Liquids and MR Flashcards
What are advantages of solutions
Homogenous system
* Drug uniformity is not necessary
Facilitate drug administration by oral and parenteral routes
Faster therapeutic responses
* Avoid first hepatic pass
Reduce potential for drug irritation in GIT
* With caps/tabs they can disperse on GI wall
Administrable by almost all routes of administration
What are disadvantages of solutions
More difficult to store and transport
* May require refrigeration
* Cold chain = costly
More difficult to stabilise compared to solid product
More difficult to achieve accurate dosing for oral route
More difficult to mask unpalatable drug taste
More difficult to modify rate of drug release
How can you enhance solubility of solutions
Co-solvency
pH adjustment and salt formation
Solubilisation
* Surfactant micelles
o Should not introduce foaming and toxicity
Complexation
How can you enhance stability of solutions
Drug stability
* Use compatible excipients
* Reduce oxidation
o Antioxidants
o Chelating agents
o Control pH with buffering agents
o Sparging
* Formulate as powders for reconstitution
* Preservatives
What are formulation requirements for solutions
Aqueous based
Neutral pH
What are formulation requirements for topical
Aqueous or non-aqeuous vehicle
Formulated to evaporate to produce cooling effect
What are formulation requirements for parenteral
Aqeuous or oil based
Comply wiht limits for pyrogens, endotoxins and visible particles
Neutral pH
What are formulation requirements for nasal solution
Aqueous based with cosolvents
pH 5.5-6.5 preferred
Low buffering capacity
What are formulation requirements for ocular
Aqueous based
Sterile with preservatives
Isotonic
What are excipients required for solutions
Solvent
Solubilising agents
Stabilising agents
Preservatives
Viscosity modifiers
Tonicity adjusting agents
Taste modifiers
Colouring agents
Examples of solvent
Water - purified, highly purified, water for injection and sterilised water for injection
Non aqueous solvents - alcohol, fixed oils
Esters
Dimethyl sulfoxide
Glycofurol
Examples of pH modifying agents
Acidifying - HCl, Citric acid
Alkalising - NaCO3, NaOH
Buffering agents - Citric acid + sodium citrate, sodium acetate
Examples of surfactants
Anionic - sodium stearate, sodium oleate
Cationic - cetrimide
Nonionic - Span, Tween, cetyl alcohol
Ampholytic - lecithin
Examples of preservatives
Alcoholic and phenolic - ethanol, chlorbutol
Organic acids - benzoic acid, sorbic acids
Esters - methyl and propyl parahydroxybenzoic acid
Quaternary ammonium - cetrimide
Examples of viscosity modifiers
Cellulose - methylcellulose, hydroylpropyl methylcellulose
Natural - xanthan gums, alginates
Vinyl - polyvinyl alcohol
Silicates - magnesium aluminium silicate
Polyacrylates - carbomers
Examples of sweeteners
Nutritive - dextrose, fructose
Sugar alcohol - mannitol, sorbitol
High intensity - saccharin, aspartame
Quality standards and compendial requirements for solutions
- Uniformity of dosage units
- Preservative and antioxidant concentration
- Sterility, preservative efficacy and microbial tests
- Physical attributes
- Stability over proposed shelf life
Differentiate the different drug release profiles
When do you need to use MR formulations
Maintain drug therapeutic range over longer periods
Achieve chronotherapy
Improve therapeutic compliance
Achieve better health outcomes
What are key features of MR formulations
Max dose for a unit peroral dosage form is 0.5 to 1g
Biological half life
Therapeutic index
Ideally BCS Class I
Mechanisms required for MR
Drug dissolution - controlled
Diffusion of dissolved drug molecules
Swelling o carrier system
Erosion of carrier system
Stimuli responsive system
Methods to achieve modified drug release
Polymer membrane system - diffusion through polymer membrane
Polymer matrix system - drug is distributed throughout polymer matrix
Polymer membrane-matrix system - drug diffusion through polymer membrane per polymer matrix
Inert bead system - drug coated on inert seed
Microporous membrane system - dissolves intestinal fluid
Repeat action delivery systems - multilayers of drug and coat \
Osmotically controlled systems
Explain the components of osmotically controlled systems
Patient counselling for MR
Dose and dosing frequency
Do not interchanged with conventional tablets dosage forms of the same drug
Do not interchange with another modified release system of the same drug
Do not crush or chew tablets
Ghost membranes may appear
Quality standards and compendial requirements for MR
- Physical characteristics
- Uniformity of dosage units - content
- Disintegration profile
- Drug dissolution profile
