Test 2: Solutions Flashcards

(38 cards)

1
Q

Contamination

A

Microbes grow in all conditions – most typically 37 degrees C, pH 7
Yeasts and molds in sugar and glucose solutions

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2
Q

Prevention

A

Hygienic laboratory
Frequent disinfection
Minimize Traffic
Refridgeration
Laminar flow hoods
USP microbe free water for preps (presterilized?)

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3
Q

Initial removal of air from chamber

A

Pulsed Vacuum
Dynamic Vacuum

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4
Q

Heating Sterilization

A

A condensate trap at bottom of chamber
Dynamic steam

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5
Q

Post-sterilization phases

A

Vacuum and time-controlled vacuum maintenance
Cooling by circulating cold water in the jacket
Cooling by spraying water on the load
Ampule tightness with fast vacuum
Spontaneous cooling
Ampule tightness test with dye solution penetration.

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6
Q

Chemical Cold Sterilization

A
  • Ethylene Oxide
  • Hydrogen Peroxide
  • Hydrogen Peroxide plus steam
  • Formaldehyde
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7
Q

Partition Coefficient (K)

A

Describes how drug will partition between a
non-polar organic phase and a polar water
phase.

 K= [HA]o / [HA]
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8
Q

Partition Coefficients and Drug Solubility

A

– Used to indicate relative lipophilicity of drug
molecules.
– Affects drug solubility, permeability,
bioavailability, and drug binding.
– Most models describe partition coefficient
using octanol - water system.

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9
Q

Partitioning and Extraction of Drugs

A

Partitioning is the ability of a compound to distribute in two immiscible
systems.
It is of paramount importance, as many pharmaceutical processes such
as absorption from the gastrointestinal tract after oral administration,
diffusion across skin and other epithelia, distribution following entry into
systemic circulation, extraction and isolation of pure drugs after synthetic
manufacturing or from crude plant sources, formulation of a stable dosage
form (emulsion, suspensions, etc) and assay of plasma concentrations are
all based on partitioning phenomenon.
All drugs traverse one or more biological membranes from the time they
are administered until they are eliminated.
Biological membranes are made of protein and lipid materials, but they act
primarily as lipid barriers.
Passive diffusion is the predominant mechanism by which many drugs are
transported, and thus the lipophilic nature of the molecules is important

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10
Q

Transport/Permeation of Drugs

A

Transport of drug molecules from dosage form to target sites often involves several partitioning
processes. For example, in oral dosage form, followed by dissolution in gastrointestinal (GI) tract, the
drug has to partition between GI fluid and the inner GI membrane, followed by a second partitioning
between the outer GI membrane and systemic circulation before it will reach the target organ. Similarly,
the drug has to partition between its vehicle and skin before the efficacy of a drug molecule can be
achieved following topical application on skin

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11
Q

Formulation of drugs

A

Partitioning may be a factor in the stability of finished dosage forms where both oil and water phases
exist, for example, in emulsion systems. Antimicrobial preservatives must be present in the aqueous
phase of an emulsion to prevent spoilage. If the preservative chosen partitions into the oil, then additional
preservatives may be needed to maintain an adequate water phase concentration. (This problem
becomes more complicated if the preservative is a weak acid, HA, whose partitioning is pH dependent.)

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12
Q

Industrial processes

A

Many manufacturing processes involve extracting desirable (or undesirable) substances from a liquid
phase with another immiscible liquid. Such processes depend upon partitioning and permit one to obtain
purer drugs and chemicals.

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13
Q

Analytical procedures

A

Often these procedures involve an extraction or partitioning step to obtain the desired substance in a
system where it can be analyzed. HPLC (high performance liquid chromatography) is the most widely
used procedure for assaying drug concentrations in biological fluids and is fundamentally dependent
upon a partitioning step.

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14
Q

Partitioning as a function of pH

A

Most pharmaceuticals are either weakly acidic or weakly basic.
Weak electrolytes exist in un-ionized forms in octanol or lipid
phase
In aqueous phase, both unionized and ionized forms exist in
equilibrium
Therefore partition co-efficient K can be calculated as described
below:

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15
Q

The characteristics of colligative properties are:

A
  1. Colligative properties are related and a change in any one of them will
    be reflected in the corresponding changes in the others.
  2. A given colligative property of equimolar solutions of electrolytes and
    nonelectrolytes will not be identical
  3. Colligative properties of different solutes in a solution are additive
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16
Q

Boiling Point Elevation:

A

Normal boiling point is defined as the temperature at which
the vapor pressure of the liquid becomes equal to the
external atmospheric pressure (760 mm Hg). The boiling
point of a solution containing a nonvolatile solute would be
higher than the pure solvent because the solute would lower
the vapor pressure of the solvent. The increase in boiling
point can be written as T – T0 = Tb. The ratio of the
elevation of boiling point, Tb, to the lowering of vapor
pressure, p, is approximately a constant at 100°C.

17
Q

Freezing Point Depression

A

The normal freezing point of a compound is defined as the temperature at
which the solid and liquid phases coexist under an external pressure of 1
atm.
In general, solutions have a lower freezing point than the pure solvent
If a solute is dissolved in a liquid, the vapor pressure of the liquid solvent is
lowered below the solid solvent.
Then the temperature will drop to re-establish equilibrium between the liquid
and solute.
Thus the freezing point of the solution is always lower than that of the pure
solvent.
The depression of the freezing point of a solution with respect to the pure
solvent is analogous to boiling point elevation
Both pure solid and pure liquid phases of the solvent can coexist with their
vapor, and therefore, both phases have a non-zero vapor pressure.
In solution, solvent co-exists with its vapor, so, at the freezing point of a
solution, the solvent in the solution and the solvent in the solid (which
is composed only of solvent) must co-exist.

18
Q

Osmotic Pressure:

A

Water Concentration: Concentration of water in a solution
depends upon the number of solute particles in the solution, not
on their chemical composition
Osmotic pressure: Is defined as the pressure required to offset
the movement of solvent through a semi-permeable membrane
from a dilute aqueous solution to a more concentrated one.
Van’t Hoff Equation: V = nRT
 = Osmotic pressure in atmospheres
V is volume of solution in litres
n is the number of moles in solute
R is the universal gas constant equal to 0.082 1 atm mole-1K-1,

19
Q

Vapor Pressures of Solutions

A

– Vapor pressure of the system is influenced by
the mole fraction of components.
– Systems can be classified as ideal or nonideal.

20
Q

Vapor Pressure Lowering

A

– Addition of a solute lowers the vapor pressure
of the solvent.
– Can be calculates using the molal
concentration of the solute.

21
Q

Boiling Point Elevation

A

Addition of a solute to a solvent results
in a solution of higher boiling point that
the pure solvent.
–To calculate this, you need molal
concentration of the solute and the
ebullioscopic constant, Kb.

22
Q

Freezing Point Depression

A

Addition of a solute to a solvent results in a
solution of lower freezing point that the pure
solvent.
– To calculate this, you need molal
concentration of the solute and the cryoscopic
constant, Kf.

23
Q

Osmotic Pressure ()

A

Free energy of solvent in solution is less that
free energy of solvent in its pure form
– Solvent moves from high free energy state of
pure solvent to lower free energy state of
solution.

24
Q

Colligative Properties of Electrolytes

A

Can be obtained by modifying equations with
the van’t Hoff factor (i).
– Factor represent the number of ions
generated per molecule.

25
shots
SQ: 24-27 G. 2. IM: 21-23 G. 3. IV: Variable (needle or cannulation)
26
Advantages and Limitations of Parenteral Administration
Advantages: Alternative to patients that cant take oral dosage forms Some drugs are therapeutically inactive when taken orally Some drugs cause irritation in the gut, are unpalatable or nauseating Faster onset of action – generally more effective than oral Can be used to produce a local effect Depots of drugs in long acting delivery systems given by injection offer prolonged therapy Limitations: Method is inconvenient Pain or discomfort can be associated with direct injection Once injected, a parenteral product cannot be removed – overdosing/adverse effects? Parenteral products are more difficult and costly than other dosage forms – regulations for sterility, pyrogenicity, and particulate matter.
27
Pyrogen free
– Free from fever-causing organic compounds from bacteria or microorganisms. • Most common: lipopolysaccharides (LPS) or endotoxins
28
Special Requirements
• Isotonicity – Osmotic pressure equal to blood • Examples: 0.9% sodium chloride (normal saline) and 5% dextrose • Free of Particulate Matter – Lint, fibers, glass, rubber, chemical crystals can be introduced during manufacturing. • Stability – Should be physically and chemically stable during duration of shelf life.
29
Solvents and Vehicles
– Isotonic vehicles • 0.9% Sodium Chloride Injection, USP • Bacteriostatic 0.9% Sodium Chloride Injection, USP • 5% Dextrose Injection, USP • Lactated Ringer’s Injection, USP – Hydroalcoholic vehicles • Non-aqueous solvents such as PEGs, propylene glycol, glycerin, and ethanol
30
Excipients
• Preservatives – Inhibit microorganism growth – Benzyl alcohol (1-2%) or parabens • Antioxidants – Inhibit drug oxidation – Sulfites, bisulfites, metabisulfites • Solubilizers – Co-solvents such as low mw alcohols – Cyclodextrins
31
Excipients 2
Containers • Vials • Ampoules • Cartridges • Prefilled syringes • Glass vials – 4 different classes of USP glass Enclosure Systems • Stoppers • Plungers • Rubber disks • Made of: – Natural rubber – Neoprene – Butyl rubber
32
Methods of Sterilization
Moist heat sterilization Saturated steam autoclaves Superheated water autoclaves Air over steam autoclaves Dry heat sterilization Batch sterilizers Continuous tunnel sterilizers Chemical cold sterilization Ethylene oxide Vaporized hydrogen peroxide Hydrogen peroxide/steam Other gases Radiation sterilization Electromagnetic Particulate Filtration Membrane
33
Definitions
1. Sterilization- complete destruction or elimination of microbial life. 2. Aseptic - a controlled process in which microbial contamination is reduced to the degree that microorganisms are excluded during processing. It describes an “apparently” sterile state. 3. Pyrogens - metabolic products of living microorganisms, or the dead microorganisms themselves, which cause a specific pyretic (fever) response upon injection.
34
Freedom from Pyrogens
•It wasn’t recognized until 1923 that the frequent fevers experienced by patients receiving injections were bacterial in origin. •The pyrogenic reaction in humans consists of fever and chills. •45 to 90 minutes after an injection there is a rapid rise in body temperature, followed by chills, headache, and general malaise. •A pyrogenic reaction indicates a manufacturing problem or shoddy technique on the part of a pharmacist preparing the product for administration to a patient. •If pyrogens do contaminate a product they are typically either from the water used as the solvent, containers with which the solution has come into contact, or the chemicals used in the preparation of the solution.
35
1. Ionizing Radiation
a) Emitted from radioisotopes or produced by electron accelerators. b) Destroy organisms by ionizing biological compounds – enzymes, DNA, proteins, etc. c) Can be a continuous process with material passing through a tunnel containing radiation source. d) May cause deterioration of drugs.
36
2. Filtration (also, know as cold sterilization)
a) Typical filter pore size is 0.22 microns since bacteria and their spores or not smaller than 0.5 microns. When delivering parenterals, inline filtration with a 0.45 μm filter can reduce phlebitis by 70%. b) Must test integrity of filter to be sure that is intact. c) Must remove microorganisms without removing drug or other desired components and introduce no undesirable components into the formulation. d) Does not remove viruses. e) Applicable only to solutions and low viscosity nonaqueous liquids – not applicable to sterile suspensions or sterile emulsions.
37
38
The characteristics of colligative properties are:
1. Colligative properties are related and a change in any one of them will be reflected in the corresponding changes in the others. 2. A given colligative property of equimolar solutions of electrolytes and nonelectrolytes will not be identical 3. Colligative properties of different solutes in a solution are additive