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Webinar on Dissolution Performance on SCG – Q&A Session

We want to thank all of our May 18 webinar attendees! Those who weren´t able to join us on the live session can still watch the webinar on-demand by clicking on the following link
 
The Q&A session during the event was a huge success, unfortunately we weren´t able to answer all of them live, so here are the answers to each one of the questions submitted during the webinar. If you have more questions related to this topic please feel free to contact us at Softigel@procaps.com.co


Does it make any sense to perform disintegration test on non-dryed capsules as an IPC during encapsulation of SGC? Would it give any significative information relating to how the product will behave once dried?

Non-dried capsules show low disintegration times, as expected. They could detect formulation deviations in regards to the gelatin or the plasticizer content as well as deviation in the process parameters such as thickness. However, there is not any indication that these results predict the disintegration behavior during the shelf life of the product.
 


How do you demonstrate that your method is discriminating: manufacture of different batches (different properties) or testing stability samples ?

A discriminative method should be demonstrated at the analytical development phase and during the method validation. To evaluate if the analytical method is discriminative, the FDA guideline recommends to test batches with relevant differences on critical formulation and process parameters to challenge the method. For example, at the preformulation phase, some parameters in the fill formulation that affect the bioavailability , such as particle size distribution, pH and surfactant concentration should be tested at different levels. At the manufacturing phase, the dissolution profiles of different batches using the validated method are compared through the similarity factor (F2). At the stability studies, the critical parameters that are affected by stability conditions should reflect differences in dissolution profiles that must be detected by the analytical method. 
 



If a RLD rug uses B-type gelatin, can one use RXL gelain to avoid crosslking in the generic drug. What are the difference in compositions? and how the two be distinguished physically?

In general terms, it is not required to use the same excipients of the RLD product. The selection of type A or type B gelatin is related to the chemical compatibility, then it is recommended  to select type A for acid drug substances or type B for basic APIs. In our understanding, RXL gelatin is available either type A or B, then it is possible to use the required type to reduce the crosslinking in a generic product. 
 


Does thickness of the shell plays an important role in dissolution as well as disintegration test?

Gelatin thickness is a critical parameter since it could affect the disintegration test. It should be determined by the optimal thickness in regardsto the gelatin formulation (% gelatin, % plasticizer) and the product formulation (i.e suspension as a fill content) since it determines the product performance in the encapsulation process.



How cross linking will effect the drug release from the dosage form

The effect of crosslinking in SGC is the increase on disintegration times that in some cases avoids or delays the release of the fill content. This results on a non-compliance of the dissolution test or a high variability between the results of each tested capsule.


How to prove the discriminatory power of dissolution method for soft gelatin capsules containing microemulsion preconcentrates

These kind of formulations should be evaluated by means of some alternative in vitro techniques, such as the dispersion testing and the digestion assay, since the conventional USP dissolution testing does not provide an adequate indication of their in vivo dissolution performance. The discriminatory power of these tests is determined by testing the critical parameters such as API particle size distribution and surfactant type and concentration at different levels. Then it is expected that the analytical method is able to detect the difference between batches.
For more information on the development of in vitro methods to assess the performance of Lipid based Drug Delivery Systems by means of dispersion and digestion, please consult: http://www.lfcsconsortium.org



Will the plasticizers and high amount of colorants (iron oxides) affect dissolution rate?

The type of plasticizer and its concentration affects the dissolution rate, since these determine some other parameters such as hardness and mechanical resistance of the softgel. In the case of colorants,  the interactions API-colorants and API-gelatin should be evaluated, since some colorants are involved with crosslinking reactions, with exception of the  iron oxides. In the case of high amounts of colorants, the effect on disintegration and dissolution should be tested case  by case, particularly in colorants such as red #40 and yellow #10, among others which are known to promote the crosslinking reactions.
 



What is your experience in achieving dissolution bioequivalence with respect to Japan submissions for SGC

Currently, we do not manufacture products for Japan, but if you have some particular concerns about dissolution, we could provide some information based on our experience.