PHA-044: Physical Pharmacy Lecture

Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

Lesson title: Solids and Polymorphism Materials:

Pen, SAS
Lesson Objectives:
At the end of the module, you should be able to: References:
1. Describe the properties of the various classes of solids and • Chemistry the Central
their structures. Science 12th ed (Brown et
2. Discuss the application of polymorphism in pharmaceutics. al., 2012)
• General, Organic, and
Biological Chemistry 6th ed
(Stoker, 2013)
• Martin’s Physical Pharmacy
and Pharmaceutical
Sciences 7th ed (Sinko,
2016)

Productivity Tip:
Do not give up! Try to work way towards developing good study habits and soon enough, you will see your
grades soar, your knowledge increase, and your ability to learn and absorb information improve.

A. LESSON PREVIEW/REVIEW

Introduction (2 mins)

A solid is the physical state characterized by a dominance of potential energy (cohesive forces) over
kinetic energy (disruptive forces). The particles in solid are drawn close together in a regular pattern by the strong
cohesive forces present. Each particle occupies a fixed position, about which it vibrates because of disruptive
kinetic energy. Solids can be classified based on their structure, composition, and bonds and forces involved.
These substances can also undergo polymorphism or take more than one form which results different physical
properties of solids. We can relate the types of solids and polymorphic forms that exist also in drugs that can
affect pharmaceutical formulations. The topic of this lesson is all about the different classification of solids and
types of polymorphism. As you progress in this study, you can connect the properties of the various classes of
solids to the structures involved within these substances. You will also learn the types of polymorphism that also
exist in drug substances.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

Activity 1: What I Know Chart, Part 1 (3 mins)

Instructions: “In this chart, reflect on what you know now. Do not worry if you are sure or not sure of your
answers. This activity simply serves to get you started on thinking about our topic. Answer only the first column,
“What I know”. Leave the third column “What I learned” blank at this time.

What I Know Questions: What I Learned (Activity 4)

1. What are some common
properties of solids?

2. Why some solids are hard and

others are soft?

3. How come that the other solid

substances of the same kind have
other forms?

B. MAIN LESSON

Activity 2: Content Notes (30 mins)

Instructions: Please take note, highlight, or outline some important and striking information.

PROPERTIES OF SOLIDS

Solids have strong cohesive forces that hold particles in essentially fixed positions resulting in definite
volume and definite shape. The constituent particles of solids are located as close together as possible (touching
each other). Therefore, a given volume contains large number of particles, resulting in a high density. Solids
have very little space between particles, increased pressure cannot push the particles any closer together;
therefore, it has little effect on the solid’s volume. An increased temperature increases the kinetic energy
(disruptive forces), thereby causing more vibrational motion of the particles. Each particle occupies a slightly
large volume and the result is a slight expansion of the solid. The strong cohesive forces prevent this effect from
becoming very large.

CLASSIFICATION OF SOLIDS

Solids in which atoms are arranged in an orderly repeating pattern are called crystalline solids. These
solids usually have flat surfaces or faces, that make definite angles with one another. The orderly arrangement
of atoms that produce these faces also caused the solids to have highly regular shapes. Examples of crystalline
solids include sodium chloride, quartz, and diamond. Amorphous solids lack the form found in crystalline solids.
They are being considered as supercooled liquids because the molecules are arranged in a somewhat random
manner as in the liquid state. Amorphous solids do not have well-defined faces and shapes of a crystal hence
have no definite and sharp melting points. Familiar amorphous solids are rubber, glass, and obsidian (volcanic

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

glass). The atoms in crystalline solids repeat in an orderly, periodic fashion that leads to well-defined faces at
the macroscopic level which is lacking in amorphous solids (see Figure 1).

Figure 1. Examples of crystalline and amorphous solids.

STRUCTURES OF SOLIDS

In a crystalline solid there is a relatively small repeating unit, called a unit cell, that is made up of unique
arrangement of atoms and embodies the structure of the solid. The structure of the crystal can be built by stacking
this unit over and over in all three dimensions. Thus, the structure of crystalline solid is defined by (a) the size
and shape of unit cell and (b) locations of atoms within the unit cell. The geometrical pattern of points on which
the unit cells are arranged is called a crystal lattice. The crystal lattice is, in effect, an abstract (that is, not real)
scaffolding for the crystal structure. We can imagine forming the entire crystal structure by first building the
scaffolding and then filling in each unit cell with the same atom or group of atoms.

Figure 2 shows a two-dimensional array of lattice points. Each lattice point has an identical environment.
The positions of the lattice points are defined by lattice vectors a and b. Beginning from any lattice point it is
possible to move any other lattice point by adding together whole-number multiples of the two lattice vectors. A
vector is a quantity involving both a direction and a magnitude. The magnitudes of the vectors in Figure 2 are
indicated by their lengths and their directions are indicted by arrowheads. The parallelogram formed by the lattice
vectors, shaded region in Figure 2, defines the unit cell. In two dimensions the unit cells must tile, or fit together
in space, in such a way that they completely cover the area of the lattice with no gaps. In three dimensions the
unit cells must stack together to fill all space.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

Figure 2. A crystalline lattice in two dimensions.

In a two-dimensional lattice, the unit cells can take only one shape of the four shapes shown in Figure
3. The most general type of lattice is the oblique lattice. In this lattice, the lattice vectors are of different lengths
and the angle γ between them is of arbitrary size, which makes the unit cell an arbitrarily shaped parallelogram.
A square lattice results when the lattice vectors are equal in length and perpendicular to each other. If the two
vectors are perpendicular to each other but of different lengths, a rectangular lattice is formed. The fourth type
is two-dimensional lattice, where a and b are the same length and γ is 120°, is a hexagonal lattice. The lattices
in in Figure 3 represent tiling of four basic shapes: squares, rectangles, hexagons, and arbitrary parallelograms.
Other polygons such as pentagons, cannot cover space without leaving gaps as Figure 4 shows. Tiling means
covering a surface entirely, which is impossible for some geometric shapes, as shown in Figure 4.

Figure 3. The four two-dimensional lattices. Figure 4. Not all shapes tile space.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

To understand real crystal, we must move from two dimensions to three. In three dimensions, a lattice is
defined by three lattice vectors a, b, and c (see Figure 5). These lattice vectors define a unit cell that is
parallelepiped (a six-sided figure whose faces are all parallelograms) and is described by the lengths a, b, c of
the cell edges and the angles α, β, γ between these edges. These are seven possible shapes for a three-
dimensional unit cell, as shown in Figure 5 including example substances.

If we place a lattice point at each corner of a unit cell, we get a primitive lattice. All seven lattices in Figure
5 are primitive lattices. It is also possible to generate what are centered lattices by placing additional lattice points
in specific locations in the unit cell. This is illustrated for a cubic lattice in Figure 6. A body-centered cubic lattice
has one lattice point at the center of the unit cell in addition to the lattice points at the eight corners. A face-
centered cubic lattice has one lattice point at the center of each of the six faces of the unit cell in addition to the
lattice points at the eight corners. Centered lattices exist for other types of unit cells as well. Examples include
body-centered tetragonal and face-centered orthorhombic Counting all seven primitive lattices as well as the
various types of centered lattices, there are 14 three-dimensional lattices. For the crystals discussed in this
lesson we need only consider the lattices shown in Figure 5 and 6.

Figure 5. The seven three-dimensional primitive lattices and example substances.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

Figure 6. Three types of cubic lattices.

TYPES OF CRYSTALLINE SOLIDS

Crystalline solids may exist in one of four general groups or types (see Figure 7). Metallic solids are held
together by a delocalize “sea” of collectively shared valence electrons. This form of bonding allows metals to
conduct electricity. It is also responsible for the fact that most metals are relatively strong without being brittle.
Ionic solids are held together by the mutual attraction between cations and anions. Differences between ionic
and metallic bonding make the electrical and mechanical properties of ionic solids very different from those of
metals. Covalent-network solids are held together by an extended network of covalent bonds. This type of
bonding can result in materials that are extremely hard, like diamond, and it also responsible for the unique
properties of semiconductors. Molecular solids are held together by the intermolecular forces: dispersion forces,
dipole-dipole interactions, and hydrogen bonds. Because these forces are weak, molecular solids tend to be soft
and have low melting points. The form of unit particles, forces between particles, properties and examples of the
different types of crystalline solids are summarized in Table 1.

Figure 7. Classification of crystalline solids according to predominant bonding type.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

Table 1. Types of crystalline solids.

POLYMORPHISM AND ITS TYPES

Some substances may exist in more than one crystalline form and are said to be allotropic, which is a
special case of polymorphism. Polymorphism is defined as the ability of a solid material to exist in two or more
crystalline forms with different arrangements or conformations in the crystal lattice. Perhaps the most common
example of polymorphism is the contrast between a diamond and graphite, both of which are composed of
crystalline carbon. When polymorphism exists as a result of a difference in crystal packing, it is called packing
polymorphism. Polymorphism can result from the existence of different conformers of the same molecule in
conformational polymorphism. In pseudopolymorphism, the different crystal types are the result of hydration or
solvation (interaction between solvent and dissolved molecules). This is more correctly referred to as
solvomorphism, as different solvates or cocrystals (products of solvation) have different chemical formulae. An
example of organic polymorph is glycine, which is able to form monoclinic and hexagonal crystals. Silica is known
to form many polymorphs, the most important of which are α-quartz, β-quartz, tridymite, cristobalite, moganite,
coesite, and stishovite. A classical example is the pair of minerals, calcite and aragonite, both forms of calcium
carbonate.

Depending upon relative stability, there are two forms of polymorphs which are stable and metastable
form. Stable form having least aqueous solubility and metastable form having high aqueous solubility. True
polymorphs can be classified into two different types; enantiotropic and monotropic polymorphs. If one polymorph
can reversibly change into another one (e.g. from stable to a metastable form or vice versa) by varying the
temperature or pressure, it is said to be enantiotropic. If the change between the two forms is irreversible or
when the transition takes place in one direction only (e.g. from stable to a metastable form only), it refers to be
monotropic. Amorphous substances, as well as cubic crystals, are usually isotropic, that is, they exhibit similar
properties in all directions or they are direction independent. Crystals other than cubic are anisotropic, showing
different characteristics in various directions along the crystals. The properties or characteristics being referred
to are electric conductance, refractive index, crystal growth, and rate of solubility.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

TECHNIQUES OR METHODS IN CHECKING POLYMORPHIC PURITY OF DRUG SAMPLES

In pharmaceuticals, polymorphism is important in the development of pharmaceutical ingredients. Many

drugs receive regulatory approval for only a single crystal form or polymorph. Polymorphism in drugs can also
have direct medical implications. Medicine is often administered orally as crystalline solid and dissolution rates
depend on the exact crystal form of a polymorph. Polymorphic purity of drug samples can be check using
techniques such as x-ray diffraction method, differential thermal analysis (DTA), differential scanning calorimetry
(DSC), thermogravimetric analysis (TGA), optical crystallography, and hot stage microscopy.

Insulin preparations are used to control blood sugar in people who have Diabetes mellitus. Amorphous form of
insulin dissolves rapidly while crystalline insulin takes time to dissolve thus slowly absorbed in the body after
administration. Why is it so?

Answers:
➢ Crystalline solid is generally much more stable toward chemical degradation than amorphous solid.
The fixed geometrical arrangement of crystalline solid makes it more stable compared to amorphous
solid. For that reason, crystalline solid does not dissolve easily or slowly absorbed in the body.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

Activity 3: Skill-building Activities (with answer key) (18 mins + 2 mins checking)

A. Differentiate between crystalline solid and amorphous solid as follows. Check your answers against
the Keys to Corrections found at the last pages of this SAS. Write your score on your paper. Example
answers are already given below as your guide.

Property Crystalline Solid Amorphous solid

Order of
Arrangement

Shape

Melting point

General
Anisotropy
(Anisotropic
or
Isotropic?)
Diagram of
the
arrangement
of the
particles

Example

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

B. Discuss the importance of polymorphism applied from each following scenario / case below.
Example answer for scenario no. 1 is already given as your guide. Check your answers against the Keys
to Corrections found at the last pages of this SAS. Write your score on your paper.

Scenario / Case Importance of Polymorphism applied

Paracetamol powder has poor Prevents manufacturing problem in making Paracetamol tablets by
compression properties; this finding another polymorph which is more compressible.
poses difficulty in making tablets,
so a new polymorph of
paracetamol was found which is
more compressible.
One polymorph may be more
active therapeutically than
another polymorph of same drug.

Chloramphenicol palmitate exists

in three polymorphic forms and
each form has different solubility.

Activity 4: What I Know Chart, Part 2 (2 mins)

Instruction: To review what was learned from this session, please go back to Activity 1 and answer the “What
I Learned” column. Notice and reflect on any changes in your answers.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

Activity 5: Check for Understanding (15 mins)

Instruction: Now it’s time for you to figure one out on your own! Take time to read, analyze, and understand to
following scenarios. Answers will be discussed by the instructor after. Write your score on your paper.

A. Analogy. Complete the analogous pair by writing the word/s that has the same relationship. Example:
Cubic : Sodium chloride : : Tetragonal : Urea

1. Diamond : _____________________ : : Plastic : Amorphous

2. Covalent bond:____________________: : Ionic bond : : Ionic solid
3. Cubic : Sodium chloride : : ________ : Boric acid
4. Thermogravimetric Analysis: TGA: : ________________________: DSC
5. Fairly soft: Molecular solid : : _____________ Covalent-network solid
6. Aluminum oxide: Rhombohedral : : ________________: Monoclinic
7. Enantiotropic: ______________ : : Monotropic : Irreversible
8. Crystal lattice: Geometrical pattern : : ____________ Repeating unit
9. Three-dimensional : ______________ : : Two-dimensional : Oblique
10. Vibration: Solid : : __________: Gas
11. NaCl: Ionic solid: : ________: Molecular solid
12. Polymorphism: Crystalline solid: : ____________ : Amorphous solid
13. 3D Lattice : Parallelepiped: : 2D Lattice : ________________
14. Disruptive force: _______________: : Cohesive force: Potential energy
15. Isotropic : Amorphous : : Anisotropic : ______________________

C. LESSON WRAP-UP

Activity 6: Thinking about Learning (5 mins)

A. Work Tracker: You are done with this session! Let’s track your progress. Shade the session
number you just completed.

P1 P2
1 2 3 4 5 6 7 8 9 10

B. Think about your Learning. Tell me about your thoughts! Today’s topic is all about structures and
properties of solids and their different polymorphic forms. What surprised you about the lesson
today? Explain why.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

FAQs

1. Why is the arrangement of the constituent atoms or molecules more important in determining
the properties of a solid than a liquid or gas? Ans: The arrangement of the atoms or molecules is
more important in determining the properties of a solid because of the greater persistent long-range
order of solids. Gases and liquids cannot readily be described by the spatial arrangement of their
components because rapid molecular motion and rearrangement defines many of the properties of
liquids and gases.

2. Why most of the drugs exist in crystalline solid? Ans: Many drugs exist in the crystalline solid state
due to reason of stability and ease of handling during the various stages of drug development. Crystalline
solids can exist in the form of polymorphs, solvates or hydrates. It is desirable to choose the most suitable
and stable form of the drug in drug formulation.

3. Can amorphous solids show polymorphism? Ans: Yes! An analogous phenomenon material is called
poylamorphism, when a substance can take on several different amorphous modifications.

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

KEY TO CORRECTIONS

Activity # 3

A. Differentiate between crystalline solid and amorphous solid as follows. NOTE: Answers may vary.

Property Crystalline Solid Amorphous solid

Order of Long-range order Short-range order
Arrangement
Shape Definite shape Irregular shape

Melting point Sharp melting point Melting point is not sharp

General Anisotropic Isotropic

Anisotropy
(Anisotropic
or
Isotropic?)
Diagram of
the
arrangement
of the
particles

Example Diamond Plastic

This document is the property of PHINMA EDUCATION

 PHA-044: Physical Pharmacy Lecture
Student Activity Sheet #3

Name: ______________________________________________________ Class number: ______

Section: ____________ Schedule: _______________________________ Date: _____________

B. Discuss the importance of polymorphism applied from each following scenario / case below.
NOTE: Answers may vary.

Scenario / Case Importance of Polymorphism applied

Paracetamol powder has poor Prevents manufacturing problem in making Paracetamol tablets by
compression properties; this finding another polymorph which is more compressible.
poses difficulty in making tablets,
so a new polymorph of
paracetamol was found which is
more compressible.
One polymorph may be more In drug formulation, it is suitable to use another polymorph of a certain
active therapeutically than drug which is more effective.
another polymorph of same drug.

Chloramphenicol palmitate exists Solubility is one of the most critical formulation properties that have a
in three polymorphic forms and significant impact on performance of a molecule.
each form has different solubility.

Citations:
• https://chem.libretexts.org/

This document is the property of PHINMA EDUCATION