Solutions Flashcards
Name and discuss 5 ways you could increase solubility of a poorly water soluble API?
- Salt screens - form a. salt which has higher solubility and bioavailability. Easy and simple, best way of increasing solubility, could form chloride or acetate salts e.g: R-NH2 + HCL –> R-NH3+ Cl - // R-NH2 + CH3COOH –> R-NH3+ CH3COO-
- Make amorphous - tend to be more soluble due to less tightly packed arrangements - convert it from crystalline to amorphous using freeze or spray drying. BUT risk of conversion back to more stable crystalline form
- Form a co-crystal e.g crystallise it out of solution using an inactive molecule e.g nicotinamide - the co crystal may be more soluble. BUT patent/test safety.
- Complex the API using cyclodextrins -forms hydrophoic pocket complex to increase sol
- Polymorph screening - Find different crystalline forms of the API by recrystallisation. One polymorph may be more soluble, but again the risk of converting back to less soluble forms.
What are the main excipients in oral solutions (apart from the solvent vehicle )
Reducing agents// Antioxidants Buffers Viscosity enhancers Preservatives Colourants Flavours Sweetening agents
Name4 common solvent vehicles
Water mainly.
- Alcohol
- Glycerol (glycerine) - clear, syrupy, sweet, miscible in water and alcohol. Used as stabiliser in conjunction with water/alcohol, can also be used as preservative
- Propylene glycol - often substituted for glycerin
What is the role of buffers in solutions?
Control and maintain the pH of the solution - they are a solution of weak acid and conjugate base or Visa versa
Give examples of buffers
Phosphate
Citrate
acetate
What does the phosphate buffer do?
Used to buffer pH 7 with salts -
Monosodium Phosphate - conjugate acid
Disodium Phosphate - conjugate base
These are in equilibrium to be a buffer
What is role of viscosity enhancers?
Increase viscosity to increase surface tension - improving pouring quality
What ingredients are used for viscosity enhancement?
Gelling agents - Hydrophilic polymers e.g Hydroxyethylcellulose Providone Carbomer Poly(acrylic acid)
What is the role of preservatives?
Killing bacteria essentially. Adsorption to containers - efficiency impaired by pH or other ingredients.
Name preservatives used
Methyl or propyl parabens:
- Benzoic acid 0.1-0.2%
Sodium benzoate 0.1-0.2%
Combination of parabens at 0.1%
Role of reducing agents/antioxidants and name an example
Stop the breakdown of the API i.e preserve it if its prone to oxidation.
e.g Ascorbic Acid (vitamin C)
What are sweetening agents used for? give examples
Mask flavours e.g sucrose is colourless and very soluble
- Sorbitol
- Mannitol
- Sodium or Ca salts of saccharin
Why are flavours and perfumes used? What would you use if you want to mask: - Salty - Bitter - Sour - sweet
To make it palatable when sweetening agents not enough.
Salty = Apricot, liquorice
Bitter = Anise, mint, raspberry, marshmallow
Sour = citrus
Sweet = raspberry/vanilla
Give examples of colourants used in oral solutions
Amaranth - for identification and safety, matching the colours to the flavours.
Isotonicity modifiers are excipients that are used in drug solutions for injections, ophthalmic solutions, mucous membranes. WHY?
Contribute to osmotic pressure to ensure denisities are the same i.e must be iso-osmotic with the tissue fluid. If the solution has a different isotonicity as the surroundings it will cause osmotic flow, damage eg inflammation
Name isotonicity modifiers
Dextrose
Sodium chloride
Give advantages of using oral solution dosage forms
Easy to swallow
Fast therapeutic onset/effect as it is immediately available - no disintegration or dissolution
- Homogenous
- Minimal irritation to gastric mucosa
Give disadvantages of oral solution dosage forms
Bulky / inconvenient
Less stable
Could get microorganism growth - need for preservatives
Issues with accuracy of dose i.e with spoons
Taste is pronounced
Give example of a oral solution
Fluoxetine liquid HCL - 20mg/5ml, antidepressant
Diphenhydramine HCL - elixir 12.5mg/5ml, antihistamine
If you had a poorly soluble weak acid drug or weak basic drug, what salts would be formulated?
Weak acid - formulate with salt as a base - Sodium hydroxide e.g ibuprofen sodium
Weak base - formulate with acidic salt - hydrochloric acid e.g cetirizine hydrochoride
How can you improve solvency of a weak electrolyte / non polar compound?
Co-solvency - adjusting the polarity of the solution e.g adding glycerol, propylene glycol, ethanol
Can also use buffers - adding electrolytes
What does co-solvency do?
Lowers the dielectric constant and increases solubility of the unionised form
What do you need to avoid if you’re adding a buffer to a solution to improve the solvency of a weak electrolyte/non polar?
If adding buffer to a weak electrolyte you need to ensure you are not adding common ions i.e dont add buffers that have the same ions as what is in the salt - this would actually reduce solubility due to the fact that the buffer ions would interact with water, take up space, no space for interactions between ionised and water to be soluble.
What does complexation do?
Solubilising agent - Cyclodextrin = it has a hydrophobic pocket inside so water insoluble APIs can sit in it, and hydrophilic outside - forms a complex. Improves solubility
What else apart from complexation agents can be used as solubilising agents?
Surfactants
Larger micelle size = higher solubilisation (and temp)
- can protect against hydrolysis too and is more stable.
Has a hydrophobic core (paraffin like) and non-ionic head group
What factors affect the rate of dissolution?
- Crystallinity / crystalline form of solid
- Temp
- Agitation / mixing
- Particle size
- Presence of other compounds/common ions/solubilising agents
- Co-solvency/nature of dissolution medium
- Molecular structure of the solute e.g salts of weak acids of bases
3 different types of pharmaceutical solutions?
Syrup
Elixir
Solution
Suspension
Which group is most soluble? -CO2H, OH, CH3
OH most polar - like dissolves like
How would you increase the solubility of a weak base?
Formulate in its salt form - an acidic salt such as hydrochloride e.g react with hydrochloric acid to form chloride salt. E.g cetirizine hydrochloride
Weak acids dissociate completely in solution - T or F?
F - only partially dissociate as its a weak acid
Why are buffers added to pharm solutions?
Maintain and control pH of solution - e.g phosphate, acetate, citrate
Excessive hydrophilicity can compromise drug absorption - T or F?
T
