D3 Polymers and oral liquid dosage forms Flashcards
what are macromolecules?
molecules made of a large number of atoms
what are polymers?
substances of a high molecular weight consisting of repeating monomer units
in polymer names, what doesn’t tend to get mentioned?
termination groups (groups outside the square brackets at the ends of the molecule)
what are defoaming agents used to do? how do they do this?
- relieve trapped wind / bloating
- lower the surface tension of gas bubbles so smaller bubbles fuse into larger ones
- larger bubbles are more quickly passed out by burping/farting
what is simeticone? describe its structure
- activated dimeticone
- polydimethylsiloxane (PDMS)
- homopolymer (all the monomeric units are the same)
- linear
active ingredients in Gaviscon double action
sodium alginate
sodium bicarbonate
calcium carbonate
explain how raft-forming agents were discovered serendipitously
- alginate containing formulations were originally developed as carriers for radiological contrast agents
- realised it was also relieving heartburn in trial participants
state some examples of drugs/medicines that were discovered serendipitously, like raft-forming agents
- natural product medicines (or derived from)
- penicillin antibiotics
- sildenafil (Viagra)
- sulfonylureases eg. gliclazide
- valproic acid
describe the mode of action of raft-forming agents
- if pH drops below 3.5, alginic acid precipitates as a gel (becomes insoluble) because the free acid is the more stable compound
- this precipitate swells and can absorb up to 100 times its own mass in water
why is 3.5 the pH at which alginic acid will precipitate in a raft-forming agent?
this is the pKa of alginic acid
why do many alginate-based medicines also contain bicarbonate or carbonate?
- the bicarbonate or carbonate produces carbon dioxide
- the precipitate / gel traps the carbon dioxide gas, which produces a low-density raft that can float on the stomach contents and prevent stomach contents from refluxing into the oesophagus
state some of the excipients of Gaviscon cool liquid
- carbomer
- methyl parahydroxybenzoate
- propyl parahydroxybenzoate
- saccharin sodium
- mint flavour no. 4 and 5
- sodium hydroxide
- purified water
state some of the uses of carbomer
- emulsifying agent
- bioadhesive polymer
- suspending agent
- viscosity-increasing material
describe carbomer as an excipient in Gavsicon cool liquid
- polymeric suspending agent / viscosity modifier
- inclusion increases the formulation’s viscosity (helps with palatability and pouring)
- enhanced physical stability of medicine
describe the structure of carbomer
- synthetic high molecular weight homopolymers of acrylic acid
- cross linked
describe the function of parahydroxybenzoates (paragons) as excipients in Gaviscon cool liquid
- antimicrobial preservatives (a mixture of different paragons often employed as this enhances activity)
- less active at higher pH values when the phenolate ion is more likely to form
describe the solubility and antimicrobial activity of different parabens
- methyl- derivative has a higher aqueous solubility than the propyl- and butyl- esters
- the longer chain esters have a greater antimicrobial activity
what does a longer alkyl chain in parabens give?
longer alkyl chain reduces solubility but gives better antimicrobial properties by inserting themselves into the walls of microbes
describe sodium saccharin as an excipient in Gavsicon cool liquid
- added to improve taste
- 300-600 times sweeter than sugar
- used in food and beverages as well as pharmaceuticals
- suitable for diabetic patients
why is the sodium salt of saccharin used as an excipient in Gaviscon cool liquid instead of saccharin itself?
sodium salt has a greater aqueous solubility than saccharin
what is reported form 1 in 4 people about medicines containing sodium saccharin?
a metallic / bitter aftertaste
why are the flavourings in Gaviscon cool liquid listed as mint flavourings no. 4 & 5?
- the food and pharmaceutical industries are notoriously secretive
- they are trade secrets
- ‘flavour is satisfactorily controlled by an in-house specification and conforms to the requirements of Directive 88/388/EC relating ti flavourings in foodstuffs’
why are mint flavours used in Gaviscon cool liquid?
- mint flavours are traditionally used for indigestion and heartburn remedies
- peppermint oil is used to relieve irritable bowel syndrome
describe sodium hydroxide as an excipient in Gavsicon cool liquid
- included to adjust the pH
- at low pH values (below 3.5 / pKa of alginic acid), the alginate may precipitate
- at higher pH (5-9), the maximum viscosity occurs
- acidic carbomer will reduce pH so NaOH is required to raise it
what is Peptic peppermint liquid?
- a generic equivalent to Gaviscon
- Gaviscon was the innovator product
- the MA can be abridged (do not need to unnecessarily test again)
active ingredients of Peptic peppermint liquid
same as Gaviscon cool liquid
each 5 ml contains:
- sodium bicarbonate
- sodium alginate
- calcium carbonate
what are the excipients of Peptac liquid?
carbomer
sodium hydroxide
saccharin sodium
ethyl parahydroxybenzoate
propyl parahydroxybenzoate
butyl parahydroxybenzoate
isopropyl alcohol
peppermint oil
purified water
describe peppermint oil including its appearance, what it mixes with and how it is obtained
- obtained by steam distillation from the fresh overground parts of the flowering plant of Mentha x piperita
- it is a colourless, pale yellow or pale greenish-yellow with a characteristic odour and taste followed by a sensation of cold
- miscible with alcohol and with dichloromethane
what will the addition of isopropyl alcohol do to formulations?
make them slightly more lipophilic
describe what parabens are used in formulations with isopropyl alcohol
- methyl parahydroxybenzoate replaced with the more lipophilic ethyl- derivative
- butyl parahydroxybenzoate (more lipophilic than the other parabens) is therefore included
describe the shelf lives of Gaviscon cool liquid and Peptac
- Gaviscon cool liquid is only supplied in glass bottles
- Gaviscon cool liquid has a 2 year shelf life
Peptic shelf lives depend on packaging
- amber glass bottles = 24 months
- HDPE bottles = 18 months
- PET bottles = 12 months
what is HDPE?
high-density polyethylene
what is PET?
polyethylene terephthalate
storage precautions for Gaviscon cool liquid and Peptac
- do not store above 25 degrees C
- do not refrigerate or freeze
why should Gaviscon cool liquid and Peptic not be stored above 25 degrees C?
- microbial growth
- preservative hydrolysis
- more than 60 degrees C leads to alginate depolymerisation
describe glass as a storage material for medicines
- non-reactive and totally impermeable
disadvantages
- heavy
- fragile
- alkali components may leach from glass
why should Gaviscon cool liquid and Peptic not be refrigerated or frozen?
- sodium alginate solubility issues
- freezing leads to caking
what are the 2 main types of glass used in pharmaceutical packaging?
- neutral glass (type I)
- soda-lime-silica glass (type II or III)
describe neutral (type I) glass
- a borosilicate glass containing significant amounts of boric oxide, aluminium oxide alkali and / or alkaline earth oxides
- high hydrolytic resistance
- high thermal shock resistance
describe HDPE as a storage material for medicines
- not permeable to vapours
- there have been concerns about the compatibility of plastics and paragons for years
- methyl parahydroxybenzoate probably acceptable with HDPE containers
list glass, HDPE and PET in order from least to greatest potential for parabens absorption
glass (least)
HDPE
PET (most)
describe PET as a storage material for medicines
- less permeable to oxygen than HDPE
- parabens absorption has caused concerns
describe soda-lime-silica (type II or III) glass
- a silica glass containing alkali metal oxides, mainly sodium oxide and alkaline earth oxides, mainly calcium oxide
- moderate hydrolytic resistance
- type III is the glass used for Peptic packaging and most oral formulations
- type III is usually avoided for aqueous parenteral products
what may leach from glass and what does this lead to?
- alkali components may leach from glass
- leads to chemical instability
how is it proven that alkali components leach from glass?
bottles filled with water, autoclaved and then titrated against 0.01M HCl with methyl red as the indicator
