formulation of liquid medicines

what is the kinetic theory of matter: gases

assumptions of kinetic molecular theory:

• consist of a large number of tiny particles

• are in constant, rapid, linear motion → collisions are soon to be completely elastic, with no net loss or gain of kinetic energy

• molecules are independent of one another, unless during collisions → no forces of attraction/repulsion

• there is a wide range of molecular speeds that contribute to kinetic energies 

how well does the kinetic theory of matter correlate with observed gas properties

• majority of gas volume is empty space → gas is very compressible 

• gases will expand to fill the container → Brownian motion supports the random nature of gas molecules 

• they move in a random, rapid motion

• the ability to fill a container at any pressure supports the lack of forces between molecules 

• there is distribution of kinetic energies 

what are the key properties of liquids

• flow readily

  • not locked in fixed position

  • more resistant to deformation than gases

• diffuse slower than gases

  • greater IMFs

  • less space between molecules

• less compressible

  • little free space

  • repulsion occurs between electron clouds

• can maintain a characteristic volume

  • shape depends on container

  • volume doesn’t change

conversion of a gas to a liquid is depend on..

temperature and pressure

what is critical temperature, T_c

the maximum temperature at which a gas becomes a liquid at critical temperature

what is critical pressure, P_c

the pressure that is required for gas to become a liquid at critical temperature

what are the three different forms of of solids 

• crystalline

• polymorphism

• amorphous (non-crystalline)

what are the feature of crystalline solids

• sharp transition from solids to liquids

• defined melting point

• incompressible due to fixed structure 

• fixed geometric pattern/lattices

• have different conformations of arrangement: cubic/hexagonal

each small unit is called a unit cell, each each unit cell has the same number of molecules or ions in it, all arranged in the same way

what are the features of polymorphism solids 

• molecules arranged differently in the crystal 

• exist in different states

• internal structure detected by X-ray diffraction 

• different chemical/physical properties to original (causes challenges when formulating products, as well as different therapeutic/adverse effects)

• examples: paracetamol and spironolactone

what are the features of amorphous (non-crystalline) solids

• without form → molecules are arranged randomly 

• similar arrangement to supercooled liquids (liquids that are heated, then cooled very quickly)

• change gradually and continuously → eventually crystallise to become more stable 

• in morphic state, flow when sufficient pressure applied over time 

• no discrete melting point 

• recrystallise over time 

• example: novobiocin, is absorbed and active when in amorphous state 

what are the two types of pharmaceutical liquids

• non electrolytes 

• electrolytes 

electrolytes → ions are able to migrate and therefore conduct electricity

what is a solution

a type of dispersion that is a homogenous, physical mixture of two or more substances, in a single phase system 

in terms of dispersion, what are the three types of solutions

solution 

• a chemically and physically homogenous mixture of 2 or more substances 

• solute (solid) → minor component, is completely dissolved 

• solvent → major component 

colloidal solution 

• solution of particulate material that is more than 1μm

• not completely dissolved 

suspension 

• a mixture of insoluble material in a fluid 

concentration expressions

what are the types of pharmaceutical solutions

internal

• oral for GI (local) or systemic disorders 

• parenteral (often injected for systemic effects)

external 

• local or tropical effects

• otic (ear)

• ophthalmic

• vaginal

• rectal

• oral rinses/gargles

• dermal

what are the advantages of pharmaceutical solutions

• complete and rapid release of API due to higher bioavailability compared to other formulations 

• ease of use/swallowing 

• uniform dose 

• only dosage form that can be given by IV route

what are the disadvantages of pharmaceutical solutions

• bulky for storage/transport

• specialist containers required 

• may have poor chemical stability 

• taste-masking is difficult 

• preservatives required to prevent microbial growth 

what do colligative properties for ideal solutions depend on 

• depend on the number of solute molecules present, not physical or chemical characteristics

• if one property is known, the can calculate another → number of moles of substance can be calculated

colligative properties → the properties of a solution that are dependent on the ratio between the total number of solute particles (in the solution), to the total number of solvent particles

what is vapour pressure of a liquid

• when a liquid is in an enclosed container, some molecules have enough kinetic energy → gaseous molecules are released and turn into liquid vapour

• as more molecules enter the vapour phase, some of them collide with the liquid surface and condense back into the liquid.

• eventually, the rate of molecules vaporising equals the rate of molecules condensing back to liquid → dynamic equilibrium

• no molecules turn to vapour

what happens when you add a solute to a solvent 

• reduces vapour pressure → increases boiling point → decreases freezing point

• this is controlled by Raoult’s law

what determines the phase of a solution

a solvent

what is dissolution

transfer of molecules from a solid into a solution

what is solubility

the extent to which dissolution proceeds under a set of experimental conditions

what is saturation

amount of dissolved solute = amount of undissolved solute

what can you change if a drug has poor aqueous solubility 

• increase dose to achieve desired effect

• change or add in other solvents

but all this increases the risk of adverse effects in the end product