PARENTERAL PREPARATION + PREFORMULATION STUDY.

1. Prepared By-
Arpan Dhungel
Guided by Mr. SUJIT
DAS (ASST. PROFF.
HPI)
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
Preformulation assessment
Stability
• Most important piece of information prior to beginning developmental
studies. Unless the developmental scientist can detect if the drug is
not breaking down during the developmental process, it is useless to
proceed
Thermal
Stability
• Does the Drug degrade in response to high temperature?
Oxidation
Potential
• Does the drug degrade whenexposed to oxygen ?

9. Information taken from
Preformulation assessment
Light
Stability
• Does the drug degrade in the presence of light?
Bulk Drug
Preparation
• How is the bulk drug made, and are there any
residual solvent present from the manufacturing
processes?
Polymorph
Existence
• Do other crystalline forms of the bulk drug exist ?

10. Information taken from
Preformulation assessment
pKa or pI
• This is the dissociation constant for small molecules
or the isoelectric points for proteins. This provides
information about the solubility of the bulk drug.

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