of viscosity agents?
- To ensure the accurate measurement of the volume to be dispensed
- May increase palatability
How are viscosity agents administered and controlled?
- Administration performed using a
- Syringe
- Small-metered cup
- Traditional 5-ml spoon
- Increased (and controlled) by the addition of non-ionic or ionic hydrophilic
polymers
What is an antioxidant?
Molecules that exhibit higher oxidative potential
than the therapeutic agent, to inhibit free radical-induced drug
decomposition
What is the purpose of antioxidants + examples?
- To enhance the stability of therapeutic agents that are
susceptible to chemical degradation by oxidation - aqueous
- oil based
What is the purpose of chelating agents?
- To form complexes with heavy-metal ions involved in oxidative
degradation of therapeutic agents - Ethylenediamine tetraacetic acid (EDTA)
- Citric acid
What is the purpose and properties of 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
