Salt form & Co-solvents and surfactants Flashcards
why form salts ?
formation of salts can often increase solubility.
formation of salts can often increase bioavailability
how does formation of salts improve solubility
the crystal properties of a salt, which affect the energy required to dissociated solute-solute bonds: more regular crystal structure can decrease solubility and dissolution rate.
How to form salts ?
A salt is a chemical combination of two ionisable components
A salt may be formed between a weak base and a strong acid
or
a weak acid and a strong base
It can also be formed by the combination of a weak base and a weak acid.
What are the formulation requirement for salts ?
Changes in drug solubility will affect the drug absorption
Normally a base will dissolve in its ionic form in the stomach and then be absorbed in its neutral form in the small intestine . The ionized form has low lipid solubility (but high water solubility—ie, hydrophilic) and high electrical resistance and thus cannot penetrate cell membranes easily.
Different dosage forms may require different pH levels.
They should compatible with other excipients.
What is a co-solvent?
Cosolvents are substances added to a primary solvent in small amounts to increase the solubility of a poorly-soluble compound.
What are the general considerations when using a co-solvent for a particular formulation include :
increasing the drug solubility
the co solvent must be non toxic at the concentration used and by the route of administration
the cost of the formulation.
What are the uses of co-solvents?
In order to increase the solubility of non polar drugs in aqueous phase, the polarity of an aqueous phase should be lowered.
A water-miscible organic liquid normally has a low polarity. Such a liquid when used are used to enhance the solubility of the drugs that do not contain ionisable groups and whose solubility cannot change with the pH, is called a co-solvent.
Examples of commonly used co-solvents
Glycerol - used in oral and external preparations
Propylene glycol - injections and ear drops
Poly(ethylene glycol) - injections
Surfactants
The surfactants have two distinct regions in their chemical structure. Hydrophilic (water liking) and hydrophobic ( water hating ) regions.
Containing both hydrophobic and hydrophilic groups. The Hydrophilic regions can be anionic, cationic, zwitterionic, or nonionic. The hydrophobic regions are usually saturated or unsaturated hydrocarbon chains, or heterocyclic or aromatic rings
Surfactants are generally classified according to the nature of the hydrophilic group.
Uses of the different types of surfactants
Anionic Surfactants - used in household products such as toothpastes, shaving foam. Pharmaceutical use as a preoperative skin cleaner due to its bacteriostatic action against Gram-positive bacteria.
Cationic Surfactants - the quaternary ammonium and pyridinium cationic surfactants have a bactericidal activity against a wide range of Gram Positive and some Gram Negative organisms. Pharmaceutical use- solutions are used to clean the skin and wounds.
Zwitterionic Surfactants - the use of this is fairly limited. They have become popular in the use of hair care products, skin care products as mild detergents, conditioners etc.
Nonionic Surfactants - compatible with all classes of SAAs. Some can be used in oral and parenteral products. Hydrophilic and hydrophobic groups tend to be equally balanced. They constitute the largest groups of emulsifying agents.
Micelle Formation 1
In low concentration of surfactant solution, surfactants will collect. Very few or no molecules will remain distributed in bulk phase
The surface tension of this solution progressively with increase of concentration as more surfactant molecules enter the surface
Micelle Formation 2
At a certain concentration, the surface becomes saturated, the surface tension wont decrease. The surfactants interact with each other to shield the hydrophobic chains from the aqueous phase through the formation of aggregates. This formation is called Micelle
What is critical micelle concentration ? (CMC)
This is the concentration at which the micelles first form in solution.
What are some of the effects of surfactants ?
Surfactants may decrease activity of drugs because the drug is less freely available
Surfactants may decrease hydrolysis or oxidation of drug
High concentration of surfactants thicken solutions
Some types of surfactants have greater toxicity
What are some other uses of surfactants ?
Wetting agents
Flocculating agents
Emulsifying agents
Additive in ointments, suppositories, capsules, tablets etc.
