This document discusses pre-formulation studies, which involve investigating the physical and chemical properties of drug substances alone and when combined with excipients. Some key areas covered include polymorphism, hygroscopicity, particle size characterization, and solubility analysis. Thermal analysis techniques like DSC and XRD are described as useful for characterizing polymorphs. The importance of solubility studies at various pH levels and temperatures is highlighted for developing oral dosage forms with appropriate dissolution profiles.
Preformulation involves determining the physicochemical properties of new drug substances to establish parameters that may impact drug performance and dosage form development. Some key goals of preformulation testing include establishing a drug's physical characteristics, solubility, stability, and compatibility with excipients. Understanding properties like solubility, hygroscopicity, and powder flow help determine how a drug should be processed, stored, and formulated to ensure quality. Preformulation is an important first step in rational dosage form design.
Polymorphism is the ability of a solid material to exist in two or more crystalline forms. The document discusses the different types of polymorphism, factors that influence polymorphism, and methods to identify and produce polymorphs. It also outlines several applications of polymorphism in pharmaceuticals and organic chemistry. Specifically, selecting the right polymorph is important for drug stability, solubility, and bioavailability.
The document discusses key concepts and steps in preformulation testing. Preformulation involves investigating the physical and chemical properties of a drug substance alone and when combined with excipients. This generates useful information for formulating stable and safe dosage forms with good bioavailability. Some important properties discussed include solubility, particle size and shape, melting point, thermal analysis profile, hygroscopicity, and polymorphism potential. Determining these properties of a new drug substance is an important first step before developing drug formulations.
The document discusses preformulation studies for a new drug. It aims to characterize the physical and chemical properties of the drug substance and determine its stability. The objectives are outlined as determining solubility, kinetics, physical characteristics and compatibility with excipients. Key areas covered include analyzing the physicochemical properties, bulk characterization, solubility and stability of the drug. Analytical techniques discussed for characterization include microscopy, thermal analysis, powder X-ray diffraction and particle size determination methods. The importance of preformulation studies to develop a stable dosage form is highlighted.
This document discusses pre-formulation studies, which involve investigating the physical and chemical properties of drug substances alone and when combined with excipients. Some key areas covered include polymorphism, hygroscopicity, particle size characterization, and solubility analysis. Thermal analysis techniques like DSC and XRD are described as useful for characterizing polymorphs. The importance of solubility studies at various pH levels and temperatures is highlighted for developing oral dosage forms with appropriate dissolution profiles.
Preformulation involves determining the physicochemical properties of new drug substances to establish parameters that may impact drug performance and dosage form development. Some key goals of preformulation testing include establishing a drug's physical characteristics, solubility, stability, and compatibility with excipients. Understanding properties like solubility, hygroscopicity, and powder flow help determine how a drug should be processed, stored, and formulated to ensure quality. Preformulation is an important first step in rational dosage form design.
Polymorphism is the ability of a solid material to exist in two or more crystalline forms. The document discusses the different types of polymorphism, factors that influence polymorphism, and methods to identify and produce polymorphs. It also outlines several applications of polymorphism in pharmaceuticals and organic chemistry. Specifically, selecting the right polymorph is important for drug stability, solubility, and bioavailability.
The document discusses key concepts and steps in preformulation testing. Preformulation involves investigating the physical and chemical properties of a drug substance alone and when combined with excipients. This generates useful information for formulating stable and safe dosage forms with good bioavailability. Some important properties discussed include solubility, particle size and shape, melting point, thermal analysis profile, hygroscopicity, and polymorphism potential. Determining these properties of a new drug substance is an important first step before developing drug formulations.
The document discusses preformulation studies for a new drug. It aims to characterize the physical and chemical properties of the drug substance and determine its stability. The objectives are outlined as determining solubility, kinetics, physical characteristics and compatibility with excipients. Key areas covered include analyzing the physicochemical properties, bulk characterization, solubility and stability of the drug. Analytical techniques discussed for characterization include microscopy, thermal analysis, powder X-ray diffraction and particle size determination methods. The importance of preformulation studies to develop a stable dosage form is highlighted.
Here you can find a simple and short note on Pharmaceutical Preformulation studies.
Reference book:
The theory and practice of industrial pharmacy by Lachman and Lieberman.
This document discusses preformulation for new drug development. A change in formulation, dosage, route of administration, or dosage form of an existing drug causes it to be considered "new" and requires safety and efficacy evaluation. Preformulation aims to optimize a drug's physical and chemical properties for a stable, effective dosage form. It involves characterizing the drug molecule and developing the dosage form. Some goals of preformulation include establishing the drug's physicochemical parameters, kinetic profile, physical characteristics, and compatibility with excipients. Polymorphism, or the ability of a drug to exist in different crystal forms, is also evaluated as it can impact properties like solubility, dissolution rate, and bioavailability.
Preformulation studies characterize the physical and chemical properties of new drug molecules to aid in developing safe, effective, and stable dosage forms. The objectives are to establish physico-chemical parameters, determine kinetics and stability, and establish compatibility with excipients. Major areas of investigation include organoleptic properties, bulk characterization like crystallinity and polymorphism, solubility analysis including pH effects, and stability analysis of solutions and solids. Understanding these properties provides insights for processing and storage to ensure drug quality.
The document provides an overview of hot-stage microscopy (HSM), which couples thermal analysis with optical microscopy to observe solid-state materials as a function of temperature and time. HSM is used to support DSC and TGA and detect small changes missed by other techniques, such as desolvation and recrystallization. The instrumentation consists of a computer-controlled hot stage, optical microscope, and camera. HSM has various applications in pharmaceuticals for morphology studies, polymorphism, cocrystal screening, and detecting incompatibilities. It allows visual observation of processes like solid-solid transitions, phase changes, and desolvation.
This document discusses polymorphism as part of a preformulation study seminar. It defines polymorphism as the ability of a substance to exist in two or more crystalline forms that have different molecular arrangements. The key points covered include:
- The need to study polymorphism to select the most stable and soluble form for formulations. Metastable forms often have better bioavailability.
- Various methods to identify and characterize polymorphs such as X-ray diffraction, thermal analysis techniques like DSC and TGA, and microscopy.
- Factors that can influence polymorphic transitions like temperature, humidity, solvents, grinding, and compression during tableting.
- The importance of understanding polymorphism for properties like
The document discusses the use of metastable polymorphs to enhance oral bioavailability. It begins by defining polymorphism as the ability of a compound to crystallize in more than one distinct crystal structure. Metastable polymorphs are excited crystalline states that have longer lifetimes than ordinary excited states but shorter than the ground state. Using metastable polymorphs can improve properties like solubility and bioavailability. Several techniques to produce metastable polymorphs are described, like seeding, additives, and solvent control. Case studies demonstrate how metastable forms of drugs like famotidine and terazosin hydrochloride were approved generically. Regulatory considerations for showing sameness to the reference listed drug are also covered.
The document discusses polymorphism in pharmaceutical compounds. It provides definitions of key terms like polymorphism, crystalline, and amorphous forms. It also summarizes regulatory considerations from the FDA around approving generic drugs that may have different physical forms than the branded drug. The FDA requires demonstrating that different physical forms are the "same" and meet standards for identity, stability, and bioequivalence. Understanding polymorphism is important for ensuring product performance and consistency in manufacturing.
Crystallization processes and crystal structures are often complex and unpredictable, requiring extensive trial and error screening to identify optimal crystal forms. The Crystal16TM is a valuable tool for automating polymorph and salt screening experiments at a small 1-mL scale using minimal amounts of compound. It improves reproducibility and efficiency by running up to 16 experiments in parallel under different temperature profiles while collecting in-situ turbidity data. Well-designed screening studies using the Crystal16TM can test many conditions over different concentrations, solvents, and counterions to identify new crystal forms within a couple weeks, aiding pharmaceutical companies in controlling their manufacturing processes as required by regulators.
The document discusses preformulation studies, which characterize the physicochemical properties of drug substances. Some key points:
- Preformulation studies are conducted early in drug development to understand how a drug's properties will influence formulation, stability, bioavailability and the development process.
- Areas of study include bulk properties, solubility, stability and more. Properties like solubility, dissolution, polymorphism can impact the drug's performance.
- Various analytical techniques are used to characterize aspects like crystallinity, particle size, hygroscopicity and more which provide essential information for designing drug products.
- Understanding a drug's properties is important for selecting excipients, manufacturing processes, container closure systems and developing analytical
Polymorphism refers to different crystalline forms of the same substance that have different molecular arrangements and conformations. There are three main types of polymorphism: packing, conformational, and pseudopolymorphism (due to hydration or solvation). Polymorphs can be monotropic, where only one form is stable, or enantiotropic, where different forms are stable under different conditions. Monotropic polymorphs often have different melting points and properties. Polymorphism can impact drug properties like stability, dissolution, and bioavailability, so it is important to control the polymorphic form during drug development and manufacturing.
The document discusses research conducted to optimize the lyophilization process for Drug-X, which has both stable and unstable polymorphic forms. Characterization of Drug-X and the excipient Mannitol was performed using DSC, TGA, and XRD. Freeze drying parameters were optimized using DSC. Six batches were produced varying freeze drying conditions and analyzed for water content and solid state using KF titration and XRD. Studies on the effect of relative humidity on Drug-X found that the monohydrate form is stable between 20-30% RH, with the anhydrous form forming at lower or higher humidity levels. Optimal storage conditions for the monohydrate were determined to be below 25°
Polymorphism refers to a solid material existing in two or more crystalline forms with different arrangements in the crystal lattice. Over 50% of active pharmaceutical ingredients have more than one polymorphic form, which can exhibit different properties like solubility, dissolution rate, and stability. Methods to identify polymorphs include x-ray diffraction, differential scanning calorimetry, and thermal microscopy. The choice of polymorph is important for drug formulations, as the metastable form may have better bioavailability but convert to the stable form, impacting suspension stability or drug absorption. Case studies show certain polymorphs can be medically inactive or cause production issues if they convert dominant forms.
1. Preformulation studies characterize the physical and chemical properties of drug molecules to develop safe, effective, and stable dosage forms.
2. Key areas of preformulation include evaluating organoleptic properties, bulk characterization, solubility analysis, and stability analysis.
3. Important parameters studied are particle size, hygroscopicity, crystallinity, polymorphism, and powder flow properties which can impact drug dissolution, bioavailability, stability and manufacturability of dosage forms.
The document discusses states of matter and pharmaceutical materials. It begins by comparing gases, liquids, and solids, noting that solids have molecules in close contact that do not move. It then discusses intermolecular forces, ideal gas laws, liquefaction of gases, and the solid state including crystals, unit cells, polymorphism, and amorphous solids. It notes that polymorphism can impact properties like solubility, melting point, and bioavailability which are important for pharmaceutical processes and drug performance.
The document discusses preformulation studies for solids. The objectives are to develop a stable, safe and effective dosage form with maximum bioavailability. Preformulation testing characterizes the physical, chemical and other properties of a new drug to aid in dosage form development. Studies include analyzing the drug's crystallinity, polymorphism, particle size, solubility, stability and compatibility with excipients. Analytical techniques used include microscopy, spectroscopy, chromatography and thermal analysis to understand the drug's properties and develop an optimal dosage form.
This document discusses crystallinity and polymorphism. It begins by defining a crystal and crystallinity study. It then covers classifications of solids including amorphous, polymorphs, solvates, and clathrates. It compares properties of crystalline and amorphous forms. It also discusses crystal structure, habit, modification techniques, crystallization methods, analytical characterization methods, and importance in preformulation studies. Finally, it briefly mentions some latest crystallization techniques such as spherical crystallization and supercritical fluid crystallization.
This document discusses the need for dosage forms and pre-formulation studies. It notes that dosage forms are needed to safely and conveniently deliver accurate drug doses while protecting drugs from environmental factors. Pre-formulation studies characterize the physical and chemical properties of drug substances to aid in the development of stable and effective dosage forms. These studies determine properties like solubility, stability, and compatibility with excipients. Understanding these properties provides insights to ensure quality during processing and storage.
Preformulation studies for bulk characterizationmangu3107
The document discusses preformulation studies, which generate information to help formulate stable and effective drug dosage forms. The overall goals of preformulation are to improve drug stability, bioavailability, and reduce incompatibility. Some key tests described include determining the drug's physical properties like color, odor, taste, purity, and thermal behavior. Melting point analysis can provide information on a drug's identity and purity. Preformulation studies are important to identify suitable drug candidates and formulations before clinical development.
Hot melt extrusion is a process that converts raw materials into a uniform product by forcing it through a die under controlled conditions. It can be used to create solid dispersions of drugs to improve solubility and bioavailability. The key materials used are active pharmaceutical ingredients, polymers, and additives. Extruders provide mixing and agitation to uniformly disperse ingredients. The extruded material can be used to produce various dosage forms like tablets, pellets, and implants after characterization. Hot melt extrusion is an emerging drug delivery technique for solubility enhancement and modified drug release.
Here you can find a simple and short note on Pharmaceutical Preformulation studies.
Reference book:
The theory and practice of industrial pharmacy by Lachman and Lieberman.
This document discusses preformulation for new drug development. A change in formulation, dosage, route of administration, or dosage form of an existing drug causes it to be considered "new" and requires safety and efficacy evaluation. Preformulation aims to optimize a drug's physical and chemical properties for a stable, effective dosage form. It involves characterizing the drug molecule and developing the dosage form. Some goals of preformulation include establishing the drug's physicochemical parameters, kinetic profile, physical characteristics, and compatibility with excipients. Polymorphism, or the ability of a drug to exist in different crystal forms, is also evaluated as it can impact properties like solubility, dissolution rate, and bioavailability.
Preformulation studies characterize the physical and chemical properties of new drug molecules to aid in developing safe, effective, and stable dosage forms. The objectives are to establish physico-chemical parameters, determine kinetics and stability, and establish compatibility with excipients. Major areas of investigation include organoleptic properties, bulk characterization like crystallinity and polymorphism, solubility analysis including pH effects, and stability analysis of solutions and solids. Understanding these properties provides insights for processing and storage to ensure drug quality.
The document provides an overview of hot-stage microscopy (HSM), which couples thermal analysis with optical microscopy to observe solid-state materials as a function of temperature and time. HSM is used to support DSC and TGA and detect small changes missed by other techniques, such as desolvation and recrystallization. The instrumentation consists of a computer-controlled hot stage, optical microscope, and camera. HSM has various applications in pharmaceuticals for morphology studies, polymorphism, cocrystal screening, and detecting incompatibilities. It allows visual observation of processes like solid-solid transitions, phase changes, and desolvation.
This document discusses polymorphism as part of a preformulation study seminar. It defines polymorphism as the ability of a substance to exist in two or more crystalline forms that have different molecular arrangements. The key points covered include:
- The need to study polymorphism to select the most stable and soluble form for formulations. Metastable forms often have better bioavailability.
- Various methods to identify and characterize polymorphs such as X-ray diffraction, thermal analysis techniques like DSC and TGA, and microscopy.
- Factors that can influence polymorphic transitions like temperature, humidity, solvents, grinding, and compression during tableting.
- The importance of understanding polymorphism for properties like
The document discusses the use of metastable polymorphs to enhance oral bioavailability. It begins by defining polymorphism as the ability of a compound to crystallize in more than one distinct crystal structure. Metastable polymorphs are excited crystalline states that have longer lifetimes than ordinary excited states but shorter than the ground state. Using metastable polymorphs can improve properties like solubility and bioavailability. Several techniques to produce metastable polymorphs are described, like seeding, additives, and solvent control. Case studies demonstrate how metastable forms of drugs like famotidine and terazosin hydrochloride were approved generically. Regulatory considerations for showing sameness to the reference listed drug are also covered.
The document discusses polymorphism in pharmaceutical compounds. It provides definitions of key terms like polymorphism, crystalline, and amorphous forms. It also summarizes regulatory considerations from the FDA around approving generic drugs that may have different physical forms than the branded drug. The FDA requires demonstrating that different physical forms are the "same" and meet standards for identity, stability, and bioequivalence. Understanding polymorphism is important for ensuring product performance and consistency in manufacturing.
Crystallization processes and crystal structures are often complex and unpredictable, requiring extensive trial and error screening to identify optimal crystal forms. The Crystal16TM is a valuable tool for automating polymorph and salt screening experiments at a small 1-mL scale using minimal amounts of compound. It improves reproducibility and efficiency by running up to 16 experiments in parallel under different temperature profiles while collecting in-situ turbidity data. Well-designed screening studies using the Crystal16TM can test many conditions over different concentrations, solvents, and counterions to identify new crystal forms within a couple weeks, aiding pharmaceutical companies in controlling their manufacturing processes as required by regulators.
The document discusses preformulation studies, which characterize the physicochemical properties of drug substances. Some key points:
- Preformulation studies are conducted early in drug development to understand how a drug's properties will influence formulation, stability, bioavailability and the development process.
- Areas of study include bulk properties, solubility, stability and more. Properties like solubility, dissolution, polymorphism can impact the drug's performance.
- Various analytical techniques are used to characterize aspects like crystallinity, particle size, hygroscopicity and more which provide essential information for designing drug products.
- Understanding a drug's properties is important for selecting excipients, manufacturing processes, container closure systems and developing analytical
Polymorphism refers to different crystalline forms of the same substance that have different molecular arrangements and conformations. There are three main types of polymorphism: packing, conformational, and pseudopolymorphism (due to hydration or solvation). Polymorphs can be monotropic, where only one form is stable, or enantiotropic, where different forms are stable under different conditions. Monotropic polymorphs often have different melting points and properties. Polymorphism can impact drug properties like stability, dissolution, and bioavailability, so it is important to control the polymorphic form during drug development and manufacturing.
The document discusses research conducted to optimize the lyophilization process for Drug-X, which has both stable and unstable polymorphic forms. Characterization of Drug-X and the excipient Mannitol was performed using DSC, TGA, and XRD. Freeze drying parameters were optimized using DSC. Six batches were produced varying freeze drying conditions and analyzed for water content and solid state using KF titration and XRD. Studies on the effect of relative humidity on Drug-X found that the monohydrate form is stable between 20-30% RH, with the anhydrous form forming at lower or higher humidity levels. Optimal storage conditions for the monohydrate were determined to be below 25°
Polymorphism refers to a solid material existing in two or more crystalline forms with different arrangements in the crystal lattice. Over 50% of active pharmaceutical ingredients have more than one polymorphic form, which can exhibit different properties like solubility, dissolution rate, and stability. Methods to identify polymorphs include x-ray diffraction, differential scanning calorimetry, and thermal microscopy. The choice of polymorph is important for drug formulations, as the metastable form may have better bioavailability but convert to the stable form, impacting suspension stability or drug absorption. Case studies show certain polymorphs can be medically inactive or cause production issues if they convert dominant forms.
1. Preformulation studies characterize the physical and chemical properties of drug molecules to develop safe, effective, and stable dosage forms.
2. Key areas of preformulation include evaluating organoleptic properties, bulk characterization, solubility analysis, and stability analysis.
3. Important parameters studied are particle size, hygroscopicity, crystallinity, polymorphism, and powder flow properties which can impact drug dissolution, bioavailability, stability and manufacturability of dosage forms.
The document discusses states of matter and pharmaceutical materials. It begins by comparing gases, liquids, and solids, noting that solids have molecules in close contact that do not move. It then discusses intermolecular forces, ideal gas laws, liquefaction of gases, and the solid state including crystals, unit cells, polymorphism, and amorphous solids. It notes that polymorphism can impact properties like solubility, melting point, and bioavailability which are important for pharmaceutical processes and drug performance.
The document discusses preformulation studies for solids. The objectives are to develop a stable, safe and effective dosage form with maximum bioavailability. Preformulation testing characterizes the physical, chemical and other properties of a new drug to aid in dosage form development. Studies include analyzing the drug's crystallinity, polymorphism, particle size, solubility, stability and compatibility with excipients. Analytical techniques used include microscopy, spectroscopy, chromatography and thermal analysis to understand the drug's properties and develop an optimal dosage form.
This document discusses crystallinity and polymorphism. It begins by defining a crystal and crystallinity study. It then covers classifications of solids including amorphous, polymorphs, solvates, and clathrates. It compares properties of crystalline and amorphous forms. It also discusses crystal structure, habit, modification techniques, crystallization methods, analytical characterization methods, and importance in preformulation studies. Finally, it briefly mentions some latest crystallization techniques such as spherical crystallization and supercritical fluid crystallization.
This document discusses the need for dosage forms and pre-formulation studies. It notes that dosage forms are needed to safely and conveniently deliver accurate drug doses while protecting drugs from environmental factors. Pre-formulation studies characterize the physical and chemical properties of drug substances to aid in the development of stable and effective dosage forms. These studies determine properties like solubility, stability, and compatibility with excipients. Understanding these properties provides insights to ensure quality during processing and storage.
Preformulation studies for bulk characterizationmangu3107
The document discusses preformulation studies, which generate information to help formulate stable and effective drug dosage forms. The overall goals of preformulation are to improve drug stability, bioavailability, and reduce incompatibility. Some key tests described include determining the drug's physical properties like color, odor, taste, purity, and thermal behavior. Melting point analysis can provide information on a drug's identity and purity. Preformulation studies are important to identify suitable drug candidates and formulations before clinical development.
Hot melt extrusion is a process that converts raw materials into a uniform product by forcing it through a die under controlled conditions. It can be used to create solid dispersions of drugs to improve solubility and bioavailability. The key materials used are active pharmaceutical ingredients, polymers, and additives. Extruders provide mixing and agitation to uniformly disperse ingredients. The extruded material can be used to produce various dosage forms like tablets, pellets, and implants after characterization. Hot melt extrusion is an emerging drug delivery technique for solubility enhancement and modified drug release.
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2. List of
contents:-
4/21/2016 Sagar KishorSavale 2
1. Definition
2. Need to study polymorphism (rational for selecting
polymorph)
3. Types of polymorphism
4. How to differentiate them
5. Pseudo polymorphism
6. Properties
7. Method for identify polymorphism
8. Significance of polymorphism
9. Conclusion
10. References
3. Definition1,2
When a substance exists in more than one crystalline form, the different form
are designated as polymorphs and the phenomenon as polymorphism.
e.g.:-
carbon: diamond in a cubic ( tetrahedral lattice arrangement)
Graphite in sheet of a hexagonal lattice.
4/21/2016 Sagar KishorSavale 3
4. True polymorphs can be classified into two
different types2
4/21/2016 Sagar KishorSavale 4
1. Enantiotropic— one polymorph can be reversibly
changed into another one by varying the temperature or
pressure. eg. sulfur
2. Monotropic— the change between the two forms is
irreversible. eg. Glyceryl stearates
5. Difference between enantiotropy and monotropy.3
Enantiotropic pair monotropic pair
Reversible phase transition Irreversible phase transition
Metastable stable Metastable stable
Transition is endothermic Transition is exothermic
Lower melting form is
thermodynamically stable below the
transition temp.. And higher m.p .
form is stable above the transition
temp..
Higher melting form is always
thermodynamically stable form.
lower m.p. has lower heat of fusion. Higher m.p. has high heat of fusion.
4/21/2016 Sagar KishorSavale 5
6. Method to identify polymorphism.3
Optical crystallography:
4/21/2016 Sagar KishorSavale 6
Use in the identification of polymorphs crystal exist in isotropic and
anisotropic form
Isotropic examine the velocity of light is same in all direction
Anisotropic crystal have 2 or3 different light velocities or refractive index.
Video recording system and polarizing microscope fitted during according
to heating and cooling stage for investigating polymorph.
cont…
7. Applicatio
n
4/21/2016 Sagar KishorSavale 7
To study of degree of stability of metastable form.
Transition temperature
Melting point
Rate of transition under various thermal and physical condition.
Whether to peruse polymorphism as a route to an improved dosageform.
8. Hot stage microscope
Fluid stage transformation as a function of temperature is observed
Silicon oil stage microscopy is used for detection of pseudopolymorph.
APPLICATION:
in the study of solid-state active pharmaceutical ingredients
(APIs), EXCIPIENTS and pharmaceutically relevant polymers and lipids.
4/21/2016 Sagar KishorSavale 8
9. x ray diffraction method
4/21/2016 Sagar KishorSavale 9
It provide the most complete information about solid state (identification &
description)
This method is based on the scattering of x-ray by crystals
By this method one can identify the unit cell dimensions & conclusively
establish the crystalline lattice system & provide specific differences between
crystalline forms of given compound.
In an X-ray diffraction measurement, a crystal is mounted on a goniometer and
gradually rotated while being bombarded with X-rays, producing a diffraction
pattern of regularly spaced spots known as reflections.
It is tedious time consuming so it is not used or unsuitable for routine use.
11. Applicatio
n
4/21/2016 Sagar KishorSavale 11
many materials can form crystals—such as salts, metals,
semiconductors, as well as various inorganic, organic
molecules—X-ray crystallography has been fundamental
minerals,
and biological
in the
development of many scientific fields
12. Melting point
4/21/2016 Sagar KishorSavale 12
M.P. determination are often useful technique, but only when substance
undergoing investigation heated through phase transition without
decomposition.
13. Differential Scanning Calorimetric (DSC)
4/21/2016 Sagar KishorSavale 13
DSC is also like to DTA except that the instrument measures the amount of energy
required to keep the sample at the same temperature as the reference i.e. it measures
the enthalpy of transition.
When no physical or chemical changes is occurring within the sample then there is
neither a temperature change nor the need to input energy to maintain an isotherm.
Samples that may be studied by DSC or DTA are: Powders, fibers , single crystals,
polymer films, semi-solids.
DSC measures endothermic and exothermic transitions as a function of temperature.
–Endothermic heat flows into a sample.
–Exothermic heat flows out of the sample.
15. Applications of DTA / DSC in preformulation studies
4/21/2016 Sagar KishorSavale 15
1. To determine the purity of a sample
and to determine
drug or
2.To determine the number of polymorphs
the ratio of each polymorph
3.To determine the heat of solvation .
4.To determine the thermal degradation of a
excipients .
5. To determine the glass-transition temperature(tg) of a
polymer.
16. Effect of polymorphism on bioavailability
4/21/2016 Sagar KishorSavale 16
If the absorption of active ingredient in drug through G.I.T polymorphism is
an important preformulation tool.
Here successful utilization of polymorph having significant greater
thermodynamic activity (solubility)may provide good therapeutic blood
level from otherwise inactive drugs. Eg novobiocin .
two different forms : crystalline and amorphous. In tablet or capsule
formulation
17. PSEUDO POLYMORPHISM4
Term - pseudo means = false
4/21/2016 Sagar KishorSavale 17
The phenomenon in which solvent molecules get incorporated into crystal
lattice of solid are known as solvates.
This solvates exist in different crystal form called pseuodopolymorph and
the phenomenon is called as Pseudopolymorphism .
also known as a hydrate when water is solvent.
E.g.- synthetic estrogen ‘ethynylestradiol ’ is
crystallized from the solvent acetonitrile , methanol , chloroform and
saturated with water four different crystalline solvates are form.
18. Differentiate pseudopolymorph form true polymorph.
4/21/2016 Sagar KishorSavale 18
By observing melting behavior in silicon oil using hot stage microscopy.
Here in this technique pseudopolymorph evolve the gas causing bubbling of
the oil.
While true polymorphs merely melts, forming second globular phase.
19. Application
4/21/2016 Sagar KishorSavale 19
1. For improvement of therapeutic activity of drug.
2. To prevent loss of raw material.
3. For better bioavailabity of drug.
.
20. Need to study polymorphism.5
4/21/2016 Sagar KishorSavale 20
One of the several polymorphic form will be physically more stable than
others.
Stable polymorph represent s the lowest energy state, has highest melting
point and least aqueous solubility.
Metastable form represent the higher energy state, have lower melting point
and high aqueous solubility .
Metastable form converted to the stable form due to their higher energy state.
Metastable form shows better bioavailability and
therefore preferred in
formulations.
Cont..
21. Polymorphism is remarkably common particularly within certain structural
4/21/2016 Sagar KishorSavale 21
group.
E.g. –
Cont..
CLASS %OF POLYMORPHISM
Barbiturates 63
Steroids 57
Sulphonamides 40
22. Significance of studying
polymorphism
4/21/2016 Sagar KishorSavale 22
Different polymers exhibits different solubility, therapeutic &
stability.
The desire forms consistently manufactured.
The effect of pharmaceutical manipulations are understood.
E.g. granulation, milling & compression.
Effect of storage condition on the dosage form can be evaluated &
predicated. E.g. crystal growth in suspension, cream.
23. Properties of polymorphs.5
4/21/2016 Sagar KishorSavale 23
Polymorphs show the same properties in the liquid or gaseous state but they
behave differently in solid state.
Melting and sublimation temperature.
Solubility and dissolution rate
Stability
Crystal habit
Hygroscopicity
Compression characteristics
24. Conclusion
4/21/2016 Sagar KishorSavale 24
Differences in the solubility and melting point must also be assessed and
then a decision can be made to determine which form to progress through to
the next stage.
Metastable form may lead to a preferential choice of a polymorph other than
stable form .
As polymorphism can have such serious consequences for the
bioavailability of drugs with low aqueous solubility.
25. References
4/21/2016 Sagar KishorSavale 25
1. M.E. Aultan, The science of dosage form design, 2nd
edition 2002,
p.no
8,26,124-126,142-144.
2. Brahmankar D. M., Sunil B. Jaiswal, Biopharmaceutics &
Pharmacokinetics- A Treatise,1st edition, Vallabh Prakashan, New
Delhi 2007, p.no-27-29.
3. Leon Lachman, Herbert A. Lieberman, The Theory Practice Of
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