logging in or signing up Solid state properties robin_vinnu Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 982 Category: Education License: All Rights Reserved Like it (1) Dislike it (0) Added: October 31, 2010 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: babuagoodboy (12 month(s) ago) hiiii ur presentation is so nice ..can u plz send this ppt to my mail ID babuagoodboy@yahoo.com .. Saving..... Post Reply Close Saving..... Edit Comment Close By: nasrallah (14 month(s) ago) How download Saving..... Post Reply Close By: robin_vinnu (12 month(s) ago) need mail id Saving..... Edit Comment Close By: vidya.kanamarlapudi (14 month(s) ago) sir,i am unable to download ppt...piz forward this presention to my mail id(vidya.kanamarlapudi@gmail.com).pls forward as soon as possible..thank you sir Saving..... Post Reply Close Saving..... Edit Comment Close By: thrisai1988 (17 month(s) ago) sir, iam unable to download the ppt.....................plz send to my mail id thrisai1988@yahoo.co.in Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Solid state properties : Solid state properties Presented by: Gopidi Ravi chaithanya M.pharmacy(pharmaceutics) St.peter’s institute of pharmaceutical sciences Hanmakonda,warangal. Contents: : Contents: Introduction Crystallization Polymorphism Hydrates and solvates The amorphous state Techniques for study of crystal properties References Introduction : Introduction The three states of matter are solid, liquid and gas. Solid particles are made up of molecules that are held together by intermolecular forces , such as through hydrogen bond and van der waal forces. Crystal habit and the internal structure of a drug can effect the bulk and physiochemical properties, which ranges from flow ability to chemical stability. Habit is the description of the outer appearance of a crystal where as the internal structure is the molecular arrangement with in the solid. The internal structure of a compound can be classified as crystalline and amorphous states. Slide 4: chemical compound habit internal structure crystalline amorphous polymorphs molecular adducts nonstoichiometric stoichiometric inclusion compounds solvates(hydrates) channel layer cage(clathrate) crystallization : crystallization Crystals are characterized by repetitious spacing of constituent atoms or molecules in three dimensional array. A characteristic property of crystal is that it has a melting point. This is the temperature at which the crystal lattice break down, owing to the molecule having gained sufficient energy from the heating process to overcome the attractive forces that hold the crystal together. Preparation of crystals: : Preparation of crystals: Crystals are prepared by inducing a change from the liquid to the solid state by colling a molten sample to below its melting. Pharmaceutical examples of crystallization through cooling include the formation of suppositories, creams and semisolid matrix dosage forms. The other method of crystallization is to have a solution of the material and to change the system so that the solid is formed i.e. through supersaturated solution. The process by which a crystal forms are called nucleation and growth. Nucleation is the formation of a small mass on to which a crystal can grow. Growth is the addition of more solute molecules to the nucleation site. Polymorphism: : Polymorphism: When a substance exists in more than one crystalline form, the different forms are designated as polymorphs and the phenomenon as polymorphism . The polymorphs differ from each other with respect to their physical properties such as solubility, melting point, density, hardness and compression properties. Polymorphs are of two types: Enantiotropic polymorph is the one which can be reversibly changed into another form by altering the temperature and pressure e.g. sulfur. Monotropic polymorph is the one which is unstable at all temperatures and pressure e.g. glyceryl stearates. Slide 8: The existence of the polymorph can be determined by using techniques such as optical crystallography, X-ray diffraction, differential scanning calorimetry, etc. Depending on their relative stability, one of the several polymorphic forms will be physically more stable than the others. Such a stable polymorph represents the lowest energy state, has highest melting point and least aqueous solubility. The remaining polymorphs are called as metastable forms which represent the higher energy state, have lower melting points and higher aqueous solubilities. High melting point = strong lattice = hard to remove a molecule = low dissolution rate Slide 9: Since the metastable form have greater aqueous solubility, they show better bioavailability and are therefore preferred in formulations for e.g. ,of the three polymorphic forms of chloramphenicol palmitate-A,B and C, the B form shows best availability and the A form is virtually inactive biologically. The polymorphic form III of riboflavin is 20 times more water soluble than the form I. However ,because of their poor thermodynamic stability, aging of dosage forms containing such metastable forms usually result in formation of less soluble ,stable polymorph-for example, the more soluble crystalline form II of cartisone acetate converts to the less soluble form V in an aqueous suspension resulting in caking of solid. Slide 10: Such a transformation of metastable to stable form can be inhibited by dehydrating the molecule environment or by adding viscosity building macromolecules such as PVP, CMC, pectin or gelatin that prevent such a conversion by adsorbing on to the surface of the crystals. The stable polymorphic form will have the slowest dissolution rate, and so there may be occasions when it would be desirable to speed the dissolution by using metastable form . However, the risk associated with using metastable form is that it will convert back to the stable form during the product’s life, and give a consequent change in properties. As polymorphism can have such serious consequences for the bioavailability of the drugs with low aqueous solubility, it is essential that manufacturers check the existence of polymorphism and ensure that they use the appropriate polymorphic form every time they make a product. Hydrates and solvates : Hydrates and solvates The crystalline form of a drug can either be a polymorph or molecular adduct or both. The stoichiometric type of adducts where the solvent molecules are incorporated in the crystal lattice of the solid are called as the solvates. and the trapped solvent as solvent of crystallization. The solvates can exist in different crystalline forms called as pseudopolymorphs. This phenomenon is called as pseudopolymorphism. When the solvent in associated with the drug is water ,the solvate is known as a hydrate. Slide 12: Generally, the anhydrous form of a drug has greater aqueous solubility than the hydrates. e.g. theophylline and ampicilline. In this situation, water could form a hydrogen bond between two drug molecules and tie the lattice together; this would give a much stronger, more stable lattice and hence a slower dissolution rate. Although anhydrous forms are usually more rapidly soluble than the hydrate, there are examples of opposite being true. In such circumstances once could think of water as a wedge pushing two molecules apart and preventing the optimum interaction between the molecules in the lattice. here water would be weakening the lattice and would result in a more rapid dissolution rate. E.g. erythromycin. The amorphous state: : The amorphous state: When the material is in the solid state but the molecules are not packed in a repeating long range ordered fashion, it is said to be amorphous. Such material represent the highest energy state and can be considered as super cooled liquid. Amorphous forms are typically prepared by rapid precipitation, lyophilization, or rapid cooling of liquid melts. They have greater aqueous solubility than the crystalline forms because the energy required to transfer a molecule from crystal lattice is greater than that required for non aqueous solids. For e.g. , the amorphous form of novobiocin is 10 times more soluble than the crystalline form. Chloramphenicol palmitate, cortisone acetate and phenobarbital are other examples where the amorphous forms exhibit higher water solubility. Slide 14: Amorphous form have a characteristic temperature at which there is a major change in properties. this is called the glass transition temperature ( Tg ) If the sample is stored below the Tg the amorphous form will be brittle and is described as the glassy state. If the sample is above its Tgit becomes rubbery. The Tg, is a point where the molecules in the glass exhibit a major change in the mobility. The lack of mobility when the sample is glassy allows the amorphous form to exist for longer, whereas when Tg is below the storage temperature the increased molecular mobility allows rapid conversion to the crystalline form. Slide 15: The glass transition temperature of an amorphous material can be lowered by adding a small molecule, called a plasticizer, that’s fits between the glassy molecules, giving them greater mobility. Water acts as a good plasticizer for many materials. Crystallization occurs because the absorbed water has plasticized the sample to such an extent that the Tghas dropped below room temperature and allowed sufficient molecular mobility that the molecule are able to align and crystallize. The fact that processing can make crystalline materials partially amorphous means that it is possible for very complex material to form that contain different metastable states. Slide 16: for e.g., when b-polymorph chloramphenicol palmitate was milled it become partially amorphous, which could make the plasma level even higher than when the crystalline form were used. However ,milling the b-polymorph could also provide the necessary energy to convert it to the stable a-polymorph, which would reduce the effective plasma level. Equally, milling could disrupt the a-polymorph giving a partially amorphous form that might have a higher bioavailability than the crystal. In other words ,the effect of processing on the physical form can be very complicated, and often unpredictable. Techniques for study of crystal properties : Techniques for study of crystal properties Powder X-ray diffraction Infrared spectroscopy (IR) Water vapour sorption Isothermal Microcalorimetry Dissolution Calorimetry Macroscopic techniques Differential Scanning Calorimetry (DSC) Fusion method Scanning electron microscopy Thermogravimetric analysis References : References Jens T. Cartenson- Advanced pharmaceutical solids Graham buckton –particle science and powder technology Buckton,G. Interfacial phenomenon in drug delivery and targeting. Harwood Academic press , Amsterdom Florence, A.T. and Attwood physicochemical principles of pharmacy, Macmillan, London D.M. Brahmankar- Biopharmaceutics and pharmacokinetics Lachman-The throry and practice of industrial pharmacy Slide 19: thank you You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
Solid state properties robin_vinnu Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 982 Category: Education License: All Rights Reserved Like it (1) Dislike it (0) Added: October 31, 2010 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: babuagoodboy (12 month(s) ago) hiiii ur presentation is so nice ..can u plz send this ppt to my mail ID babuagoodboy@yahoo.com .. Saving..... Post Reply Close Saving..... Edit Comment Close By: nasrallah (14 month(s) ago) How download Saving..... Post Reply Close By: robin_vinnu (12 month(s) ago) need mail id Saving..... Edit Comment Close By: vidya.kanamarlapudi (14 month(s) ago) sir,i am unable to download ppt...piz forward this presention to my mail id(vidya.kanamarlapudi@gmail.com).pls forward as soon as possible..thank you sir Saving..... Post Reply Close Saving..... Edit Comment Close By: thrisai1988 (17 month(s) ago) sir, iam unable to download the ppt.....................plz send to my mail id thrisai1988@yahoo.co.in Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Solid state properties : Solid state properties Presented by: Gopidi Ravi chaithanya M.pharmacy(pharmaceutics) St.peter’s institute of pharmaceutical sciences Hanmakonda,warangal. Contents: : Contents: Introduction Crystallization Polymorphism Hydrates and solvates The amorphous state Techniques for study of crystal properties References Introduction : Introduction The three states of matter are solid, liquid and gas. Solid particles are made up of molecules that are held together by intermolecular forces , such as through hydrogen bond and van der waal forces. Crystal habit and the internal structure of a drug can effect the bulk and physiochemical properties, which ranges from flow ability to chemical stability. Habit is the description of the outer appearance of a crystal where as the internal structure is the molecular arrangement with in the solid. The internal structure of a compound can be classified as crystalline and amorphous states. Slide 4: chemical compound habit internal structure crystalline amorphous polymorphs molecular adducts nonstoichiometric stoichiometric inclusion compounds solvates(hydrates) channel layer cage(clathrate) crystallization : crystallization Crystals are characterized by repetitious spacing of constituent atoms or molecules in three dimensional array. A characteristic property of crystal is that it has a melting point. This is the temperature at which the crystal lattice break down, owing to the molecule having gained sufficient energy from the heating process to overcome the attractive forces that hold the crystal together. Preparation of crystals: : Preparation of crystals: Crystals are prepared by inducing a change from the liquid to the solid state by colling a molten sample to below its melting. Pharmaceutical examples of crystallization through cooling include the formation of suppositories, creams and semisolid matrix dosage forms. The other method of crystallization is to have a solution of the material and to change the system so that the solid is formed i.e. through supersaturated solution. The process by which a crystal forms are called nucleation and growth. Nucleation is the formation of a small mass on to which a crystal can grow. Growth is the addition of more solute molecules to the nucleation site. Polymorphism: : Polymorphism: When a substance exists in more than one crystalline form, the different forms are designated as polymorphs and the phenomenon as polymorphism . The polymorphs differ from each other with respect to their physical properties such as solubility, melting point, density, hardness and compression properties. Polymorphs are of two types: Enantiotropic polymorph is the one which can be reversibly changed into another form by altering the temperature and pressure e.g. sulfur. Monotropic polymorph is the one which is unstable at all temperatures and pressure e.g. glyceryl stearates. Slide 8: The existence of the polymorph can be determined by using techniques such as optical crystallography, X-ray diffraction, differential scanning calorimetry, etc. Depending on their relative stability, one of the several polymorphic forms will be physically more stable than the others. Such a stable polymorph represents the lowest energy state, has highest melting point and least aqueous solubility. The remaining polymorphs are called as metastable forms which represent the higher energy state, have lower melting points and higher aqueous solubilities. High melting point = strong lattice = hard to remove a molecule = low dissolution rate Slide 9: Since the metastable form have greater aqueous solubility, they show better bioavailability and are therefore preferred in formulations for e.g. ,of the three polymorphic forms of chloramphenicol palmitate-A,B and C, the B form shows best availability and the A form is virtually inactive biologically. The polymorphic form III of riboflavin is 20 times more water soluble than the form I. However ,because of their poor thermodynamic stability, aging of dosage forms containing such metastable forms usually result in formation of less soluble ,stable polymorph-for example, the more soluble crystalline form II of cartisone acetate converts to the less soluble form V in an aqueous suspension resulting in caking of solid. Slide 10: Such a transformation of metastable to stable form can be inhibited by dehydrating the molecule environment or by adding viscosity building macromolecules such as PVP, CMC, pectin or gelatin that prevent such a conversion by adsorbing on to the surface of the crystals. The stable polymorphic form will have the slowest dissolution rate, and so there may be occasions when it would be desirable to speed the dissolution by using metastable form . However, the risk associated with using metastable form is that it will convert back to the stable form during the product’s life, and give a consequent change in properties. As polymorphism can have such serious consequences for the bioavailability of the drugs with low aqueous solubility, it is essential that manufacturers check the existence of polymorphism and ensure that they use the appropriate polymorphic form every time they make a product. Hydrates and solvates : Hydrates and solvates The crystalline form of a drug can either be a polymorph or molecular adduct or both. The stoichiometric type of adducts where the solvent molecules are incorporated in the crystal lattice of the solid are called as the solvates. and the trapped solvent as solvent of crystallization. The solvates can exist in different crystalline forms called as pseudopolymorphs. This phenomenon is called as pseudopolymorphism. When the solvent in associated with the drug is water ,the solvate is known as a hydrate. Slide 12: Generally, the anhydrous form of a drug has greater aqueous solubility than the hydrates. e.g. theophylline and ampicilline. In this situation, water could form a hydrogen bond between two drug molecules and tie the lattice together; this would give a much stronger, more stable lattice and hence a slower dissolution rate. Although anhydrous forms are usually more rapidly soluble than the hydrate, there are examples of opposite being true. In such circumstances once could think of water as a wedge pushing two molecules apart and preventing the optimum interaction between the molecules in the lattice. here water would be weakening the lattice and would result in a more rapid dissolution rate. E.g. erythromycin. The amorphous state: : The amorphous state: When the material is in the solid state but the molecules are not packed in a repeating long range ordered fashion, it is said to be amorphous. Such material represent the highest energy state and can be considered as super cooled liquid. Amorphous forms are typically prepared by rapid precipitation, lyophilization, or rapid cooling of liquid melts. They have greater aqueous solubility than the crystalline forms because the energy required to transfer a molecule from crystal lattice is greater than that required for non aqueous solids. For e.g. , the amorphous form of novobiocin is 10 times more soluble than the crystalline form. Chloramphenicol palmitate, cortisone acetate and phenobarbital are other examples where the amorphous forms exhibit higher water solubility. Slide 14: Amorphous form have a characteristic temperature at which there is a major change in properties. this is called the glass transition temperature ( Tg ) If the sample is stored below the Tg the amorphous form will be brittle and is described as the glassy state. If the sample is above its Tgit becomes rubbery. The Tg, is a point where the molecules in the glass exhibit a major change in the mobility. The lack of mobility when the sample is glassy allows the amorphous form to exist for longer, whereas when Tg is below the storage temperature the increased molecular mobility allows rapid conversion to the crystalline form. Slide 15: The glass transition temperature of an amorphous material can be lowered by adding a small molecule, called a plasticizer, that’s fits between the glassy molecules, giving them greater mobility. Water acts as a good plasticizer for many materials. Crystallization occurs because the absorbed water has plasticized the sample to such an extent that the Tghas dropped below room temperature and allowed sufficient molecular mobility that the molecule are able to align and crystallize. The fact that processing can make crystalline materials partially amorphous means that it is possible for very complex material to form that contain different metastable states. Slide 16: for e.g., when b-polymorph chloramphenicol palmitate was milled it become partially amorphous, which could make the plasma level even higher than when the crystalline form were used. However ,milling the b-polymorph could also provide the necessary energy to convert it to the stable a-polymorph, which would reduce the effective plasma level. Equally, milling could disrupt the a-polymorph giving a partially amorphous form that might have a higher bioavailability than the crystal. In other words ,the effect of processing on the physical form can be very complicated, and often unpredictable. Techniques for study of crystal properties : Techniques for study of crystal properties Powder X-ray diffraction Infrared spectroscopy (IR) Water vapour sorption Isothermal Microcalorimetry Dissolution Calorimetry Macroscopic techniques Differential Scanning Calorimetry (DSC) Fusion method Scanning electron microscopy Thermogravimetric analysis References : References Jens T. Cartenson- Advanced pharmaceutical solids Graham buckton –particle science and powder technology Buckton,G. Interfacial phenomenon in drug delivery and targeting. Harwood Academic press , Amsterdom Florence, A.T. and Attwood physicochemical principles of pharmacy, Macmillan, London D.M. Brahmankar- Biopharmaceutics and pharmacokinetics Lachman-The throry and practice of industrial pharmacy Slide 19: thank you