1 / 23

PHC 222 Part(I) Dr. Huda Al Salem

PHC 222 Part(I) Dr. Huda Al Salem. Lecture (10). How to improve water solubility?. 1- Salt formation. 1- Salt formation. -Salt formation usually improves the water solubility of acidic and basic drugs as the salts of these drugs dissociate in water.

carla-wynn
Download Presentation

PHC 222 Part(I) Dr. Huda Al Salem

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. PHC 222Part(I)Dr. Huda Al Salem Lecture (10)

  2. How to improve water solubility? 1- Salt formation

  3. 1- Salt formation -Salt formation usually improves the water solubility of acidic and basic drugs as the salts of these drugs dissociate in water. -The degree of water solubility depends on the structure of the acid or base used to form the salt

  4. 1- Salt formation Many GIT disturbances can be treated by ingestion of water-soluble compounds. Example 1 Tartaric acid >>>>Na K tartrate is used as mild laxative

  5. 1- Solubility - Salt formation is also used to change the taste of drugs to make them more palatable to the patient Example 2: Chlorpromazine HClis water soluble but it has a very bitter taste. However, the water insoluble embonate salt is tasteless.. So it can be administered orally in the form of a suspension

  6. How to improve water solubility? 2- Incorporation of water-solubilizing groups

  7. 2- Incorporation of water-solubilizing groups a- Type of group introduced b- Degree of permanency c- The biological effect of the group d- Methods of introduction

  8. a- Type of group introduced 1- Incorporation of strongly polar alcohol, amine, amide, carboxylic acid, sulphonic acid and phosphorus oxyacid groups give analogues with water solubility higher than those formed by introduction of ether, aldehyde & ketonic functional groups. 2- Introduction of acidic and basic groups give a wide range for dosage forms that increase water solubility.

  9. a- Type of group introduced 3- Zwitterions reduces water solubility. 4- Incorporation of weakly polar groups such as carboxylic acid esters, aryl halides & alkyl halides increases lipid solubility.

  10. b- Degree of permanency 1- Groups that are bound directly to the carbon skeleton of the lead compound by C-C, C-O & C-N bonds are attached to by irreversible bonds. 2- Groups that are linked to the lead compound by ester, amide, phosphate & glycosidic links are more likely to be metabolized to reform the parent lead compound.

  11. C- The position of the group In order to preserve the type of activity exhibited by the lead, the introduced group should be attached to a part of the structure that is not involved in the drug-receptor interaction (Pharmacophore).

  12. C- The biological effect of the group Some groups have certain biological activity.. 1- acidic groups exhibit haemolytic properties. 2- aromatic acid groups exhibit anti-inflammatory activity 3- carboxylic acids with an alpha functional group exhibit chelation property. 4- Basic groups have a tendency to change the mode of action

  13. d- Methods of introduction 1-Water-solubilising groups may be introduced at any stage in the synthesis of a drug. 2-Many methods involve the use of protecting groups. 3- Groups protected are either the water- solubilizing group or groups already present in the lead structure.

  14. d- Methods of introduction e.g.: Acetal protection of a ketone during Reductionof an Ester.

  15. d- Methods of introduction 1- COO- by acylation Chloramphenicol sodium succinate is supplied as a lyophilized powder which is dissolved only in water when needed & not more than 48 hours

  16. d- Methods of introduction 2- Sulphonic acid groups (-SO3H)

  17. d- Methods of introduction 3- Basic groups -By alkylation or acylation -Amide derivatives are usually more stable than esters in aqueous solutions

  18. d- Methods of introduction 4- Polyhydroxy groups

  19. d- Methods of introduction 5- Ether groups

  20. Solubility 3- Formulation Methods

  21. 3- Formulation Methods Cosolvents Colloidal Solutions

  22. 3- Formulation Methods A-Cosolvents a second solvent added to the original solvent, in small concentrations, to form a mixture that dissolve the solute. Requirements 1- Minimal toxic effect 2- Should not affect stability of the drug Example Paracetamol elixir in an aqueous solution is dissolved by the use of mixture of ethanol & 1,2-dihydroxypropane,

  23. 3- Formulation Methods B-Colloidal Solutions Prepared by dissolving a high concentration of the drug in an organic solvent that is miscible with water. Then, the concentrated solution is rapidly mixed with an aqueous solution containing a suitable stabilizer which adsorbed on the surface of the colloidal particles. Ex: Shaving Cream (Foam) (g in L) Mayonnaise (L in L) Blood (S in L)

More Related