Polymorphism Terms in Physical Pharmacy | Pharmaceutics Series | 102c


Hey! and welcome to Dahmash Tips! I decided to make my intro showing this wonderful background of the River Wear in
Sunderland, as I came back two days ago from Amman Jordan! Anyway, so this part
c video in physical pharmacy would continue to define some basic terms
that relate to the topics of the drug solubility and the drug dissolution, among
the other important topics in the physical pharmacy. Now, I will leave you
to focus on the content of this video not on me not on this wonderful River
behind me and that’s being said let’s get started! thank you.. welcome to the
part c video in the physical pharmacy this video will continue to define the
important terms in the physical pharmacy the upcoming videos in the physical
pharmacy will focus on simplifying the linkage of these tips regarding the
effect of the polymorphic term on the drug saturated solubility, alright! So, the sub-topic of today for the drug
solubility and the drug dissolution will be in the polymorphism terms. A very
quick recap of the part b video, we talked about three main solubility terms, the first term was the saturated solubility, the second term was the intrinsic
solubility, and the third term was about the ideal solubility. And, I mentioned as
they are listed obviously here right and as I mentioned that the intrinsic
solubility can be affected if we change the pH of the gastrointestinal tract, or the
GRT for short. However, I didn’t explain yet how the solubility of an
ionizable drug can be differed with different pH values, because I will leave
this explanation to other videos or other video that have
more appropriate scope for that, right. So, hence, I mean the the scope in the
Biopharmaceutics tips videos will give me that room for
further explanation alright.. so, also we talked about how
the ideal solubility term is useful to calculate the temperature
dependence of solubility if you remember. that yeah and let’s say a nutshell the
intrinsic term relate to the ionization concept, and the ideal term
relate to the temperature concept okay just in in very general
statement let’s say you know all right when I talk about Polymorphism, I mean these topics here that are these ones, where are they, these topics,
these ones, yes yeah, I can do it up to here so, these topics about crystals and
amorphous forms all rights and the other considerations here, so these
topics okay can exhibits.. the polymorph let’s say can exhibit mono-tropic
or enan-tropic polymorphism yeah so sometimes we have the mono-tropic or the enan-tropic polymorphs, so what that means okay the former means that one
polymorph, which is the mono-tropic, means from the word mono, which means just one
polymorph only is stable and all other polymorphs of the same drug let’s say are
metastable, the latter term which is the enan-tropic term okay, enan-tropic means that there is more than one “stable” form that yeah, so, at
specific conditions the polymorph can transform reversibly let’s say between
more than one stable form that is enan-tropic polymorphs can reverse the forms between forms that are more than one of which.. that are more than one of which are stable yeah, oh yeah so, the examples yeah I mean yeah mono just remember mona is just one
stable form that you have and once you reach it you can’t reverse you know
the situation unless if you do something unless if you do something, it will be too difficult, because it will be very stable okay, so remember the word mono okay, and the enantropic is
not this is not necessarily I mean no this is not the way the case in the
enan-tropic okay, example of polymorphs are crystals, amorphous, co-crystals, hydrates, and anhydrous forms. As I’m highlighting them right now, so these amorphous forms, I mean the amorphous form this one okay is the non
crystalline one okay right and it’s the other co-crystals are crystals obviously,
hydrates and anhydrous forms are yeah we have them in different crystal shapes and
forms and we can have them in different crystal yeah like salt anhydrous or
yeah so we can have them in different forms as well, not just hydrous, we can
have it like salt hydrate as well or we can have a dihydrate or trihydrate, things like things it depends, not all medicines, or not all of the drug substances like that, I’ll come back to this in a second okay the amorphous form let me focus a little
bit about the amorphous form because this is a very important form, it’s very distinctive from the other forms, because it’s not
crystalline, it’s just not.. it can not.. it’s an amorphous, which is the
opposite of a crystalline form all right it is because it has no.. this
large distinction from the crystalline form is because it has a very..
it has no actually it has no long-range order, it has no order that has a long
range okay, which means it has no distinctive melting point, but what it
has it has actually something we called a glass transition instead okay, or TG for
shorts, that TG indicates an increase in the molecular mobility alright I’ll
explain what that means okay, where the material start to soften, so the
mobility, it cannot.. it’s just not ordered, so you don’t.. you can’t
have a sharp you know a breakage point where you can have a molten
material immediately, it actually just soften, because it has no melting
point, it’s just.. it has no order no long-range order, so it has no melting
point, and it’s just soften rather than molten okay, which means a transition
occurred, it gives you an indication that the heat, the absorbance of heat is
causing a transition okay, from the hard glassy state of yeah to a soft rubbery
state okay, so you soften the material but you don’t melt it you don’t melt it
because it’s it’s an amorphous not crystalline, but or
I don’t want to say but, hahaha I mean.. in real life, the polymers for instance are..
that’s why I included the polymer, one of the reasons I included the polymer science
term here is because polymer is behaving.. can usually have both amorphous yeah..
it usually have both the amorphous and crystalline forms in the
same polymer okay, the polymer is a very big you know “structure”. It can
be very big, so it “has” sometimes different domains, and some of these
domains can be very distinctive in their physical properties, like when we
say we have an amorphous domain and crystalline domain okay all right, so in
this case we called the polymer.. if I wanna say what is the physical state of this
polymer for instance we say it’s as a semi-crystalline state okay, it’s a semi
crystalline because it’s not fully crystalline, it’s not completely crystal
okay, it has something disorder in it and so there’s no.. it’s not all about the long
range order in the polymer usually okay, so that I mean and this
can be evident if you wanna prove that this specific polymer that you have, “has”
both domains of crystals and amorphous forms, then you can test that using the differential scanning calamity, or DSC for short, where you can get the DSC thermogram, to show us a distinctive melting point and a glass transition,
respective to the crystalline and amorphous domains in the polymer, here
both melting and TG are endothermic reactions as I say because they need to
absorb heat in order to give that.. or they need to absorb yeah.. they need
energy actually from that heat source to produce the peaks or changes okay hence, when we produce.. when we.. if we want to reverse these transitions we do some cooling to
solidify the soften or the molten, and probably the molten
because it will reach a point where the crystal also will melt, so it will
become molten as well the polymer. At specific conditions, this cooling
will cause maybe an amorphousization or crystallization of the polymer, and these
processes are considered as exothermic reactions that release heat alright, because it’s easier, it’s easier to have exothermic..
okay, it’s not when I say it’s easier, I mean the crystallization is
not easy to control okay, but I mean the nature of the process can occur
spontaneously okay that’s what I mean by easier but it’s
not easy to control okay crystallization is not an easy thing to control okay, but..
you can have that in a spontaneous way because it’s an
exothermic reaction right isn’t it?! when you think about cooling just think
about freezing as well which is also the opposite of boiling and
evaporation, so the freezing actually is an exothermic process when compared to the boiling and heating yeah, so I mean when compared with boiling and yeah evaporation So, in 1990 okay, I’m gonna talk a
little bit about the hydrous and anhydrous forms, I’m trying to you know
to define.. I finish the definitions of stability, and now I’m defining the
polymorphs terms, then I will jump to the next slide okay, I’m not gonna go into
that for now probably not everything will be covered
in the other videos as well, so I’m just trying to be specific to give you
some taste of what is important in some of these topics alright, so in 1990
it is the..which is the year that where based on the
Cambridge Structures Database in 1990, about 11% of all recorded
structures existed as hydrates okay nearly 16,000 compounds existed as
hydrates and 50% of which are monohydrates, so just 11%
of all structures are contributed to the 16,000 compounds which is a big
number so, 50% of which are mono-hydrates. so, the more that you do hydration to you crystal for instance, the more it will be..
the more difficult it will.. I mean the more difficult it
will become when you.. I mean it is more difficult let’s say when you do more
hydration to your crystal because maybe the percentage of the dihydrates I think
is around 20 percent and the trihydrates is even less, and so on, so that’s it okay. Although that the can be
very different sometimes they are called inelegantly
as pseudo-polymorphs, which is not as appropriate as I mean as it seems for
too many people okay because it’s not always suitable.. like I
mean these anhydrous and hydrous forms not always have that pseudo you know
character to it because it’s not always okay, so first I have to mention what
pseudo means for those who don’t know what it means it means a false or fake
okay so pseudo is false or fake so it’s like false polymorphs but it’s not
always the case so it’s not elegant to to use this term all right according
to many professionals, so the pseudo polymorph could be referred to a
thermodynamically metastable polymorph that have a supersaturated kinetic
solubility, but this is not an elegant terminology as I mentioned, because
metastability can be stable for enough period to be impactful okay so the
metastability here is gonna be the.. I will give a video.. I mean a full video for explaining the impact of
metastability or let’s say to explain what metastability
really means okay and the things that happening in a thermodynamic system in the upcoming video, However, this is not
always the case as it will I mean as I’ll explain with more details about
this interesting topic in polymorphism later okay, now, I think I’m repeating some you know some words I mentioned maybe I will talk about polymorphism couple of times alright okay I’ll talk
okay I’ll just define which where are they too many terms in this slide, but
you know solubility is a very important topic so I have to, so I’m talking a
little bit about this one okay so, anisotropy! Anisotropy is a term often used in the polymer science so the isotropic and anisotropic
behaviors are attributed to the amorphous and crystalline forms
respectively, so I mean so isotopic is amorphous and anisotropic
is crystal okay, because the amorphous form is isotropic because it has a
uniform yet not ordered structure and that uniformity will mean that the
amorphous form has properties that are not dependent on the structure direction,
while the crystal is anisotropic because it is packed in a
certain arrangements where its properties depend on the direction okay,
it is good to know that anisotropy is also relevant to the polarizability
of the chiral molecules as well so yeah this is more relevant to the analytical
chemistry so I’ll not go further in this I’m a bit sleepy here huh I got
some coffee but still.. this topic is very lengthy so I’m trying to catch up here
lots of important things I need to lots of basic like important things that are
basics considered as basics which is the terminologies here, so I have to make the
terms clear because it’s not gonna be easy if I’m gonna talk about these terms
and I haven’t defined them you know, so I I’m gonna use some of these or
yeah some of these terms later in different videos, so I got to make
sure that these terms are defined properly, so I know it’s a bit boring but
yeah we got to do the basics first right we basically “decrease” in annealing the
atomic dislocations in the crystal lattice and that occurs at specific
conditions, this annealing position is of interest for stabilizing protein
formulation okay, this is of interest when you try to formulate the protein
with an excipient for lyophilization, which is where the sublimation.. i’m not gonna
get into it for now maybe and definitely not in this series because this is a
very big topic and is not within the scope of this series okay alright! from the previous discussion about the polymorphic terms or the polymorphism terms, the viewer can be able to understand the differences
between these terms for now right! in this slide the pseudo-polymorphism will
be a topic of interest in the last videos of the physical pharmacy, however
before delving more into polymorphism and the complications of that, the next
video will talk a bit more about the saturated suitability just to make sure
that we addressed that term sufficiently because I didn’t talk much about it yet,
and then we can swiftly move forward to talk a bit more about the meta-stability
and the pseudo-polymorphism, and after which, we will be happy to finish this
set of videos in physical pharmacy or I’ll be happy at least alright.. so, the same references again or the same bibliography, I mean I’m using the same..
these five sources are the references that are.. the ones I’ve read the most, because these are where my head is getting around to understand the
physical pharmacy, the additional recommended reading is also very very
important so, I’ll leave that to.. I mean.. let’s.. okay first I want to say that these chapters as a reminder okay I’m moving the whole slide now okay, so these chapters as a reminder I relied on the most to tell
you about polymorphism, hence most of the contents in the upcoming videos as well
about polymorphism were taken from here and also these books in general
helped me to construct and get my head around the physical pharmacy videos okay
as I just said okay, for the recommended readings here I know these
books are very important right because, obviously they are very
specialized in physical pharmacy, but yeah so if I need, but I mean if I need
to deliver a full lecture yeah I mean about physical pharmacy this will be my
you know these will be my books of choice maybe and but definitely not
within the context of this channel because I’m trying you know to
be easygoing about the this subject because this subject can be can get so
harsh so quickly so I will leave these books maybe for another purpose maybe..
definitely not..probably not in this channel because these books are a bit
advanced so I’m trying to be generalist about the physical
pharmacy I’m choosing you know the very basic
concepts and some of their applications in pharmaceutics, but I’m not delving
too much into the calculations okay I’m not using lots of mathematical
relations here okay, so yeah okay alright thank you! Thank you for listening and I hope these physical pharmacy tips here in parts a, b, and c helped you to quickly and
easily get introduced to one of the most important topics the physical pharmacy I
mean the drug solubility and the drug dissolution, now as you feel more
motivated to understand the applicability of these terms
stay tuned for some of the practical depth in knowledge and some rational
criticality regarding the drug solubility and the drug dissolution.. regarding the drug solubility and the factor of polymorphism in the upcoming videos okay so and that
to be discussed within the basic thermodynamics and kinetics umbrellas let’s say, so and that’s being said, thank you all again and have a
good night or have a good day depending where you are this planet, and see you
later with another pharmaceutics tips video and Dahmash Tips! Bye!!

3 thoughts on “Polymorphism Terms in Physical Pharmacy | Pharmaceutics Series | 102c

  1. Hey!

    Are you enthusiastic to know about the polymorphism terms!? like the mono-tropic vs the enan-tropic, amorphous vs crystal, hydrous vs anhydrous, anisotropy and annealing!!

    If Yes! then it is the time to check this informative video!
    The next videos will be probably about the saturated solubility, energy during dissolution, metastability, crystals solubility, and super-saturated solubility!! Hence, the upcoming topics will be sequentially related!!

    So, let's understand, at least, one of the risks that may appear in your next dissolution run, and it’s effect on the “drug bioavailability”, by watching all of these videos in physical pharmacy!

    Then, I'll move forward to the next set of videos (103); Pharmaceuticals!!

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