Lecture 2 “Influence of pharmaceutical factors, such as physical state, simple chemical modification of medicinal substance on the therapeutic efficiency of medicines ”.
Lecture 2“Influence of pharmaceutical factors, such as physical state, simple chemical modification of medicinal substance on the therapeutic efficiency of medicines”
The maximal usage of «pharmaceutical factors» is the primary purpose of pharmaceutical technology for providing of high quality of medicines that coincides with the strategic task of biopharmaceutics which consists in the maximal increase efficiency of medications and decline to the minimum of possible side action on an organism.
Therapeutic activity of medicinal substances caused by:
Physical state of medicinal substance
and ways of application
Auxiliary substances (their nature, physical state and quantity)
Simple chemical updating of medicinal substance
Studying of pharmaceutical factors is obligatory from the point of view of biopharmaceutics in a view of their essential influence on dynamics of bioavailability of medicinal substances, stability of medicines during storage term and many other parameters.
Polymorphs have different stabilities and may spontaneously convert from a metastable form (unstable form) to the stable form at a particular temperature. They also exhibit different:
So, due to differences in solubility of polymorphs, one polymorph may be more active therapeutically than another polymorph of same drug:
According to the dispersive classification medicines are represented as all-round binary disperse system.
The solubility of substances depends on surface properties and their degree of crushing.Diferency of particles size of medicinal substances can cause to nonequalabsorbtion rate and their content in biological liquids of the same medicine. So, the clinical non-equivalence is possible.All these should be taking into account while preparing of liquid medicinal forms for grounded a technological operations and composition of medicines.
Standard dissolution method for highly soluble APIs
Therapeutical activity of medicinal substances depends on:
Among optical isomers there is no chemical distinction, but each of them revolves the plane of polarization ray in certain direction. In spite of the fact that the chemical analysis fully confirms the presence of the same substance in medicine with different isomers, they will not be therapeutically equivalent.
Depending on concentration of hydrogen ions the medicinal substances can be in the ionized or unionized form. pH index influences also on the solubility, coefficient of distributing of medicinal substances, membrane potential and superficial activity.
Degree of ionization
The waterless medicinal substances and crystallohydrate has a different solubility that causes change of their pharmacological action. For example, the waterless forms of caffeine, ampicillin, teophylline dissolve quickly, as compared to their crystallohydrate and consequently is quickly sucked.
Contain in molecul crystalline
The clinical researches of application a simple chemical modification of medicines showed a differect results: For example:Chinin-baseChininsulphatesolubilityis 1 : 800Chininchloridesolubilityis 1 : 34Chinin bromide solubilityis 1 : 16Tthese substances has a different pharmacokinetic (because a solubility is differ) but the activity is saved.
While glucose mix in medicinal form with following substances:
Simple chemical modification
The same substanceisrepresentedasadifferenttypeofchemicalcompound (salt, base, esther, complexetc.), but the pharmacological activity is stable
While replacing one substance by other we should be recalculate their amount in molecular mass or unit of action:
On the basis of biopharmaceutics researches proved that arbitrary replacement some ion in the molecule of medicinal substance, coming from cleanly technological or economic indicators is unpossible.