Download Pharmaceutical Technology

Pharmaceutical Technology I
Lecture 1
College of Pharmacy
3rd class
2016
Radhwan Al-Zidan (B.Sc. Pharm, M.Sc. Med. B. Tech.)
Pharmaceutical Technology
Pharmaceutical technology is a collective term for
technologies to develop candidate compounds that have
either been discovered or created into commercial
pharmaceutical products.
Formulation Technology involves the rational
design and manufacture of dosage forms to
ensure that the required biological and physical
performances of the therapeutic agent are
attained.
Liquids Dosage Forms /
Solutions
Pharmaceutical solutions are defined as liquid preparations in which
the therapeutic agent and the various excipients are dissolved in the
chosen solvent system.
Table 1: Traditional Terms for Different Pharmaceutical Solutions
Advantages of Solutions
Disadvantages of Solutions
• The drug is already dissolved in
the solvent system, hence drug
action is rapid.
• Solutions provide dose
uniformity, and specific volumes
of the liquid solutions that can
be measured accurately; this
allows a range of different doses
to be easily administered
• Oral solutions are easily
swallowed and are beneficial for
patients for whom swallowing
may be difficult, e.g. children
and older people.
• Solutions are easier to
manufacture compared to other
dosage forms.
• Some drugs are inherently
unstable, and instability is
increased when a drug is
present in solution.
• Some drugs are poorly soluble
in water.
• Liquids are bulky and less easy
for the patient to carry
compared to solid dosage
forms. Liquids are also more
expensive to transport, which
increases the medicine’s cost.
• Pharmaceutical solutions may contain a range of
excipients, each with a defined pharmaceutical
purpose. Examples of these include:
■ the vehicle
■ co-solvents
■ surface-active agents
■ buffers
■ preservatives
■ sweeteners
■ viscosity modifiers
■ antioxidants
■ colours
■ flavours
Solubility: The solubility of a solute in a particular solvent indicates the maximum concentration to which a solution
may be prepared with that solute and that solvent. The maximum possible concentration prepare a solution
varies greatly and depends in part on the chemical constitution of the solute.
Enhancement of Drug Solubility
1- pH Adjustment – most existing drugs are either weak acids or weak bases. In solution, an equilibrium
exists between the undissociated drug molecules and their ions. The equilibrium may be represented as:
Weak acid: H-A ↔ H + + A − ….. [Eq. 1]
Weak base: B-OH ↔ B+ +OH −.... [Eq. 2]
where [H+] and [A–] are the concentrations of the ionized form of the acid, while [HA] is the concentration
of the unionized form. And [B+] and [OH–] are the concentrations of the ionized form of the base, while
[BOH] is the concentration of the unionized form.
Since ions are more soluble in water than neutral molecules, changing the pH of the medium to increase
ionization of the drug is a common technique for increasing drug solubility in an aqueous medium. Weakly
acidic drugs are ionized when the pH of the solvent is increased. Conversely, lowering pH favours ionization
of weakly basic drugs. The pH required to achieve drug ionization can be calculated using the Henderson –
Hasselbalch equations:
-Weak Acidic Drugs / pH = pKa + log ([A–]/[HA]) …..[Eq. 3]
Where pH = pHp, the pH below which the free acid will precipitate out of solution..
-Weak Basic Drugs /pH = pKa – log ([B+]/[BOH]) ….. [Eq. 4]
Where pH = pHp, the pH above which the free base will come out of solution as a precipitate.
The pH of a pharmaceutical solution is a compromise between drug solubility, stability, bioavailability, the
function of excipients and physiological acceptability of the product.
2 - Co – Solvents: are often used to increase the water solubility of drugs which do not contain
ionizable group(s) and whose solubility can not be increased by pH adjustment, i.e. ‘like
dissolves like’. Thus, non-polar drugs are poorly soluble in water – a polar solvent. To increase
the solubility of such drugs in water, the latter’s polarity should be lowered. This can be achieved
by adding a third component such as a water-miscible organic liquid with a low polarity. Such a
liquid, when used in this context, is called a co-solvent. Typically, a linear increase in co-solvent
fraction results in logarithmic increases in drug solubility.
3 - Surfactants and Micelles - surfactants (surface active agents) and amphiphiles are molecules
which have two distinct regions in their chemical structure. One region is hydrophilic and the
other hydrophobic. Because of this, such molecules tend to accumulate at the boundary between
two phases, such as water-air or water-oil interfaces. They reduce the surface tension of liquids,
and self-assemble to form micelles once the critical micellar concentration (CMC) is reached.
Poorly water soluble drugs can be solubilized in micelles to enhance their aqueous solubility. The
location of the solubilisate (the drug which is solubilized within the micelles) depends on its
nature. Non-polar solubilisates being located within the micelles’ hydrophobic interior cores,
wheras solubilisates containing polar groups are oriented with the polar group at the micellar
surface.The maximum amount of solubilisate which can be incorporated into a given system at a
fixed concentration is known as the maximum additive concentration (MAC).
Complexation with Cyclodextrins:
The cyclodextrins (CDs) are cyclic oligosaccharides consisting of 7, 6, or 8 (respectively)
glucopyranose units. A hollow truncated cone cavity has different diameters dependent on the number
of glucose units in the ring; α – CD has a cavity diameter of about 0.55 nm, β – CD about 0.70 nm and
γ – CD about 0.90 nm. Many metabolically important compounds, such as lipid-soluble vitamins and
hormones, have very low solubilities in aqueous solutions. A frequently used approach is to use
cyclodextrin as a “carrier” molecule to facilitate the dissolution of these compounds.
Figure 1: Structural representations of β-cyclodextrin, α-cyclodextrin, and γ-cyclodextrin.
The hydrophilic exterior results in CDs being soluble in water. Concurrently, the less polar interior can
accommodate non-polar drug molecules via non-covalent interactions, thereby allowing the non-polar
drug to be ‘hidden’, thus enabling it to be molecularly dispersed in water. Thus, drug inclusion within
CDs effectively increases their aqueous solubility. Each cyclodextrin molecule can form complexes
with one or more drug molecules. Upon administration, for example orally, of a solution containing a
drug – CD complex, the drug will be released from the CD molecule and the free drug can then be
absorbed through the gastrointestinal tract.
Solubility Expression: Table 2: Approximate Relative Terms of Solubility
Descriptive Term
Parts of Solvent Required for 1 Part of Solute
Very soluble
<1
Freely soluble
1 – 10
Soluble
10 – 30
Sparingly soluble
30 – 100
Slightly soluble
100 – 1000
Very slightly soluble
1000.– 10000
Practically insoluble or insoluble
>10000
Pharmaceutical Solutions: Solutions are one of the oldest pharmaceutical formulations. They are administered by
many different routes. Therefore, they are often classified by the intended route (e.g.
oral, otic , parenteral).
Table 3: Requirements of Pharmaceutical Solutions, with Respect to their Route of
Administration