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Pharmaceutical Development - Science topic

Group dedicated to all people involved in the development of pharmaceutical products.
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I am trying with GC-FID.
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Hi Raju,
I know this is after a quite long time but would it be possible to share your GC method to determine white petrolatum, this would be very helpful. You can directly share your method copy/article to sathish.tanneru@gmail.com.
I appreciate your assistance in advance.
thank you
Sathish
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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.
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How the calculate optamic products as per ICH guideline because of optamic products dose is very low and impurity calculate as per ICH is very high
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The source is a new gelatin source. Methods given are by HPLC, amino acid analyzer and LCMS; are there any new methods?
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I would recommended to use the LC-MS/MS, UPLC-MS, HPLC and amino acid analyzer apparatuses for detecting the amino acids compounds.Of course, you should to consider your research fund/budget.
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please share detail information on osmotic systems. my topic is controlled porosity osmotic tablet
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Drug development professional skilled in study design, protocol writing, monitoring, presentation and investigator relationships. Adept in team work, mentoring, liaising with investigators, auditing, site visits and study overview.
Assist the clinical team in the preparation, handling, distribution, filing and archiving of clinical documents and reports. # Preparing clinical SOPs and Administer clinical trial records according to Good clinical practices. # Contact person between the contract laboratory, study team and study site. # Provide general logistical support for clinical trials such as creating and taking minutes of meetings. #Conduct clinical trial monitoring and assist in source data verification. #Designing essential documents and data collection logs and forms. # Training the site staff to trial specific GCP and GDP. # Maintain Trial master files (TMF) #Conducting Scientific literature search. # Assist in the prepare the dossier for SAEs and trial related communication with regulatory submission. # Perform any other function assigned by organization.
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An indicator of a biological state
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Biomarker is the Early biological signal. Actually it is something New or Chang in the protein which act as marker. According to the such protein signal we can design drug molecules .Biomarker is helpful to New drug development.
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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.
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Zeta potential can be improved by varying the stabilizer concentration, or by surface modification with cationic agents.
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Many thanks.
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Interesting question
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With acceptable hardness and friability.
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Dear sir,
for paracetamol tablet you need 2.5-3.5% moisture in granules and optimized granules fine ratio. if higher % of fines present in blend, tablet will fail in friability test.
in paracetamol tablets optimal LOD is 2.5-3.5%, when we take batch with starch and pvp k-30 paste. if you take gelatin and starch as a binder then optimal LOD will change from 2-3%.
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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 ?
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Would you please inform me, how should prepare AOM for IP injection to mice?
We should dilute it in dH2O?
How much should prepare the final volume for IP injection?
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Tell me the weight and thickness relation regarding tablet formulation...if the wt of tablet is 150mg then wht is the thickness for that...is it correct that the thickness of tablet is half of the punch size used?
Plz solve my problem
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Dear Mr. Roa,
Please explain how to calculate the thickness for capsule shape tablet.
What if the tablet is capsule shape?
Which side we need to consider for estimating tablet thickness?
Thank You.
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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.
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Hey, even if it's probably not that relevant anymore - you could try sucralose as sweetener. Works pretty well!
Regards,
Niklas
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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.
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2 ml of span60 in 1 liter of liquid paraffin
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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!
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Hello Elaine,
I have encountered the same problem and came across your question. May I ask, what did you do in the end? Did you publish those results?
Best regards,
Tamara
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Uniformity of dispersion test for tablets is carried out by passing through 22 mesh, is there any physiological relation with that?
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Uniformity of Dispersion test is generally meant for *Dispersible Tablets*, which are uncoated or film-coated tablets intended to be dispersed in water before administration giving a homogeneous dispersion.
In *Uniformity of Dispersion test*, 2 Tablets are placed in 100 ml of water & stirred gently until completely dispersed. A *smooth dispersion* should be obtained which should be passed through 22# (710 microns).
Here smooth dispersion (less than 750 micron) is must *to promote acceptable mouth feel without producing any type of grittiness in the oral cavity* which may compromise patient acceptance compliance.
Moreover, as the PSD of dispersed particle reduced, it will be readily available for absorption through mucosa.
(In *other types of IR Tablets*, Disintegration test is generally performed to ensure only disintegration of tablets into granules through 10# (2000um=2mm)
Because these tablets are meant to be swallowed with water which will be directly reach into stomach where it is meant to be disintegrated & dissolved.)
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-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?.
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Thank you to All.........
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Particularly for BCS class II drugs such as NSAIDs
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Hello all
I am also trying to make pellets of Famciclovir 250mg. Its an orodispersible formulation in which the pellets should dissolve in Stomach. The total weight of the tablet should not be more than 800mg. Can anyone suggest what are the extrusion aids and binder combinations for this product.
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ICH Guidelines, 
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ICH basically provides a common set of guidance documents for submission of dossiers to ICH member countries. It harmonizes the process, as earlier each country had its own set of regulations and formats for dossier submission in order to achieve marketing authorisation in the respective country. ICH tries to bring these countries on the same page to make the filing process smooth.
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In dissolution study of gastro retentive tablet , How to select dissolution fluid and their volume if drug's formulation is not official in pharmacopoeia.
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For gastro retentive preferable medium is acetate buffer pH 1.2 or 0.1 N HCl as gastro retentive we assume to be used in the empty stomach conditions. Volume of dissolution medium you can select on the basis of drug content of your formulation means the concentration of drug in each collected sample should be sufficient enough for the detection thorough your analytical method. Secondly, we should try to correlate with the empty stomach conditions (specially volume). 
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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...
Best regards,
Swapnil
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you can try to get blood via caudal vein, no cannulation, less wound infection. as for me,end of the test, the liver and kidneys function are normal. i think use same animal model for in vivo and in vitro PK is possible .
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In dissolution study of colon targeted tablet , How to select dissolution fluid and their volume if drug's formulation is not official in pharmacopoeia.
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Hi Vipul,
Besides checking Pharmacopeia protocols, find the attached pdfs, where you will get all the details of simulated gastric, intestinal, colonic fluid types, volume, conditions etc. 
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Hi
Which one is suitable for treatment in cell cultures: Analytical or pharmaceutical drugs?
Which of these drugs has more permeability to the cell?
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Doesn't really matter as long as the form you are using is pure (normally >99%) and bio-available. Either grade is fine the drug is the drug obviously for certain methods like HPLC contaminants may be a problem. The main thing is  will it go into solution in your culture medium at the concentration you want to use it, which may dictate whether you but a base or salt form of the drug. In genrral you want to minimise the need or amounts of adding organic solvents to your media (EtOH, DMSO, DMF).
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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. 
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I do not see how carrs would be a preservative. They are added as texturizers. In other words to either make a gel or modify the flow of the products.
But isn't aloe already a viscous product?
Regarding carrs safety . . . The battle is still going on. Industry claims carrs are safe to ingest and a bunch of others claim it is not.
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what bacterial-cell wall component that must not be in any pharmaceutical products?
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Lipopolysaccharides, endotoxin containing fragments and mutagenase fragments.
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the the levofloxacin disintegrates in stomach.. Can we make it colon specific by using enteric coating so that it absorption take place in colon??
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Levofloxacin is a weakly acidic drug with carboxylic acid moiety. pKa value = 6.24 and as per handerson hasselbalch equation drug will not shows ionization in any pH below 6.24 thus drug will be completely insoluble in gastric fluid (stomach). Drug will be soluble only if the pH of the medium increases above 6.24. So, ideal for colon delivery.
But for this drug matrix formulation will also be much better as compared to enteric coating since drug is itself not soluble in acidic pH and as coating increase cost of formulation then you should go for matrix of levofloxacin using Eudragit as retarding polymer which do not shows any disintegration in stomach. One more important is permeability of drug which is very less and for this addition of some lipid particles is necessary.
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microspheres, liposomes, etc
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Hi,
Have a look at the following literature:
(68)Ga-labeled peptides in tumor imaging. - NCBI
by HR Maecke - ‎2005 - ‎Cited by 327 - ‎Related articles
Among these, (68)Ga deserves special attention, because it is available from an ... Animals; Clinical Trials as Topic; Drug Delivery Systems/methods*; Gallium ...
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Development of Drugs and Technology for Radiation Theragnosis ...
by HJ Jeong - ‎2016 - ‎Cited by 3 - ‎Related articles
Many nanodrug delivery systems, including liposome, use this strategy for the passive ... For the targeted drug delivery of albumin to the liver or a hepatocellular ..... [6]: V. Prasad, R.P. BaumBiodistribution of the Ga-68 labeled somatostatin ...
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Chelator free gallium-68 radiolabelling of silica coated iron oxide ...
by BP Burke - ‎2015 - ‎Cited by 10 - ‎Related articles
Aug 13, 2015 - 68Ga (t1/2 = 68 min) is an attractive radioisotope for PET due to ... NRs radiolabelled with gallium-68 for PET/MR multimodal imaging ... based systems have deprotonated carboxylic acid groups at pH 7. ..... C. Sun, J. S. H. Lee and M. Zhang, Adv. Drug Delivery Rev., 2008, 60, 1252 CrossRef CAS PubMed .
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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
Thanks  
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Respected Sir, Please try to make co crystal with di-carboxylic acids in different ratio. I think, as per suggestion of Prof. Mayank Joshi 1:1 or 2:1 ratio will work. 
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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.
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you can use lower mw PLGA or PGA itself. Vit E TPGS used in previous paper also work. Not sure about your main intention as PLG is hydrophobic by nature to slow release esp. as MP unless size reduction, too many articles on this aspect. 
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list of drugs with NDA approved and those who qualify for phase IV trial is required?
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Try on their web page. Ichecked quickly and found this:
Home -> Drugs ->Drug Approvals and Databases
and for last 14 days:
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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
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I agree with Riaz. Such compounds (macrocycles, antibiotics, etc) may be actively transported for which there are no reliable in silico models of sufficient size and chemical diverstity.
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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.
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And my final advice is for you: only tablets and ampoules for parenteral use that have a clear manufacturer's declaration, date of manufacture, expiry date of drug, dosage and dosage form, description of undesirable effects of drug action, Prescribes the law of each state individually is ok!
Drugs that do not have it from the black market and can not be given to patients because it is contrary to the common practice and laws regulating that area!
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I'm looking for a good comparison across different routes of administration, and how the route affects bioavailability. Thanks!
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This is a  general question and as mentioned before there is no easy answer. The answer would depend on several aspects. For example is this an academic exercise or a drug discovery project? Second how many compounds are we talking about? Third what are you going to use the data for? Also when you say lypophilic compounds, there is a wide range of lipophilicity. As a general rule, again talking about oral absorption to narrow the discussion down, two factor, in general, that influence oral absorption. First is permeability and second is solubility. Usually compounds with log P of 1-3 has better permeabilty although there are some exceptions. There are software that can usually predict these two parameters fairly well. But you have to do some studies on a few compounds to confirm the prediction. Now bioavailabilty is a composite of oral absorption and first pass effect. The compound could be well absorbed but shows poor oral bioavailabily. You can get an idea about first pass by determining the metabolic stability using in vitro system such as liver microsomes or hepatocytes, although IV clearance in animal is the best estimate of first pass effect. I would suggest that the compounds that shows the best permeability and solubility and low metabolic stability can be tested in a PO/IV study in animals (usually rats or mice). When you do the PO study it will be best to dose it as a solution to avoid compromising bioavailability because of low solubility. There are many relatively safe vehicles you can use to solubilize  hydrophobic compounds (Gad et al., International Journal of Toxicology 2016). One of them I used a lot is 20% aqueous hydroxypropyl beta cyclodextrin for both IV and oral administration..Hopefully this will help
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"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?
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Good question and I must say I am not sure.  For openers, some form of clinical trial data that say that (Q1) and (Q2) have been explored (say in the original NDA or supplements) over sufficient ranges to make it clear that efficacy and /or safety were not affected over wide range.  Say, clinical trials were conducted and the efficacy and safety were shown to be functions of log of dose and the proposed formulation differs by only 10% in concentration.  That would certainly be enough to get a waiver.  
Could be that similar data, showing that log dose was shown in animal experiments would be sufficient evidence (using biomarkers of pharmacological activity) if it the drug is well known from a mechanism of action point of view.
Both clinical (and or animal) data would need to be shown for the active mouthy as well as all of the other inactive components of the new formation.
gets harder from there.
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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.
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Thanks Dr Gilles Dollo for the detailed answer. I have applied zero order, first order, Higuchi's model, Hixson Crowell's model and korsmeyer peppas models on my data however, release was best fitted into korsmeyer peppas model because of the high R value but the reviewer asked me  that why you applied Hixson crowell model on sustained release system as it is only for microspheres, thats why i asked here to reconfirm it because I have seen in many papers on sustained release Hixson crowell's model is applied.
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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?
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Hi Shilpa,
Apart from dissolution, lipolysis studies can give you a good piece of information about which formulation would performe better in vivo. I leave you link below:
Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model.
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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.
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Try to gradually test with somewhat lower temperatures than those you mention, and I think we should have less hygroscopic bonding material is then spray it with HSO at the nozzle gun!
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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..
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You can isolate nuclear proteins by first isolating the nuclei only (separating nuclei from cytosol) and then extract the nuclear protein with buffer containing high concentration of salt (NaCl or KCl up to 1 M). You need to know the chemical nature of your drug as well, to know if or how the binding of you drug can be/is affected by the component of buffer you are using.
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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 ??
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Normally, in all these cases the main point is about the drug dissolution in the simulated GIT media. Basically, pH, ionic strength, and surfactant presence are the composition variables. Time of residence and motility simulation are the other parameters under consideration. Colonic drug release implies pH near to 8.0 at 37 °C.
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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)?
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I was just having a peruse through some DMPK related questions and looked at this out of interest......I know it's a while since the question was posted but just in case it helps.......I'm no expert on enzyme kenetics but I'm not so sure you actually have an issue here, if the Km for drug A is lower than drug B would you not expect the IC of the inhibitor to be higher?  The binding of drug A occurs with higher afinity than B and therefore (without knowledge of 'K off' assuming an equal rate of transport for A and B)  would require an increased level of inhibitor to reduce transport by half in comparison to B.
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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. 
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Dear Shanker,
Dissolution and broadly speaking any release testing have one of two purposes namely (a) to provide information on the in-vivo behaviour/performance or (b) as a quality control method to provide information on the impact of changes in the formula and/or manufacturing process (on purpose or accidental) on the product release kinetics.
In your particular case I’m not sure you have a problem with the release medium. Most probably it will reside somewhere in the sample preparation and/or analytical determination (just a guess). You state that increasing the dialysis pore size increases the release. I'm afraid that's not so! The release does not depends on the dialysis membrane. What changes is your perception of the release, most probably because you are quantifying also the nanocapsules that are able to cross the dialysis membrane together with the free drug.
If you are only concerned in getting the drug dissolved after 5 hours, all you just need to use a medium in which the drug is soluble! Maybe methanol or dichloromethane can do the job.
However I guess it’s not what you want and that was the reason for my previous questions. Try to figure out the reason why you are getting a low (I’m just guessing) release. Unfortunately, based on the available info, I can’t suggest any dissolution/release medium other than increasing the SLS amount (you may go up to 2% with proper, sound and solid justification). Try 0.5% or 1% and check if there are any changes (there are however drawbacks -some of them severe - in using surfactants in dissolution media).
Regards, Luis
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HI GUYS, CAN WE IMPROVE DRUG PERMEATION THROUGH RAT SKIN BY INCREASING LOADING DOSE IN TRANSDERMAL DELIVERY
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yes
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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.
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I am already studying effect of diffrent plant extracts in psoriasis. Would be interested for inteacting & may be collaborative work in due course.
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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.
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Hello,
First I would go to the website of the DSC manufacturer and look up how to process your data after the experiment (hopefully using their software). This will be best since it would involve the same software you used to obtain your data and you would not need to convert your data back and forth. From a first glance you need to do two major things (assuming you have not already done them):
1) Display your data in the same way. Have the same tranisitions (like crystallization peaks) pointing in the same direction on all graphs. This does not seem to be the case and it causes lots of confusion. I also normalize my heat flow (y-axis) by the mass of the sample so the integrals can be directly compared in terms of crystallinity, etc.
2) You should do a baseline subtraction. This could be as simple as running an empty sample pan and subtracting that data from what you have. This will flatten your baseline and hopefully remove any odd stuff NOT caused by your samples.
In addition, I would search if anyone has done DSC on your pure drug so you can see what the result should look like and compare it to yours. Hopefully this would put you in a better position to analyze your data. Good Luck.
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I didn't get consistent results with HPMC K100, and Povidone SR.
Any ideas?
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 Dear Ahmed,
Try using HPMC K15M. I've used this before to develop Aceclofenac 200 mg SR tablets and follow the dissolution profile as per Diclofenac ER Tablets USP.
Regards,
Abhishek
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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!
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Dear wu Wenbo,
Would it be possible to attach a file containing the chemical structures and IC50 of the studied compounds?
Thanks,
Rafik
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We are formulating a film forming gel and we need to dissolve the HEMA in the organic solvent. So please is it reported anywhere regarding its solubility then it will be fruitful to carryout the work. Thanks
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It would probably dissolve in strong polar aprotic solvents such as DMSO, DMF, NMP...
It is soluble in protic solvent ethanol also..
When the polymer is subjected to water, it will swell due to the molecule's hydrophilic pendant group but it will not be dissolved.
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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.
Thanks
Shahid
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Dear Mohammad,
The half maximal inhibitory concentration (IC50) is a measure of the effectiveness of a substance in inhibiting a specific biological or biochemical function.
This quantitative measure indicates how much of a particular drug or other substance (inhibitor) is needed to inhibit a given biological process (or component of a process, i.e. an enzyme, cell, cell receptor or microorganism) by half. The values are typically expressed as molar concentration
It is commonly used as a measure of antagonist drug potency in pharmacological research. According to the FDA, IC50 represents the concentration of a drug that is required for 50% inhibition in vitro.[1] It is comparable to an EC50 for agonist drugs. EC50 also represents the plasma concentration required for obtaining 50% of a maximum effect in vivo.
The IC50 of a drug can be determined by constructing a dose-response curve and examining the effect of different concentrations of antagonist on reversing agonist activity. IC50 values can be calculated for a given antagonist by determining the concentration needed to inhibit half of the maximum biological response of the agonist.[2] IC50 values can be used to compare the potency of two antagonists.
The term half maximal effective concentration (EC50) refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time.[1] It is commonly used as a measure of drug's potency.
The EC50 of a graded dose response curve therefore represents the concentration of a compound where 50% of its maximal effect is observed.[2] The EC50 of a quantal dose response curve represents the concentration of a compound where 50% of the population exhibit a response,[3] after a specified exposure duration.
It is also related to IC50 which is a measure of a compound's inhibition (50% inhibition). For competition binding assays and functional antagonist assays IC50 is the most common summary measure of the dose-response curve. For agonist/stimulator assays the most common summary measure is the EC50.[4] Sometimes it is also expressed as pEC50 = - LOG(EC50) (with EC50 in M/l).
A small change in ligand concentration typically result in rapid changes in response in the biological system, following a sigmoidal function.The inflection point at which the increase in response with increasing ligand concentration begins to slow is the EC50. Which can be mathematically determined by derivation of the best-fit line. While relying on a graph for estimation is more convenient, this typical method yields less accurate results and less precise.
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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.
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 Given that folic acid is cheap and likely innocuous, it may be worth a trial figuring out whether is helps. The mentioned study may be point to depart from, but I advise to be careful: (1) it is a small, unblinded trial, (2) in neurology, there was a lot of homocysteine, MTHFR, and folic acid substitution addressed in huge trial called VITATOPS, which failed to demonstrate any effect of supplementation despite some studies and pathophysiological ideas supporting supplementation. Maybe a placebo effect as well, which would seem ok to me if it helps...
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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? 
Thank you!
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Drosophila survival assays
For intestinal infection, survival was assayed as previously described (Blow et al., 2005). Briefly, 30 male flies were divided evenly between three vials either containing a cellulose acetate plug saturated with 2 ml of LB broth supplemented with streptomycin alone or containing a 1:10 dilution of an overnight culture of V. cholerae that had reached early stationary phase. Viable flies were counted at least once in 24 h. For septic injury, 20 flies were pricked in the dorsal thorax with a 29-gauge needle dipped in a solution containing early stationary-phase bacteria diluted to an OD600 of 0.05 in fresh LB media. Flies were maintained in vials containing a cellulose acetate plug saturated with 5% sucrose in phosphate-buffered saline (PBS). Flies were inoculated in the evening, and the numbers of viable flies were recorded hourly during the following day. Survival curves were constructed for both intestinal and systemic infections, and log-rank tests were used to determine statistical significance. Reproducibility of all survival data was confirmed in at least three independent experiments.
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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.
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Thank you Dr. Rafik for your reply, 
in pharmaceutical manufacture we have to make sure that all the raw materials comply to specifications as stated in the official pharmacopeial monograph before incorporating it in a product ( GMP & local regulations requirement ) In this case we can't do this as the DL is not stated, and when tested according to the monograph, it will fail in the optical rotation and melting point tests !.
I think that the purity of the DL differs also being synthesized in different method than the L isomer. Note that the optical rotation is required by the BP, USP, Japanese pharmacopeias & the Hand book of pharm excipients
When a decision is to be taken, Do you think that the DL consignment should be rejected or used ?
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please dear all i would like to know few in vitro models for hair growth, that are easy to estimate in a common laboratory/ college.
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thanking you sir @ Alok Nahata
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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.
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The test will depend crucially on your hypothesis to be tested.
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How to prepare N,N-Di phenyl methyl amine from diphenyl oxime ?
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Dear Srinivas,
You may conduct a one step reduction of the oxime to furnish the corresponding amine as shown below:
A Mild Single-Step Reduction of Oximes to Amines
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 18, Issue 8, 1988
Abstract
A mild and convenient procedure has been developed for the reduction of oximes to amines in a single step involving treatment of the oxime with TiCl3 in the presence of NaBH3 CN. This method is especially useful for those substrates in which the intermediate imine is readily hydrolyzed.
Hoping this will be helpful,
Rafik
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Dear All
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.
Regards
Pasha
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Did you gave same dose for IV/IM/Sc?
Bioavailability more than 1 (more than 100%) is a common phenomena, not only in i.p. and Sc but also in oral administration. F greater than 1 is relative to i.v. administration and assuming that in any of the routes compared, Clearance does not change. This is a big assumption and many a times rate of elimination is controlled by rate of absorption. Thats what happens in im/ip/Sc. or sustained release dosages.
During regular NCE research it has been observed that with same vehicle when, an NCE was administered i.v. and orally, Fwas greater than 1.
This can be due to many reason.
Detailed investigation can be done as in following paper published in two parts. These papers are must read.
1. xenobiotica, april 2004, vol. 34, no. 4, 353-366
Apparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in rat. I. Investigation of potential experimental and mechanistic explanations
K. W. WARD*, L. M. AZZARANO, C. A. EVANS and B. R. SMITH
Preclinical Drug Discovery, Cardiovascular & Urogenital Center of Excellence in Drug
Discovery, GlaxoSmithKline, King of Prussia, PA 19406, USA
2. xenobiotica, april 2004, vol. 34, no. 4, 367-377
Apparent absolute oral bioavailability in excess of 100% for a vitronectin receptor antagonist (SB-265123) in rat. II. Studies implicating transporter-mediated intestinal secretion
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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.
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Eudragit RSPO is neither soluble nor biodegradable. You can use Eudragit S 100, 12.5, Eudragit or FS 30D for colon targeting. They all dissolve above pH 7.
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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 ?
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The FDA is suggesting to you that you need to know enough about the release mechanism of your active to guarantee that your chosen dissolution test is selective at discriminating variations in the manufacturing process that lead to dosage forms with different release profiles in vitro. Said test should be (at least) as sensitive at discriminating differences as would an in vivo release profile (what the FDA is really interested in making sure you control; but it's prohibitively expensive to test this in routine manufacturing!); usually this is easy to achieve if the release is controlled by disintegration of the dosage form to any substantial degree. In vivo the turbulent mixing in the stomach aids the release of active, whereas in vitro the dosage form may form a wetted layer which releases drug slowly through the matrix, and the stirring of the (paddles) may not be sufficient to cause this layer to fall off. If different tablets, to take an example, have even slight differences in the wetting and disintegration speed of that layer, the in vitro profiles may differ considerably, whereas the in vivo absorption profiles of the two may be quite similar. That's what the FDA is interested in; you could present either another dissolution test with different turbulence, or other equivalent types of observations --e.g., a dissolution vs. disintegration study across manufacturing ranges, with reasoned analysis of the results, or a coupled dissolution + proton NMR 3-D scan on tablets (to visualize water intrusion during dissolution). The rigor with which you pursue this point would depend on the type of dosage form you have -- unusual forms might require more testing.
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Any physiological logic behind the mesh size?
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In USP, 10 # size is to pass all type pf granules or particle even big size as of 1.5 to 2 mm size  like sprinkle granules and coated beads etc. Disintegrating apparatus is having some big size mesh to avoid blockage too because it does not effect on DT time.
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How can we compare the In vivo studies results with antimicrobial studies results of a particular active constituent drug for a particular activity?
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I'm not a specialist in the field of your question but think that the paper, "Methods for in vitro evaluating antimicrobial activity: A review," in the link below might be useful for you:
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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? 
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For protonation: you wouldn't expect a basic molecule to maintain separate neutral and protonated states in a protic solvent (with methanol)? The spot would migrate per the average protonation proportion, relative to the separate neutral and protonated species. Only specially constructed protonatable species would be able to show main spots, connected to some degree by a streak -- very-hindered-rotation tautomers, for example. Agree related compounds likely. TEA is useful in any event to decrease tailing on silica - you don't necessarily need to pretreat the plate, just add a bit to the eluent. Seeing spots connected by a bridge doesn't necessarily mean that the different species were present in the spotting solution -- they might also be reacting during the chromatography (try running them on a different phase plate to check this, say reverse vs. normal phase).
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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?
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Dear Anaide Bonjour,
A lack of entrepreneurial behavior has often been highlighted as a contributor to the decline in the research and development (R&D) productivity of the pharmaceutical industry. Academic pharmaceutical science research is expanding further from the University setting to encompass the for-profit private company setting, such as pharmaceutical companies. This parallels the NIH momentum to include multiple funding opportunities for University and private company collaboration. It has been recognized that the non-profit and for-profit combination research model can accelerate the commercialization of pharmaceutical products, and therefore more efficiently improve human health. Entrepreneurial activities require unique considerations in the University environment, but can be modeled after the commercialization expansion of the academic healthcare enterprise. The commercialization of the healthcare enterprise can provide a good model to mimic, as far as oversight and support for entrepreneurial activities. The challenges and rewards of the academic entrepreneurial lifestyle appeal to many faculty members, and this opportunity can be integrated and monitored in the University environment. Universities and entrepreneurs benefit in many ways from a well-designed economic development initiative, and this initiative helps to not only stimulate the economy, but accelerate development of products to improve human health.
For more on this topic, please see the publications contained in the following links:
Hoping this will be helpful,
Rafik
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blank 0.208
values of samples ranges from (0.165-2.2080)
a lot of sample values below blank value
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What I do when having many different samples is to add diluted samples to an inert 96 well plate (made of polypropylene, which does not bind proteins to a significant degree) in the same distribution that they will have in the ELISA plate (but in a volume slightly larger than the one I will use for ELISA). Once all the samples are there, it is vey easy and quick to transfer the desired volume (i.e. 50 microliters) from each well to the equivalent well of the ELISA plate with a multichannel pipette to avoid huge delays between the first and the last samples.
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I need to know about excipients that could match the taste and grittiness of metronidazole.
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  1. thanks Anwar
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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?
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Dear Tadesse Fikre Teferra,
My experience through 30 years teaching and research would go with natural antioxidants. It is Eco friendly products, however, what  these  bio-molecules chemical state? see if you looked at the nutritional value of an orange has vitamin C, precursors of vitamin A plus more than 150 phytochemicals that may protect form heart disease and some types of cancer. On the other hand,  vitamin C is available in a tablet with unbalanced chemical state usually in reduced form that not always safe. However, the chemical state of vitamin C from an orange have the the state of a chemical balanced in redox and reduced state plus more than 150 phytochemicals.
Also see what victor Herbert said about that:
Based on twenty years of research, The Vitamin Pushers addresses every aspect of this lucrative business and exposes its widespread misinformation campaign. The authors reveal how many health-food companies make false claims about products or services, promote unscientific nutrition practices through the media, show little or no regard for the rules of scientific testing and evidence, and often skirt the law in their schemes for making quick profits while eluding government watchdog agencies. Drs. Barrett and Herbert counter the phony assertions of health-food hucksters with reliable, scientifically based nutrition information, and they suggest how the consumer can avoid "getting quacked." They also include five useful appendices on balancing your diet, evaluating claims made for more than sixty supplements and food products, and much more. The Vitamin Pushers is a much-needed expose of a nationwide scam, which will definitely save you money and might even save your life. 
 Best regards
Aly
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publication problem. Can yop help me
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hi ..
some time problem in case using same name or its founded in researchgate and you need some change in title(of your work) and then write  different title(within researchgate) then it will be ok to upload your work  please try this ,,,
regards...
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I want to know these sizes for my new project to give a new pharmaceutical preparations. 
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Tavşan dili üst yüzey alanı :)
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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.
Thanks
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Dear Seran,
Please read the following text. The direct answer to your question is the example marked with bold line.
First, remember the structure and function of a virus. Once attached to its specific target cell, it injects its DNA (or RNA) into the host cell. Once inside the 'infected' cell, this viral DNA (or RNA) replicates itself as well as using the existing machinery within the 'infected' cell to make more viral proteins. It then assembles itself and can now leave this cell to infect other cells. Second, remember the structure and workings of DNA (or RNA). All the DNA strand consists of are 5-carbon deoxyribose (or ribose) sugars linked together by phosphate groups. Additionally, each 5-carbon sugar has one of four possible bases attached: A, G, C, or T. So in order to elongate a strand of DNA (or RNA), the cell simply links the 'sugar-base-phosphate' unit onto the existing 'sugar-base-phosphate' units already linked together forming the strand of DNA. We oversimplify this by saying that the DNA strand grows by adding additional bases. For example, our simplified explanation says that the DNA strand grows by adding an "A", or "G", or "C", or "T" base, one at a time. Remember that this "A", or "G" or "C" or "T" is the 'sugar-base-phosphate' unit with the base being either A, G, C, or T. Thirdly, this is an oversimplified but essentially accurate explanation of how several antiviral drugs work. The antiviral drug will be incorporated into the growing DNA (or RNA) strand as if it were another 'sugar-base-phosphate' unit. Once this drug is incorporated into the growing DNA strand, no other 'sugar-base-phosphate' units can be attached, and so any further grows stops. Hence, terminating the growth of viral DNA within the infected cell.
As an example, let's discuss acyclovir as an antiviral drug for herpes simplex infection. Acyclovir is an analog of 2-deoxyguanosine ("G"). The acyclovir is in fact modified by enzymes made only by the virus so that the acyclovir can now be incorporated into the growing viral DNA strand instead of the "G". Once incorporated, any further elongation stops because unlike "G" that should be there, the acyclovir cannot attach any further nucleoties (acyclovir cannot attach any further "A"'s, or "G"'s, or "C"'s, or "T"'s). A herpes simplex virus attaches to a susceptible host cell (seen on the right), fusing its envelope with the cell membrane, and releasing naked capsids that deliver viral DNA into the nucleus of the host cell, where it initiates the synthesis of viral DNA. Acyclovir molecules entering the cell are converted to acyclovir monophosphate by virus induced thymidine kinase enzyme. Host-cell enzymes add two more phosphates to form acyclovir triphosphate, which is transported to the nucleus. Shown in red is the cleavage of phosphate from the acyclovir triphosphate by the herpes simplex's own enzymes, the herpes simplex's DNA polymerase enzyme incorporates the acyclovir monophosphate into the growing DNA strand as if it were 2-deoxyguanosine monophosphate (a "G" base). Further elongation of the chain is impossible because acyclovir monophosphate lacks the attachment point necessary for the insertion of any additional nucleotides.
I. The acyclovir (as do other antiviral drugs) is mistakenly incorportated into the growing DNA strand. The enzymes adding in "A"'s, or "G"'s, or "C"'s, or "T"'s recognize acyclovir as a "G" and add it in.
II. The acyclovir does not have the proper structure to add any additional "A"'s, or "G"'s, or "C"'s, or "T"'s to it, and so the DNA strand cannot continue to elongate or grow. Once the acyclovir is incorporated, any further growth of viral DNA is terminated.
III. If I swallow my acyclovir drugs, isn't acyclovir going into all of my cells, and blocking the growth (or replication) of all my cell's DNA, not just the cells infected with virus? Not necessarily. As you read, the conversion of the original acyclovir into the form that is incorporated into the DNA is carried out by the virus's own enzyme. Therefore, only those cells that are infected with the virus will have this specific enzyme and convert the original acyclovir into the acyclovir that can be incorporated as a "G" base. Also, only the cells infected with virus have the enzyme that mistakenly recognizes acyclovir as a "G" base and puts it into the growing DNA strand. So, again, all of your non-virally infected cells will not that this viral enzyme and so not put acyclovir into growing DNA.
For more information, please use the following links:
Hoping this will be helpful,
Rafik
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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!
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Dear Joshua,
Good luck!
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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)? 
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Thank you so much!
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I would like to know how  the drug protein interaction in vitro can be done
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Dear Trisha Bansal,
Yes. It can be done.
Plasma Protein Binding Assay
Understand the distribution potential of your compound using our plasma protein binding assay.
Plasma protein binding is one of Cyprotex's in vitro ADME screening services. Cyprotex deliver consistent, high quality data with cost-efficiency that comes from a highly automated approach.
Determination of fraction unbound in plasma using equilibrium dialysis
The extent of binding to plasma influences the way in which a drug distributes into tissues in the body.
Etensive plasma protein binding also limits the amount of free compound available to access sites of action in the cell, and metabolism and elimination may be slower.
Equilibrium dialysis is the most widely accepted method for assessing plasma protein binding as non specific binding effects are minimised compared with other methods such as ultrafiltration.
Cyprotex's Plasma Protein Binding assay is performed using an equilibrium dialysis method and delivers a value of fraction of compound unbound to proteins (fu).
There is a choice of three methods for assessing plasma protein binding using three different percentages of plasma to provide flexibility depending on budget and compound characteristics.
Equilibrium dialysis is the preferred method to determine the free drug fraction, because it is less susceptible to experimental artifacts.
Kariv I, Cao H and Oldenburg KR. (2001) J Pharm Sci 90(5); 580-587
For the protocol details, please use the following link:
Hoping this will be helpful,
Rafik
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i have hydrophilic compound, which i want to encapsulated into liposome .. could suggested my the best protocol that you used or help me with one?? 
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Use Pro Lipo Neo (Lecithin derived) to prepare hydrophylic API Liposomal.
Please see its brochure
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Which release medium we should use for curcumin for permeation studies?
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My route of administration is topical
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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
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The particles aggregate over the time. We have used Span 80 and Solutol but aggregation was seen after a day. Viscosity agent can be tried next...thank you
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A method to encapsulate a liquid and this still being liquid in the center of the capsule?
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Dear Claudia,
The following publication entitled " Challenges and Opportunities in The Encapsulation of Liquid and Semi-Solid Formulations into Capsules for Oral Administration " fully covers the answer to your intersting and important question. Please note that this publication contains some figures for illustrating the method:
The encapsulation of liquids and semi-solids provides solutions for convenient delivery through improved oral absorption of poorly water-soluble drugs. In addition, low dose (content uniformity), highly potent (containment), low melting point drugs, those with a critical stability profile and those for which a delayed release is required are candidates for liquid or semi-solid formulations. Both hard and soft capsules can be considered and in each case the capsule wall may
comprise gelatin or some other suitable polymer such as hypromellose. The choice of a hard or soft capsule will depend primarily on the components of the formulation which provides the best absorption characteristics as well as on the physical characteristics, such as the viscosity of the formulation and the temperature at which the product needs to be filled. Numerous excipients are available for formulation of lipid-based systems and their compatibilities with hard gelatin capsules have been tested. The availability of new enhanced manufacturing equipment has brought new opportunities for liquid-filled hard capsules.
Filling and sealing technologies for hard capsules, provides the formulator with the flexibility of developing formulations in-house from small scale, as required for Phase I studies, up to production.
To view the full publication, please use the following link:
Hoping this will be helpful,
Rafik
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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?
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Thank you very much Juan! I guess a similar strategy can be used when assessing and comparing efficacy and EC50s or ED50s for different drugs, even if we have drug combinations. Most of what I have read about pertains to dose-response curves and probit analysis in Finney's textbook (1971).  
-David
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Vaginal drug delivery, pharmaceutical industry 
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Dear Rishabh,
The following publications describe methods for drug release from vaginal suppositories:
1-J Drug Target. 2003 Apr;11(3):177-85.
In-vitro evaluation and vaginal absorption of metronidazole suppositories in rabbits.
Ozyazici M1, Turgut EH, Taner MS, Köseoglu K, Ertan G.
Author information
 
Abstract
Vaginal suppository formulations of metronidazole were prepared using six different bases as Witepsol H15, Cremao, Ovucire WL2944, Ovucire WL3264, PEG 1500, PEG 6000. Three different dissolution methods were used to evaluate the in vitro drug release from the suppositories. The diffusion studies were performed through synthetic (cellophane) and natural membrane (rabbit vagina), but the drug did not show good permeation characteristics from natural membrane. Ovucire WL3264 suppositories of metronidazole labeled with 99mTc (Tecnetium-99m) were used for the vaginal absorption and biodistribution studies in the rabbits. Scintigraphic images were collected after vaginal administration of the labeled suppositories using SPECT gamma fitted with a low energy, high-resolution parallel hole collimator. The labeled drug showed high biodistribution in urine beside vaginal site. The results of this study suggested that the Ovucire WL3264 suppository of metronidazole prepared for vaginal infections could also be effective in the urinary infections.
2-METRONIDAZOLE BIOADHESIVE VAGINAL SUPPOSITORIES: FORMULATION, IN VITRO AND
IN VIVO EVALUATION
Research Article
HAIDY ABASS*1, RABAB KAMEL2, AHMED ABDELBARY3
1Department of Pharmaceutical Technology, Faculty of Pharmacy, German University in Cairo, El tagamoo El Khames Main Entrance Cairo,
Egypt, 2Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt, 3Department of pharmaceutics and
Industrial Pharmacy ,Faculty of Pharmacy ,Cairo University, Kasr El -Aini St., 11562, Cairo, Egypt. Email:haidy_miu2002@yahoo.com
Received: 29 Aug 2011, Revised and Accepted: 26 Nov 2011
ABSTRACT
Drug administration via mucosal membranes, including the vaginal, has the advantage of by passing the hepatogastrointestinal first pass metabolism associated with oral administration. Metronidazole suppositories were prepared using different suppository bases viz., water soluble bases ( PEGs and gelatin ) emulsion and fatty bases. The physicochemical properties of most of the prepared MTZ suppositories comply with the pharmacopoeial limits and passed the quality control tests. In general, water soluble suppository bases gave higher release than did the emulsion in citrate buffer pH 4. PEG base (F14), gelatin base (Fl8) and emulsion base (F23) gave the highest drug release and selected for further investigation. The release of MTZ from polyethylene glycol bases followed, first and Higuchi order release model, while gelatin and emulsion obeyed first model.
The tested suppository showed enhancement of drug absorption from tested suppository and the One way ANOVA analysis for AUC(0-∞) showed that the P value is 0.0502, considered not significant. The microbiological results showed that the bioadhesive formulae that released the concentration of 0.25 mg/ml of the drug and sustained this concentration for 120 min can be effective on C. albicans moreover bioavailability study was performed on flagyl ® vaginal suppository (market product) and the prepared pluronic127 –cp934 bioadhesive vaginal gel ,eight female rabbits were randomly divided into two groups, each containing four rabbits the results showed that the tested formulae did not exhibit enhancement in bioavailability in comparison to the market product which mean lower side effects and localized effect inside the vagina. 
3-Comparative bone uptake study of alendronate sodium from vaginal suppositories prepared with polyethylene glycol and massa estarinum bases
INTRODUCTION Bisphosphonates are used in the management of various disorders affecting the skeleton, includ- ing osteoporosis, metastatic bone disease and Pa- get’s disease of bone. Bisphosphonates are selec- tively uptake at active bone sites, suppressed the osteoblast and osteoclast mediated bone resorp- tion (1-4). Alendronate sodium (ALD) is a second generation amino bisphosphonates that selec- tively inhibits osteoclast-mediated bone resorp- tion, increases bone mineral density and reduces the incidence of vertebral, hip and other fractures (5-7). Like all bisphosphonates, ALD is poorly ab- sorbed from the gastrointestinal tract, with an oral bioavailability of around 0.9–1.8% (8). Its ab- sorption is markedly reduced by food (9). In recent years, there is a challenge for novel drug delivery systems to achieve improved bio- availability and safety. Various researchers have described new formulations to treat bone dis- ease with minimal side effects and high efficien- cy. Because of the poor gastrointestinal absorp- tion several administration routes have been at- tempted to enhance the bioavailability of bis- phosphonates like intravenous, subcutaneous and intramuscular injections (10-13). Also Asikoglu et al. have demonstrated rectal ab- sorption of ALD (14). The unique properties like rich blood supply and the large surface area makes vagina an important area for systemic drug delivery (15). The advan- ABSTRACT: The aim of this study was to compare the bone uptake of alendronate sodium (ALD) from vaginal suppositories prepared with massa estarinum AB (ME) and polyethylene glycol 1500 (PEG) bases. For this purpose, ALD was radiolabeled with 99mTecnetium Pertech- netate (99mTc) by direct method. Radiochemical purity and stability of 99mTc-ALD was per- formed with chromatographic studies. 99mTc-ALD containing suppositories were prepared with ME and PEG bases. Physical properties of suppositories were evaluated. The physico- chemical diffusion study was carried out to compare the release of ALD from different sup- pository bases. The bone uptake of 99mTc-ALD was observed by gamma scintigraphy stud- ies. 99mTc-ALD containing suppositories were administrated to rabbits via vaginal route. The scintigraphic images were obtained with a gamma camera at different time intervals up to 240 minutes. According to our studies, radiochemical purity of 99mTc-ALD was observed more than 95% up to 6 hours. At 240 minutes of physicochemical diffusion studies, released ALD has 0.620 ± 0.091 mm and 10.465 ± 0.651 mm diameter zone from ME and PEG base suppositories respectively. According to the gamma scintigraphy studies, although no bone uptake observed after ME suppositories application, rabbit’s bones were clearly visible after PEG suppositories applied. The results of physicochemical diffusion and gamma scintigra- phy studies were found compatible in each other. KEY WORDS: Alendronate sodium, bone uptake, vaginal suppository, massa estarinum, polyethylene glycol Comparative bone uptake study of alendronate sodium from vaginal suppositories prepared with polyethylene glycol and massa estarinum base
4- Formulation and in vitro study of antibacterial vaginal suppositories
ARTICLE in PHARMACEUTICA ACTA HELVETIAE 69(3):141-8 · JANUARY 1995 
Vaginal suppositories frequently used in gynaecological therapy were studied. Several antibacterial pharmacons are used for the topical treatment of vaginitis of various origins. In view of the fact that the liberation of the given active substance and the subsequent therapeutic effect may be improved or inhibited by the vehicle, our aim was to find the optimal suppository base for vaginal suppositories containing sulfadimidine, chloramphenicol and gentamicin sulfate by means of in vitro experiments. On the basis of breaking hardness, disintegration time and spreading properties the French Suppocire NA product, and compositions of macrogols with lower molecular weight proved to be the best lipophilic and hydrophilic bases, respectively. Among the lipophilic bases the in vitro drug liberation of Suppocire NA was significantly better (P < 0.05) than the other lipophilic bases. This vehicle is recommended for the topical treatment of vaginitis, as these suppositories have the further advantage that they can easily be produced on a magistral, galenical or industrial scale as well.
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I would like to the websites where I can search more information related to this tropic
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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
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Dry in vacuum at lower temp below 30 degrees .