Lecture 13: 4/12
Pharmaceu)cal development
Introduc)on
Formula(on of drug candidate
- Essen(al In development of new drug
- Complex, (me-consuming and expensive
- Chemist/researchers versus pharmacists
- Now: more sophis(cated drug delivery system
o Targe(ng to relevant cells/(ssues (nanoformula(ons, liposomes, ..)
o Intelligent systems adjust dosage according to clinical response
- Formula(on that have been tested preclinically
- For oligonucleo(des -> bind to certain groups, GalNAc
o Liver will take up everything
- Formula(on will also be dependent by the route of administra(on
o Oral: can be tablet (ideally), can be a capsule (if it has a biMer taste), it could be a
solu(on or even an emulsion in some cases
Solu)on
What?
- Homogeneous mixtures of 2 or more components
o One or more solutes
o One or more solvents
Solu(ons for oral dosage
- Administered volume: usually a mul(ple of 5 ml
- Advantages over solid dosage form:
o Easier to swallow (children, elderly pa(ents)
o Readily absorbed from the GI tract
- Disadvantages over solid dosage for
o Bulky and not convenient to carry around
o Less microbiologically and chemically stable
o “Unpleasant taste” difficult to formulate
- Dose volume will be limited depending on the animal species you use
- O[en easily absorped compared with the tablet
- Some forms o Syrups
- Oral drops (e.g. vitamins) o...
Solu(ons for other pharmaceu(cal uses
- Mouthwashes and gargles (e.g. hextril®)
o Contain an(sep(cs, analgesics or weak astringents
o External use!
- Nasal solu(ons
o Drops or sprays
o Isotonic and buffered at pH 5.5-6.5
o Use: decongestant, local steroids, ...
- Ear drops
o Vehicles: propylene glycol, glycerol and water
, o Use: so[ening earwax, trea(ng infec(ons and inflamma(on
o O[en oily -> more easily to stay in the ear
Suspension
What?
- Contain one or more insoluble medicaments in a vehicle
- Disperse system in which one substance is homogeneously distributed in par(culate
form throughout another
o Par(cle size > 1 μm
o Slowly separa(ng (!) on standing
Advantages and uses
- If drug has low solubility
- Drugs with unpleasant taste;
o chloramphenicol (soluble) → chloramphenicol palmitate (insoluble)
- Dissolu(on rate: solu(on > suspension > solid form
- Slower degrada(on of drug in water
- Drugs suscep(ble to water → suspend in non-aqueous phase
- Bulky, insoluble powders → easier to take as suspension
- IM and SC injec(ons → prolonged release of drug
Formula(on of suspen(on
- Control par(cle size (using a mortar and pestle)
- Thickening agent to increase viscosity of vehicle
o To avoid that the conpount will be precipitate and will not be longer in solu(on
o To slow down sedimenta(on
o Thixotropic → semisolid on standing & flow readily a[er shaking !!
o Semisynthe(c polysaccharides: methylcellulose, carboxymethylcellulose
- Use a wekng agent
o To prevent solids to float
o Reducing interfacial tension between solid & vehicle o Surfactants, such as
polysorbates
o Ethanol, glycerol, ...
Emulsion
What?
- Consists of two immiscible liquids, one of which is uniformly dispersed throughout the
other as fine droplets (diameter: 0.1-100 μm)
o Emulsifying agent is required !!
Pharmaceu(cal applica(ons
- Oral, rectal and topical administra(on of oils & oil-soluble drugs
- Formula(on of oil- and water-soluble drugs together
- To enhance palatability of oils
- Increasing absorp(on through intes(nal wall
Pharmaceu)cal development
Introduc)on
Formula(on of drug candidate
- Essen(al In development of new drug
- Complex, (me-consuming and expensive
- Chemist/researchers versus pharmacists
- Now: more sophis(cated drug delivery system
o Targe(ng to relevant cells/(ssues (nanoformula(ons, liposomes, ..)
o Intelligent systems adjust dosage according to clinical response
- Formula(on that have been tested preclinically
- For oligonucleo(des -> bind to certain groups, GalNAc
o Liver will take up everything
- Formula(on will also be dependent by the route of administra(on
o Oral: can be tablet (ideally), can be a capsule (if it has a biMer taste), it could be a
solu(on or even an emulsion in some cases
Solu)on
What?
- Homogeneous mixtures of 2 or more components
o One or more solutes
o One or more solvents
Solu(ons for oral dosage
- Administered volume: usually a mul(ple of 5 ml
- Advantages over solid dosage form:
o Easier to swallow (children, elderly pa(ents)
o Readily absorbed from the GI tract
- Disadvantages over solid dosage for
o Bulky and not convenient to carry around
o Less microbiologically and chemically stable
o “Unpleasant taste” difficult to formulate
- Dose volume will be limited depending on the animal species you use
- O[en easily absorped compared with the tablet
- Some forms o Syrups
- Oral drops (e.g. vitamins) o...
Solu(ons for other pharmaceu(cal uses
- Mouthwashes and gargles (e.g. hextril®)
o Contain an(sep(cs, analgesics or weak astringents
o External use!
- Nasal solu(ons
o Drops or sprays
o Isotonic and buffered at pH 5.5-6.5
o Use: decongestant, local steroids, ...
- Ear drops
o Vehicles: propylene glycol, glycerol and water
, o Use: so[ening earwax, trea(ng infec(ons and inflamma(on
o O[en oily -> more easily to stay in the ear
Suspension
What?
- Contain one or more insoluble medicaments in a vehicle
- Disperse system in which one substance is homogeneously distributed in par(culate
form throughout another
o Par(cle size > 1 μm
o Slowly separa(ng (!) on standing
Advantages and uses
- If drug has low solubility
- Drugs with unpleasant taste;
o chloramphenicol (soluble) → chloramphenicol palmitate (insoluble)
- Dissolu(on rate: solu(on > suspension > solid form
- Slower degrada(on of drug in water
- Drugs suscep(ble to water → suspend in non-aqueous phase
- Bulky, insoluble powders → easier to take as suspension
- IM and SC injec(ons → prolonged release of drug
Formula(on of suspen(on
- Control par(cle size (using a mortar and pestle)
- Thickening agent to increase viscosity of vehicle
o To avoid that the conpount will be precipitate and will not be longer in solu(on
o To slow down sedimenta(on
o Thixotropic → semisolid on standing & flow readily a[er shaking !!
o Semisynthe(c polysaccharides: methylcellulose, carboxymethylcellulose
- Use a wekng agent
o To prevent solids to float
o Reducing interfacial tension between solid & vehicle o Surfactants, such as
polysorbates
o Ethanol, glycerol, ...
Emulsion
What?
- Consists of two immiscible liquids, one of which is uniformly dispersed throughout the
other as fine droplets (diameter: 0.1-100 μm)
o Emulsifying agent is required !!
Pharmaceu(cal applica(ons
- Oral, rectal and topical administra(on of oils & oil-soluble drugs
- Formula(on of oil- and water-soluble drugs together
- To enhance palatability of oils
- Increasing absorp(on through intes(nal wall
