1 Flashcards
Difference between three formulation and formulation
- Formulation is the process of developing a drug candidate into a drug product
- Preformulation is an investigation of physical and chemical properties of a new chemical entity (NCE) alone and when combined with excipients to identify suitability of the NCE to develop an efficacious dosage form.
- Preformulation is a stage that must be undertaken before the formulation can begin
- Starts once NCE shows sufficient pharmacological effect on animal models to forward to evaluation in man
What is the purpose of preformulation studies in drug discovery?
To choose a preferred compound based on formulation and manufacturing needs.
At what stage of drug discovery do preformulation studies begin?
After the hit-to-lead phase, when a compound has shown pharmacological effects.
Why are preformulation studies important for drug development?
They ensure the selected compound has suitable properties for formulation and large-scale production.
What are the key stages in early drug discovery?
→ Target Identification → Target Confirmation → Hit → Hit-to-Lead → Lead Optimization.
What happens at the hit-to-lead stage in drug discovery?
Compounds that show promising activity are further optimized for pharmacological effects.
What is the role of preformulation in pre-clinical studies?
To determine the best formulation for animal studies.
Why are preformulation studies important for volunteer studies?
To optimize the drug formulation for safe and effective human volunteer testing.
At what phase of clinical trials is the final formulation determined?
→ Phase III Clinical Trials, where the formulation is finalized for large-scale manufacture.
What is the last stage of drug development before commercial launch?
Scale-up for launch, ensuring the formulation is viable for mass production.
What is the objective of preformulation studies?
To generate information useful for developing a stable, bioavailable, and mass-producible dosage form.
Why is preformulation important in drug development?
It ensures the drug has suitable physical, chemical, and mechanical properties for formulation.
What are the key properties assessed during preformulation?
Solid-state properties, solubility, partition coefficient, dissolution, stability, rheology.
Why are solid-state properties important in preformulation?
They affect the drug’s crystal form, polymorphism, and stability, influencing its performance.
What are the two main categories of properties in preformulation?
Organoleptic properties and Bulk properties.
What are organoleptic properties, and why are they assessed?
→ Odour, colour, taste, state
- They impact patient acceptability and quality control.
What are bulk properties in preformulation?
Melting point, crystallinity & polymorphism, hygroscopicity, fine powder characterization, powder flow properties
What factors are analyzed in solubility analysis?
pH effects, pKa, solubilization profile, partition coefficient, dissolution.
Why is pKa important in preformulation?
It determines the ionization state of the drug, affecting its solubility and absorption.
What are the key factors in stability analysis?
Solution stability, solid-state stability, stability in toxicology, excipient compatibility.
Why is the melting point measured in solid drugs?
It provides information about purity, thermal properties, and polymorphism.
What technique is used to measure a drug’s crystal structure?
X-ray diffraction.
How does visual inspection help in preformulation?
It assesses the shape and uniformity of the drug’s crystals.
How are solid drugs classified?
Into Crystalline solids and Amorphous solids.
What are the key characteristics of solid drugs?
→ Rigid structure, mechanical strength, definite volume and shape.
What defines a crystalline solid?
A highly ordered arrangement of atoms, ions, or molecules, held by van der Waals, ionic, or hydrogen bonds.
What is a crystal habit?
The external appearance of a crystal (e.g., cubic, prismatic).
What is a crystal lattice?
The molecular arrangement within a solid crystal.
What is a unit cell in crystallography?
The smallest repeating structure that forms the 3D pattern of a crystal.
What are crystalline solids?
Crystalline solids have a highly ordered molecular structure arranged in a geometric lattice.
How do crystalline solids differ from amorphous solids?
Crystalline solids have a sharp melting point, high stability, and lower solubility, while amorphous solids lack order, dissolve faster, and do not have a definite melting point.
What are the three main types of crystalline solids?
Ionic, Atomic, and Molecular solids
What are ionic crystals? Give an example.
Lattice units consist of ions held together by ionic bonds (e.g., NaCl - Table Salt).
What are atomic crystals? Give an example.
Lattice units consist of atoms held together by covalent bonds (e.g., Diamond).
What are molecular crystals? Give an example.
Lattice units consist of molecules held together by van der Waals forces (e.g., solid CO₂ - Dry Ice).
What factors influence crystal habit formation?
Solvent, temperature, concentration, and presence of impurities.
Why is crystal habit important in pharmaceuticals?
It affects solubility, flow properties, and injectability of drugs.
How does crystal habit impact drug injection?
Platelike crystals are easier to inject through fine needles than needle-like crystals.
Why do equidimensional crystals have better flow properties?
Because they have better packing and compaction, making them more suitable for tableting.
What are the main steps in crystallization?
Nucleation (formation of crystal “seeds”) and Growth (addition of molecules to crystal faces).
What are four ways crystallization can be triggered?
Supersaturation, cooling, solvent evaporation, and chemical reactions.
What is crystal engineering?
The process of designing and synthesizing crystals with desired properties.
How can crystal habit be modified?
By changing crystallization conditions or adding surfactants.
What is the role of surfactants in crystal growth?
They adsorb onto growing crystal faces, altering their final shape.
What are amorphous solids?
Solids with random molecular arrangement similar to liquids but in a solid state
How do amorphous solids behave under pressure?
They flow when subjected to sufficient pressure over time.
Why do amorphous solids have higher solubility?
Because their disordered structure allows molecules to dissolve more easily.
What is Preformulation?
The process of generating information useful in developing a stable, bioavailable, and mass-producible dosage form.
What are the key properties determined in preformulation?
Solid-state properties (polymorphism, crystal forms)
Solubility
Partition Coefficient
Dissolution
Stability
Rheology
What are Organoleptic Properties?
Odour
Colour
Taste
State
What are Bulk Properties?
Melting point
Crystallinity & polymorphism
Hygroscopicity
Fine powder characterization
Powder flow properties
What is Solubility Analysis?
pH effects & pKa
Solubilization and solubility profile
Partition coefficient
Dissolution
