Pharmaceutical Formulation - Science topic

I am working on tablet dosage form development of amorphous API. My API in tablet is in amorphous form and likely to convert to crystalline form on shelf. I wanted to monitor the fraction of API that might be converting to crystalline form. Tablet weight is 500 mg and contains API 50 mg ie 10% w/w. Other ingredients in tablet includes MCC, Aerosil and Mg Stearate. I am searching for nondestructive technique that enables chracterization of solid form of API in intact tablet. 

Thank you

There are many indications that artificial intelligence technology can be of great help in terms of discovering and creating new drugs. Artificial intelligence can help reduce the cost of developing new drugs, can significantly reduce the time it takes to design and create new drug formulations, the time it takes to conduct research and testing, and can thus provide patients with new therapies for treating various diseases and saving lives faster. Thanks to the use of new technologies and analytical methods, the way healthcare professionals treat patients has been changing rapidly in recent times. As scientists manage to overcome the complex problems associated with lengthy research processes, and the pharmaceutical industry seeks to reduce the time it takes to develop life-saving drugs, so-called precision medicine is coming to the rescue. It takes a lot of time to develop, analyze, test and bring a new drug to market. Artificial intelligence technology is particularly helpful in this regard, including reducing the aforementioned time to create a new drug. When creating most drugs, the first step is to synthesize a compound that can bind to a target molecule associated with the disease. The molecule in question is usually a protein, which is then tested for various influencing factors. In order to find the right compound, researchers analyze thousands of potential candidates of different molecules. When a compound that meets certain characteristics is successfully identified, then researchers search through huge libraries of similar compounds to find the optimal interaction with the protein responsible for the specific disease. In contrast, many years of time and many millions of dollars of funding are required to complete this labor-intensive process today. In a situation where artificial intelligence, machine learning and deep learning are involved in this process, then the entire process can be significantly reduced in time, costs can be significantly reduced and the new drug can be brought to the pharmaceutical market faster by pharmaceutical companies. However, can an artificial intelligence equipped with artificial neural networks that has been taught through deep learning to carry out the above-mentioned processes get it wrong when creating a new drug? What if the drug that was supposed to cure a person of a particular disease produces a number of new side effects that prove even more problematic for the patient than the original disease from which it was supposed to be cured? What if the patient dies due to previously unforeseen side effects? Will insurance companies recognize the artificial intelligence's mistake and compensate the family of the deceased patient? Who will bear the legal, financial, ethical, etc. responsibility for such a situation?

I described the key issues of opportunities and threats to the development of artificial intelligence technology in my article below:

OPPORTUNITIES AND THREATS TO THE DEVELOPMENT OF ARTIFICIAL INTELLIGENCE APPLICATIONS AND THE NEED FOR NORMATIVE REGULATION OF THIS DEVELOPMENT

In view of the above, I address the following question to the esteemed community of scientists and researchers:

What do you think about this topic?

What is your opinion on this issue?

Please answer,

I invite everyone to join the discussion,

Thank you very much,

Best wishes,

Dariusz Prokopowicz

Dear,

What is the most suitable conductivity cell (k=0.1; K=1) for evaluating the conductivity of pharmaceutical formulations such as liposomes, LNPs...

Hello everyone!

I am considering the possibility of assisting Congress or Conferences on Drug Delivery Systems or Pharmaceutical Formulation. However, I do not have much experience in this field.

After conducting some research, I came across "Formulation & Delivery 2024" organized by Oxford Global. I am wondering if any of you have had any experience with this event or with Oxford Global in the past, and if you could share your opinion on it.

Thank you in advance

Can anyone help me on it for initiating the progress for my research paper

I have herbal extracts obtained by maceration in 80% ethanol that are desired to be evaluated for their wound healing activity using excision and incision wound model on albino rats.

Although the extracts are prepared using the same solvent they have different solubility profile in water (some form clear solution while others results in a homogeneous suspension).

We intend to formulate the extracts into a semisolid dermal preparation using either aqueous cream base or simple ointment base as they are the most frequently used bases with the least intrinsic efficacy.

Is there a suitable method to measure and compare the release of the extracts from the aqueous cream base and the simple ointment base in order to evaluate their suitability.

Need to know about the excipients.

I did forced degradation studies on an ocular eye drops formulation. Is it possible to calculate the stability and shelf life of the formulation using that data (which is in actual the % degradation)?

I plan to used a Bourne reaction system or similar to study reactive mixing. I wish to vary the viscosity of the system between experiments to understand how the viscosity influences the reactive mixing. This could normally be done using different concentrations of CMC or other additive. However during the Bourne reaction systems a neutralization reaction occurs resulting in change in pH which affects many additives and alters the viscosity.

Does anyone know a compound which can be used to increase the viscosity of an aqueous solution such that the viscosity is stable over a range of pHs?

Some drugs appear to be more quickly absorbed by the body with smaller particle size while some undergo better sustained release with larger particles. Why?

Is it related to the absorption mechanism (capillary action for smaller particles vs. lymphatic system for larger) by any means?

Hi

Can anyone suggest me a recent and simple topic on pharmaceutical formulation development for seminar presentation. Regards.

An indicator of a biological state

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.

Force feeder wheel speed is very important particularly for those formulations that are very sensitive to over-lubrication. High residence time and speed of force feeder wheel are equally responsible for over-lubrication. On the other hand, low speed of force feeder wheel could cause fill weight variation and there by tablet weight variation. Therefore, force feeder speed needs to be optimized. Is there any equation/concept available to optimize force feeder wheel speed optimization?

This is in order to determine the gastrointestinal behavior of microcapsules.

Particularly for BCS class II drugs such as NSAIDs

Chitosan coated lipid vesicle system for ocular delivery.

I have prepared a topical mosquito repellent patch by incorporating a volatile compound in it. The volatile compound is supposed to get released in to the environment. To obtain the release of volatile, the content of the volatile compound is determined at each time interval with the help of calibration curve. For example, at 0 hour the content is  "X" and at 1 hour the content is "Y". Apparently the release of volatile compound at 1 hour will be =X-Y.   Am I doing the right way or is there any other procedure to calculate it. Moreover, I do not know the exact procedure to calculate the cumulative % release of volatile. Someone please help.

As per IP titanium dioxide has water soluble substance as a test parameter. It's limit is 0.5% (W/W). What does it indicate if the result is obtained more that 0.5% and what does that lead to in the pharmaceutical formulation?

moleculer weight of protein and generation of dendrimer are important for drug formulation, ıts size- zeta potential. which chemical bonds are observed?

I performed a dissolution test on number of nano formulation that contains my drug with different stabilizers that have different concentrations

but when it came to dissolution test all the drug was released in less than 10 min compared to the raw drug which took 90 min . after that the UV spectrophotometer stops reading  the absorbance , like the drug isn't available in the samples

I changed the volume of the media from 500 to 250

the amount of the formulation to 10, 25, 50 mg

the rotation speed from 100 rpm to 50 rpm

the filtration with  non, 0.45 um, 0.22 um

used both apperatus1 and 2 

used a sinker

nothing seemed to change the result

has anybody faced this problem before ? how can I asses the drug release in this case

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?

I am working on control release of drug by PLGA PEG PLGA copolymer. this polymer is very sticky. I could not dissolve this polymer? please guide me how can i dissolve this polymer well? How can i sterile this polymer for cell culture and invivo? filter is not good 

NLCs were prepared by probe sonication technique. Prepation prepared after sonication was found to be clear with no sediments after centrifugation. Organic acid (medium chain length) was chosen as drug. Size of drud loaded NLC was around 30-50nm while that for blank was around 100-200nm.

Also product obtained after lyophization was in a paste form and not solid, is it acceptable?

Hello! I'm doing a literature review regarding injectable formulations and I noticed a convention of using lactic acid within the formulation. The handbook of pharmaceutical excipients lists the purpose of lactic acid as an acidulant. I couldn't find any reference relating to the purpose/rationale behind using acidulants within an injectable formulation. 

Best regards! 

a Formula of anti-hypertensive drug ,very poor water solubility 

the formula contain sodium hydroxide+meglumin+mannitol

we tried wet granulation by using 70% ethanol dissolved in it sodium hydroxide.

the problem is that the granules remain wet and never dry, even after exposing to heat 50 c in oven for several hour, and if the granules exposed to room temperature and moister it become more soft.

we also suspecting in SODIUM HYDROXIDE ! which is highly liquefied at room temp and moisture.

I am wondering for the suitable method for the preparation of microspheres of water soluble drug. I tried for emulsion solvent difussion method (o/w) but I found less drug entrapment. I also tried w/o method (containing aqueous phase and liquid parafin as oil phase and emulsifier) but microspheres were not formed. Please suggest suitable method for the same.

Thanking You all for replying my questions earlier. 

I work with a 2 similar but structurally different PEGylated polymeric nanoparticles encapsulating a traditional chemotherapeutic drug. The nanoparticles are developed to be administered orally. Preliminary efficacy studies shows good tumor control compared to free drug for both nanoparticle formulation. But size distribution studies of the drug encapsulated nanoparticles shows 2 peaks (suggesting breakdown of nanoparticles at acidic gastric pH), implying drug release as soon as nanoparticles reach stomach for one and significant difference in size (small size about 60 nm at pH 2, 120 nm at pH 7 and 150 nm size at pH 8) with a single peak for the other. What does these results imply? Why is there a size difference with pH.

facing problems in drug and excipient selection

Any physiological logic behind the mesh size?

I have a precipitated dried sample of hemoglobin and I am using urea/β-ME solution to solublize the precipitated samples of hemoglobin. However, the hemoglobin sample is not solublizing after vortex and soaking it for a while in the urea/β-ME solution. I am trying to find another resolublzing solution that could be strong enough to solublize the Hemoglobin sample in order to run Bradford assay and find out the amount of Hemoglobin in the sample. 

Dear Folks, struggling for a good intra-nasal delivery of vaccine although my vaccine is working perfectly by SC and IM routes. Tried with same IN route but is not working. Could you please suggest about the possible excipients or compounding materials to formulate, so it will be staying into the nasal cavity or thereby lungs for a while. It's need to be stayed as well as uptaken by antigen presenting cells, macrophages or other immune cells for better IgA or IgG response. Do I need to think about something to be included in the vaccine that can help or enhance the penetration of intranasal membrane barrier or mucous around the nostril's or nasal cavity? Your advice or suggestions will be highly appreciated. Thanks.

Where can I find the article about cinitapride formulation ,pharmacology of all dosage form ?

I have developed polymeric patch by incorporating polymers and drugs and characterized by different analytical tools including SEM, DSC and others. The product is undergone accelerated stability testing for six months at 40 degree temperature and 75 relative humidity. The physical property have been evaluated at different time points. The drug content was also dtermined at different time points. But I don't have exact idea to detrmine chemical stability of the product during the course stability testing. Whether thermogravimetric analysis will be sufficient to confirm the chemical stability or is there any other technique to confirm chemical stability of the product. Please explain.

We prepared four liposomal formulations varying in their main phospholipid constituents. These preparation consisted of PEG2000-DSPE (5% mole ratio), Chol (38%) and either of HSPC, DPPC, DMPC and Egg-PC with the respective transition temperature (Tc) of 55, 40, 28, 0 centigrade degrees plus 0.3% DiD fluorescent dye as tracer. Upon treating C26 colon carcinoma Cells in vitro with these liposomes in PBS, the result of the flow cytometry of the washed cells was contrary to what I presumed. After 3 hour incubation of cells with liposomes at 37 centigrade degree, more fluorescent intensity was found HSPE-, DPPC-, DMPC- and Egg-PC-liposome-treated cells, respectively. I thought that the dye was transferred to cells more intensively from Egg-PC-, DMPC-, DPPC-, and HSPC-liposomes, respectively. As the pore defects in these liposomes can lead to the Dye leakage from liposome to cell. Please present your comment.

i have a problem with this drug..

I'm doing a project plan for new formula which included new active ingredient. The preparation of active ingredient will be included in this project. I was asking about a validation method for the manufacturing of this newly active ingredient and if there is any health organization make a regulation to organize this process?

 The shelf-life of a pharmaceutical product is estimated based on the rate of degradation of the API. This rate of degradation is estimated based on the assay results of API during the product stability study.

During conduct of accelerated stability study of a pharmaceutical products, degradants must also be assayed. How the assay results of degradation products will be used for estimation of the shelf-life of a pharmaceutical product?

Dear All

We have combined a phytoconstituent with Active pharmaceutical Ingredient(API) in a tablet. Kindly guide me in assessing the toxicity of the formulation using some model

we are working on niosomal formulation of hydrophobic drug. Upon centrifugation, the drug precipitated out. Give a suitable(feasible) method of purification.

What are various types of mechanical characterization techniques for pharmaceutical dosage forms?

currently i am working with cyanocobalamin and i need help for literature about cyanocobalamin vit B12 if any one have literature about this please send me

thank you

Hi is there any ingredient or design which can improve the magnesium absorption in the body. Generally only 50% of magnesium is absorbed into the body and remaining is excreted before it gets absorbed. 

Many works have been reported so far on various drugs belonging to many categories like anihypetensives, anti-lipidemia, etc etc. But i want to know if any of the drugs have been marketed?

Dear All,

We have tried some essential oil in some of our solid dosage forms as a natural ingredient. But on analysis, content of essential oil is decreasing significantly.

We have adsorbed essential oil onto Sio2 then added to the compression mix to formulate tablets.

Open for Suggestions please?

Thanks for your time.

We want to improve bioavailability of plant based lipophilic compound. Please let me know various pharmacological mechanism to improve kinetics.

Regards,

Shankar

The objective is a composition for a continuous few days i.v. infusion for short term tox studies in rat. The formulation should be well tolerated but still able to solubilize 5-20 mg/ml of the drug, which is a poorly water soluble weak base with intrinsic solubility of 0.01mg/ml, pKa ~4, and logP ~3. The vehicle or components should not have any major effects on hemodynamics of the rat.

Several standard formulation options based on e.g. co-solvents, surface active agents, and lipid systems have already been tested but  a well-functioning and tolerated formulation has not been achieved so far. Non-conventional lipid vehicles would be fine also if there’s any prior experience on suitability for tox use.

Any insight and ideas related to composition, formulation technology, infusion system, devices etc. will be highly appreciated. Thank You!

we are developing a formula for drug with very poor solubility, we are using MCC and lactose as diluent sodium starch glycolate as super disintegrant,sodium lauryl sulphate as solubilizing agent and magnesium stearate as lubricant.

the dose is low so we are using wet granulation as preparation technique,

dissolution results are always come very low, we are using official dissolution method from USP:

media : 0.01 HCL, 900 ml

apparatus 2 : 50 RPM

time : 30 min

is there any method to enhance solubility of this product ??

Paracetamol suppositories made with PEG 4000 and PEG 6000 as suppository bases undergo dissolution test. After 45 minutes, both batches have mean % of drug release that is higher than 100%.

PEG 4000- 150% and PEG 6000- 120%

Why does the cumulative drug release exceed 100%? Is there error during measuring of absorbance or is it some form of degradation or hydrolysis of the medicine during manufacture/storage?

How do we perform optical resolution of Orphenadrine drug?

I am looking for development of topical formulation, including preformulation and stability studies. Is there any GLP certified lab which can perform the development and clinical manufacturing. 

Hello Everyone,

We are facing disintegration issue in one of our product development. Its an ODT (orally disintegrating tablets) dosage form with a target DT of less than 30 sec. We are not able to achieve a DT of 30 sec with a hardness of 30 N with wet granulation. If we lessen the hardness DT would be around 25 sec but that's not preferable as the hardness is very low and chances of friability will increase. 

Though the solution seems easy by using disintegrant like Croscarmellose and Crospovidone but we already tried with many of them .As the extracts are very hygroscopic tablets are not able to disintegrate within 30 sec. 

With MCC its giving good results but the mouth feel is unpleasant.

Any suggestions?

i need a review article that gather all possible excipients involved in solid dosage form  manufacturing?

if so how it is prevented? 

thanks in advance 

Placebo pills are needed to form a matrix for pharmaceutical formulations. If my company does not have budget for it, is it possible to use sugar-free pills and/or panadol tablets to compensate for its use? Can they meet the minimum requirement? In my humble knowledge, they have some although not all of the characteristics of the placebo pills.

Regarding official monographs; every single API can be analyzed by titration methods. Is it possible to analyze each API alone with its own official method with the presence of the other APIs or this may lead to error in the analysis.

Retinyl palmitate is a pre-formed version of Vitamin A, is a synthetic supplement available in dry or oily form. It can be taken orally or by injection to treat Vitamin A deficiency. It will get converted to an alcohol in the small intestine when ingested. Overdosing preformed Vitamin A forms such as retinyl palmitate leads to adverse physiological reactions known as: hypervitaminosis A, which can be harmful to liver, bones and skin, causing weakness and brittleness, even leading to fatigue and vomiting.

Can anybody have reference paper or official document on dose of vitamin A palmitate and its effect?

How Can I calculate stability constant between drugs and cyclodextrin.

 if the stability constant have a value of negative sign what is the reason for this?

Hi everyone,

I'm working on the SB334867 (Cat. No. 1960; orexin 1 receptor antagonist). We tried to dissolve it with pure DMSO, but the DMSO is harmful to neurons. Could you please tell me a better method to dissolve it ? Thank you~

is that tablet which is produce with B type punch have better dissolution compare to tablet which is produce with D type punch?

how about tablet porosity between the type of tooling (type B and type D)?

is there any method to complex natural drugs with anionic or cationic liposomes

Please help me with the detail method for the dissolution of clotrimazole extended release vaginal tablets.

Dear Researchers,

We developed one product with wet granulation process and the IPA is used in binder preparation, so after the wet granulation, we were dried the wet mass in FBD but we observed the case hardning as well as even after dried the granules i.e. upto the LOD 1.5 % .. and moreover after that we kept the milling step, and also after that the two steps are ahead i.e. compression and followed by coating but still after final formulation we got the IPA more than 5000 PPM..

So could you suggest any solution for the drying like humidity or dew point control...

Awaited for your responses....

Is there any effect of temperature generation during compression?

Dear sir,

We are in to manufacturing of pharmaceutical oral dosage forms. We develop thin oral medicated films of size 32 x 25 mm of 50 micron thickness. Our idea is to fill such 30 films in to small cassettes. A cassette is made with food grade HDPE material ( silica desiccant preferably) with self locking mechanism.

For this, we have two requirements.

1. Food grade HDPE cassettes (silica desiccant preferably).

2. A machine which fill the films into cassettes.

I request you to look in to this requirement and give us you possibilities.

Waiting for the reply.

siRNA delivery in Bilosomes

I've been trying to develop Metformin 500 mg SR + Sitagliptin 50 mg IR bilayer tablets but the assay of sitagliptin drops by almost 10% in 1 month accelerated stability. Metformin is quite stable but the problem is only with the sitagliptin layer. Please give your valuable suggestions.

I would appreciate some advice on how to encapsulate an amphiphilic small molecule into a liposome.

My small molecule is amphiphilic – it has a hydrophobic aromatic core, to which two alkyl linkers are attached. These linkers have a basic nitrogen atom each, so these constitute hydrophilic groups. The salts of this small molecule are water soluble, while the neutral form is poorly soluble in virtually everything (except acids and DMSO).

Unfortunately, the only lipids I have on disposal to prepare the liposomes are standard, 99% pure Sigma Aldrich egg yolk phosphatidylcholine and cholesterol. I have tried the standard approach: made a thin film out of the lipids + compound salt, suspended the film in water and sonicated the suspension. I extruded through 0.2 µm filters, precipitated the liposomes via centrifugation and had only about 9% encapsulation (which is to be expected, since the compound salt is water soluble, only 9% could statistically be “captured” by the forming liposome, the rest remained in solution, out of the liposome). How can I increase this yield? On the other side, when I took the neutral form, which is poorly water soluble, I had a higher encapsulation % (which is to be expected) but the precipitate after centrifugation could not be resuspended in water, and had a very high compound to lipids ratio (meaning these are not “good” liposomes).

The additional problem is that I have a really small amount of both my compound and the pure egg yolk phosphatidylcholine, so I can’t afford “throwing them away” on too many different experimental approaches. Also, this is a completely new area of work for me, and I have no experience in liposome preparation. Any piece of advice would be helpful. Thank you!

I have dissolved limonoid aglycone in 100 % DMSO at a concentration 10mg/ml. It completely dissolved. But when i add the stock to serum free media [ 10-200ug/ml] for treating cancer cells. Media becomes turbid and when viewed under microscope it looks like crystal clusters. No toxicity is seen even in higher concentration.

Currently we dissolve it in minimal DMSO then add cremophore-EL. This mixture is then diluted in buffer immediately before injecting. It’s a struggle to keep the compound in solution it readily precipitates out. Any suggestions would be appreciated.

I have used PLGA:DCC:NHS in molar ratio of 1:10:10. after 12 hrs of reaction no precipitate of dicyclohexyl urea is seen. The reaction was carried out at room temp. Do I have to change the reaction condition in order to cause precipitation.

I have my amount of drug in mg/mL and amt of drug+nanocapsule in mg/mL as I weighed the mass of my nanoparticles after freeze drying their solution forms.

I followed the equation Loading ratio= amt of drug (mg/ 1 mL)/amt of drug+nanocapsule (mg/1 mL).

However, I was asked to multiply this ratio by 1000 so that I can have a loading content of µg/mL.

How does this work? I thought the ratio would give units of mg/mg. But why does multiplying by 1000 give units of µg/mL? 

(It was mentioned that this concentration unit was needed when testing samples in vivo.)

I would like to use aspartame in an orally disintegrating tablet. In literature there is lot of variation for the %age of aspartame so I would like to know the safe limit which I can use.

I want to micronize curcumin,and I would like to prove that after micronization the curcumin has already activity as a drug. How can I do? and what instrument can I use?

Dear collagues. We planned a new study to evaluate effects of resveratrol ana CAPE on pregnant rats in endocrine disorder. However, because of low water solubility we cannot transffered all the LD50 dosage. could you answer please which solution is more preferrable for solving Resveratrol and also CAPE?