Oral Solution Dosage Forms I Flashcards
1
Q
Properties
Pharmacutical solutions
A
- Rate of absorption can be limited by precipitation
- Chemical stability is lowest in solutions
2
Q
Definition
Pharmacutical solutions
A
- liquid preparations in which the therapeutic agent and the various excipients are dissolved in the chosen solvent system
3
Q
Solution
A
- Easily administered for individuals who have difficulty in swallowing
- The therapeutic agent is dissolved in the formulation and is therefore immediately available for absorption
- Reduces the chance of forming a precipitate
- Taste-masking of bitter therapeutic agents
4
Q
Disadvantages
A
- 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 (packaging might break)
5
Q
Co-solvents
A
- Ethanol
- Glycerol
- Proylene glycerol
6
Q
Examples of Excipients
A
- Anti oxidents
- Antimicrobial preservatives
- pH adjuster
- Viscosity enhancer
- Sweetners
7
Q
Water for non-parental
A
Purified by distilation, ion exchange reverse osmosis
8
Q
Water for injections
A
Futher purified to remove pyrogens
9
Q
Drug solubility
A
- Both the therapeutic agent and the excipients are required to be present in solution over the shelf-life of the formulated product
- Needs to be homogeneous
10
Q
High solubility
A
Readily incorporated into the vehicle and formulated as an oral solution
11
Q
Moderate solubility
A
- Solubility enhanced using co-solvents or by related methods (changing pH, salt conversion)
- Aqueous solubility is less than the requested concentration of therapeutic agent
12
Q
Low solubility
A
Formulated as an alternative-dosage form, e.g. a suspension
13
Q
Drug dissolution
A
- 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
14
Q
Propeties that effect solubility
A
- Molecular weight - less soluble
- Particle size
- Solubility ∝ “1” /”melting point”
- Number of hydrogen bonds
- Hydrophilic groups (OH-, COO-, NH4+) >
- lipophilic - groups (methyl, ethyl)
- Crystalline/amorphous properties
15
Q
Factors effecting theraputic agents
A
- Vast majority of drugs are either weak acids or bases and therefore solubility are pH-dependent
- The solubility of acids and bases increases as the degree of ionisation increases
16
Q
Weak acidic drugs and solubility
A
pH > pKa solubility increases
less ionised when pH is lower (mainly ionised)
17
Q
Weak basic drugs solubility
A
- pH < pKa solubility increases
- Mainly ionised at lower pH (less ionised at high pH)
18
Q
Optimisation of formulation pH
A
- Adding buffer in the range of pH 5 to 8 suitable to be consumed orally
19
Q
Weak acid into a salt
A
- The dissolution rate of a weakly acidic drug in gastric fluid is low
- ↑ pH in the diffusion layer, ↑ dissolution rate, ↑ saturation solubility
- ↑ pH of the diffusion layer by changing weakly acidic drug from free acid to basic salt
20
Q
Conversion of weak acid to salt benifits
A
- The sodium salt (naproxen sodium) is absorbed faster and is more effective in indications, such as mild to moderate pain
21
Q
Disadvantage of converting some weak acid to salt
A
- The sodium salt of aspirin, sodium acetylsalicylate, is much more prone to hydrolysis (phenolicesterbond) than aspirin
- difficult for manufacuring
22
Q
Co-solvent
A
- Water used to make it more soluble
- liquid components (miscible in both phases) incorporated into a formulation to enhance the solubility of poorly soluble drugs
23
Q
Micellular solublisation
A
- Incorporating drugs into or onto micelles
- Micellar solubilisation can also increase the solubility of drugs in the GI tract
24
Q
Cyclodextrin complexation
A
- Aids with solublisation due to outside being hydrophilic
- Place the hydrophobic solvent into the cyclodectrin
- Enzymatically modified starches composed of glucopyranose units beta-cyclodextrin
25
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
26
Buffers
- 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
- Acetates, Citrates and Phosphates
27
Sweeting agent
- To increase the palatability of the therapeutic agent
- Avoid in oral formulations for children and patients with diabetes mellitus
28
Flavours
- Flavour adjuncts (e.g. menthol, chloroform) that add flavour and desensitise the taste receptors
- To mask the taste of the drug substance
29
Colourants
- To impart the preferred colour to the formulation
- The selected colour should ‘match’ the flavour
30
Viscosity enhancing agent
- To ensure the accurate measurement of the volume to be dispensed
- Admistration via Syringe, Small-metered cup and Traditional 5-ml spoon
- Syrups, due to the inherent viscosity, do not require the specific addition of viscosity-enhancing agents
- Increased (and controlled) by the addition of non-ionic or ionic hydrophilic polymers
31
Antioxidants
- Molecules that exhibit higher oxidative potential than the therapeutic agent, to inhibit free radical-induced drug decomposition
- enhance the stability of therapeutic agents that are susceptible to chemical degradation by oxidation
- Aqueous soluion and oil based solution
32
Chelating agents
To form complexes with heavy-metal ions involved in oxidative degradation of therapeutic agents with antioxidants e.g. Citric acid & EDTA
33
Preservatives
- To control the microbial bioburden of the formulation
- Broad antimicrobial spectrum
- Chemically and physically stable over the shelf-life of the product
- Low toxicity
- A combination of two members enhances the antimicrobial spectrum
