Hi,

Some thing wrong in your calculation.

Entrapment and encapsulation efficiency are different parameters.

The theoretical percentage of drug loading (TDL) was calculated using the following equation.

TDL = (Weight of drug added (g)/Weight of polymers and drug added (g)) x 100 (1)

For eg if you use 2 g of drug and 8 g of polymer, then the theoretical loading is

2/10 x 100 = 20, hence the theoretical loading is 20% w/w.

Assume that, during analysis each gram of microspheres contains 100 mg of drug.

Then actual loading is 100/1000 x100 = 10% w/w.

The percentage of drug entrapment efficiency (DEE) was calculated according to the following

DEE = (Experimental drug loading/Theoretical drug loading (TDL)) x 100 (2)

As per the above example the DEE = 10/20 x100 = 50% w/w.

Lets assume the yield of the microsphere is 9 g. Remaining one gram lost during the manufacture.

In the 9 gm, we have 10% of drug that mean 900 mg of the drug.

Encapsulation efficiency = total amount of drug in the yield (g)/ actual amount of drug added during microencapsulation (g) x 100

hence, 0.9/2 x 100 = 45% w/w . It means only 45% of employed drug was encapsulated and remaining 55% was lost during washing/recovery etc.

Hope this will help you.

Hi,

Some thing wrong in your calculation.

Entrapment and encapsulation efficiency are different parameters.

The theoretical percentage of drug loading (TDL) was calculated using the following equation.

TDL = (Weight of drug added (g)/Weight of polymers and drug added (g)) x 100 (1)

For eg if you use 2 g of drug and 8 g of polymer, then the theoretical loading is

2/10 x 100 = 20, hence the theoretical loading is 20% w/w.

Assume that, during analysis each gram of microspheres contains 100 mg of drug.

Then actual loading is 100/1000 x100 = 10% w/w.

The percentage of drug entrapment efficiency (DEE) was calculated according to the following

DEE = (Experimental drug loading/Theoretical drug loading (TDL)) x 100 (2)

As per the above example the DEE = 10/20 x100 = 50% w/w.

Lets assume the yield of the microsphere is 9 g. Remaining one gram lost during the manufacture.

In the 9 gm, we have 10% of drug that mean 900 mg of the drug.

Encapsulation efficiency = total amount of drug in the yield (g)/ actual amount of drug added during microencapsulation (g) x 100

hence, 0.9/2 x 100 = 45% w/w . It means only 45% of employed drug was encapsulated and remaining 55% was lost during washing/recovery etc.

Hope this will help you.

Hi Dr Saravanan,

Thanks for the feedback!

If you don't mind, can I ask:

1) What is the difference between entrapment and encapsulation efficiency? As both words refers to the amount of drug inside the spheres? How do I choose which calculation to use. As you mention both are different parameters?

2) I am not so clear on Actual Loading calculation. 

The assumption that 1gm microsphere= 100mg drug

is this a self assumption? Or  like I make from calculation from absorbance?

That is 10 mg powder/microsphere= 372µg drug

So if i calculate based on your example:

Theoretical drug loading: (1.5/6.5) X 100 = 23.08%

Based on concentration absorbance calculation:

10 mg powder/microsphere= 372µg drug

= 1 gm powder/microsphere = 37200 µg drug

Actual Drug loading: (0.0372gm/1gm) x 100 = 3.72%

DEE% = (3.72/23.08) x 100 = 16.11%

Yield of microsphere= 1.6532gm

in 1.6532gm, there are 0.0615gm drug

Encapsulation Efficiency = (0.0615gm/1.5gm) x 100 = 4.1%

Hi,

% Encapsulation/Entrapment/Association efficiency= (Amount of drug recovered/Total amount of Drug used) *100

Theoretical Drug Loading = Amount of drug weighed at beginning/Total amount of Drug+Excipients

Practical Drug loading= Amount of drug extracted from microsphere/Total amount (weight) of microsphere(i.e. Yield)

 In your case, you are determining %EE and the formula is correct. I will also suggest to go for Mass-balance calculation. You have to determine the drug in supernatant (unentrapped drug), drug from the washing and drug extracted from microspheres/matrix. The sum should be near to 100%. If the sum deviating too much from 100%, then check your calculations and also dilution factor which you use for UV measurement. 

Hope this answer help you.

Hi Maryam,

Scientifically the drug should be extracted from nano/microparticles (direct method) and use the same for encapsulation efficiency (EE) calculations. In case of nanoparticles, sometimes it is difficult to extract drug from them and thus free drug content from supernatant (indirect method) is used to calculate EE. Direct method is more reliable and scientifically acceptable.

If my particles are matrix/microspheres

By subjecting the dried microspheres with solvent (methanol) and stirring/sonicating it, then centrifuge and then measuring the supernatant absorbance. I should be getting the amount of drug extracted from microspheres or is it unentrapped drug?

or if i just hand shake the dried microspheres with solvent (methanol)  and then measuring the supernatant  absorbance, would that be consider the amount for unentrapped drug?

When you centrifuge your microparticles/matrix dispersion, then amount of drug in supernatant is unentrapped drug. Also the amount of drug adsorb on microparticles/matrix surface is also unentrapped drug which you can remove by washing. After this when you extract drug from microparticles/matrix by addition of methanol and then sonication, this is entrapped drug. The sum of unentrapped and entrapped drug should be near about total amount of drug you used at the beginning. If it is too low then there is problem in your extraction method.

I think my extraction method might be a problem.

Would the type of solvent used (methanol etc) might affect the results?

Yes. Off course, solvent affect your analysis method. You need to have calibration curve in same solvent which you use for extraction. Also you need to check for method of extraction, solubility of your drug and excipients in the solvent. Also you need to check effect of excipients on your analysis method. Lot of things you need to do. Just do it one by one and you can solve this problem.

1) I find so far that the drug dissolve more in ethyl acetate (10mg/ml)  than methanol (2mg/ml).

But strangely when I measure absorbance and calculate the concentration & finally EE%.

The drug concentration in 10 mg microparticles is higher in methanol than in ethyl acetate.

Could such thing happen?

2) By the way, is this right?

= the wall material/excipients should not be dissolve in the solvent; only the drug to measure the absorbance?

= After sonification, centrifuged, filtering the supernatant and measure the absorabance. My blank is methanol. is this adequate enough? Because I centrifuge and use a filter?

3) Can I use ultrasonic homogenizer instead of sonification to break the dried microparticles to release the drug?

Hi Zi Teng

1) Before filtration is milky. After centrifuge is 2 layer with the supernatant quite clear. Then I filter the supernatant with 0.45μm before measuring the absorbance, so it looks clear like water. So cant really be the turbidity?

2) So lets say example 3 wash (each wash 5ml)  before absorbance near zero.. and you calculate concentration from standard curve

Wash 1= 1ppm x 5ml = 5μg

Wash 2= 0.5ppm x 5ml = 2.5μg

wash 3 =0.1ppm x 5ml = 0.5μg

Amount of untrapped drug =5=2.5+0.5 =8μg

AMount of drug added to formulation = 500000 μg

So Encapsulation Efficiency = [1-(8μg / 500000 μg] x100 = 99.998%

Its the calculation suppose to be like this for your method?

3) I do not really understand something. 

If my drug dissolve in ethyl acetate around 13mg/ml. How would filtering the drug like your method able to dissolve the drug immediately to pass through the filter paper?Should it not have some kind of force/shear to facilitate the dissolving of the drug?

4) If Matrix /microsphere system should have the drug inside and outside on the surface. Why would there be entrapped drug?Since there are suppose to be drug on the surface?

1) why so the loss of drug wit 0.45um?if the drug dissolved,wont it pass easily through?wat pore size is recommended then?

2)my calculation correct!will the effect be same if microparticle+solvent is handshake then filter n measure absorbance?

3)i'm still unsure why matrix surface drug is consider unentrapped since its part of the matrix.

THANKS ALOT!

Hi Zi teng,

1) Ok I understand that some volume of drug adhere to the membrane hence the lost. But if the drug already dissolved into the solution making up a X ppm before filtering. Does not matter if there is lost of volume?because u r measuring the absorbance of the already formed X ppm?

2) I shall try handshaking it. By the way, do you have any recommendation on filter pore size?

Centrifuge and Filter?

1) Hi zi teng,

Your control for absorbance reading is:

- Solvent  or 

-Solvent+blank mircrosphere

2) By the way ; are these formulas the same?

i) Encapsulationefficiency (%) = [1-(Drug in 

supernatant liquid / Total drug added)] x100

ii) Encapsulation efficiency (%) = (Total drug added - Drug in supernatant liquid) / Total drug added)] x100

thanks for the feedback~

dear all, would like you to help me?

it's my case, in my research i maked curcuminoid loaded in solid lipid nanoparticle (SLN) and i got the problem to calculate Entrapment Efficiency (EE).

this is my composisition a part to make SLN, 0.1 gram curcuminoid, 0.5 gram poloxamer, 1 gram palmitic acid, all mix in 100 mL reverse osmotic water (RO).

i followed  Yadav V et al. 2008 method to calculate EE.

1th. 3 mL SLN solution is setrifugated to separate SLN and unentrapped curcuminoid

2th, the pelet (assuming contain curcuminoid in SLN) is added 3 mL methanol                   to extract and suck out the curcuminoid. Next is sentrifugated this                             solution to separate lipid and curcuminoid solution.

3th, solution contain 2 part, pelet and supernatant

4th. check supernatant absorbance 

5th. by using a standart curve, the concentration of curcuminoid is 0.019489 mg/mL.

6th.EE = 0.019489 /1  = 1.948%

is it true? 

%EE is ( total drug present in pellet and supernated-drug in supernated i.e free drug) is a drug encapsulated in SLNs. then divide it with total drug present in pellete and supernated then multiply with 100.

Hi,

I'm having problems with finding references that compare and discuss the direct and indirect way of determining encapsulation efficiency, can you recommend any?

Actually, I still dont really get it.

Some say there are no difference between encapsulation and entrapment efficiency; some say got.

According to Dr Saravanan example, there seems to be a difference between the both.

Hi all.. What if i just have UV data(Difference in absorbance values for pellet and supernatent ) and if my sample is liquid ? i jus found the concentration using calibration curve and the concentration is in uM (micro molar) How to calculate encapsulated efficiency?

As per my understanding on this subject the drug loading will have direct impact on the assay of the product.

Question 1) For calculation of drug loading is assay required?

2) From  Assay value how we can determine the drug loading?

3) How to determine the drug loading for RLD product?

Kindly provide the solution for these questions. 

In order to calculate the encapsulation efficiency , you have to fully dissolve your powder using a suitable solvent. then only full amount of drug entrapped come out. sonicating  for 12 minute will resale some of the drug in your power not all 

percentage of loading capacity (LC) was determined according to the following equation:

LC (%) = (Total amount of drug incorporated into nano/microparticles/ Amount of nano/microparticles used) ×100

drug entrapment efficiency  (EE) was expressed according to the following equation:

EE (%) = (Actual drug content in nano/microparticles /Initial drug content of nano/microparticles used) ×100

Hi

Can i compare two EE% with two differents therotical initial drug??

What do you mean Federico Karp ?