Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pceut 531 > Midterm #1 > Flashcards

Midterm #1 Flashcards

1
Q

Intro to Drugs:

Definition: Dosage Form

A

Is a pharmaceutical delivery system that incorporates an active drug ingredient(s) along with excipients to

  • ensure accurate dosing
  • protect drug integrity
  • prevent contamination
  • improve clinical effectiveness
  • afford a means of identification of strength of dose

Packaging is an integral part of the dosage form.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Intro to Drugs:

Definition: Pharmaceutics

A

Is the science discipline concerned with the formulation, manufacture, quality and effectiveness of pharmaceutical dosage forms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Intro to Drugs:

Drug Substance Sources

A
  • Chemical synthesis (most drugs)
  • Plants and herbs, e.g., morphine from opium poppy, Papaver somniferum, artemisinin agent against malaria from A**rtemisia annua, St. Johns wort (Hypericum perforatum) extract
  • Animals, e.g., insulin from pancreas of pigs
  • Fish, e.g., cod liver oil-omga-1-fatty acids, Vitamins A and D
  • Microorganisms, e.g., penicillin from *Penicillium *fungi
  • Biotechnology, e.g., insulin, growth hormone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Intro to Drugs:

Drug Substance Chemical Forms

A
  • Small organic molecules (MW < 800 Daltons)
  • Peptides, polypeptides, proteins, antibodies
  • MicroRNA molecules for RNA interference (e.g., siRNAs)
  • DNA vaccines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Intro to Drugs:

Drug Substance Physical Forms

A
  • Solids (most small molecule drugs)
  • Liquids e.g., cyclosporine
  • Gases, e.g., volatile anesthetics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Intro to Drugs:

Drug Formulation Requirements: Overview

A
  • Uniformly precise drug
  • Stability
  • Prevent microbial contamination
  • Ameliorate taste problem
  • Appearance and Identification
  • Enhance clinical effectiveness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Intro to Drugs:

Formulation Requirements: Stability

-How keep stable?

A
  • Avoid degredation of drug ingredient during stoarge and use by preventing exposure to moisture (blister pack, coated tablets) or oxygen (sealed ampules)
  • Additives to prevent protein aggregation with parenteral formulations of protein pharmacuticals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Intro to Drugs:

Formulation Requirements: Prevent Microbial Contamination

A
  • ​Preservatives to prevent microbial contamination of oral, liquid, topical and opthalmic formulations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Intro to Drugs:

Formulation Requirements: Ameliorate Taste Problems

A
  • Tablet coating or encapsulation to avoid drug contacting taste buds
  • Flavoring of liquid formulations to mask taste
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Intro to Drugs:

Formulation Requirements: Apperance and Identification

A
  • Size, shape, color and imprinting give oral medications unique look and feel that allows easy identification by patients, avoid mix up error
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Intro to Drugs:

Formulation Requirements: Enhance Clinical Effectiveness

A
  • Micronization or nanoparticles to enhance bioavailability of poorly soluble drugs
  • Enteric-coating (polymer barrier) to minimize drug degradation in gastric secretion or minimize gastric irritation, e.g., erthromycin
  • Slow release oral dosage forms or intramuscular injections to prolong drug action
  • Single-unit packaging for unit dose dispensing to minimize medication errors or bacterial and viral contamination; compliance packaging (oral contraceptive)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Intro to Drugs:

Pre-Formulation Studies

A
  • The physical and chemical characteristics of the active drug ingredient(s) must be fully characterized (pre-formulation studies) in order to design a clinically effective pharmaceutical formulation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Intro to Drugs:

Pre-Formulation Studies: Basic Physiochemical Characteristics

A
  • Solid phase characteristics: melting point, crystallinity (polymorphism)
    • Something can exist in multiple crystal forms
  • Solution chemistry: water solubility, dissolution rate, acid-base ionization (pKa), colligative properties
  • Lipid bilayer cell membrane permeability, partition coefficient (e.g., LogP value)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Intro to Drugs:

Routes of Administration: Table

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Intro to Drugs:

PCEUT 531 Roadmap

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Solutions & Solubility:

Pharmaceutical Significance: Activity

A
  • Solid Drug –> Dissolution –> Drug in Solution–>Permeation–>Drug in Blood
  • Release of active drug from the solid dosage form via disintegration and dissoluiton
  • Following release, drug molecules crosses the gastrointestinal mucosa vaia diffusion or mediated transport
  • Drug must dissolve before it can be absorbed. Only drug in solubilized form (molecularly dispersed) can effectibely penetrate across membrane barriers (e.g., gastrointestinal mucosa) and be absorbed into the systemic circulation.
  • Drug absorption from an oral solution is usually more rapid and complete than a solid dosage form (e.g., tablet)
  • Gut wall=1 layer of entrocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Solutions & Solubility:

Pharmaceutical Significance: Practicality

A
  • Preparation of pharmaceutical solution is generally much easier than that of other dosage forms such as tablets, capsules and emulsions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Solutions & Solubility:

Pharmaceutical Significance: Aids formulation

A
  • Note that not all drugs are easily soluble
  • In fact, many drugs have low solubility
  • General expressions of relative solubility of drugs defined in the USP
  • In g/mL
  • The knowledge of solution and solubility aids the preparation of pharmaceutical solutions.
    • Ex: how to increase drug solubilty and thus drug dissolution rate from a solid dosage form
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Solutions & Solubility

Pharmaceutical Significance: Vehicle and Drug Compatibilities

A
  • The knowledge of solution and solubility hleps predict vehicle and drug incompatibilities
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Solutions & Solubility

Definitions: Solutions

A
  • A solution is a homogenous mixture of two or more substances (molecular dispersion).
    • Ex: surcorse dissolved in waster
    • H2PO4 dissolved in water
  • One component is called “solvent” (ex: water) and the others are “solute”
  • Note: Most of the pharmaceutical solutions are aqueous solutions because the majority of biochemical reations occur in an aqueous environment.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Solutions & Solubility:

Solutions: Colligative Properties

A
  • osmotic pressure, lowering of vapor pressure, depression of freezing point, elevation of boiling point
  • ​Depend ONLY on the number of particles (solute or drug molecules) in a solution.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Solutions & Solubilities:

Solutions: Additive Properties

A
  • Depend on the total contribution of atoms in the molecules (ex: MW) or the sum of properties of the contituents (ex: mass of a solution)
    • Ex: the total mass of a solution containing A and B= mass of A + mass of B
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Solutions & Solubilities:

Solutions: Constitutive Properties

A
  • Depend on the arrangment, the number and kind of atoms within the molecule
    • Ex: the refraction of light and electric properties
  • Not discussed any further
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Solutions & Solubility:

Units of Solubility

A
  • ​Overall definition
    • Concentration units
    • (quantity of solute)/quantity of Solvent or solute
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Solutions & Solubility

  • Molarity
  • Normality
  • Molality
  • Mole Percent
  • Percent by weight
  • Percent by volume
  • Precent weight in volume
A
  • Molarity
    • M
    • Moles solute in 1 L of solution
  • Normality
    • N
    • Gram equivalent or equivalents of solute in 1 L of solution
  • ​Molality
    • m
    • Moles of solute in 1000 g of solvent
  • Mole percent
    • Moles of one constituent of a solution to the total moles of all constituents expressed as a percent
  • Percent by weight
    • %w/w
    • Grams of solute in 100g of solution
  • Percent by volume
    • %v/v
    • mL of solute in 100 mL of solution
  • Percent weight in volume
    • %w/v
    • grams of solute in 100 mL of solution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Solutions & Solubility

Equivalent Concentration or Normality (N)

A
  • In chemistry, the equivalent concentration, or normality, of a solution is defined as the molar concentration divided by an equivalence factor
  • N, equivalent (Eq), milliequivalent (mEq), equivalent weight
  • N=equivalents (the number of equivalent weight) of solute in 1 L of solution
  • The number of equivalent weight of solute=mass of solute (g)/equivalent weight of solute. The unit of equivalent weight is g/Eq.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Solutions & Solubility:

Equivalent Weight for Atoms

A
  • Equivalent weight (q/Eq)=Atomic weight/# of equivalent per atomic weight (valence)
  • Ex: F and O
    • The number of equivalents per atomic weight is 1 for fluorine and 2 for oxygen
  • Ex: Mg
    • Number of equivalent per atomi weight of Mg is 2. Therefore, the equivalent weight is 24/2. this is 12 g/Eq
  • More than one valence, more than one equivalent weight. Depends on the reaction
  • Equivalent concentration is the only concentration unit that is dependent on the type of chemical reaction under consideration.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Solutions & Solubility:

Equivalent Weight for Molecules

  • Ex: 58.5 g NaCl in 1 L H2O
  • Ex: 35 g MgCl2 in 1 L H2O
  • Ex: equivalent weight K3PO4
  • Ex: 100 mEq of K+ in 1 L H20, how much K3PO4?
  • Ex: equivalent weight Ca3(PO4)2
A
  • Equivalent weight (g/Eq) = MW (g/mole)/equivalents per mole
  • Ex: 58.5 g NaCl in 1 L H2O
    • 58.5g/(58.5g/mol)=1M
    • Is 1 equivalent per mole, so 58.5/1=58.5 g/Eq
    • 58.5/58.5=1N
  • Ex: 35 g MgCl2in 1 L H2O
    • 35g/(95.3g/mol)=0.37 M
    • 2 Eq per mole
      • 95.3/2=47.65 g/Eq
      • 35/47.65=0.74 N
  • ​Ex: equivalent weight K3PO4
    • 3 Eq per mole
    • MW/3, 212/3=70.7 g/Eq
  • Ex: (0.1 Eq)*(70.7 g/Eq)=7.07 g in 1 L water
  • Ex: Ca3(PO4)2
    • 6 Eq per mole
    • 310/6=51.7 g/Eq
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Solutions & Solubility

Why/How is Normality used in pharmacy?

A
  • Normality is often used in pharmacy to calculate the content of individual ions
  • For example, n electrolyte replacement therapy, concentrations of electrolytes are ordinarily expressed as equivalets/L or mEq/L
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Solutions & Solubility:

Intermolecular forces in solutions

A
  • solvent-solvent
  • solvent-solute
  • solute can dissolve in a solvent because the solvent-solute interaction>solvent-solvent interactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Solutions & Solubility

Electrostatic Intermolecular Forces

A
  • Ion-ion
  • Ion-dipole
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Solutions & Solubility

Dipole-Dipole Interactions (e.g., water)

A
  • water has a permanant dipole
  • Unequal sharing of electron pairs between atoms due to a difference in electronegativity of atoms.
  • Net result of such interactions lead to polarization of molecules
  • if the center of negative charges does not perfectly overlap with the center of positive charges in a molecule
  • Electron charge is assymetric
  • Longer distance between negative adn positive charge center, the greater the polarity (D value, dipole moment)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Solutions & Solubility

Induced Diople-Induced Dipole

A
  • Van Der Waals
  • temporary dipole
  • non specific attractition when two atoms are 3-4 angstrom apart
  • at any time, electron charge distribution around the atom is not perfectly symmetric
  • transient asymmetric charge distribution around one atom encourages a similar asymmetric distribution of charge around its neighbooring atoms
  • weak attractive force between atoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Solutions & Solubility:

Hydrogen Bond

A
  • Weak chemical interaction
  • H and O, F, N and acidic carbon (electronegative elements)t
  • Hydrogen bonds are formed between charged and uncharged molecules. In this bond, a hydrogen atom is shared by two other atoms (donor and acceptor, usually oxygen or nitrogen)
  • The atom in which the hydrogen is tightly linked is the donor
  • Acceptor has partial negative charge that attracts the hydrogen
  • H bonds strongest when the three atoms are in a straight line
  • The shorter the length between the proton donor and acceptor, the greater the hydrogen bond
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Solutions & Solubilities

Bond Energies

A
  • induced dipole<dipole></dipole>

</dipole>

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Solutions & Solubilities

Mechanisms of Solvent Action: Solvation

A
  • e.g., NaCl
  • solvent molecules orient around the ions of solute
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Solutions & Solubility:

Mechanisms of Solvent Action: Hydrogen Bonds

A
  • e.g., methanol and glucose solutions
  • H-bonds are formed between the solvent and the solute
  • polarity of solvent and solid must match
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Solutions & Solubility

Mechanisms of Solvent Action: Interactions between induced dipoles

-specific example

A
  • e.g., cyclosporine (very hydrophobic) dissolved in a non-polar solvent such as polyoxyethylated castor oil
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Solutions & Solubility:

Classes of Solvents: Polar

A
  • e.g., H2O
  • Due to high dielectric constant, reduce ionic attractions between oppositely charged inons, thus breaking ionic bonds of strong electrolytes
    • Ex: water and salt
  • Results in dissociation
  • Interact with molecules through hydrogen bond
  • D>50
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Solutions & Solubility

Classes of Solvents: Semi-Polar

A
  • e.g., ketones, alcohols
  • can induce polarity in non-polar solvent molecules
  • often used as a co-solvent
  • D between 20-50
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Solutions & Solubility

Classes of Solvents: Non-Polar

A
  • e.g., vegetable oil, mineral oil and hydrocarbons
    • Dissolve non-polar compounds through induced dipole interactions
  • D lower than 20
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Solutions & Solubility

Temperature Affect of Solubility

A

Van’t Hoff Equation

R=gas constant, 1.99 cal/mol/Kelvin

T=absolute temperature

delta H= heat of solution (cal/mole) or change in enthalpy during solubalization

Enthalpy is teh thermodynamic potential, which is a measure of internal energy of the solution

J=constant

Ks= solubility in mole/L

  • If delta H is positive, then increasing temperature increases solubility
    • because Ks proportional to logKs proportional to -1/T
  • if delta H is negative, then increasing temperature decreases solubility
    • because Ks proportional to logKs proportional to 1/T
  • if delta H is zero, there is no temperature effect on solubility
  • logKs=J
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Solutions & Solubility

Relationship of solubility (LogKs) with Temperature based on van’t Hoff equation

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Solutions & Solubility

Factors affecting Solubility: List

A
  • ​Temperature
  • Salts
    • “salting out effect” for non-electrolytes i.e. glucose
    • competition between salt and glucose for solvent
    • salt and water=electrostatic interaction
    • salt and glucose=hydrogen bond
  • pH
    • weak bases
      • Low pH: ionization: high solubility
      • High pH: un-ionized: low solubility
    • weak acids
      • Low pH: un-ionized: low solubility
      • High pH: ionization: high solubility
  • ​​Solvent polarity
    • polar-polar; nonpolar-nonpolar
  • Other factor such as surfactants (increase solubility of hydrophobic drugs) and particle size (smaller are more water soluable)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Solutions & Solubility

Methods to Increase Solubility

A
  • Temperature increase/decrease
    • not practical in vivo
  • Adjust pH
    • not practical in vivo
  • Chemical modifications
    • phosphates and succinates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Solutions & Solubility

Water and alcohol solubilities of some selected weak acids, weak bases and their salts

A
  • Salts of organic acids or bases are more soluble in H2O than the parent compound
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Solutions & Solubility

Mixed Solvent System

A
  • Mixed solvents to form a solvent system of favorable polarity
  • Note: These D values of solvents are approximate
    • Human toxicity: chloroform, octane, benzene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Solutions & Solubility

Solvent Blending/Co-Solvency

A
  • Definition: To form a solvent system at optimum polarity to dissolve the solute
  • Such solvents must be miscible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Solution & Solubility

Solvent Blending: Ethanol and Drug Example

  • Formulate a vehicle containg H2O, EtOH and glycerin with a D=47, limit ethanol to 20% v/v
  • DEtOH=25, Dwater=80, Dglycerin=46
A
  • DA+B+…=(fA*DA)+(fB*DB)
  • fA, fB-volume fraction of each solvent
  • (25*0.2)+(80*x)+(46*(0.8-x))=47
  • X=0.15
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Solutions & Solubility

LogP

A
  • Measure of differential solubility of a compound or a drug in two solvents
  • log ratio of the concentrations of the compounds in the solvents at equilibrium
  • Octanol and water
  • LogP is indidcation of lipophilicity or hydrophobicity
    • related to absorption
  • Shake Flask method
    • P=[s in octanol]/[s in water]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Solutions & Solubility

Crystal Form & Polymorphism

  • Definition and Beginings
A
  • different forms of crystal=polymorph
  • arise through packing of the molecules in different arrays within the crystal or by differences in the orientation or conformation of molecules at lattice sites
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Solutions & Solubility

  • 7 possible crystal systems
A
  1. Cubic
  2. Tetragonal
  3. Orthorhombic
  4. Monoclinic
  5. Triclinic
  6. Trigonal
  7. Hexagonal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Solutions & Solubility

Crystals differ in physical properties

A
  • Same chemical structure
  • Different physical properties
    • density, melting point, solubility
  • Often intentionally choose the polymorph that has a higher solubility so that its absorbtion can be increased
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Solutions & Solubility:

Drug Dissolution & Permeation

A
  • Drug dissolution rate is dependent on drug solubility
    1. may change as function of pH
    2. may change based on formulation factors (salt form, polymorphic form, particle size, addition of surfactants)
  • Permeation is dependent on
    1. partitioning from the GI fluid into the GI membrane, which is favored by high logP, of the non-ionized drug molecule
    2. Fraction ionized (pKa/pH consideration). Entry into the GI membrane is favored by large fraction non-ionized
    3. ​Entry into the GI membrane is favored by low molecular weightt (below 500)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Solutions & Solubility

Temperature, Pressure, and Crystal Form

“metastable”

A
  • At any T and P, only one crystal form is stable
    • other polymorphs convert to stable form
  • Conversion rate weeks-years
    • “metastable”
    • high energy, higher aqeous solubility than stable form
  • Higher solubilty means **Less Stable **
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Solutions & Solubility

Amorphous vs. Crystalline

A
  • Amporphous
    • e.g., powder
  • E.g., crystalline novobiocin poorly soluable, amorphous novobiocin readily soluable
  • usually, drug solubility increases with decreasing particle size (largely due to increase in surface area of drug particles in contact with solvent)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Solvents & Solubility

How to dissolve hydrophobic drugs

A
  • add surfactants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Acid-Base

Definition: Electrolytes

A
  • Substances whose aqueous solutions conduct electricity
    • e.g., inorganic acids, inorganic bases and salts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Acid-Base

Definition: Arrhenuis (apply for strong acid or strong base)

A
  • Acid: any species that will donate H+
  • Base: any species that will donate OH-
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Acid-Base

Definition: Bronstead Lowry*

A
  • Acid: a substance, charged or uncharged, which is capable of donating protons
  • Base: a substance, charged or uncharge, which is capable of accepting a proton
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Acid-Base

Definition: Lewis

A
  • Acid: a substance capable of accepting a share in an electron pair made available by another substance called base
  • Base: a substance capable of donating a share in an electron pair to another substance called an acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Acid-Base

Significance

A
  • Formulate efficacious and stable preparations
  • Detect and understand incompatibilities in vitro and in vivo
  • in vitro-phenytoin (weak acid)
  • in vivio- sodium bicarbonate and tetracycline (amphoteric compounds)
    • either acid or base depending on pH
  • pH change solubility of drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Acid-Base

Rf and Rr

A

​

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Acid-Base

k

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Acid-Base

Ka and Kb

A

Since water almost in large excess, assume that it remains constant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Acid-Base

Definitions: pH, pKa, pKb, pOH

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Acid-Base

Correlation between acidity, pKa, and Ka

A
  • Strong Acid
    • Ka large​
    • pKa small
  • Strong Base
    • Kb large
    • pKb small
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Acid-Base

Theory of Electrolytic Dissociation

A
  • Strong electrolyte completely ionized in pH 0-14
  • Weak electrolytes as incompletely ionized in pH 0-14
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Acid-Base

Henderson-Hasselbach and Derivative

A
  • pH=pKa+log(b/a)
  • a=b*10^(pka-pH)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Acid-Base

% ionization

A
  • is a chemical equilibrium phenomenon
  • only for weak acids
    • ((b)/(a+b))*100=(100/(1+(10^(pKa-pH)))
    • pKa=pH; 50%
    • pH>>>pKa; ~100%
    • pKa>>>pH; ~0%
  • For weak base, (pKa+pH-pKw)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Acid-Base

Common Weak Acid and Common Weak Base

A
  • Weak Acid
    • formic acid, acetic acid, trichloroacetic, hydrofluoric, hydrocyanic, hydrogen sulfide, water, conjugate acids of weak bases
  • Weak Base
    • ammonia, trimethyl ammonia, pyridine, ammonium hydroxide, water, conjugate bases of weak acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

Acid-Base

  • Percent Ionization and Solubility
A
  • As % ionization increases, solubility increases
  • solubility can be altered by adjusting pH
  • e.g., phenytoin weak acid (pKa=8.1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Acid-Base

Amphoteric Electrolytes

A
  • Function as both acids and bases
    • e.g., amino acids and proteins
  • pH 3-9 glycine exists as + on NH3 and - on COO
    • Zwitterion
  • pH when + and - only equal each other is called the isoelectric point. At this point, there is not net charge in the solution.
  • Many drugs are amphoteric, e.g., tetracycline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Acid-Base

Definition: Buffers

A
  • One compound or mixture of compounds that, by their presence in solution, resist chagnes in pH upon addition of small quantities of acid or alkali
  • E.g., human blood maintains pH 7.4 due to buffers present in plasma (natural buffer system which consits of physiological electrolytes at certain concentrations)
    • albumin, carbonic acid, and bicarbonate tears-pH 7.4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Acid-Base

Significance: Buffers

A
  • to maintain optimal pH of the formulated product within a certain range upon addition of various additives
  • to maintain pH on storage
    • e.g., glass is alkaline
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Acid-Base

Henderson Hasselbach for weak base

A

pH=pKw-pKb+log(base/salt)

77
Q

Acid-Base

Equivalence Point and Buffering Zone

A
  • ​is the point where titrant added is stoichiometrically equal to the amount of moles of substance present in sample
  • the smalles amount of titrant that is sufficent to fully neutralize or react with the analyte
  • buffering zone is area before “acceleration” on graph
78
Q

Acid-Base

Buffer Capacity

A
  • Sufficient but not excessive
  • max capacity at pH=pKa
  • e.g., Ac pKa=4.76, so pH range is 4 to about 6 for buffer
  • Cbuffer is defined as the total concentration of a buffer which is equal to the concentration of salt plus the concentration of the weak acid or weak base`
79
Q

Acid-Base

Pharmaceutical Applications of Buffers

A
  • buffers used widely in formulating drugs, especially opthalic solutions
    • e.g, pilocarpine eye drops, phenyl ephrine eye drops
  • pharmacists should consider:
  1. pH-solubility, stability and activity
  2. buffering capacity-sufficient but not excessive
  3. volume of buffered product to be used relative to volume body fluid with which it will come into contact
    • ​parenteral sln (do not go through GI) not buffered/buffered to low capacity
    • Injection/infusion should minimally affect the body’s natural buffering system
80
Q

Acid-Base

Why large volume not buffered?

A
  • if solution is buffered to a high capacity at a different pH other than physiological pH, infusion at a large volume of such sln may change physiologcial pH
  • Even if the solution has the same pH as the blood, a highly buffered solution means that the solution may posses a high total buffer concentration. Since the natural buffering system of blood is maintained by the prescence of physiological electrolytes at certain concentrations and concentration ratios, infusion of a large volume of highly buffered solution could still affect the natural buffering system by changing concentration and concentration ratios.
81
Q

Colligative Properties

Definition of Colligative Properties

A
  • The colligative properties of a solution are those that depend ONLY on the number of solute particles in solution, irrespective of whether they are molecules, ions, large or small and of their chemical nature
82
Q

Colligative Properties

Solutes Modulate These Colligative Properties

A
  1. Lowering vapor pressure (Raoult’s Law)
  2. Boiling point elevation (“ebulioscopy”)
  3. Freezing point depression (“cryoscopy”)
  4. Osmotic Pressure
83
Q

Colligative Properties

Osmotic Pressure

  • Definition
  • Passive difussion
  • Semipermeable membrane
A
  • Osmotic Pressure: The force per unit area required to prevent passive diffusion of solvent molecules across a semipermeable membrane
  • Passive Diffusion: Movement of particles or molecules by internal kinetic motion down a concentration gradient
  • Semipermeable Membrane: Thin, porous film that selectively allows the passage of substances based on particle size. Typically solvent may pass and solute may not
84
Q

Colligative Properties

Osmolarity

A
  • the molarity of solute particles in solution
    • measure of osmotic pressure
  • 1 Osmolar=1mol/L=(6.02*10^23)particles/L
  • glucose = 1 osmolar
  • NaCl= 2 osmolar
85
Q

Colligative Properties

Osmosis

A
  • The passage of solvent molecules across a semipermeable membrane which maintains a solute concentration gradient across itself; direction is from low to high solute concentrations; driven by;
    • solvent concentration gradient (high to low Xw)
    • vapor pressure gradient of solvent (Pw=Pw0*Xw)
    • Free energy gradient of solvent (µw=µw0+RTlnXw)
86
Q

Colligative Properties

Tonicity vs. Isotonicity

A

Tonicity: the effective osmotic pressure of a solution when compared to a physiological body fluid or tissue. COMPARATIVE TERM

Isotonicity: The quality of possesing and maintaining an uniformed tone or tension across a physiological barrier. An isotonic solution is a solution that has the same osmotic effect as the physiological body fluid

87
Q

Colligative Properties

Hypertonic, isotonic, hypotonic

A
  • Hypertonic: osmotic pressure of the solution is higher than that of the body fluids. Net loss. Shrink
  • Isotonic: osmotic pressure of the solution is the same as body fluids
  • Hypotonic: osmotic pressure of the solution is lower than that of body fluids. Net gain. Blow up.
88
Q

Colligative Properties

Normal Saline

A
  • 0.9% NaCl solution is isotonic. Its osmolarity is 308 mOsm/L
89
Q

Colligative Properties

Isoosmotic vs. Isotonic

A
  • Isoosmotic means having the same osmotic pressure
  • Isotonic means having the same tonicity as teh body/tissue fluid with which contact is made
  • Might be same, depends on what body/tissue fluid with which the solution contacts
  • Ex: RBC in 1.9% boric acid
    • overtime penetrate cell and cell swell
    • Isotonic for lens of eye, but hypotonic for RBC
90
Q

Colligative Properties

Expressions of Osmotic Pressure

  • 1 Osmol
  • Osmolality
  • Osmolarity
A
  • 1 Osmol: amount of particles in a solution
  • Osmolality: Osmol concentration based on weight; a 1 Osmolal solution= 1 Osmol/1000g water
  • Osmolarity: Osmol concentration based on volume; a 1 Osmolar solution 1 Osmol/L solution
  • Osmolarity is the measure of number of dissolved particles in solution. It is independent of the nature of solute
  • Clinical laboratory osmolality determinations are made by freezing point analysis; normal serum freezes at -0.520C, and the “osmolarity” is approximately 308 mOsmol/L
  • USP requires that solutions for injection be labeled with the osmolar concentration
91
Q

Colligative Properties

Pharmaceutical Significance of Osmotic Pressure

A
  1. Some medical solutions are administered specifically for their osmotic effect
  • Mannitol IV as diuretic used to promote excretion of urine. Increases osmotic pressure of the tubular filtrate. Therefore, pulling more water into the tubules and increasing diuresis
  • Mg Citrate as laxative. Increases osmotic pressure for the luminal contents of the intestinal tract, water fills and evacuation is promoted
  1. Perdominate consideration is to minimize osmosis. Generally, all medical solutions intended to come in contact with tissues other than G.I. tract are formulated to have the same osmotic pressure as the tissues contacted
  • ​opthalmics: iotonicity= 0.5-1.8% NaCl
  • parenterals: 0.8% NaCl for IV
92
Q

Colligative Properties

“V” Method

A
  • Definiton of V-value: The volume of sterile water to be added to 0.3 g of a drug to make it isotonic.
    • Make isotonic 30 mL of a 1% solution of homatrotopine hydrobromide
    • Amount of drug need=30*(1/100)=0.3g
    • Weigh out 0.3g, add 5.7 mL H2O=5.26%
    • Dilute with 0.9% NaCl to 30 mL
  • Mixing one isotonic solution with another isotonic solution still results in an isotonic solution
93
Q

Colligative Properties

E Method

  • 5% cocaine, 120 mL isotonic sln
  • E value= 0.14
A
  • Definition of Sodium Chloride Equivalent (E value): The weight in grams of NaCl which has the same osmotic effect as one gram of the drug prepared as an isotonic solution; expressed as an E-value in units of grams of NaCl per gram of drug.
  • Ex: 5% cocaine, 120 mL isotonic solution
  • E value of cocaine=0.14 (g NaCl/1g drug)
  • 1st: Calculate amount of NaCl
    • 120mL of 0.9% NaCl
    • 120mL(0.9/100)=1.08 g NaCl
  • 2nd: Amount cocaine for 120 mL of 5% cocaine
    • 120 mL (5/100)=6 g cocaine
  • 3rd step Isotonic effect of cocaine
    • 6g*(0.14)=0.84 g NaCl
    • Amount NaCl = 1.08-0.84=0.24 g NaCl
  • Weigh out 0.24 g NaCl and 6 g cocaine add water to 120 mL
94
Q

Pharm Sln

Intro to Pharm Sln

  • Solution, solvent, solute
A
  • Solution: a homegeneous mixture of two or more substances
  • Solute: a drug substance
  • Solvent: Alcohol, water, diluted alcohol, glycerin, propylene glycol
95
Q

Pharm Sln

USP-NF definition

A
  • Contains standards for medicines, dosage forms, drug substances, excipients, medical devices and dietary supplements
  • Info found in monographs
96
Q

Pharm Sln

Opthalmic Sln

A
  • Sterile sln that are suitably compounded for instillation into eye
  • Prescription, OTC, contact lens sln products:
    • Treat surface/intraocular conditions
    • bacterial, fungal, viral infections
    • allergic/infectious conjuctivitis or inflammation
    • dry eye
97
Q

Pharm Sln

Opthalmic sln difficulties

A
  • tear volume is 7 µL
  • eye drops range from 50-70 µL
  • can result in brief contact between the medication and absorbing surfaces
98
Q

Pharm Sln

Critical Considerations for Opthlamic formulations

8

A
  • Sterility
  • Isotonicity
  • Buffering for stability and comfort
  • Clarity
  • Particulates
  • Antimicrobial preservatives
  • Viscosity
  • Stability (e.g., oxidation and hydrolysis)
99
Q

Pharm Sln

Opthalmic Sterility

A
  • absolute requirement
    • steam (autoclave) container must be compatible
  • Gas (ethylene oxide)
  • Filtration
    • preferred under USP, container must be pre-sterilized
  • microbial contaminated=ulcers and blindness
    • *​Staph *and Pseudomonas
    • Complete blindness in 24-48 hours
  • Sterilization standards set by USP 797
100
Q

Pharm Sln

Antimicrobial preservatives for multiple dose opthalmic solutions

A
  • Most multi-dose opthalmic solutions contain effective anti-microbials
  • Preservatives vary in solubility
  • Preservative vary in effectiveness
  • Benzalkonium chloride, Benzethonium chloride, Cetylpyridium chloride has slow action
    • 7 minutes for bacterial count to be decreased by 50%
    • quarternary ammonium compounds
    • lytic action on membrane
    • 0.004-0.02%, 0.01% most common
    • Incompatible with soap, anionic materials, salicylates, nitrates
  • **Phenylmercuric Acetate, Phenylmercuric Nitrate, Thiomerosal, **
    • ​organic mercurials
    • denaturation of enzymes by combining thiol groups
    • 0.001%-0.01%
    • Incompatible with F, Br, Cl and phenylmercuric acetate
  • Methylparaben, Propylparaben
    • ** **Benzoic acid, boric acid, and parahydroxy benzoate esters (parabens)
    • denaturation of proteins
    • Max 0.1%
    • Incompatibilies: Adsorption by macromolecules; marginal activity (highly protien bounded)
    • Ineffective at pH greater than 5, good against fungi
  • Chlorobutanol
    • substituted alchol
    • lytic and denaturation action on membranes
    • 0.5%
    • close to max solubility, hard to prepare
    • stabilty is pH dependent
101
Q

Pharm Sln

Preservatives must be tested for

A
  1. safety
  2. efficacy
  3. stability
  4. compatibility
  5. comfort
102
Q

Pharm Sln

Opthalmic sln Clarity

A
  • absolute requirement
  • free from foreign particles
  • usually through filtration
    • filtration equip must be clean
  • filtration and sterilization can be in same step
103
Q

Pharm Sln

Stability of opthalmic slns

A
  • Total product stability depends on chemical nature of drug substance, solution pH, solution prep method (temp), solution additives, packaging/storage (light, metal ions, heat)
  • Compromise sometimes needed
  • 2-3 yr shelf life is common
104
Q

Pharm Sln

Opthalmic Buffering and pH

A
  • For comfort
  • Improved stability
  • balance contribution to the pH of all the ingredients
  • improve solubility of active drug substance
  • to maximize the effectiveness of the preservative
105
Q

Pharm Sln

Tears and pH

A
  • pH of tears is about 7.4
  • sufficient but not excessive buffer capacity
    • ~0.01-0.1M
  • eyes appear to be less sensative to alkaline buffering compared to acidic buffering
  • 7.4 goal, seldom acheived
  • many drug active ingredients are salts of weak bases and are most stable at acidic pH
  • optimum pH is a compromise (stability, comfort, capacity)
106
Q

Pharm Sln

Tonicity of Opthalmic Sln

A
  • Osmotic pressure considerations are important
  • Eye is tolerant of some tonicity variation (0.5-1.8% NaCl)
  • isotonicty for comfort, not overriding concern
107
Q

Pharm Sln

Opthalmic Viscosity

A
  • prolong contact
    • drug absorption and activity
  • increase ease of use
  • polymers for visocity agents
  • **methylcellulose **
    • ​more units means higher viscosity
  • hydroxypropylmethylcellulose
  • **polyvinyl alchol **
108
Q

Pharm Sln

Antioxidants in opthalmic sln

A
  • oxidants:loss of an electron or an increase in oxidation state of a molecule, atom, or ion; iorganic oxidation often involves electron transfer
  • Organic oxidation doest not actively involve electron transfer
    • involves addition of oxygen
  • series of free radical chain
  • antioxidant need to interfere intiation/propogation or participate in termination
109
Q

Pharm Sln

Antioxidants

A
  • Oxygen scavenger, easily oxidized
    • sodium bisulfite
    • sodium metabisulfite

​known to cause allergic reactions

  • Reducing agents, reduce oxidized drugs
    • ascorbic acid
  • ​Chelating agents tie up metal
    • Fe, Cu, Co, Ni, Mn, unshared electron in outer shell​
    • EDTA, citric acid, tartaric acid
  • Drugs in terminating step
    • Vitamin E
    • provide H atoms and free radicals, not sustain chain rxn
  • Storage issues (amber vial)
110
Q

Pharm Sln

Oral Sln

A
  • in water or water-cosolvent system
  • additives for palatability, stability, aesthetic appeal
    • flavor agents
    • sweeting agents
    • coloring agents
    • buffers
    • antioxidants
    • preservatives
    • no isotonicity requirement
111
Q

Pharm Sln

Solvents or Co-Solvents for Oral Sln

A
  • purified water
  • alcohol
  • glycol
  • glycerin
    • internal and external uses
  • propylene glycol
    • internal and external uses
  • polyethylene glycol (PEG)
    • water soluble
      • decrease as MW increase
    • 900>=waxy at RT
    • lot of things b/c of solubility and compatibility
112
Q

Pharm Sln

Syrups

A
  • concentrated aqueous prepartions of sugar or sugar substitue w/ or w/o medicine
  • simple syrup
    • sucrose 850 mg
    • purified water q.s. 1000 mL
  • correctly prepared is self-preserving
  • fully saturated
  • 85% w/v or 65% w/w
  • clear and colorless
  • also sorbital sln
113
Q

Pharm Sln

Elixir

A
  • clear and pleasantly flavored, sweetend hydroalcholic liquid inteded for oral use (0-23% alcohol)
    *
114
Q

Pharm Sln

Aromatic Water

A

Aromatic waters are clear, saturated aqueous solutions of volatile oils or other volatile substances (sometimes referred to as medicated waters)

  • *Peppermint Water**, USP
  • *Stronger Rose Water**, USP
115
Q

Pharm Sln

Spirits

A
  • Spirits are alcoholic or hydroalcoholic solutions (usually contain 50-90% alcohol) of volatile substances (sometimes referred to as essences)
  • Some used internally for medicinal value, some for inhalation, and some as flavoring agents
  • Historically, Brandy (Spiritus Vini Vitus) and Whisky (Spiritus Frumenti) were in the official compendia (USP or NF) as medicinal agents
116
Q

Pharm Sln

Rehydration Sln

A
  • Used to restore fluid and electrolyte balance after severe diarrhea and/or vomiting
  • Contain sodium, potassium, bicarbonate, and glucose with reduced osmolarity (e.g. ~245 mOsm/L).
  • Pedialyte® for children
117
Q

Pharm Sln

Oral Colonic lavage solution

A
  • Combination of electrolytes (sodium, chloride, bicarbonate, potassium) and high molecular weight nonabsorbable polyethylene glycol (PEG 3350); (GoLightly®)
  • Available as a solid product. When reconstituted, it becomes an iso-osmotic large volume fluid for preparation of the bowel for colonoscopy to prevent net loss of water or electrolytes as the bowel is evacuated. Colonoscopy is a diagnostic procedure to exam GI disorders such as colon cancer.
118
Q

Pharm Sln

Parenteral Sln (MUST BE STERILE AND ISOTONIC): Routes of administration

A
  • Small volume parenterals: Injection of small volumes: (concept of bolus vs. infusion)
    • into a vein (intravenous, IV) or artery (intra-arterial, IA)
    • under the skin (subcutaneous, SC, sub-Q, SQ, hypodermic, hypo)
    • into the skin (intradermal, ID, intracutaneous)
    • into the muscle (intramuscular, IM)
    • into spinal fluid (intrathecal)
    • into spinal column (intraspinal)
    • into the joint space (intra-articular) or synovial fluid of the joint (intra-synovial)
    • into the heart (intracardiac)
  • Large volume parenterals: Infusion of large volumes:
    • into veins (intravenous, IV) or arteries (intra-arterial, IA)
119
Q

Pharm Sln

Vehicles for parenterals: Water

A
  • Purified Water, USP
    • contains ≤ 1 mg solids/100 mL
    • Not suitable for direct injection use
    • Must be filtered or autoclaved before use
  • Water for Injection, USP
    • Must be pyrogen free
    • Pyrogens = fever-producing organic substances arising from microbial contamination
    • Used in manufacturing pharmaceuticals (therefore not required to be sterile, sterilization occurring during manufacture of injectible)
  • Sterile Water for Injection, USP
    • No additives (can be used for neonates [1st 4 weeks], pediatrics)
    • Must be pyrogen free (some endotoxin is allowed)
    • Available as single dose containers not greater than 1 liter (not for infusion because it has no tonicity) to be used to prepare injections by aseptic technique
  • Bacteriostatic Water for Injection, USP
    • Use in small volumes only (because of the antimicrobial agent)
    • NOT FOR USE IN NEONATES (NEWBORNS)
120
Q

Pharm Sln

Relationship of Sterility, Pyrogenicity, Endotoxin

A
  • Sterility is the absence of viable organisms.
  • Pyrogenicity is the presence of pyrogens which are materials which when injected into a patient (therefore bypassing usual “defense mechanisms”) will cause a rise in body temperature because of an immunoresponsive reaction (pyrexia).
    • Normally the products of microbial growth
    • Most commonly encountered pyrogens are thought to be endotoxins
      • Endotoxins are the lipopolysaccharides that comprise the major part of the cell wall of gram-negative bacteria
  • Bacterial cells may be pyrogenic even when they are dead and when they are fragmented, so a solution that passes a test for sterility will not necessarily pass a pyrogen test. On the other hand, a solution that passes a pyrogen test may not pass a sterility test either. This is because:
    • A pyrogen test just detects bacterial cell wall materials. Even if there are no viable bacteria in the product that allows it to pass the sterility test, there still may be dead bacteria which will give a positive reaction in the pyrogen test.
    • A sterility test always tests bacterial growth. A product that passes a pyrogen test may have just a few bacteria at a level that does not have enough cell wall materials to cause a detectable pyrogen reaction. However, with the 14 day sterility test, bacteria may grow sufficiently to show growth observed as turbidity or a lack of clarity in the growth media.
    • Both tests can have interferences so that each test has to be carefully validated for the formulation prior to use for product quality assurance.
121
Q

Pharm Sln

Other aqueous vehicles for parenterals

A
  • Sodium Chloride Injection, USP
    • Isotonic (0.9% NaCl)
  • Bacteriostatic Sodium Chloride Injection, USP
    • Contains benzyl alcohol
    • Labeled: NOT FOR NEONATES (NEWBORNS)
    • Small volume (< 5 ml) even for adults
  • Ringer’s Injection, USP
    • NaCl + KCl + CaCl2
    • An electrolyte replenisher and plasma volume expander
    • Concentrations of salts are comparable to those in physiological body fluids
  • D5W IV
    • 5% w/v dextrose (glucose) in water
    • used to supply water and calories to the body.
    • also used as a mixing solution (diluent) for other IV medications
122
Q

Pharm Sln

Water miscible vehicles for parenterals

A
  • Ethyl alcohol
  • Polyethylene glycol
  • Propylene glycol
  • Glycerin

Cosolvents typically used

123
Q

Pharm Sln

Nonaqueous vehicles for parenterals

A
  • Usually for formulations to be administered IM
    • Fixed vegetable oils: peanut, corn, cottonseed, sesame, castor, olive
    • Ethyl oleate
    • Isopropyl myristate
    • Dimethyl acetamide
124
Q

Pharm Sln

Additives for parenteral formulations

A
  • Antibacterial preservatives (the same as in ophthalmics).
    • No coloring agents are allowed.
    • Buffers (citrate, acetate, and phosphate acid salts) with low capacity.
    • Antioxidants (sulfites, EDTA, sulfur dioxide)
    • Sometimes also add solubilizers
    • Agents for isotonicity
  • Air in container above the injectible solution is frequently replaced with nitrogen or argon to prevent oxidation.
  • Sterilization is required (steam, dry heat, filtration, gas [ethylene or propylene oxide], or ionizing radiation)
125
Q

Pharm Sln

Non-aqueous: Collodions

A
  • liquid preparations containing pyroxylin (a nitrocellulose) in a mixture of ethyl ether and ethanol
  • may be made more flexible by addition of camphor and castor oil
  • New Skin; Compound W for warts (add 10% salicylic acid)
126
Q

Pharm Sln

Liniments: non-aqeuous

A
  • solutions or mixtures of various substances in oil, alcoholic mixtures of soap, or emulsion (may contain preservatives)
  • used for their counterirritant, mildly astringent (toughen and shrink tissues) and penetrating effects
127
Q

Pharm Sln

Non aqueous: extracts

A
  • solutions containing medicinally active portions of plant or animal tissue separated from the inactive portions by extraction with solvent
  • Examples:
    • Tincture: alcoholic or hydroalcoholic solutions prepared from vegetable materials or from chemical substances
      • Tincture of Iodine
      • Thimerosal
      • Paregoric, USP (camphorated tincture of opium)
      • Opium Tincture, USP (laudanum, much more potent than Paregoric, USP)
128
Q

Pharm Sln

Expressions of strengths

percent strengths

Concentrated Acids

A
  • Concentrated acids (e.g., HCl) are often labeled % w/w with specific gravity; Determine mass in a given volume by multiplying volume (mL) by specific gravity (g/mL) and by percent strength (as decimal).
  • M = VSF
  • M = mass of solute in grams
  • V = volume of the solution in mL
  • S = specific gravity of the solution in g/mL
  • F = % strength w/w
129
Q

mg%

A

mg/100mL total solution

130
Q

W and M

Precision

A

The state of being exact; the extent to which a given set of measurements of the same sample agree with their mean.

  • perform something the same way each time
131
Q

Accuracy

A

The state of being correct; the extent to which a given measurement agrees with the standard value for that measurement.

  • agreement between data and true value
    • hitting the bullseye
132
Q

Error

A

The difference between the observed value and the true value in a set of data.

  • true value-observed value
133
Q

Percentage of Error

A
  • The error (see C above) expressed as a percent. In pharmacy error should be ≤ 5%.
134
Q

Sensitivity

A

The state of being constructed to indicate, measure, or be affected by small amounts or small changes in amount.

  • not only is affected by very small change in amount, but one that can detect change
135
Q

Weight

A

The measurement of the gravitational force acting on a body; proportional to its mass and expressed in terms of standard weights which exactly balance the body to equilibrium.

136
Q

English System

Avoirduois

A

1 pound(lb) = 16 ounces(oz) = 7000 grains (gr)

137
Q

Apothecary

A
  • 1 pound = 12 ounces = 5760 grains
  • 1 ounce = 8 drams = 24 scruples
138
Q

Avouriduous to Metric!!!!!!

A
  • 1 gr (grain) = 65 mg or 60 mg
    • e.g. Aspirin V gr can be 325mg or 300mg
  • 1 oz = 28.35 grams or round it up to 30.00 grams
  • 1 lb = 454 g
  • 2.2 lbs = 1000 g = 1 kg
139
Q

Sensitvity Requirement

A

The maximum change in load that will cause a specified change, one subdivision on the index plate, in the position of rest of the indicating element of the balance

140
Q

% error

A
  1. % error =(Sensitivity Requirement) * 100%
                        Amount Weighed
141
Q

MWQ

A

Sensitivity Requirement) * 100%

  Allowed Percentage of Error
142
Q

Aliquot Method

A

Use when the desired amount of drug to be weighed is less than the least amount weighable.

  1. Weigh excess drug in some amount equal to or greater than the least amount weighable.
  2. Add enough diluent to make a mixture that has some convenient total weight from which a part or aliquot can be weighed which contains the desired amount of drug.
  3. Weigh the aliquot of the mixture that contains the desired amount of drug.
143
Q

Measuring Liquids

General Consideration

A
  1. Accuracy is limited by the interval size of the graduations.
  2. Readings are made at the bottom of the meniscus for aqueous and alcoholic liquids.
  3. Small volumes (< 1.5 ml) should be measured with a pipet (in our lab, use a syringe)
144
Q

Measurement Systems MEMORIZE!!!

Apothecary

A
  • 1 gallon (gal) = 4 quarts (qt) = 8 pints (pt)=4 L
  • 1 pt = 16 fluid ounces (fl oz)
  • 1 fl oz = 8 fluidrachms or drams = 480 minims
145
Q

Household

A
  • 1 pint = 2 cups
  • 1 tablespoonful (tbp) = 3 teaspoonfuls (tsp)= ½ fl. oz=15 mL
146
Q

Apothecary to Metric

A
  • 1 fl oz = 29.57 ml or 30.00 ml
  • 1 pt = 473 ml=480 mL
  • 1 gal = 3785 ml or 4000 ml
147
Q

Household to Metric

A

1 tsp. = 5 ml

148
Q

graduated cylinder

A

use a graduated cylinder that has a capacity greater or equal to the volume to be measured

149
Q

IV fluids definition

A
  • IV solutions are liquid substances suitable for administration via intravenous route.
  • Intravenous means “within a vein”–>directly into the vein
  • The intravenous route is the fastest way to deliver fluids and medications throughout the body. Some medications, as well as blood transfusions, can only be given intravenously.
150
Q

IV fluids used to

A
  • To correct disturbances in electrolyte balance.
  • To replace body fluids loss.–>in dehydration, bleeding
  • To provide basic nutrition.–>TPN
  • To use as vehicles for other drug substances–>use in mixing IV antibiotics, IV electrolytes or other meds..
151
Q

EC vs. IC fluids

A
  • Extracellular fluids : interstitial fluid and blood plasma. 25% of body water is outside the cells with 7.5% found in theintravascular space and 17.5% found in the interstitial space. Interstitial fluid fills the spaces between most of the cells of the body.
  • Intracellular fluids: 75% of all the body water. Liquids within cell membranes, containing dissolved solutes essential to fluid and electrolyte balance and metabolism.
  • Most of the materials in the IC fluid and EC fluid are the same, but differ in proportions
  • (e.g. Potassium in IC >Potassium in EC).
152
Q

Sodium

A

Sodium (Na+): regulates water distribution, transmission of nerve impulses

153
Q

Potassium

A

Potassium (K+): transmits electrical impulse

154
Q

Calcium

A

Calcium (Ca++): major role in muscle contraction and nerve impulse

155
Q

Magnesium

A

Magnesium (Mg++): important for biochemical processes in the body

156
Q

Chloride

A

Chloride (Cl-): fluid balance and renal function

157
Q

Bicarbonate

A

Bicarbonate (HCO3-): neutralizes acids in the body

158
Q

Phosphate

A

Phosphate (HPO4-): buffer and regulation of energy received from metabolism

159
Q

Crystalloids

and NORMAL SALINE!!!

A
  • salts and sugars in water.
  • Contain no proteins or other high molecular weight solutes.
  • Remain in the intravascular space for a short time before diffusing across the capillary wall into the tissue.
  • Examples: normal saline, lactated ringers.
  • ***one liter of Normal saline 0.9% contains 154 mEq Na+***
160
Q

Colloids

A
  • contain large molecules such as protein that do not readily pass through the capillary membrane.
  • Remain in the intravascular space for an extended period.
  • Increase osmotic pressure, causing fluid to move from the interstitial and intracellular space to the intravascular space.
  • “Volume expanders”.
    • Examples: albumin, steroids.
    • Uses: reduce edema –> Albumin pulls water outside of cells
161
Q

IV

Isotonic

A
  • close to the same osmolarity as serum. They stay inside the intravascular compartment, thus expanding it.
  • Helpful in hypotensive or hypovolemic patients.
  • Risk of fluid overloading, e.g. CHF, hypertension.
  • Examples: Lactated ringers, Normal saline (fyi: 154 meq Na+/L)
162
Q

IV

Hypotonic Sln

A
  • less osmolarity than serum.
  • Water is pulled from the vascular compartment into the interstitial fluid compartment.
  • As the interstitial fluid gets diluted, its osmolarity decreases, which draws water into the cells.
  • Helpful when cells are dehydrated.
  • Harmful because it can cause cardiovascular collapse or increased intracranial pressure in some patients.
  • Examples: 0.45% normal saline, 2.5% dextrose
163
Q

IV

Hypertonic Sln

A
  • higher osmolarity than serum –> generally infused via central IV (for dilution) line not peripheral IV line
  • Pulls fluid and electrolytes from the intracellular and interstitialcompartments into the intravascular compartment.
  • Helpful in reducing edema, stabilizing blood pressure.
  • Dangerous in the setting off cell dehydration.
  • Examples: 3% sodium chloride, Total Parenteral Nutrition (TPN)
164
Q

Peripheral IV line

A

Short catheters inserted through the skin into a peripheral vein.

165
Q

Central IV line

  • Subclavian
  • Hickman
  • Portacatch
  • PICC
A

Catheters with its tip inserted into a large vein, usual the superior vena cava, or into the right atrium of the heart.

Subclavian : long into –>chemotherapy

Hickman: for chemo, surgeon put in, more permanent

Portacath: see buton–>stay longer than into elbow

PICC: Peripheral Inserted Central Catheter: ultrasound guided

Advantages: fluids and medications that are irritating to peripheral veins.

  • Vancomycin,
  • Dopamine
  • high concentration of Potassium

Medications can reach the heart immediately and are quickly distributed to the rest of the body.

Provide multiple lumens within the catheter, so multiple medications can be delivered at once.

166
Q

Risks of IV therapy

6

A
  1. Infection: Break in the skin can cause Staph infections, fungal infections such as Candida albicans or other infections caused by contaminated equipment, needles, tubings, catheter left in for too long.
  2. Phlebitis: inflammation/irritation of the vein caused not by infection but from the presence of a foreign body (catheter, IV fluids, medications)
  3. Infiltration: extravasation –> catheter gets out of the vein or pokes through the vein causing fluids leaking out to surrounding tissues.
  4. Fluid overload: more than the body can absorb or excrete –> heart failure, pulmonary edema.
  5. Electrolyte imbalance:
  6. Embolism: life threatening, blood clot or other solid mass or air bubble blocking the blood vessel. Risk is less with peripheral line because the catheter is smaller and shorter.
167
Q

Parenteral Incompatibility

3 groups

A
  1. Physical: can be observed most easily, can be detected by the changes in appearance of the admixture, can be predicted by knowing the chemical characteristics of the drugs.

Calcium and Phosphorus –> Calcium Phosphate –> white precipitate

  1. Chemical: decomposition of drug substances resulting from combination of parenteral dosage forms, from hydrolysis, oxidation, reduction or complexation and can only be detected with an analytic method.

Therapeutic: most difficult to observe because the combination results in undesirable antagonistic or synergistic pharmacologic activity. This is rare.

168
Q

incompatibility mizimzed by

A
  • checking with reference texts: Handbook of Injectable Drugs by Trissel, Micromedex
  • changing to other routes of administration
  • mixing less additives together
169
Q

Hard Gelatin Capsule

A

Ingredients include gelatin, sugar, water, and usually titanium oxide as an opacity agent and one or more colorants.

b. If too dry becomes brittle. If moist decomposes due to microbial growth
c. Soluble in hot water. Relatively insoluble in cold water. Absorbs water and gets soft. Use desiccant when storing.
d. Composed of two parts, body and cap.
e. Brand names
1. ) KapsealsÒ - Park-Davis. eg. Dilantin (Phenytoin) colored band to seal seam of cap
2. ) PulvulesÒ - Eli Lilly. e.g. Ceclor (Cefaclor) body has tapered ends
3. ) SpansulesÒ - Smith, Kline, Beechman. Eg. Compazine (Prochlorperazine)
4. ) Coni-SnapÒ - Warner-Lambert Co.

170
Q

Soft Gelatin Capsules

A

Soft gelatin capsules are useful to seal in liquid drugs, volatile drugs, or drugs susceptible to deterioration in the presence of air.

a. Made soft by addition of glycerin or some polyhydric alcohol such as sorbitol.
b. Rarely used in compounding.

heat sealed

171
Q

Capsule Dilutents

A
  1. Lactose
  2. Microcrystalline cellulose - poorly soluble in H2O - good binding and disintegrant properties.
  3. Pregelatinized starch - granule of corn, wheat or potato; processed such that the granules are ruptured making the starch more easy to compress and flowable
172
Q

Capsule size

A

the bigger number capsule size, the smaller the capsule actually is

173
Q

Powder

A

Dry substances composed of finely divided poweder

into, Tablet, capsule, liquids, suspensions

174
Q

Dissolution Rate

A

Dissolution rate of drug dosage form is increased on decreasing particle size. Micronized particles give rise to higher drug concentration more rapidly in the blood, e.g. insulin and glyburide. Increasing dissolution rate is not always desirable e.g. nitrofurantoin

175
Q

Sieve Number

A
  • The larger the seizer #, the finer the particles
  • Fine: all through #60 and not more than 40% through #100
176
Q

Extemporaneous Techniques

A
  • Prepared at the time in response to current need.
  • Compounding a prescription order in the pharmacy.
177
Q

Comminution

A

The mechanical process of reducing the size of particles or aggregates to fine powders

178
Q

Trituration

A

The process of mixing two or more powders in a mortar with a pestle or reducing the particle size of a drug

179
Q

Pulverization by intervention

A

With the aid of additional material which can be easily removed following the procedure. e.g. ethanol with camphor.

180
Q

Levigation

A

With the aid of a nonsolvent that remains in final product. e.g. incorporating drug into ointments to prevent feeling of grittiness. Paste of drug in a nonsolvent (levigating agent) is made and then triturated to reduce particle size and than added to the ointment. e.g. mineral oil with sulfur powder.

181
Q

Wedgewood

A

coarser surface, easier to reduce particle size of hard crystals and large lumps of material. Porous, stains easily.

182
Q

Porcelain

A

Semi-coarse surface, makes less fine particles. Glazed and therefore less porous.

183
Q

Glass

A

Smooth surface makes coarse particles; best for preparing solutions, suspensions, ointments. Does not stain easily.

184
Q

Mortor and Pestle Marriage

A

Pestles usually made of the same material as the mortar do not interchange pestles from different mortars. A pair of pestle and mortar are specifically designed to fit together.

185
Q

Order of Geometric Addition

A

Method of mixing solids whereby a small portion of one substance is added to an equal portion of another substance and mixed; the process is repeated serially until the total amount has been mixed; also referred to as geometric dilution. Makes well mixed product when drug is present in small quantity and the diluent quantity is large.

186
Q

Volatile substances

A

camphor, menthol, essential oils require air tight packaging.

187
Q

Eutectic Mixtures:

A

Combination of two or more substances of low intermolecular attractive forces such that their combined melting point is less than room temperature, resulting in a product that softens and liquefies.

a. Occurs with aldehydes, ketones, phenols, and alcohols. e.g. camphor and menthol.
b. Prevented by separation of the crystalline components by trituration with inert powders such as magnesium carbonate, magnesium oxide, lactose, or starch.

188
Q

Explosive mixtures

A

Never triturate strong oxidizing agents (potassium permanganate, potassium chlorate, nitrates) with strong reducing substances (powdered acacia, powdered sugar, tannic acid, charcoal).

189
Q
A

Pceut 531 (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions