Questions related to Pharmaceutical Development
I usually face a problem regarding the specification limits for impurities in new drug products. It is difficult to use the calculations mentioned in ICH-Q3B(R2) guidelines. The reason is that our products (Ophthalmic preparations) contain very low concentrations of active pharmaceutical ingredient and accordingly the total daily intake (TDI) of these materials may not exceed 1 mg. Using ICH-Q3B(R2) guidelines gives very low specification limits that might become below detection limit or are somehow not practical.
I need your advice regarding specification limit determination for impurities in new drug products. We need a method for specification determination and justification because this is continuously requested by several regulatory authorities, within and outside my country.
We are developing newer technique for development of Solid Lipid Nano Suspension. but we stuck with zeta potential.
We got z-average size 215 nm but zeta potential -5. Now please help us how to improve zeta potential? We are using Compritol ATO as lipid, Tween 80 as stabilizer and Albendazol as Drug.
We tried KCL, and K2SO4 as electrolyte withing range of 10 to 1000 PPM.
When i get the Azoxymethane (AOM) i have stored it at -20. Before use i diluted it with %0.09 SF. After diluting i store AOM at -20 C again. In this condition, does AOM work or not ?
During formulation of syrup , the after taste is feel bitter because of tween 80's bitter taste. How to use tween 80 to avoid that.
I am preparing microspheres of chitosan but a simple emulsification method using liquid paraffin as an external phase and chitosan in acetic acid and glutaraldehyde 25% as an internal phase. So for emulsification I need to prepare 0.2% of span 60 solution in 1 liter of liquid paraffin.
How to calculate IC50 values to drugs that does not reach a 100% of inhibitory activity, for example? If I find a experimental value of 45% inhibition in the maximal concentration of solubility (for example 10uM), should I say that IC50 value is "higher than 50uM"? If one compound presents a inhibitory activity around ~60% at the highest concentration tested (total solubility), the 60% will be the "top" value to use to calculate IC50 ? thank you all!
Uniformity of dispersion test for tablets is carried out by passing through 22 mesh, is there any physiological relation with that?
-What are the latest techniques used for masking of the bitter taste in drugs how stable are they? Can we mask the bitterness of API's /drug's only with using Flavors? mostly in Orally Disintegrating Strip / Tablet. Could anyone suggest me?.
In dissolution study of gastro retentive tablet , How to select dissolution fluid and their volume if drug's formulation is not official in pharmacopoeia.
To reduce the number and suffering of animals, while focusing on drug-disease-drug/herb interaction(s), how much is it logically and/or scientifically accepted to use the same rats for invivo pharmacokinetics and invitro metabolomics experiments?
When invivo pharmacokinetics experimentation involves jugular vein cannulation for frequent blood sampling, this is a kind of major injury with temporary presence of foreign body in rat leading to alteration in immune cascade and/or body homeostasis.
On the other hand, even acute alteration in body homeostasis and/or immune cascade may alter the functional ability of certain drug metabolizing enzyme(s).
Considering these facts, how much is it logically and/or scientifically accepted to use, liver, kidney and/or intestine of the same rats for further invitro metabolomics experimentation after completion of invivo PK experiment.
If you want any additional information, I’ll be happy to provide it promptly.
Thanking you for your time and consideration of my request.
Looking forward for fruitful interactions...
In dissolution study of colon targeted tablet , How to select dissolution fluid and their volume if drug's formulation is not official in pharmacopoeia.
It was observed that the national branded company making aloe vera formulation for management of various ailment. In the same formulation Carrageenan is aided as adjuent. This formulation is frequently used by the patients with acidity, heart burn and ulcers. Let us discuss the impact of this formulation in these patients on chronic use.
the the levofloxacin disintegrates in stomach.. Can we make it colon specific by using enteric coating so that it absorption take place in colon??
pKa value of omeprazole is 4, while oxalic acid have 1.23 and 4 (diprotic).
I heard, if the difference between pKa values is less than 3, there will be chances of co-crystal formation. Kindly also suggest any software that predict co-crystal formation between molecules.
Need help in this regard
I am doing reserch on the preparation of PLGA microsphere by phase seperation,and i have made many trials to accelerate the release ,but it doesn't work. Does anyone who do related researches can share some experiences with me, for your help, i really appreciate.
I believe that we cannot consider Lipinski's RO5 since it does not apply to natural product compounds. Hence, I am not sure either Veber/Egan/Ghose rules can be implemented as well
The parenteral formulation of the drug is not available in the market.
The oral dose is known as the drug is available in tablet form and as an oral solution.
I'm looking for a good comparison across different routes of administration, and how the route affects bioavailability. Thanks!
"For a topical solution drug product, in vivo bioequivalence may be waived if the inactive ingredients in the product are qualitatively (Q1 ) identical and quantitatively (Q2 ) essentially the same compared to the listed drug. In this setting, quantitatively essentially the same means that the amount/concentration of the inactive ingredient(s) in the test product cannot differ by more than + 5 percent of the amount/concentration of the listed drug. Where a test solution differs in Q1 and/or Q2 from the listed drug, in vivo BE may be waived, provided the sponsor submits evidence that the difference does not affect safety and/or efficacy of the product at the time a waiver is requested." Quoted from FDA draft guidance "Topical Dermatological Drug Product NDAs and ANDAs - In Vivo Bioavailability, Bioequivalence, In Vitro Release, and Associated Studies. The last sentence says that in vivo BE may be waived if Q1 and/or Q2 are different from RLD, but sponsor must submit evidence that difference doesn’t affect safety and/or efficacy. What are some examples of evidence that the FDA would be looking for to verify safety and/or efficacy?
I have seen its application in many papers on modified release tablets but i got a reviewer's response on my paper that Hixon-crowel is only applicable to microspheres.
I would like to compare formulations for drug release and/or absorption and use in vitro method to shortlist formulations. Would a simple USP Apparatus II dissolution suffice to rank order formulations and predict in vivo performance?
Initially, we had prepared aqueous emulsion of soyabean oil and then sprayed this aqueous emulsion through FBP nozzle gun onto the particle bed for encapsulation of hygroscopic material. But, melting of the HSO at temperature 60-65˚C the material got stuck to the base plate of fluidized bed processor and also the nozzle gun of the fluidized bed processor get blocked.
My drug is specific to a nuclear protein. Trying to measure the intra-cellular binding affinity of drug to the target nuclear protein. I have tried to do the lysis of the cells using liquid nitrogen. The nuclear protein was not abundant after such physical lysis. Need help whether I can use any suitable lysis buffer? Can lysis buffer (e.g. RIPA or other types) denature the drug bound protein? Concerned about degradation of the binding between drug and protein if we use any lysis buffer..
Actually I want to know what really is when we say in vitro colonic drug delivery.. I have seen many papers with title colonic drug delivery in vitro colonic drug delivey but in there there is simple Dissolution profile or drug release in colonic medium! Is invitro drug delivery means simple drug release check in colonic medium ??
As example: Drug A (Km=2uM), drug B (Km=45 uM). If we do inhibition or DDI study with known inhibitor and found IC50 for drug A is higher than drug B. what will be the explanation of the result (IC50 or Ki) for two drugs (A and B)?
currently am developing ophthalmic nano emulsion there is problem in dissolution method as of now am working dialysis method but its doesn't work it seems can any suggest the suitable method for dissolution.
API Mw-500 daltons.
I invented a creme with natural compounds, which may help to alleviate the syntoms of psoriasis and eczema too. But I need to test on volunteers for a clinical trial, then if succeed we can patent. Pleas if someone is interested please contact me.
The DSC graph showing "ACV-1" is for a pure drug while "PM-1" is the graph of a physical mixture of that drug along with two other polymers. I had made the physical mixture in accordance with my formulation where the amount of pure drug was 200 mg and the cumulative amount of other polymers were around 1100 mg. I don't have in depth knowledge about DSC. So I will be pleased if anyone explain my issue in a simpler way. Side by side I will be happy to get some link of website or article from where I can get a basic idea of interpreting DSC graphs and use them as reference.
Thanks in advance.
I’m planning to investigate a substance with potential anti-tumor effect.I carried out the MTT assay and also got the IC50. For further study, I want to set up three different groups based on the dose-level of the substance(i.e. high, medium and low groups), in order to detect the mechanisms of such as proliferation and apoptosis. No former studies referred to any suggestive info. . I’ve attached and would like some advice about how to set up 'dose-groups' according to the IC50 or what you’d consider to be the most efficient method .
thank you so much!
Can anyone explain about the minimum dose required to see any effect based on EC50 or IC50? I mean, if some drug has IC50 (24 pM) then what minimum concentration of drug would be best in animal (in vivo) to see the inhibitory effects.
Methylfolate has been shown to help SSRIs work better in patient with difficulty converting folate to methylfolate. Deplin is methylfolate and it is being widely used to augment SSRIs in partial responders. Other supplements have combinations of methylfolate with other ingredients including follinic acid.
Hey I am about to start drug survival test in drosophila does anyone has tips of how to select drug concentrations, fly density.
And also do you put either paper filter or other kind of filters in your adult cultures as a way to increase the surface for the flies? If so do you change the paper if so how often?
all pharmacopeias state the tartaric acid in the L(+) isomer only (natural) but not the synthetic racemic form (DL). Since it is used as acidulent and excipient only and no structure- activity relationship is to e expected from the isomer, why the DL form is not stated in the pharmacopeias and has no specification for medical use ? The only difference I could find between them is the optical activity and the higher melting point of the DL form than the L form.
My study is comparing the effect of X drug. I used 2 groups one with Drug and other without(control). I measured the different parameters (HR, RR, BP, PCO2, PO2…ect) at the different times (before treatment and every 5 minutes till 2 hours just administration of treatment then 4, 8 and 24 hours after treatment.
I performed a pk study of a molecule with iv, ip and sc routes of administrations. The Pk parameters showed high bioavailability of molecule in ip (>100%) and Sc (~200%). I checked the data repeatedly and ensured that all the values from bioanalysis and dosing regimens were fine. Can anyone provide your suggestions in this regard. As far as my understanding goes it could be delayed clearance of the compound!!!!. Kindly provide your views.
I am working on formulation of tablet of hydrogel based orally controlled colon targeted dds. The ingridient iam using for hydrogel formation are HPMC K100 M and Eugradit RSPO. EUDRAGIT RSPO is a copolymer of ethyl acrylate, methyl methacrylate and a low content of methacrylic acid ester with quaternary ammonium groups.
General Question : if for any product, USFDA Database suggests to perform two methods for dissolution, as test 1: USP type IV, Test 2: USP Type II, What is basic behind the concept, Does Results of both req to be submitted for the approval of the product ?
How can we compare the In vivo studies results with antimicrobial studies results of a particular active constituent drug for a particular activity?
I have repeatedly used TLC to identify 4-(1-Piperidinyl)pyridine (4-P in the image) and it always appears as two separate spots when used with a 2:1 solution of CH2Cl2:MeOH. Does anyone know if there is a reason for this?
1) The New Field of Sustainable Entrepreneurship: Studying Entrepreneurial Action Linking ‘What Is To Be Sustained’ with ‘What Is To Be Developed’
2) How important is entrepneursip in the pharmaceutical industry?
values of samples ranges from (0.165-2.2080)
a lot of sample values below blank value
I need to know about excipients that could match the taste and grittiness of metronidazole.
There have been growing interests by consumers for natural food and supplement ingredients. which one of Anti-oxidant categories are technically more efficient for application? the Natural (plant extracts) or the synthetic (petroleum based like BHA, BHT, PG) ones?
I have been told that some anti-viral drugs only enter cells which have been infected by the virus. Apparently, these drugs do not enter cells which have not been infected. I want to know the mechanism behind this, preferably with some examples of anti-viral drug.
I'm doing a drug discovery project using Streptomyces. Apart from StreptomeDB, what HPLC-MS databases are good to search to see if I have a new compound? Thanks!
I know that because Acid Black 48 is cationic and the antibody is anionic, those two could non-covalently bind. Would this hypothetically work by allowing them to bind through mixing at 4 degrees celsius (temp. required for antibody)?
Drug is of BCS II class. Bath Sonication method showed improved results however the PDI was stable for less than 24 hours. Dissolution carried using cellophane membrane showed poor release. Any suggestion regarding improvement or alternative to the above will be helpful
When estimating EC50 for a single drug, does one need all of the raw data at each drug concentration or simply the average response at each concentration? How does one decide what model or equation to choose (e.g. four versus five parameter logistic curve)? When obtaining the EC50, is there a best approach for determining the 95% confidence interval?
Is it good for normal room temperature where perforated cloth is used to cover it to prevent any fallen objects into the sample?
Drying in the oven at what temperature and the time for drying