Stability of ASD

Question 1

Definition of ASD

Answer 1

Amorphouse Solid dispersion

Question 2

Physical formulation methods to enhance the solubility

Answer 2

Amorphous Solid Dispersion and Nanosuspensions

Question 3

ASD improved dissolution profile

Answer 3

Faster dissolution and Supersaturation

Question 4

What are the main differences between amorphous and crystalline API

Answer 4

Near order, Tg and thermodyanmic instable amorphous

Near and Far order, Melting point and thermodynamic stableare

Question 5

What are the properties of polymers

Answer 5

usally high glass transition temperature and high viscosity

Question 6

What are the steps during the dissolution of crystalline APIs

Answer 6

Disruption of crystal lattic, solvation or hydration of molecules, breakage of solvent/hydrogen bonds to accomadate molecules,

Question 7

the disruption of crystal lattice is

Answer 7

endothermic

Question 8

solvation of molecules is

Answer 8

exothermic

Question 9

Breakage of solvent

Answer 9

endothermic

Question 10

engery in disolution

Answer 10

endo or exothermic depending on the dominant energies

Question 11

when do we have poor solubility

Answer 11

high lactic engergy and/ or poor solvatioan

Question 12

What does it means if there is no lattic energy

Answer 12

better solbility

Question 13

What is the driving force for crystallization?

Answer 13

the higher supersooling

Question 14

what does supercooled glasses have?

Answer 14

they have a higher Gibbs energy in comparison with crystalline materiall

Question 15

Why are amorphous API thermodynamically instable?

Answer 15

Due to their high free energy

Question 16

How can amorphous API be stabiliziert

Answer 16

with Polymer

increasing the solubility, Miscibility and Kinetic stability

Question 17

What is mix tg line

Answer 17

it is the tg of the API and that of the polymer, mixture in einer molecule level

Question 18

when can the mix tg be formed

Answer 18

when the APT has a good solubility in the polymer and mixability

Question 19

What happend if the solubility of the API is low

Answer 19

it will lead to phase separtaion, due to the different tg

Question 20

When the ASD kinetic stable

Answer 20

When it is stored below its tg

Question 21

What happend if the drug load is higher than the solubility line

Answer 21

is will be thermodynamic stable, reducing the solubility

Question 22

what happend if the drug load is high

Answer 22

it could lead to kinetic stability, but is shouldn’t go above the mix tg , which will lead to the thermodynamic instable state

Question 23

what does Spring means?

Answer 23

Amorphous API have a high energy state, which leads to a high apparent solubility. Without a stabilizing agent, precipitation will occur

Question 24

Describe the word parachut in respects of the ADS

Answer 24

Due to adding of the Polymers as a stabilizing agent, there will be an temporary inhibition of precipitation

Question 25

What's the different between the apparent solubility and the true solubility

Answer 25

the treu solubility is in the thermody.equilibrium to most stable solid form, whereby the apparent solubility is the unstable form

Question 26

Which parameters are influnces by the Polymer excipients

Answer 26

API solubility, degree of supersaturation, viscosity, molecular mobility, nucleation, configurational entropy and free energy of ASD

Question 27

how does the polymer excipient influnces the parameters of the ASD?

Answer 27

API solubility (increase), degree of supersaturation (Decrease), viscosity (increase), molecular mobility (Decrease), nucleation (decrease), configurational entropy (increase )and free energy of ASD (decrease)

Question 28

What are the effect of the ADS parachut interactions?

Answer 28

Higher activation energy for nucleation | slow crystal growth due to adsorption on crytal surface

Question 29

API with high tg

Answer 29

they are good so solubilized

Question 30

Name 4 effects on physical stability of ASD

Answer 30

Glass transition temperature of amorphose drugs and polymers drug-polymer miscibility solid solubility of drugs in the polymers molecular weight of drugs

Question 31

What are the preparation process, ASD?

Answer 31

Different thermal histories and mechanical stresse. | Using different degrees of drug-polymer mixing and drug mobility in ASD

Question 32

Production of ASDs

Answer 32

Melting and dyring processes

Question 33

what affects the stability of the ASD exstrusion

Answer 33

the resistence time, the high temperature

Question 34

What is the disadvantages of the spray drying ASD?

Answer 34

difficult to fine sovent for both API and polymer

Question 35

characterization Methods for crystallinity

Answer 35

DCS, XRPD, FTIR-Spectroscopy

Question 36

characterization Methods for Homogenity

Answer 36

FTIR, NMR

Question 37

characterization Methods for Interactions

Answer 37

FTIR

Question 38

Describe how the differential scanning calorimetry works (phases)

Answer 38

Power compensating DSC, Heat flux DSC Measurment

Question 39

Power compensating DSC

Answer 39

Recording of differential power signal, which is a function of actual sample temperature

Question 40

Heat flux DSC

Answer 40

Temperature differrents between the sample and reference and it is plotted gainst time Integration of differences Transfer into heat flux

Question 41

Measurement in the DSC

Answer 41

Sample filled up, reference and sample are heated or colled--> temperature diagram

Question 42

x-ray powder diffraction different between crystalline and amorphous state

Answer 42

Crystalline state: Angle dependent high x-ray intensities detected Amorphous state: no Bragg Peaks detected

Question 43

FTIR-spectroscopy used for?

Answer 43

Crystallinity

Question 44

which other method can be used to check Crystallinity

Answer 44

DSC, XRPD, FTIR spectroscopy

Question 45

FTIR-spectroscopy advantages

Answer 45

improved signal to noise ratio faster detection of spectra improved wave numer accuracy API-polymer interaction