Application of preformulation consideration in the development of

Pharmacy

1. Prepared By- Arpan Dhungel Application of preformulation consideration in the development of parenteral dosage form

2. What is Preformulation Study It is a part of research and development process which is used to study the mechanical as well as physicochemical properties of new drug to develop stable,effective and safe dosage form

3. Types of Parenteral Dosage form Injectable Solutions Injectable Suspensions Injectable Emulsions

4. Injectable Soluions These are the most common injectable drug products These solutions have tendency to be injected by any route (I.V.,I.M.,S.C .)

5. Injectable Suspensions Here the API is extremely insoluble to the solution used to deliver it Suspensions are prepared for release at precise location,controlled release due to slow crystal dissolution Approaches taken in consideration for injectable suspensions are - 1.Stoke’s Law 2.Flocculation 3.Structured vehicle

6. Injectable Emulsions For injectables o/w form is traditionally used The most important fundamental element for formulation of injectable emulsion is emulsifying agent

7. Preformulation Assessment It is an information gathering process to ensure that all the information is in place to begin preformulation studies. It saves both the time and effort of pre-developmental scientist.

8. Information taken from P reformulation assessment

9. Information taken from P reformulation assessment

10. Information taken from Preformulation assessment

11. Preformulation Development Preformulation studies are designed to find the condition in which the drug molecule is most stable. Preformulation studies include-1.Solubility 2.Stability

12. Solubility Solubility of a drug is a challenge for the developmental scientist. In some cases drug simply float on the solvent used to dissolve it. Here solubility studies must be conducted

13. Factors considered in Solubility studies. Ionization pH Effects of added co-solvents Effects of added complexing agents

14. Ionization Typically first and easiest way of enhancing solubility Generally the salt forms are more soluble than the uncharged species, so by creating an ionic salt form of the molecule the solubility is enhanced

15. pH The solution pH can have significant impact on the solubility of poorly soluble compounds As the pH is changed, different molecule are either protonated or deprotonated . This alters their charge on the molecule changing the solubility in H2O

16. Co-solvents According to Adage “like dissolves like”.Molecules with poor water solubility are soluble in those solvents that are less like water. As such, a solvent screening method can be initiated.This can be done by using HPLC or UV/Vis Techniques

17. Complexing Agents It is an alternative method if the above mentioned processes do not provide enough solubility These are formed when a macro-cyclic molecule having as intramolecular activity interacts with smaller molecule entering the cavity Here large molecules are called host and small molecules are called guest

18. Degradation Profile (Stability) It provides the wealth of information when transitioning into the formulation development work There are various kind of stabilty test for different factors like- Thermal stability, pH, Light,etc

19. Degradation Profile ( Stabiltly ) Thermal Stabilty - It can be measured by placing the sample into the dark, nitrogen purged environment and exposed to various temperature for extended period of time pH- It can be measured by formulating the bulk in weakly buffered systems at various pH values and placing them at accelerated temp. to speed up the results

20. Degradation Profile (Stability) Light Stability-It is measured by using Light Chamber. The sample is placed in a light chamber in a nitrogen purged environment and exposing it to light for extended period of time

21. Thank You