when comparing comparative dissolution of our product (Cefpodoxime 200 mg F.C.T) with Cefpodoxime Proxetil Tablets (Innovator), and according to USP; at pH 3.0 (Glycine), our product showed 45% after 10 mins, while the innovator showed 100% after 10 mins; in turn, at pH 1.2 (0.1N HCl), our product showed 100% after 10 mins, while the innovator showed 35% after 10 mins., although both are acidic!
Our product contains carmellose calcium, hydroxypropyl cellulose low substituted, sodium lauryl sulphate, magnesium stearate and lactose monohydrate (as much as close to the innovator).
Based on our data collection, Cefpodoxime Proxetil is BCS 4 (low solubility and low permeability) and has high molecular weight.
Any further details upon your request
Could you please help me to investigate this problem?
What do you want to achieve??45% after 10 mins, while the innovator showed 100% after 10 mins OR at pH 1.2 (0.1N HCl), our product showed 100% after 10 mins, while the innovator showed 35% after 10 mins?
how about with the visual observation? wheter all tablets disintegrate completely? if differentt behavior, those excipients are pH dependent and if disintegrate completely, check your API and innovator API properties, may be different from API form
That is why ask you. What do you want to achieve with your product? 45% dissolution or 100% dissolution?? Tell me more about marketed tablets
Of course, I wanna prepare a product has the same dissolution behavior/pattern as the innovator to be eligible to be registered according to MOH regulations and guidelines. Although we used the same excipients as the innovator, and formulated at the same punch and hardness, we didn't succeed to get the same dissolution behavior/pattern, especially at those mediums (Glycine pH 3.0 and 0.1N HCl pH 1.2). Take into your consideration, we tried with both micronized grade and compacted ingredient. I also tried to do solid dispersion and melt granulation to enhance the solubility, dissolution and bioavailability of our product, but didn't succeed. The active powder turned into YELLOW paste indicating a kind of hydrolysis (chemical structure of Cefpodoxime contains amide and ester groups).
Hi Ahmed, I think the issue is the formation of "diffusion layers" enhancing the solubility of your product. these layers are formed due to alkaline nature of your product matrix. so please measure the pH of 1% solution of your product and the innovator one. You will need to change one or more of the excepients beside sodium lauryl sulphate may play important role in that aspect
Thnx a lot Dr Ahmed Badr :)
Indeed! As a first point, I was thinking of excipients as they're pH-dependent excipients, but the innovator has the same excipients with different quantities. Then I thought of the nature of active ingredient as maybe the innovator were formulated using a co-processed active ingredient.
I didn't understand the point of SLS. It's mainly used as a wetting agent and penetration enhancer in a conc. of 1%. Do you wanna increase, decrease its conc. or remove it?. Some of my colleagues made trials using a low conc. of SLS and others without, and nothing happened. We obtained the same results in dissolution.
I guess the significant difference could be probably due to the nature of the active ingredient and to some extend the concentration of excipients.
I would like to know some points for innovator product as well as your product and I would insist to do some study and tell me the results:
1) Give micromeritics properties of your API
2) What is the solubility of 1% solution of your pure API at pH 1.2, pH 7 and pH 9.2?
3) Method of preparation of blend for compression. e.g. dry granulation, wet granulation or direct compression
4) HPMC grade
5) Magnesium stearate concentration if you have added it extragranularly
6) pKa of your API
7) Practical Saturated solubility data of your pure API at pH 1.2, 3, 4.2, 6.8, 7, 7.4 and 9 (do not provide literature data as API properties may get differed from source to source)
I will tell what is solution perfectly..
Dear Dr Himanshu Bhatt,
Thank you for your concern. Here is below the answers of your questions. I am looking forward to your help and support.
(1) I am using Cefpodoxime Proxetil (micronized grade), d(90) at least below 50 microns. It is a white to light brownish-white powder, odourless or having a faint odour.
N) we made some trials using Cefpodoxime Proxetil (compacted). It gives good results, but not as the innovator.
(2) Very slightly insoluble in all aforementioned pH (Cefpodoxime Proxetil is BCS Class VI).
(3) Direct Compression Tecnqiue
N) Wet granulation technique gives better results, using different excipients at different conc.
N) Melt granulation technique isn't applicable in our case as the powder blend turned into yellow in color with unpleasant-smelling.
N) Solid dispersion method isn't applicable as well.
(4) HPC Low Substituted (as the innovator)
(5) 0.5% Magnesium stearate as a water insoluble lubricant
(6) pKa of Cefpodoxime Proxetil ∼2.20 ± 0.10
Any further details or documents upon your request
Sincerely,
Ahmed Agiba
I agree with Ahmed Ibrahim, as API is having pH dependent solubility. But I suspect Carmellose Calcium as well. Please check whether innovator also used same salt of Carmellose.
Just to confirm, whether the dissolution different is due to change in pH of dissolution media by excipients, please check the pH of media after dissolution. If the composition, grades and amount in in your formulation is similar to innovator, the pH of media will also be same. If you find any significant difference, please play with the amount of Na-SLS and Ca-carmellose in your formulation.
Thnx Dr Sirmanta for your answer
Yes, the innovator is using Carmellose Calcium. I will try to optimise the concentration of both Carmellose Calcium and SLS. Hope it will be solved.
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