Download PPT by clicking on following link
http://pharmastuff.blogspot.com/2018/07/spherical-crystallization-ppt.html
Spherical crystallization is a particle design technique, by which crystallization and agglomeration can be carried out simultaneously in one step.
Improves flowability and compressibility.
Crystalline forms of a drug to be converted into different polymorphic form having better bioavailability.
For masking of the bitter taste of drug.
General guide lines for the spherical agglomeration of drugs
Chow et al postulated some general guide lines for the spherical agglomeration of drugs
• For compounds that are water soluble, a water-immiscible organic solvent is used as the external medium and salt solutions of high concentration without common ions can be used as the bridging liquid.
• For compounds that are soluble in one or more organic solvents water is employed as the external phase and a water-immiscible organic solvent as the bridging liquid.
For compounds that are only soluble in water-miscible organic solvents a saturated aqueous solution of the compound can serve as the external phase and an organic solvent mixture as the bridging solvent.
• For compounds that are insoluble in water or any organic solvents a water-immiscible organic solvent can act as the external phase and a 20% calcium chloride solution as the bridging liquid. In addition, a binding agent such as PVP or PEG is required for agglomeration since the powders are not sufficiently soluble in the bridging liquids to allow binding through recrystallization and fusion.
Introduction to Crystal Morphology & Variations,
Classification of Chemical Compounds, Amorphous Forms, Polymorphs, Solvates, Clathrates, Crystal Habit, Crystal Habit Modification Methods, Crystallization, Importance of Crystallization in Preformulation
Presented by
A.Siddartha Tharun Teja
Department of Industrial Pharmacy
Introduction to Crystal Morphology & Variations,
Classification of Chemical Compounds, Amorphous Forms, Polymorphs, Solvates, Clathrates, Crystal Habit, Crystal Habit Modification Methods, Crystallization, Importance of Crystallization in Preformulation
Presented by
A.Siddartha Tharun Teja
Department of Industrial Pharmacy
Spherical crystallization (SC) is a promising technique, which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result
Spherical crystallization (SC) is a promising technique, which encompass the crystallization, agglomeration, and spheronization phenomenon in a single step. Initially, two methods, spherical agglomeration, and emulsion solvent diffusion, were suggested to get a desired result
Dissolution apparatus, invivo-invitro corelation, factor affecting,BCS classification ..
Complete dissolution topic in this slide & easy way to write..
Cheak it now and give feedback
INCLUDES THE INTRODUCTION TO CRYSTALLIZATION, FOLLOWED BY MECHANISM LIKE SUPER SATURATION, NUCLEUS FORMATION, CRYSTAL GROWTH, IN DETAIL ACCOUNT HOMOGENOUS AND HETEROGENOUS NUCLEATION AS PRIMARY AND SECONDARY NUCLEATION.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
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Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
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students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
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• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
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Embracing GenAI - A Strategic ImperativePeter Windle
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This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
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Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
3. Pharmastuff.blogspot.com
Spherical crystallization is a particle design technique,
by which crystallization and agglomeration can be
carried out simultaneously in one step.
Improves flowability and compressibility.
Crystalline forms of a drug to be converted into
different polymorphic form having better bioavailability.
For masking of the bitter taste of drug.
Spherical crystallization
5. Pharmastuff.blogspot.com
General guide lines for the spherical agglomeration of
drugs
Chow et al postulated some general guide lines for the spherical
agglomeration of drugs
• For compounds that are water soluble, a water-immiscible
organic solvent is used as the external medium and salt solutions of
high concentration without common ions can be used as the
bridging liquid.
• For compounds that are soluble in one or more organic solvents
water is employed as the external phase and a water-immiscible
organic solvent as the bridging liquid.
6. Pharmastuff.blogspot.com
.
• For compounds that are only soluble in water-miscible organic
solvents a saturated aqueous solution of the compound can serve
as the external phase and an organic solvent mixture as the
bridging solvent.
• For compounds that are insoluble in water or any organic
solvents a water-immiscible organic solvent can act as the
external phase and a 20% calcium chloride solution as the
bridging liquid. In addition, a binding agent such as PVP or PEG is
required for agglomeration since the powders are not sufficiently
soluble in the bridging liquids to allow binding through
recrystallization and fusion.
General guide lines for the spherical agglomeration of
drugs
8. Pharmastuff.blogspot.com
Wet Spherical agglomeration
A near saturated solution of the drug in the good solvent is poured into the
poor solvent. Crystals will precipitate immediately.
In the spherical agglomeration method a third solvent called the bridging
liquid is added in a smaller amount to promote the formation of
agglomerates
As a result of interfacial tension effects and capillary forces, the bridging
liquid makes the crystals to adhere one another .
WSA depends of choice of bridging liquid, the stirring speed and the
concentration of solids (or of the solute) .
9. Pharmastuff.blogspot.com
• Less than the optimum amount of bridging liquid produces plenty of fines
and more thanoptimum produces very coarse particles.
• Also the choice of bridging liquid, the stirringspeed and the concentration
of solids (or of the solute) are of importance. In the case of lactose, the
agglomerate size distribution was affected by both the size of raw particles
andthe amount of bridging liquid used. At increasing stirring rate the
agglomeration was reduced because of increasing disruptive forces.
• Higher stirring rate produce agglomerates that are less porous and more
resistant to mechanical stress, and the porosity decreases when the
concentration of solid increases
• The viscosity of the continuous phase has an effect on the size distribution
of the agglomerates. The choice of bridging liquid has an influence on the
rate of agglomeration and on the strength of the agglomerates.
Wet Spherical agglomeration
10. Pharmastuff.blogspot.com
• This technique is usually applied for the preparation of
microspheres .
• Here interaction between the drug and the good solvent is stronger
than that of the good and poor solvents; hence the good solvent
drug solution is dispersed in the poor solvent, producing quasi
emulsion droplets, even if the solvents are normally miscible . This
is because of an increase in the interfacial tension between good
and poor solvent .
• Then good solvent diffuses gradually out of the emulsion droplet
into the outer poor solvent phase. The counter diffusion of the poor
solvent into the droplet induces the crystallization of the drug
within the droplet due to the decreasing solubility of the drug in the
droplet containing the poor solvent.
Quasi-Emulsion Solvent Diffusion method
11. Pharmastuff.blogspot.com
• In this method, the mixture of three partially
immiscible solvent i.e. acetone, ammonia water,
dichloromethane was used as a crystallization system.
• In this system ammonia water acted as bridging liquid
as well as good solvent, Acetone was the water
miscible but a poor solvent, thus Drug precipitated by
solvent change without forming ammonium salt.
• Water immiscible solvent such as hydrocarbons or
halogenated hydrocarbons e.g. dichloromethane
induced liberation of ammonia water
Ammonia diffusion method
12. Pharmastuff.blogspot.com
• Drug crystals are precipitated by neutralization of the base
with acid. and then poured into an acidic solution containing
polymers and bridging liquid under constant agitation
• Spherical crystals of tolbutamide and phenytoin have been
prepared by this technique.
Neutralization Method
13. Pharmastuff.blogspot.com
• It is a modification of the wet spherical crystallization
technique in which drug is crystallized andagglomerated with
an excipient or with another drug.
• This process enables design of agglomerates containing two
drugs or poorly compressible drug in combination with
diluents and is restricted to water insoluble large-dose drugs
only.
• Difference in the physicochemical properties of drug
molecules and excipient is a major challenge in the selection
of the solvent system for the Crystal-co-agglomeration
technique
Crystal-co-agglomeration technique
14. Pharmastuff.blogspot.com
flocculation zone, zero growth zone, fast growth zone and constant size zone
A)Flocculation zone: In this zone, bridging liquid displaces the liquid from the surface
of the crystals and these crystals are brought in close proximity by agitation. The
adsorbed bridging liquid links the particles by forming bridge between them.
B)Zero growth zone: During this growth phase, the entrapped fluid is squeezed out
followed by squeezing of the bridging liquid onto the surface of small flocs. Loose
floccules are transformed into tightly packed pellets
C)Fast growth zone: The fast growth zone of the agglomerate takes place when
sufficient bridging liquid has squeezed out of the surface of the small
agglomerates. This formation of large size particle after random collision of well
formed nucleus is known as coalescence.
D)Constant size zone: In this zone agglomerates cease to grow or even show slight
decrease in size. Here thefrequency of coalescence is balanced by the breakage
frequency of agglomeration. The rate determining step in agglomeration growth
occurs in zero growth zones when bridging liquid is squeezed out of the pores as
the initial floccules are transformed into small agglomerates.
Steps involved in Spherical Crystallization
15. Pharmastuff.blogspot.com
1.Solubility profile: Selection of solvent depends upon the solubility characteristics of the drug.
The proportion of solvent to be used is determined by carrying out solubility studies and
constructing a ternary phase diagram.
2.Mode and intensity of agitation: High speed agitation is necessary to disperse the bridging
liquid throughout the system. Change in the agitation pattern or fluid flow will affect the
shape of agglomerates. The extent of mechanical agitation and the concentration of bridging
liquid determines the rate of formation of agglomerates and their final size.
3.Temperature of the system: It has a significant influence on the shape, size and texture of the
agglomerates. The effect of temperature on spherical crystallization is probably due to its
effect on the solubility of drug substance.
4.Residence time: It is defined as the time for which agglomerates remain suspended in the
reaction mixture. Residence time affects the strength of agglomerates.
5.Amount of bridging Liquid: Median diameter of agglomerated crystals increases with decrease
in the amount of bridging liquid in the three-solvent system. Insufficient bridging liquid
produces plenty of fines and excess produces very coarse particles
Factors affecting Spherical Crystallization
16. Pharmastuff.blogspot.com
REFERENCES :
1.Patil et al (2009).,Spherical Crystallization: a Method to Improve Tabletability.
Research J. Pharm. and Tech.2 (2): April.-June. 2009,REVIEW ARTICLE.
2. Gokul R ghenze et al (2011).,An overview to spherical crystalisation and its
evaluation.Internation journal of applied pharmaceutics. Vol 3, Is.sue 3, 2011.REVIEW
ARTICLE
3. Mahanty et al (2010)., Particle Design of Drugs by Spherical Crystallization
Techniques.
International Journal of Pharmaceutical Sciences and Nanotechnology Volume 3 • Issue
2 • July - September 2010 .REVIEW ATICLE.
4.Gupta et al (2010)., Spherical crystallization: a tool of particle engineering for making
drug
powder suitable for direct compression.IJPRD.REVIEW ARTICLE.
5. 1.Shangraw RF. Compressed tablets by direct compression. In: Lieberman HA,
Lachman L, Schwartz JB. Pharmaceutical Dosage Forms: Tablets, vol. 1. Marcel
Dekker, New York 1989; 195-246.
17. Pharmastuff.blogspot.com
REFERENCES :
6.Sano A, Kuriki T, Kawashima Y, Takeuchi H, Hino T, Niwa T, Particle design of Tolbutamide by
the spherical crystallization technique III micrometric properties and dissolution rate of
tolbutamide spherical agglomerates produced by qesi emuslion solvent diffusion method,
Chem. Pharm. Bull. 38: 733-739 (1990)
7.Kawashima Y, Cui F, Takeuchi H, Hino T, Niwa T, Kiuchi K. Parameters determining the
agglomeration behavior and the micrometric properties of spherically agglomerated crystals
prepared by spherical crystallization technique with miscible solvent system. Int J Pharm.
1995; 119: 139-147.
8. Sano A, Kuriki T, Kawashima Y, Takeuchi H, Hino T, Niwa T.Particle design of Tolbutamide by
the spherical crystallization technique IV, Improved of dissolution and bioavailability of direct
compression tablets prepared using Tolbutamide agglomerated crystals, Chem. Pharm. Bull.
40, pp 3030-3035.
9. Chavda V, Maheshwari RK. Tailoring of ketoprofen particle morphology via novel crystallo-
coagglomerationtechnique to obtain a directly compressible material Asian J. Pharm. 2(1), pp
61-67.
10.Patil S. V. , Sahoo S. K. Pharmaceutical overview of spherical crystallization Research
Library,Der Pharmacia Lettre, 2 (1), pp 421-426.
11. P.K. Kulkarni, B.G. Nagavi. Ind. Jr. Pharm. Eudc. 2002; 36(2), pp 66-73.