Question

Water is a good solvent, but drugs are often bad solutes.

a) Explain why drugs are bad solutes and why water is not a good solvent for all drugs.

b) Discuss TWO (2) techniques that can be used to improve the solubility of drugs for the preparation of oral liquid formulations.

Answer 1

a)DRUGS ARE BAD SOLUTES BECAUSE:

Solubility is the phenomenon of dissolving process of solute in solvent to give a homogeneous system,is one of the important parameters to acheive desired concentration of drug in systemic circulation for anticipated pharmacological response.Low aqueous solubility is the major problem encountered with forming development of new chemical entities as well as for the generic development.The poor solubility of the drug is larger particle size,crystal habit,chemical properties such as pH,salt formation.complexation etc...

WATER IS NOT A GOOD SOLVENT FOR ALL DRUGS:

More than 40% NCEs (new chemical entities) developed in pharamaceutical industry are insoluble in water.Solubility is a major for pharmaceutical scientist.Any drug to be absorbed must be present in the form of solution at the site of absorption.The drugs which has poor water solubility does not present in the form of solution and fails to present them self in the site of absorption.Thus, these poorly water soluble drugs having slow drug absorption leads to inadequate and variable bioavailability and gastrointestinal mucosal toxicity.

b)PRECIPITATION TECHNIQUE:

-In preciptation technique the drug is dissolved in a solvent,which is then added to antisolvent to precipitate the crystals.

-The basic advantage of preciptation technique is the use of simple and low cost equipments,but the complication is the addition of growing drug crystals to avoid formation of microparticles.

-The limitation of this precipitation technique is that the drug needs to be soluble in at least one solvent and this solvent needs to be miscible with antisolvent.

-Moreover,precipitation technique is not applicable to drugs ,which are simultaneously poorly soluble in aqueous and non aqueous media.

-Nanosuspension of Danzol and Naproxen have been prepared by precipitation technique to improve their dissolution rate and oral bioavailability.

-The size reduction of Naproxen was also associated with an apparent increase in the rate of absorption by approximately 4-fold.

HIGH PRESSURE HOMOGENIZATION:

-High pressure homogenization has been used to prepare nanosuspension of many poorly water soluble drugs.

-In this process,the suspension of a drug and surfactant is forced under pressure through a nanosized aperture valve of a high pressure homogenizer .

-The principle of this method is based on cavitation in the aqueous phase.

-The cavitations forces within the particles are sufficiently high to convert the drug microparticlesinto nanoparticles.

-The concern with this method is the need for small sample particles beforeloading and the fact that many cycles of homogenization are required .

-Dissolution rate and bioavailability of poorly soluble drugs such as spironolactone,budesonide and omeprazole have been improved by reducing their particle size by high pressure homogenization