This document discusses colloids and factors that influence the stability of disperse systems such as suspensions. It covers topics like classification of colloids, sedimentation rates, DLVO theory, effects of electrolytes, and factors that influence stability. Suspension preparations are discussed, including issues like sedimentation, caking, and Ostwald ripening. Methods to improve stability include using flocculating agents and modifying the zeta potential.
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Uma questão fundamental na astrobiologia, é: se a vida pode ser transportada entre planetas extrassolares, e sistemas planetários? Uma equipe de astrofísicos norte-americanos propôs uma nova estratégia para responder a essa questão com base no princípio que a vida alienígena que surgiu via espalhamento – num processo chamado de panspermia – exibirá mais aglomerados do que a vida que surge espontaneamente.
Existem duas maneiras básicas para a vida ter se espalhado além de sua estrela hospedeira.
A primeira seria por meio de um processo natural de arremessamento de asteroides e cometas. A segunda seria por meio da vida inteligente que deliberadamente viajaria pelo espaço.
Um novo artigo, aceito para publicação no Astrophysical Journal Letters, não lida como a panspermia ocorre. Ele simplesmente pergunta: se ela ocorreu, nós poderíamos detectá-la? Em princípio, a resposta é sim.
O modelo desenvolvido pela equipe no Harvard-Smithsonian Center for Astrophysics assume que as sementes de um planeta vivo se espalham em todas as direções.
Zeta potential is a scientific term for electrokinetic potential (Zeta) in colloidal dispersions.
• Electrokinetic potential refers to a potential difference in a liquid characterizing electrochemical equilibrium on interfaces.
• Zeta potential is the charge that is located at the slipping point of a particle in the shear plane.
• Zeta potential is the Colloidal chemistry.
• It is usually denoted using the Greek letter zeta (ζ) hence ζ-potential.
• (ζ), is the potential difference between the dispersion medium and the stationary layer of fluid attached to the dispersed particle.
• Zeta Potential is the potential difference across an electrostatic double layer of ions that surround a solid particle dispersed in a polar liquid. In short, it is a measure of the surface charge of a particle.
• The electric potential at the boundary of the double layer is known as the Zeta potential of the particles and has values that typically range from +100 mV to - 100 mV
Uma questão fundamental na astrobiologia, é: se a vida pode ser transportada entre planetas extrassolares, e sistemas planetários? Uma equipe de astrofísicos norte-americanos propôs uma nova estratégia para responder a essa questão com base no princípio que a vida alienígena que surgiu via espalhamento – num processo chamado de panspermia – exibirá mais aglomerados do que a vida que surge espontaneamente.
Existem duas maneiras básicas para a vida ter se espalhado além de sua estrela hospedeira.
A primeira seria por meio de um processo natural de arremessamento de asteroides e cometas. A segunda seria por meio da vida inteligente que deliberadamente viajaria pelo espaço.
Um novo artigo, aceito para publicação no Astrophysical Journal Letters, não lida como a panspermia ocorre. Ele simplesmente pergunta: se ela ocorreu, nós poderíamos detectá-la? Em princípio, a resposta é sim.
O modelo desenvolvido pela equipe no Harvard-Smithsonian Center for Astrophysics assume que as sementes de um planeta vivo se espalham em todas as direções.
Zeta potential is a scientific term for electrokinetic potential (Zeta) in colloidal dispersions.
• Electrokinetic potential refers to a potential difference in a liquid characterizing electrochemical equilibrium on interfaces.
• Zeta potential is the charge that is located at the slipping point of a particle in the shear plane.
• Zeta potential is the Colloidal chemistry.
• It is usually denoted using the Greek letter zeta (ζ) hence ζ-potential.
• (ζ), is the potential difference between the dispersion medium and the stationary layer of fluid attached to the dispersed particle.
• Zeta Potential is the potential difference across an electrostatic double layer of ions that surround a solid particle dispersed in a polar liquid. In short, it is a measure of the surface charge of a particle.
• The electric potential at the boundary of the double layer is known as the Zeta potential of the particles and has values that typically range from +100 mV to - 100 mV
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
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Colloids and their classification
Colloidsmaybe classifiedaseitherlyophilicorlyophobicdependingonwhethertheyassociate with
or are repelledbyasolvent.Lyophobiccolloidsare thermodynamicallyunstable becauseof alarge
surface tensionthatresultsfromthe large surface area to volume ratiostheyshare withthe solvent.
The equilibriumforemulsionsandaerosolslieswiththe formationof twoseparate phasesandsois
not ina practical positionforformulation.
Rate of sedimentation and Ostwald ripening
Particleswill move inadisperse systembecauseof three factors;Brownianmotion,convectionand
creaming/sedimentation.The randomcollisionsof thermodynamicallyactive particlesoccurs
naturallyinthe systemandistermed“Brownianmotion”.The creaming/sedimentation of a
dispersionoccurseitherwhensolidparticlescome togethertoformaggregates,ordropletsof the
continuousphase come togethertocoalesce.The rate atwhichthisoccurs (the sedimentationrate)
can be workedoutbyusingStokes’Law,givenbelow:
𝑣 =
𝑔𝑑2(𝜌1 − 𝜌2)
18𝜂
In thisequation,the sedimentationrate isseentobe linkedtothe gravitational constant(g),the
viscosityof the medium(η),the diameterof the particle (d) andthe differenceindensitiesbetween
the particle andmedium.
The rate of sedimentationinadispersedsystemcanbe reducedinthree ways,usingStokes’Law:
Reducingthe densitydifferencebetweenthe particle andthe mediumit’sin,sothatthe
gravitational force actingonthe particleshaslessimpactonthe rate of fallinginthe liquid.
Increasingthe viscosityof the medium,sothat collisionsoccurlessfrequently,leadingtoless
coalescence of liquidmediumandlessaggregationof solidmedia.
Reducingthe size of the particlessothatthe surface areato volume ratioissmallerandthe
interfacial tensionbetweenthe twophasesislessened.
If the sedimentationisnotcontrolledinformulations,thenthe phaseswill become separatedasthe
systemtendstoequilibrium.Thisoccursfirstlythroughcreaming,as particlesof like media
associate,before eventuallythe twophasesbecome entirelyseparatefromone anotherinaprocess
called“cracking”;thisis toreduce the surface tensionbetweenthe twophasesandwill be
irreversible.
Ostwaldripeningcanalso occur ina disperse system, where elementsof the dispersedphase have
some small solubilityforthe continuousphase.Thismeansthatif the temperature increases,more
of the dispersedphase enterssolutionasequilibriummovestoresistchange tothe system.A
subsequentdropintemperaturethencausesthe solubilitytodecrease,causingmoleculesof the
dispersedphase tobecome adsorbedtothe surface of largerdispersedparticles.Thisoccurs
because largerparticlesare more energeticallyfavoureddue toa lowersurface areato volume ratio.
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DLVO theory of suspensions
There are five mainforcesof attractionthatcan existbetweencolloidal particles.Theseare:
Vander Waalsforcesof attractionbetweenmolecules,
Born forces,whichare short-range repulsive forces,
Stericforcesthat relyonmoleculargeometryandarrangements,
Electrostaticforcesof repulsion,
Solvationforcesthatdependonthe quantityof solventadsorbedtoneighbouringparticles.
Lookingindependentlyatthe van derWaals forcesof attractionand electrostaticforcesof repulsion
isthe basisof the DLVO theoryonhydrophobiccolloidalsystems.The sumof attractive energies
betweenneighbouringsphericalparticleswasdeterminedbyHamaker asbelow. Inthisequation
(where A = the Hamaker constant),the distance betweenthe twoparticles(H) andthe radiusof the
particle (a) are seento be interrelated.
𝑉𝐴 = −
𝐴𝑎
12𝐻
𝑉𝑇 = 𝑉𝐴 + 𝑉𝑅
Electrostaticforcesbetweenmoleculesleadsto repulsionwhenthe surface chargesare of like
charge andmagnitude.A particle mayaccumulate acharge at its surface whengroupsthere become
ionisedinthe medium,orwhenionssimplyadsorbtothe particle surface. Inthe latterof these two
cases,the particle’s “surface potential(ψO)”isdeterminedbythe activityof the ionsthatare
adsorbingtoit.
Due to the fact thatthese particlesinthe dispersedphase now present asurface potential,opposite
chargeswill accumulate justoutside the surface sothatthe particle maybe neutralised.Thislayerof
oppositelychargedionsiscalledthe “Sternlayer”or“fixedlayer”andisformedof ionsthatare
relativelyimmovablebecause of the strongattractionbetweenthe opposite charges.Justoutside
thislayerisa secondary,lessfixedlayerof chargesthatare mostlyopposite tothose atthe particle
surface;againthisis to evenoutthe surface charge.Thislayeriscalled the “Guoy-Chapmanlayer”or
“shearlayer”or simply;the “diffuse layer”.
As the distance fromthe surface to the bulkincreases,the potential decreasesexponentially.This
decrease maybe seentodegrade stepwise bysplittingupthe potentialsinthe differentlayers:
Surface potential (ψo):thisismeasuredatthe surface of the particle andis a reflectionof
the numberand activityof the ionsthat have absorbedtothe surface.
Sternpotential (ψδ):thisismeasuredinthe Sternlayerthatimmediatelysurroundsthe basal
charge of the particle andis a reflectiononthe counterionactivityaroundthe particle.
Zetapotential (ζ):thisismeasuredatthe shearplane of the particle,whichissaidto be the
boundarybetweenfixedanddiffuselayers.Thispotential will dependonsurface roughness,
any adsorbedmacromoleculesetcetera.
anion
cation
particle
fixed
diffuse
shear
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In reality,the zetapotentialisusedtoapproximate the Sternpotential because thiscanbe
measuredbyelectrophoresisandistherefore mucheasiertomeasure. Whenthe total potential
energyof interaction(VT) isplottedagainstthe distance betweentwoparticles(H),a DLVOgraph is
obtained. However,the equationsusedforcalculatingVT donot account for ionsof finite size,and
the aforementionedimpracticalityof measuringthe Sternpotential.
The DLVO graph isuseful forexplainingthe behaviourof particlesinadispersedsystemintermsof
theirinteractionsandthe energychangesassociatedwiththem.If the primarymaximumistoo
small,thenthe twoneighbouringparticlesmaybecome soattractedthat theyreachthe primary
minimum,which maybe of a depththat meansrevertingtoanotherstate isimpossible.In
suspensionsthissinkingtothe primaryminimum resultsin recrystallizationorcaking,whilstin
emulsionsitcausescoalescence orcracking.
Stability of disperse systems
Giventhe nature of the electrical double layersurroundingdispersedparticles,the presenceof
electrolytesinthe continuousphase willhave animpacton how stable asystemis.
Highconcentrationsof electrolytesinthe continuousphase will meanthationicmaterial penetrates
the diffuse layerandcausesadecrease inthe thicknessof the double layerasawhole.Because of
thisthinning,the repulsiveforcesbetweenparticlesare decreasedrelative totheirradiusandthis
meansthat theycan come intoclosercontact witheachother. Thismeansthat the van der Waals
forcesdetermine the DLVOshape,leavingnoprimarymaximumandasteepprimaryminimuminto
whichthe systemmayfall.These systemsare unstable andwillhave atendencytoirreversibly
aggregate.
If the electrolyteconcentrationistoolow,thenthe electrical doublelayerisverydiffuse andlarge,
leadingtoa dominance of repulsive forcesbetweenparticles.Thiswouldessentiallycreate alarge
primarymaximumanda homogenousmixture,butnosecondaryminimuminwhichsome
flocculationmayoccur;thiswouldtherefore be unstable.If the concentrationof electrolyteis
increasedsuitablythenasecondaryminimummayappear,whichisasuitable targetinthe
formulationof adispersedsystem.
The Hardy-Schultzrule statesthatthe greaterthe valence of the addedcounterion,the
greaterthe effectonthe total repulsive forces(electrostaticinteractions).
Surface potential (ψo) isanothermeasureof stability,becauseanincrease insurface potential will
cause an increase inthe total repulsive forces(VR).Therefore,asthe surface potential decreases,so
doesthe primaryminimumonthe DLVOgraph, whichmeansthatthere islessof an energetic
barrierto overcome if a systemtendstowardsaggregationatthe primaryminimum.Onlyatthe
intermediate valueof ψo,are the differencesinrepulsiveandattractive forcessuitablybalancedto
allowa secondaryminimum.
H
TOTALPOTENTIALENERGY
H
TOTALPOTENTIALENERGY
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Repulsion between molecules with macromolecular stabilisers
Whenparticleswithhydratedmacromolecularstabilisersattheirsurface come tointeract,they
become repelledfromone another.Thisarisesbecause of anentropicpenaltybeingassociatedwith
the interactingof the twomacromolecularcomponentsof the particles.Thisisbasedonthe fact
that if the two particleswere tointeract,thenthe stabilisingchainswouldhave reducedflexibility
and be stuck inone conformation,causingareductioninentropyandan increasedcontributionto
the free energyof the system,whichisenergeticallyunfavourable.
The repulsionbetweenthe moleculesiscompoundedwhenneighbouringmoleculesaddtothe
overlapregions,creatingpocketsof concentrationandosmoticpressure againstwhichthe solvent
mustwork to dilute.Thisresultsinthe separation(repulsion) of particles,andisdependentmainly
on the lengthof hydrophobicchains,the interactionof the solventwiththe chains,andthe number
of chainsperunitSA.
Suspension preparations
Suspensionsare examplesof dispersedsystemsandsocontaina drugin the dispersedphase,carried
ina continuousaqueousornon-aqueousphase.Theyare commonlyusedforadministrationviathe
oral,intramuscularorsubcutaneousroute,butare alsoused as drug reservoirsintransdermal
patchesand some topical preparations.
Whensuspendingasolidinaliquid,there are manyproblemsthatneedtobe consideredsuchas
sedimentation,cakingandOstwaldripening,thatall needtobe considereddue totheirabilityto
cause a productto become ineffective.Adsorptiontocontainerwallsisalsoaprobleminsome
preparations,particularlywithlow-dose drugs.The ideal end-pointforasuspensionwillprovidea
homogenousandtherapeuticallyuniformdose eitherreadilyoronshaking,andwill alsobe
acceptable tothe patientintermsof taste,viscosityandappearance.Inreality,thismeansthatthe
desiredsystemwill be partiallydeflocculated.
Stability of suspensions, flocculating agents and zeta potential
The stabilityandnature of a suspensionmaybe lookedatintermsof sedimentation,byobserving
the ratio (R) of sedimentvolume(VS) orheight(hinf) overtotal volume (VT) orinitial height(ho).
Flocculate are loose,porousandlarge aggregationsthatforminsuspensionswhenparticlescome
togetherbutnot underthe attractive forcesof the primaryminimum.These structuresmaycompact
to some extenttoforma sedimentbutwill notcake asthe porous nature holdssolventinthe
structure itself topreventthis.Indeflocculatedsystems,particlesbehaveindividuallyandmaysettle
on the bottomof the container,where layersof closerandcloserparticlesbuildupundergravityto
overcome repulsive forcesof the primarymaximumandformanirreversibly-boundcake.The two
systems(flocculatedanddeflocculated)canbe identifiedbytheirsedimentationratio;the sediment
ismuch smallerwhencakingoccursthanwhena simple dense flocculate forms.Thisresultsin
deflocculatedsystemshavinga lowerratio(R) thandeflocculatedones.
Flocculatingagentsare addedtosuspensionstopreventcakingandpromote residence of the
systeminthe secondaryminimumof the DLVOgraph.The effectcan be measuredthroughlooking
at the zetapotential.
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Most drug particlesdispersedinwaterwill eitheraccumulate asurface charge throughionisationof
surface groups(if present) orthroughionadsorption.Thismeansthatthe electrical double layer
formedaroundparticlescausessome repulsiondue tolike charges,withzetapotentialbeingthe
outermostcharge discriminantthatisusedtogauge the overall repulsive forcesbetweenparticles
throughinferringvaluesof ψo.
Microelectrophoresisisusedtomeasure the migrationvelocity(μE) of particlesthroughamedium,
whichcan be relatedtozeta potential (ζ) usingthe Henryequationgivenbelow:
𝜇 𝐸 =
𝜁𝜀
4𝜋𝜂
𝑓(𝜅𝑎)
Thisequationrelateszetapotential (ζ),the dielectricconstantof the medium(ε),the viscosity(η)
and the migrationvelocity(μE) andalthoughthe zetapotential isnotequal tothe surface potential,
it can be usedas a guide to the magnitude of the repulsive forcesbetweenparticles. Graphsshow
that extremesinzetapotential cause cakingdue tothinningof the electrical double layerandwill
cause inverse polaritywhenstudiesacrossthe spectrum.Onlyinthe middle whenthe balance of
positive andnegativechargesare more balanceddoesadiffuse layerarise thatislarge enoughto
keepparticlesata flocculate-capabledistance.Thisalsocoincideswithapeakinsedimentheight.
Giventhatflocculatingagentswill increase the
thicknessof the diffuse (Gouy-Chapman)layeraround
particles, itmakessense thatthe mosteffective
flocculatingagentswill be chargedoppositelytothat
of the zetapotential.SodiumCMCisusedbut the
incompatibilitybetweenanionicsuspendingagents
and cationicflocculatingagentshastobe considered.
The surface charge can be changedif necessary,but
polymersmayalsoact as flocculatingagents by
forminginterparticle bridgesbetweencolloidal
particles,if the polymerbearschemicalgroupswith
whichthe colloidcaninteract.Alternatively,the
polymermaycoat the particle ina film.
Extemporaneous production of suspensions
Suspensionsare commonlypreparedinpractice foradministrationtochildrenorthe elderly,whena
suitable productisnotavailable orwhenthe productsavailableare notsuitable foruse,i.e.
swallowingissues.Inanycase,the suspendingagentmustmeetsome criteria:
The agent mustnot be toxicor reactive towardsthe drugor otherconstituents,
It mustalloweasyandrapid redispersionof the druguponshaking,
The resultingdispersed phase mustformaloose flocculate thatdoesnotcake,
Preparationwithwatermustbe easyandwithoutthe use of special techniques.
ZETAPOTENTIAL(mV)
SEDIMENTHEIGHT
CAKING CAKINGNON-CAKING
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THEEXUDATE
Non-aqueous suspensions and particle adhesion
Solidssuspendedinanon-aqueouspropellant(aerosols) have beenknown toaggregate whensmall
volumesof wateradsorbat the interface betweenthe phases.Thisaggregationcanleadto
depositionof the solidontothe wallsof the containerwhichwillobviouslyreduce the effectiveness
of the preparation.
Electrostaticforcesact onthe surface of solidparticlesinsuspensions(aqueousornon-aqueous)
that cause interactionwithneighbouringparticles.Itispossiblethatinone dispersedsystem, there
may be particlesof the same drug that are of differentcharge andmagnitude,due tothe difference
insize and shape exhibitedbymostdispersedparticles.The presence of excipientsin
pharmaceutical preparationsalsoimpactsonthe behaviour.The adhesionof solidparticlesto
surfacessuchas those in a spacerdevice wasthoughtto be a resultof electrostaticforcesinducing
chargeson the spacer surface.However,thisisnow thoughttobe relatedtothe discretenessof the
charge producingstrongelectrostaticforces.
Whena suspensionconstantlywetsthe surface of acontainer,a thicklayerof disperse phase may
buildup.The wettingof the innercontainersurface canbe classifiedaseitherimmersional,
spreadingoradhesive wetting.Immersional wettingoccurswhenthe suspensionisinconstant
contact withthe surface,spreadingwettingoccurswhenthe suspensioncomesintocontactwiththe
surface i.e.throughpouring,andadhesive wettingoccurswhenadrop may become suspended
away fromthe suspension(i.e.atthe topof a bottle).
Adsorptiontoa containersurface will dependonthe concentrationof the suspensionandthe
presence of surfactants,whichdecrease surface tensionandmodifyforcesof interactionbetween
the particle andthe container.
Powder processing
Drugs are rarely,if ever,usedastheir pure powderformandwill require processingtoconvertthem
fromcrystalsintocoated,uniformspheres.The below flow diagramoutlinesthe process:
Cell-cell interactions and bacterial adsorption
Cellsinthe bloodcanbe consideredtobe spheres,butwhenconsideringthe adhesionbetweencells
it isbestto describe themfromaplanar perspective.Adhesionoccursnaturallyinphagocytosis,
parasitism,conceptionandotherprocessesandissurface phenomenadependentonbridging
mechanisms,electrostaticinteractionsandlong-distanceinteractions.A moleculemaybridge
betweentwocellsif itisatleastas longas twice the range of the electrostaticforcesof repulsion,
and mayevenbridge betweentwositesonthe same cell if itisflexibleenough.Polyvalentionsmay
alsoact as a mediatorbetweentwocells,andinbothcasesitcouldbe Brownianmotionthat
providesthe energyrequiredforcellstoneareachother.Electrostaticforcesare applicable when
surfacesare oppositelychargedorat leasthave a charge mosaicthat is complementarytoallow
interactionsbetweenspecificpartsof the surface.
THEPOWDER MIX THEPLASTIC MIX WETSPHERE COATED SPHERE
7. George Wild Science of Medicines
7
Emulsion stability
The adsorptionof surfactantsto the surface of dropletsinanemulsionwill reduce the interfacial
tensionbetweenthe twophasesthatwouldotherwisecause coalescence of the droplets,asthey
seektominimise the surface areasharedbetweenthe phases.Ionicsurfactantsincreasethe
magnitude of the zetapotential because theyincreasethe concentrationof ionicmaterial available
to interactinthe diffuse layer,andsowill increase VR andleadtogreaterstability.Non-ionic
surfactantswill reduce the zetapotentialbutare lesstoxicandcan stabilise the dropletsby
providingamacromolecularlayeraroundthe dropletthatrepelsotherdroplets.
Some commonnon-ionicsurfactantsinclude;polyoxyethylene esters,sorbitanpolyoxyethylene
derivativesandpolyoxyethylene-polyoxypropylene-polyoxyethylene(ABA)copolymers. Ino/w
dispersions,the hydrophobictailswill protrudeintothe oily(dispersed) phase,whilsthydrophilic
headssitin the continuous(aqueous) phase.
Emulsionsare more complex thansuspensionsbecause theyare surfactantsare able tomove in
bothphasesof the system,micellesmayforminbothphasesand liquidcrystallinephasesmayalso
formbetweendisperseddroplets.These systemsmaybe stabilisedbycombiningsurfactantsin
varyingproportionstoachieve a complex filmatthe adsorptionsite.
HLB system and stability
The HLB systemusesinformationaboutsurfactants’hydrophilicandlipophilicconstituentsto
provide ahydrophile-lipophile balance numberthatcanbe usedto gauge it’ssuitabilityinvarious
continuousphases. Surfactantsinthiscontextare called“emulsifiers”or“emulsifyingagents”.
The HLB value will be ona scale from0 to 20, withmore hydrophilic
surfactantshavinghighervaluesthanhydrophobicsurfactants.
SurfactantswithhigherHLB valueswill be usedasdetergents,
solubilisingagentsando/w emulsifiers,whilstlowervalue surfactants
have more affinityforthe oilyphase andwill be usedto stabilisew/o
emulsions.Inthese cases,itisimportantthatthe surfactantstill has
some hydrophilicitysothatthere will be anenthalpicbenefitof
stabilisingthe droplet.
HLB valuesare formedof additive componentsthatare hydrophilicorhydrophobicandso different
groups’contributionhasbeenstudiedanddocumented.These “groupnumbers”canbe usedto find
a value forthe HLB of a surfactantwhenthe structure issimple and/orknownsuingthe equation:
𝐻𝐿𝐵 = Σ(ℎ𝑦𝑑𝑟𝑜𝑝ℎ𝑖𝑙𝑖𝑐 𝑔𝑟𝑜𝑢𝑝 𝑛𝑢𝑚𝑏𝑒𝑟𝑠) − Σ(𝑙𝑖𝑝𝑜𝑝ℎ𝑖𝑙𝑖𝑐 𝑔𝑟𝑜𝑢𝑝 𝑛𝑢𝑚𝑏𝑒𝑟𝑠) + 7
The choice of an emulsifierwill be partlydependentonHLB but mixturesof differentsurfactants
shouldbe made to findoutwhichgivesthe bestcombination. Itisoftenthe case that surfactants
withhighand lowHLBs will give agoodcombination,because of the solubilityof the componentsin
bothphases.Thisallowsastronger/more stable filmtoformat the interface.Whenthese mixtures
are usedinformulation,the HLBof the mixture canbe foundusingthe equationbelow:
0
3
6
9
12
15
18
HYDROPHILIC
WATER DISPERSABLE
HYDROPHOBIC
8. George Wild Science of Medicines
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𝐻𝐿𝐵 𝑀𝐼𝑋 = 𝑓𝐻𝐿𝐵 𝐴 + (1 − 𝑓)𝐻𝐿𝐵 𝐵
The extentof creamingisuse to testHLB values,withminimumcreamingbeingattributedto
optimal values. Thiscanalsobe done usinglaser-diffractiontomeasure globule size,becauseitis
knownthat smallerdropletsare more stable.Inmanycases,the optimal HLB value isnotused
because stabilitycanbe achievedthroughcombiningsurfactantsthatforma viscousnetworkwithin
the mediumthatpreventscollisionsthatcause coalescence andthe effectsof interfacialtensions
betweendroplets.
The drawbacksof the HLB systemare that it doesnotconsiderthe effectof temperatureonthe
system,of the effectof additive components.The presenceof agentsthatcause salting-inorsalting-
out of the surfactant moleculeswillobviouslyreduce the effectiveHLBvalue of the mixture and
effectdispersionproperties.
Multiple emulsions and non-aqueous emulsions
Emulsionsmayconsistof more than two standardphases andcommon examplesof these are o/w/o
and w/o/wemulsions.Inaw/o/wemulsion,adrugwill be dissolvedinanaqueousphase whichsits
inside anoilyphase,whichexistsasdropletsinanotheraqueousphase.Thistype of emulsioncan be
useful because w/oemulsionsthatare administeredintramuscularlyorsubcutaneouslywillhave a
highviscosityandwill be uncomfortable andslightlydangerous.Bysuspendingthe oil dropletsina
secondaryaqueousmedium,the viscosityisreducedwhilststill maintainingthe delayedonsetof the
formulation.
These emulsionshave propertiesthatare differenttostandardw/oemulsionsandalsohave four
distinctpathwaysof degradationnotassociatedwithw/oemulsions:
Coalescence of the waterdropletsinthe oilyphase,
Coalescence of the oil dropletsinthe mainaqueousmedium,
Destructionof the interfacial filmbetweenoil andwater,
Osmoticflux betweenwaterinthe oilyandcontinuousphases.
Non-aqueousemulsionsare uncommonbutare a potentiallygoodformulation fordrugreservoirsor
for the deliveryof hydrolyticallyunstable drugs.Castoroil/PEGinsilicone oil canbe usedasa non-
aqueousemulsion,butHLBvaluesare lessdirectlyapplicable inthiscase,wherethe keyissolubility
of the emulsifierinthe continuousphase.
Microemulsions and cosurfactants
Microemulsionsare essentiallyswollenmicellarsystemsof twophaseswithahighconcentrationof
emulsifier(typically15– 25%),that will spontaneouslyformwhencomponentsare mixedinthe
appropriate proportions.Thesesystemshave alarge interface betweenthe continuousand
dispersedphase butare thermodynamicallystablebecause of the presence of large quantitiesof
emulsifier.Thisisonlypossible if the positiveinterfacial tension(γA) iscompensatedforbythe
negative change infree energyof mixing(ΔGm).
Most systemsrequiringemulsificationwillrequire amixture of twosurfactantstoachieve asuitable
interfacial tension(γ);the large exceptiontothisisobviouslydoublealkyl-chainsurfactantsand
9. George Wild Science of Medicines
9
some non-ionicsurfactants.The use of asecondaryamphiphile will helptoreduce the interfacial
tensionaslongas it doesn’tinteractwiththe original surfactanttoreduce itsconcentrationor
surface adsorption.
Combiningsurfactants/amphiphilesinthe rightwaywill cause anadditive reductioninthe
interfacial tensionwhichmaymeanthatthe primarysurfactantmay be presentin
concentrationslowerthanthe typical CMC(critical micelleconcentration) forthat molecule.
Thisis a useful propertyof cosurfactancythatcan be usedto achieve alowerinterfacial
tensioninmicroemulsions.
The critical packingparameterisrepresentedas;v/al,where the volume of asurfactantmolecule (v)
isrelatedtothe headgrouparea (a) and length(l),suchthata value can be usedto describe the
tendencyforo/wor w/omicrosystems.Valuesbetween0and1 indicate the o/w microemulsions,
values>1 indicate w/omicroemulsions.Whenthe valuesfortwocosurfactantsare similar,a
bicontinuousstructure where oil andwaterare separatedbya connectedinterfacial layerisa
suitable model.However,small amountsof waterinan oil system(orvice versa) are best
representedbydropletmodel,inwhichadropletissurroundedby acombinationof both
surfactants.
Semi-solid emulsions and biopharmaceutical aspects
Many topicallyappliedemulsionswill notcontainadrug/dispersedphase presentinthe dilute
quantitiesdealtwithinoral/IM/subcutpreparations.The excessof surfactantleadstothe formation
of structuresinthe bulkthat increase stability,asopposedtojustthe interfacialfilmsstabilisingthe
droplets.Stable o/wapplicationswillhave atleastfourphases;aliquidcrystalline phase,adispersed
phase,a bulkaqueousphase anda hydrated(gel) crystalline phase.
Liquidcrystallinephasesincrease emulsionstabilitythroughagreaterdegree of separationbetween
droplets,asto minimisethe effectof vanderWaals andelectrostaticforcesof attractionand
repulsion(respectively). The stabilitywillalsobe dependentonthe interactionsbetween surfactant
and fattyalcohol componentsof the emulsifier,asthe “self-bodies”thattheyformwill contributeto
the nature of the crystalline gel phase andbyextension,the overall stabilityof the preparation.
Intravenousnutritionisamodernapplicationof emulsionsthathasarisenbecause of the increased
absorptionof some drugslike griseofulvinfollowingoral administration.Medium-chaintriglycerides
as well asmono- anddiglyceridescanalsopromote absorption.
The increase inabsorptioncan be associatedpartlywiththe wayinwhichlipidsandother
fattymediaare absorbedinthe gut,throughlymphoidtissue;because lipidsare emulsified
inthe gutby our ownbodybefore beingabsorbed,presentingdrugsinalreadyemulsified
carriersaidsthe invivoprocessingof the formulation.
The release of drugfrom emulsionsisrelatedtothe partitioncoefficient,the volumeheldin
the dispersedphase andthe concentrationof surfactantusedtoemulsifythe preparation.