L18 - drug sol & dissolution rate 3

-low solubility, high permeability - need to increase SA - uses surfactants and solvents

• high permeability and solubility • simple solid oral dosage form

• low permeability, high solubility • permeability enhancers

• low permeability and solubility • increase SA • solutions using solvents and suspensions • permeability enhancers

high dissolution rate in stomach, but as pH of gi tract increases the dissolution rate decreases

low dissolution rate in stomach but as you go down gut the rate increases as pH increases

• use of salt form of a drug changes pH of diffusion layer • salt of a weak acid increases the pH of the diffusion layer • salt of a weak base decreases pH of diffusion layer

• a basic solution forms • pH of diffusion layer becomes around 5 or 6 • pH of gastric fluid is 1-3 • so you get fine precipitation of unionised acid HA of drug • if these fine particles are dissolved rapidly then there is good bioavailability

controlled pH of diffusion layer independently of the position of the gi tract, improving dissolution rate, good for developing slow/controlled release products

weak electrolytes act like strong electrolytes or like non electrolytes in solution

• when drug is ionised at a given pH of solution, so it acts like solution of strong electrolyte • when pH of solution is changed to a value that will produce the most unionised molecules causing precipitation • when the solubility of weak electrolytes/ non polar compounds in water is improved by adding water miscible solvent where the compound is soluble • vehicles used in combination with water to increase solubility of a drug = cosolvents

solubility in these mixed system is greater than that of individual solvents (if you mix alcohol with water, you decrease waters polarity)

solute is more soluble in a mixture of solvents than in one

solvents, that in combination, increase solubility of solute

• to get aq system where drug sol is higher than aq solubility • formulate higher concs of the drug • improve stability of the formulation

• organic compounds (usually non polar) • miscible with water • better solvents than water than drugs (h bond acceptor and donor groups, small hydrocarbon regions)

• decrease it • so reduce the cohesive interactions of water • reduce polarity • solution less effective than water in squeezing out non polar solutes

decreasing the polarity of solvent

• adding cosolvent increases solubility of non polar and semi polar solute in water • as the solute becomes more polar, cosolvency becomes left efficient • it will decrease solubility of a polar solute in water

high solubilisation slope when mixed with ethanol and water