Cytotoxicity assay and evaluation of thermoreversible in-situ gel for intranasal drug delivery of Sumatriptan: Preparation and Evaluation

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Intranasal route is effective alternative for drugs administration due to patient conveniency and direct delivery of drug to the brain bypassing BBB. Sumatriptan is a 5HT1d receptor agonist used mainly in migraine and cluster headache having limitation of bioavailability for oral route and patient inconveniency for parentral route. Intranasal delivery of sumatriptan may overcome these limitations using thermoreversible Poloxamer 407 gel as an alternative formulation.

Cytotoxicity assay was performed using various concentration of drug from 10 to 100µg/ml over LN-18 cell line. Sumatriptan loaded Poloxamer 407 gels were prepared in 18%w/v, 20%w/v and 22% w/v concentration using cold method. Gel was evaluated for drug content and drug content uniformity using UV spectrophotometer at 283nm wavelength, gelation and gelmelting, Bioadhesivity using bioadhesion tester, viscosity analysis using Brookfield viscometer at 370C, plain polarized microscopy, in-vitro diffusion using dialysis tube and in-vitro drug release study using nasal diffusion cell in phosphate buffer pH 6.4 and histopathological study of sheep nasal mucosa.

No significant toxicity was observed for any concentration of drug as compare to control cells. Percent drug content was 80-90% for each batch with uniform drug distribution, Gelation temperature was decreased as the concentration of Poloxamer 407 gel increased, increased bioadhesion and increased viscosity from 10000 cp to 18000 cp were observed as concentration of Poloxamer increased, plain polarized microscopy showed no physical change in gel structure, 40% in-vitro diffusion and 45% drug release was observed with zero order kinetic and histopathological analysis showed no changes in the morphology of nasal mucosa. It was concluded from the result that thermoreversible in-situ gel is good alternative for Sumatriptan drug delivery.

Author : http://www.pharmainfo.net/karim
Co-author : http://www.pharmainfo.net/bhavikjoshi
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raghavendra swamy's picture

Karim, 1) you have given

2

Karim, 1) you have given introductory pictures and it would be better if you have given some comment about it.
2) can you explain me why increase in gel concentration increases the bioadhesivity ? explain me with reason.

Pavan Kumar Alapati's picture

assay

2

Explain the procedure of MTT assay?

KINJAL B. RATHOD's picture

Question

3

Hello,

Can I know from where u got LN-18 cell line???

Regards

shobha deepthikompella's picture

hi i have a queiry

2

1.can you tell me some more methods for the evaluation of cytotoxicity.
2. tell me the methods which are under clinical trials

With Best Wishes

ROSHAN KUMAR SAHU's picture

invitro methods

2

nice

please clarify the statement with references
" i have some other in vitro methods for evaluation of cytotoxicity of my formulation"

Sandeep Bhaskar Kale's picture

Acceptability of assay and polymers for gel

3

1. Invivo versus invitro assay? can you comment on its acceptability and usefulness?

2. Thermoreversible and smart polymers for gel. are they same or different?

Dr.Sandeep Bhaskar Kale
http://www.pharmainfo.net/sanykale123

KINJAL B. RATHOD's picture

Query

3

Hello,
can u explain cytotoxicity assay MTT in detail??

regards

Dr. T.E.G.K. Murthy's picture

Quaries related to Gel

2

1. What is the concentration of sumatriptan in the gel?

2. How much amount of gel is used in these studies?

3. Is there any correlation between viscosity & mucoadhesion.

4. What is the reason for elevation of viscosity of the gel with the incorporation of drug?

5. What is the particle size of drug & its distribution in the gel?

6. Is there is any relation between particle size of drug and the efficacy safety of gel.

Jithan Aukunuru's picture

Incomplete!!

3

1. In conclusion slide why there is a different drug: Ondanestron while the title shows sumatriptan?
2. In these type of studies, being a biopharmaceutical scientist data from an animal study would be interesting, which you have not shown in the presentation.
3. Interesting but lacks punch.
4. Several similar studies are found in the literature.
5. Please comment.

komal nikam's picture

NASAL DELIVERY

3

HY KARIM!!!!!!!

CAN U PLEASE TELL ME THAT - NASAL DELIVERY HAS MANY ADV. STILL WHY IT IS NOT SO MUCH WHAT IS REASON & DRAWBACKS OF IT?
ALSO ANY NANOGEL FORMULATION USER IN CANCER?

Srujana.G.'s picture

Sumatriptan kinetic study

2

Hi...
your presentation was good. I would like to know few things about this Sumatriptan. What is the chemical composition of the drug and what is LN-18 cell line study? and what are kinetic parameters of your drug and how drug is administered through intra nasal route

Bhasker's picture

Kinetic drug release

1

Dear karim,
Let me know what is the Kinetic drug release pattern of your formulation and its difference from the conventional dosage forms?
2.Also you have commented that there was no significant toxicities with the above formulation.What are the different invivo models you have adopted and reached that conclusion?

Suhaas's picture

scientific approach of presenting the literature review

1

Dude, I don't mean to be rude but that is not a scientific approach of presenting the literature review(The works must be in chronological order)and in the drug content slide, you have mentioned the percentage drug content of sample-1 more than 100%(844).
I have a few questions,
1. The variable parameter in Brookfield's LVDV 2 model viscometer is
rate of shear. Then, howcome there is stress on the X-axis in the
rheological study graph.(The variable parameters must be on the
X-axis,Right?)
2. What is the torque range during viscosity determination?
3. What is the flow behaviour of gels?
4. What are extrusion and spreadability values of gels?
5. What is the percentage of drug in the gel?
6. How much quantity of gel was used in the diffusion studies?
7. Were there any nasal clearance studies?(If not, how can you tell
that bioavailability is improved with nasal administration?).

Suhaas

Suhaas's picture

drug-excepient interactions and any compatibility studies

1

Were there any drug-excepient interactions and were any compatibility studies conducted?

Suhaas

Varsha Bansode's picture

Relation in between sumatriptan and ondasetran

2

Dear Karim,
In your slides you have mentioned regarding sumatriptan drug and also about ondasetran. What is the relation in between them? If any, why both you have selected for ur work?

Varsha Bansode's picture

Bioavailabilty of sumatriptan and Prodrug approach

2

Dear Karim,

It’s very novel topic.

Pls clarify certain things to me...

You have mentioned that bioavailabilty of sumatriptan is very poor and all pharmacokinetic parameters such as half life etc are poor too. In such cases Can Prodrug approach will solve the problem?? Bcz all parameters which you have stated are perfect to use prodrug approach. If you will use this concept thenpls let me know how will you proceed?

Y mahalaxmi's picture

sumatriptan and ondasetron

3

Hello

Are sumatriptan and ondasetron different names for the same drug?
I just wanted to know because you started your presentation with gelation of sumatriptan and provided the data for ondasetron.

You wrote that "20% gel is easy for administration".Could you please explain the problems that you encountered while administering 18 and 22% gels.

Amol S. Malpani's picture

any other polymer

3

Dear Karim,
Are you tried to prepare this gel system by any thermoreversible polymers other than polaxomer 407?
regards,
amol

SHILPA.SAMBANA's picture

thermoreversible

3

Dear sir,

Thats a nice presentation.Can you please tell me the exact meaning of the "thermoreversible". And how far this nasal administration of sumatriptan has been developed clinically.

Regards,

shilpa.sambana

Shilpa.Sambana
http://www.pharmainfo.net/shilpasambana
St ann's college of pharmacy
Vizianagaram
Andhra pradesh, India