Term
| Why are solid dosage forms a favorite? |
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Definition
| Solid materials are stable and easy to make, process, and handle. Most drug molecules are solids at room temperature. Solids are also accepted by patients as a preferred dosage form (tablets and capsules, etc.) which increases patient compliance. |
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Term
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Definition
| A crystal is an anisotropic, homogeneous body of a three-dimensional periodic ordering of atoms, ions, or molecules. It is of an orderly, infinite arrangement of molecules or atoms in a solid. It is a specific form of solid states: a crystal should have a melting point, and have sharp regular edges and distinct morphology. A crystal can be ionic (NaCl), metallic (iron), valence (diamond), and molecular (ice) |
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Term
| Does the amorphous state belong to crystals? |
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Definition
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Term
| Does an amorphous material melt? |
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Definition
| There is no distinct melting point or sharp phase transition because the packing of molecules or atoms is random. But it can become a liquid. |
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Term
| Is the number of crystal lattices infinite? |
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Definition
| No, the combination of crystal system and lattice type results in 14 "Bravais lattices". |
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Term
| What are the lattice constants? |
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Definition
a, b, c
α, β, γ
used to define the crystal lattice |
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Term
| Are molecules in a crystal symmetrically related? |
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Definition
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Term
| What are the typical symmetry operations? |
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Definition
mirror plane, inversion center, n-fold rotation axis, n-fold screw axis, n-fold rotary-inversion axis, n-fold glide plane
(translational, mirror, inversion, rotation) |
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Term
| The purpose of the Miller Index is to identify different polymorphs. Right or Wrong? |
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Definition
| Wrong, the Miller Index marks each face of the crystal and indicates the relationship between the face and the crystal structure. |
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Term
| If a crystal face interacts more strongly with the growth solvent, will it become a major or minor face? |
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Definition
| It will become a major face. There is slower growth when the crystal face interacts more strongly with the solvent. There is faster growth if it reacts less with a solvent and in that case it would be a minor face. |
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Term
| What property does contact angle characterize? |
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Definition
Wettability
If you are using water than a smaller angle would mean that the surface is more hydrophilic. |
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Term
| What is polymorphism? Examples? |
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Definition
Same molecules but packed differently, different crystal structures
ex. graphite vs diamond |
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Term
| Why do we care about polymorphism during drug development? |
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Definition
Polymorphism can affect:
solubility and dissolution rate
absorption and bioavailability
chemical and physical stability
physical properties (hardness, density, wettability, growth morphology, etc.) |
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Term
| Why do different crystals have different solubility values? |
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Definition
| They have different intermolecular interactions. |
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Term
| Do different polymorphs of the same molecule have the same solubility? |
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Definition
| No, because different crystal structures would mean that there are different intermolecular interactions between the molecules. |
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Term
| Why is having good solubility of a drug important? |
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Definition
| Good solubility can influence/increase the dissolution rate, absorption rate and bioavailability. |
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Term
| What is the difference between the ideal and real liquids with respect to affecting solubility? |
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Definition
| Ideal liquids only consider the solvent/solute interaction and does not effect solubility. Real liquids would affect the solubility. |
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Term
| What are the assumptions made for ideal liquids? |
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Definition
the molecular size in an ideal liquid is zero
there is no intermolecular interaction |
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Term
| What are controlling factors that decide the solubility? |
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Definition
intermolecular interactions of the solid (heat of fusion, solid-solid interaction)
temperature
solvent (solid solvent interaction) |
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Term
| Can a strong solvent-solid interaction increase the solubility? |
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Definition
| yes, a strong solvent-solid interaction could increase the solubility because the solvent would "pull" the solid apart. |
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Term
| What is the reason for the diffusion/flux to occur? |
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Definition
| concentration gradient--difference in concentration |
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Term
| Why does aspirin dissolve faster in ethanol than in water? |
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Definition
| Aspirin has a higher solubility in ethanol than in water so it dissolves faster. Solvent-solute interaction. Aspirin interacts more strongly with ethanol than with water. |
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Term
| How can the temperature affect the dissolution rate? |
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Definition
the higher the temperature the faster the dissolution rate and vice versa
at higher temperatures you would also have an increased diffusion rate and increased solubility |
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Term
| According to the Noyes-Whitney model, is the concentration versus time linear? |
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Definition
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Term
| Will the concentration of a drug in liquid eventually reach ln(S) where S is its solubility in liquid? |
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Definition
| No, because plateau is not ln(S) it is the solubility (S) |
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Term
| What are the important properties of drug materials? |
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Definition
| solubility and stability (both chemical and physical) |
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Term
| What is the purpose of using a salt form? |
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Definition
| A salt increases the solubility of a poorly soluble drug if it has an ionized functional group. |
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Term
| Can reducing particle size enhance the solubility? |
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Definition
| No, but it can enhance the rate of dissolution. The solubility will be the same for a given substance, it just may take longer if it is a larger particle. |
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Term
| Why in general are Class I and II drugs expected to have IVIVC (in vitro in vivo correlation)? |
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Definition
| Class I and II drugs both show a greater permeability through the membrane so dissolution is the rate-limiting step. The dissolution profile (in vitro) may be able to predict or correlate with the in vivo response. |
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Term
| If we have a Class IV drug, what formulation strategy/strategies can we use to deliver the drug? |
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Definition
| Class IV drugs have poor permeation and poor dissolution. To increase the rate of dissolution a drug can be placed into a liquid formulation or salt formulation. It can also be changed to a different polymorph, an amorphous solid, or making a reduced particle size. Other strategies for improving the solubility limitation include chemical modification of drug candidates (by forming prodrugs), encapsulation in polymeric materials, and combinations of all these approaches. |
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Term
| Why is a drug product typically required to store at a cool and dry place? |
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Definition
| Prevent physical and chemical degradation |
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Term
| Excipients have little pharmacological effect, but we still need them to make drugs. Why? |
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Definition
| Excipients are used to maintain an accurate dosing (diluent), to facilitate the manufacturing process, to achieve an optimal dissolution profile (ex. coating), to improve the patient compliance, to appeal customers. |
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Term
| Starch and cellulose are all polysaccharides. Do they behave the same as excipients? |
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Definition
| No, starch acts as a binder and disintegrant whereas cellulose acts as a diluent*, binder, or coater. |
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Term
| What are possible consequences if more magnesium stearate is used? |
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Definition
| Magnesium stearate is a lubricant (hydrophobic) so if a lot of it is used to make the drug then it will show decreased bioavailability. It would slow the dissolution of the drug and less of it would be absorbed. |
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Term
| What are pros/cons of using a different polymorph or the amorphous state of a drug? |
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Definition
| Using different polymorphs or the amorphous state will affect drug solubility and stability. For example, the amorphous state of a drug may show a faster dissolution rate, but less stability. (cannot measure solubility of amorphous materials) |
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Term
If polymorph I changes to polymorph II spontaneously does polymorph I have...
1. stronger intermolecular interactions
2. a higher energy state
3. a higher solubility
4. dissolve faster |
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Definition
| polymorph I would have a higher energy state, higher solubility, and it would dissolve faster than polymorph II |
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Term
| One of the instability issues of suspensions is caused by Ostwald Ripening, in which the particle size changes. Do particles grow bigger or smaller? |
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Definition
| the particles grow bigger--the smaller particles will all disappear |
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Term
| Polymers are normally used in dispersion systems to stabilize the amorphous state of the API. What is the mechanism of stabilization? |
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Definition
| The polymer reduces the mobility of the drug molecules which stabilizes it. |
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Term
| A drug product is less/more stable at high RH (relative humidity)? Why? |
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Definition
| A drug product is less stable at high relative humidity because moisture uptake by the drug may loosen the product and cause potential physical and chemical degradation. |
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Term
| How can a phase transition affect the bioavailability? |
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Definition
| phase transition changes the dissolution behaviors |
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Term
| What are the major reasons to use powders in pharmaceutical industry? |
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Definition
| Powders flow well and facilitate the mixing of different types of materials. They can withstand deformation and be compressed. |
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Term
| What property does the angle of repose characterize? |
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Definition
flowability
smaller angle of repose=more flowability |
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Term
| Why should bad flowability be avoided? |
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Definition
| poor flowability can cause segregation of power which causes problems of content uniformity; variation in product quality (mainly the dissolution profile), drug recall |
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Term
| What is the purpose of granulation? |
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Definition
| granulation improves particulate properties: it improves the size and size distribution, in unifies the shape, it increases the flowability and compressibility, and it allows the substance to blend uniformly. |
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Term
| Can poor content uniformity result in product recall? Why? |
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Definition
| Yes, because there would be variations in the bioavailability. One patient may have too much drug and get a dose that was too high (may be dangerous) or another patient may get too low a dose and the drug would be ineffective. |
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Term
| When excipients and the API are blended together, should they have similar particle sizes? |
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Definition
| yes, to reduce segregation |
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Term
| Particle processing has little influence on the stability of APIs. Correct? |
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Definition
| no, a process can lead to physical and chemical stability concerns |
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Term
| Tablets are the most preferred dosage form. Why? |
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Definition
| Stable, easy and cheap to make, patient compliant |
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Term
| Tablets are the most preferred dosage forms, so why do we still need capsules? |
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Definition
| Some materials cannot be compressed, or are not chemical compatible, some need to be in a liquid or semi-liquid formulation to increase the bioavailability (increase solubility), some drugs need to be a controlled release |
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