preformulation study during drug development .pptx

Parameters of pre formulation

1. Preformulation studies PRESENTED BY VAISHNAVI P. AWTADE M. PHARM IST YR (PHARMACEUTICS) INSTITUTE OF PHARMACY AND RESEARCH, BADNERA

2. content Introduction Objective Goals of preformulation Characterization parameter Application Conclusion Reference

3. Introduction Preformulation studies are the investigations of physical and chemical properties of a drug substance, alone and in combination with other excipients. Characterization of physical, chemical and mechanical properties of new drug molecule in order to develop safe, effective, and stable dosage form. Preformulation is a branch of pharmaceutical science that utilizes biopharmaceutical principles in the determination of physicochemical properties of the drug substance. Prior to the development of any dosage from new drug, it is essential that certain fundamental physical & chemical properties of drug powder are determined.

4. Objective of Preformulation studies. To generate useful data needed in developing stable and safe dosage forms that can be manufactured on a commercial scale. To provided in-depth knowledge and understanding of the physical characteristics of a candidate drug molecule prior to dosage form development. To generate useful information on how to design a drug delivery system with good bioavailability. Preparation of safe, effective, and stable dosage form with better therapeutic values.

5. GOALS OF PREFORMULATION To formulate an elegant, safe, efficacious dosage form with good bioavailability. To formulate new dosage form of already existing drug. Determination of all the properties of drug and the best suitable dosage form for the drug molecule.

6. CHARACTERIZATION parameter Physicochemical properties Solubility analysis Drug excipient compatibility

7. Physico -chemical properties Organoleptic properties: Organoleptic properties are those properties which are evaluated after an impression on the organs of sense for eg. Colour , odour , taste, smell , etc. Particle Size : Study of particle size give an information about solubility, dissolution rate, absorption, etc. Particle size and surface area of a solid drug are inversely related to each other. Eg : Griseofulvin

8. Powder Flow Property : The flow properties of a powder will determine the nature and quantity of excipient needed to prepare a compressed or a powder dosage form. This refers mainly to factor such as the ability to process the powder through machines. Greater the standard deviation between multiple flow rate measurements greater is the weight variation in products produced from the powder.

9. BULK PROPERTIES: Bulk properties of the solid form such as crystallinity, polymorphism , particle size, powder flow property, and surface characteristics are likely to change during process development. CRYSTALINITY: Crystallinity refers to the degree of structural order in a solid. Crysal habit and internal structure of drug can affect bulk and physicochemical property of drug. Crystal habit is description of outer appearance of crystal.

10. Polymorphism Polymorphism is the ability of the compound to crystallize as more than one distinct crystalline species with different internal structure. Formation of different polymorphs depends on solvent, temperature, pressure, rate of cooling etc. Polymorphic transitions can also occur during milling, granulating, drying and compressing operations. Different polymorphs vary in physical properties such as dissolution, solid-state stability, compatibility, etc.

11. Hygroscopicity Hygroscopicity is the tendency of a solid substance to absorb moisture from the surrounding. Classified based on the amount of rate of water uptake when a solid is exposed at a specified temperature.

12. Solubility analysis One of the most widely studied techniques during preformulation analysis is solubility profile of drug candidate. It is the backbone study of preformulation stage that determines the performance of developed formulation. Solubility and permeability forms the scientific basis of biopharmaceutics classification system (BCS), which can provide framework for designing type of drug delivery. The solubility of a drug is the amount of the drug that dissolves in a given solvent to produce a saturated solution at constant temperature and pressure For conversion of drug molecule into an effective oral formulation, it must have good aqueous solubility for better absorption. Solubility is not an independent parameter but it relies on several properties like crystal characteristics, temperature, pH, complexation, and molecular structure.

13. Drug excipient incompatibilty Excipients are added along with the active pharmaceutical ingredient in formulations. Most excipients possess biological activity but having role in administration, mediating the release of the active component, and providing stability against degradation. However, inappropriate excipients can also give rise to inadvertent and/or unintended effects, which can affect the chemical nature, the stability, and the bioavailability of the API, and consequently, their therapeutic efficacy and safety. So study about interaction between active ingredient and inactive ingredient can provide idea about type of incompatibility and the justification behind the inactive ingredient selection

14. Change in organoleptic properties of formulation. Changes in in vivo performance of formulation, that is, dissolution. Decreased potency of active ingredient.Generation of toxic degradation product. Change in physical appearance of formulation, that is, color, phase conversion. This tells that drug-excipient incompatibility may result in change in physical, chemical, microbiological, or therapeutic properties of formulation.

15. Physical incompatibility Active pharmaceutical ingredient and excipients interact without undergoing changes involving like breaking or formation of new bonds. The resulting drug product retains its original chemical properties but may involve changes such as alteration in physical properties. Such interaction results in changes like change in color, odor, flow properties, and sedimentation rate. Such an example of physical incompatibility is between tetracycline and calcium carbonate. It results in formation of insoluble complex with calcium carbonate, leading to slower dissolution and decreased absorption in the gastrointestinal tract

16. CHEMICAL INCOMPATIBILTY In such incompatibility, there is interaction of active pharmaceutical ingredient and excipient through chemical degradation pathway. The chemical reaction involves bond breakage or new bond formation to produce an unstable chemical entity. Chemical reaction may take place as hydrolysis, oxidation racemization, and Maillard reactions. The resulting changes are more deleterious than physical incompatibility. This type of incompatibility can be assessed by chromatographic studies. One of the classical examples of chemical incompatibility is exhibited by reaction of lactose with amino group of active pharmaceutical ingredient referred to as “Maillard reaction” and results into darkening of formulation with characteristic odor.

17. Applications Valuable tool for formulation scientist for selection of design of dosage form Reduce cost and time for scale-up and post-approval changes. Application in clinical and pre-clinical testing Eliminates the need of human subjects to unnecessary drug exposure Pharmaceutical solutions must be administered at or near room temperature. So, it is more important factor for product storage than the formulation. To increase the solubility of sparingly soluble solute. To increase the stability by reducing the moisture content.

18. conclusion Preformulation studies on a new drug molecule provide useful information for subsequent formulation of a physicochemically stable and biopharmaceutically suitable dosage form. Prefomulation work is the foundation of developing efficacious and economical formulation

19. References Leon Lachman, Liberman: The theory and practice of industrial pharmacy , Edn 4 , pg no. 217-307 Banker GS, Rhodes CT. Modern pharmaceutics, Edn 4, pg no.167-18 https://www.researchgate.net/publication/324819639_Preformulation_lecture- https://www.researchgate.net/publication/330193840_AN_OVERVIEW_ON_ www.google.com

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