Lab 6

Question 1

APIs that are extremely lipophilic/hydrophobic are practically insoluble in water.
How can they be dissolved in water?

Answer 1

by using cosolvents or with pH modification

hydrophobic drugs can be solubilized with the use of SOLUBILIZERS and COMPLEXING AGENTS

Question 2

Oral non-aqueous solutions of lipophilic APIs may be prepared in ___ and ____

Answer 2

fixed oils (peanut, corn, soybean, sesame, olive) and medium chain triglycerides

Question 3

“oral non-aqueous solutions of lipophilic APIs may be prepared in fixed oils and medium chain triglycerides.”
these oral solutions may be flavored to improve taste, but generally are not appealing.

How are these solutions normally administered to combat this issue?

Answer 3

by mixing with food or filled in soft gelatin capsules.

Question 4

soft gelatin capsules are what dosage form?

Answer 4

solid oral dosage form

Question 5

give 7 examples of water-insoluble APIs

Answer 5

-Vitamin A
-Vitamin D
-Vitamin E
-Vitamin K
-CNS drugs (diazepam and barbiturates)
-hormones (progesterone)

Question 6

SURFACTANTS can solubilize drugs by either ___ or ____

Answer 6

surfactants can solubilize drugs by either a DIRECT COSOLVENT EFFECT or UPTAKE INTO MICELLES

Question 7

explain the structure of a surfactant molecule

Answer 7

contains a hydrophobic portion (the tail) and a hydrophilic portion (the head)

Question 8

what is the function of surfactants

Answer 8

to solubilize poorly water-soluble drugs

Question 9

the HEAD of a surfactant can be ____,____, or ____

Answer 9

CHARGED (anionic or cationic)
DIPOLAR (zwitter ionic)
NON-CHARGED (nonionic)

Question 10

give the surfactant used in vitamin D2 formulation

Answer 10

cremophor

Question 11

cremophor is a _____ surfactant used to solubilize ……..

Answer 11

NONIONIC surfactant used to solubilize a wide variety of hydrophobic CNS drugs (diazepam, barbiturates), and anticancer drugs

Question 12

explain micelles are formed

Answer 12

when surfactant molecules are dissolved in water at concentrations above CMC (critical micelle concentration), they form aggregates known as micelles

Question 13

micelles are formed when _____ molecules are dissolved in water at concentrations above CMC

Answer 13

SURFACTANT

Question 14

explain the structure of a micelle

Answer 14

the hydrophobic tails flock to the INTERIOR to minimize contact with water.
the hydrophilic heads remain on the outer surface to maximize their contact with water

the hydrophobic drug is bound to the surfactant (micelle) and go to the interior of the micelle

Question 15

the shape and size of the micelle formed depends on what FOUR things?

Answer 15

1. the chemical structure of the micelle
2. surfactant concentration
3. presence of other surfactants, ions, and molecules
4. pH

Question 16

the ____ the cmc value of a given surfactant, the more stable are the micelles

Answer 16

LOWER

Question 17

Precipitation is likely to occur if the preparation is diluted _____ the cmc concentration

Answer 17

BELOW

Question 18

name 4 water-soluble organic solvents

Answer 18

-ethanol
-propylene glycol
-glycerin
-polyethylene glycol 400 (PEG 400)

Question 19

name 6 water-insoluble solvents

Answer 19

-peanut oil
-corn oil
-soybean oil
-sesame oil
-olive oil
-medium-chain triglycerides

Question 20

name a complexing agent

Answer 20

cyclodextrins

Question 21

name 4 surfactants

Answer 21

Cremophor EL
Cremophor RH 40
polysorbate 20
polysorbate 80

Question 22

heat is used to increase the ____ and does not affect the ____ of the substance

Answer 22

heat is used to increase the RATE OF SOLUBILIZATION and does not affect the intrinsic solubility of the substance

Question 23

before using heat, what should you do??

Answer 23

check the properties of each ingredient to ensure that they do not degrade or evaporate

Question 24

heat is used when preparing _____ solutions

Answer 24

HIGHLY CONCENTRATED

Question 25

give 2 examples of highly concentrated solutions

Answer 25

simple syrup
sorbitol 70%

Question 26

heat should NOT be used with ____ substances that __ during dissolution

Answer 26

exothermic substances that give off heat during dissolution

Question 27

true or false:

when using heat, you should use the lowest temperature possible

Answer 27

TRUE

Question 28

true or false:

hot plates (direct heat) are preferred over water baths

Answer 28

FALSE – water baths should be used for heating

Question 29

when using heat, temperatures greater than ___ are usually not used

Answer 29

70 degrees celsius

Question 30

____ or ____ are used to prepare drug loaded micelles.

which did we use in this lab?

Answer 30

heat or solvents

we used heat (water bath)

Question 31

explain the process of using heat to prepare drug loaded micelles

Answer 31

heat stable oily ingredients (hydrophobic API, antioxidant, surfactant) are mixed together using heat

water is heated separately to ~65 degrees celsius then added slowly to the oily solution under constant stirring until a clear homogeneous solution is obtained.

heat-labile (destruction under heat) and water soluble ingredients are dissolved separately in water at room temp and added to the preparation just before making up the volume (QS) with the vehicle

Question 32

the minimum amount of water required to make a clear solution is calculated using…..

Answer 32

SOLUBILITY INFORMATION

Question 33

true or false

cremophor/oil micelles will not have some displacement volume

Answer 33

FALSE – they will have displacement volume

Question 34

the preservative required is based on…..

Answer 34

THE WATER VOLUME USED IN SOLUBILIZING THE OIL (forming a micelle) and in dissolving the water soluble powders

(volume of color and flavor is almost insignificant)

Question 35

what is the function of BHT (butylhydroxytoluene)

Answer 35

antioxidant – stabilizer
insoluble in water (it’s an organic compound)