Ion exchange resins are cross linked polymers of polystyrene, up on which a negatively charged or a positively charged functional group can be added to get an anion exchange resin (Resin- )or a cation exchange resin Resin +(Resin + Or Resin- ). When these resins are mixed with drug molecule which has a negative charge in its one or more functional group as a result of polarity, or as in salt form, or as a result of resonance, such a drug can form a complex with a resin as follow.
1.) Resin + Drug-
2.) Resin- Drug+
*The resulting resin drug complex stability depends on how strong are the acidic or basic functional groups on resin, stronger functional group result in to formation of very stable resin drug complex, and vice a versa , both has its applications in sustained release drug delivery systems, a resin with strong acidic or basic functional group tend to provide a much more delayed drug release, where drug release is bit faster with weak acidic and basic functional group resins.
When Resin- Drug+ or Resin + Drug- complex (drug resinate ) comes in contact with acid(in stomach) or base(in intestine), it start releasing drug molecule in exchange of similar charged ion for example if drug molecule is positively charged, then it is released from Resin- Drug+ complex when it come in contact with Hydrogen Ion( H+) , similarly a Resin + Drug- or basic drug resin complex will start releasing drug when it comes in contact with basic ions ( in intestine ) OH – NH3- .
Release of drug molecule from Resin +Drug complex takes place due to higher concentration of replacing ions (H+ , or OH – NH3- ).
Masking Taste of drug with ion exchange resin:
There are some drugs which are very bitter in taste like Bromhexin and Quinine, patients has very low acceptability for such drugs some time patients vomit and expelling all of the consumed dose which may result in to dosing error, therefore when such drugs are formulated with ion exchange resins which binds such drugs they do not release drug on taste buds over tongue as a result taste of drug is masked, and when it come in contact with gastric acid bromhexin is released in to gut.
Sustained-release drug delivery system:
Ion exchange resins may not alone give capability to formulate it in to a sustained release dosage form , to make it a good sustained release drug delivery system , proper selection of resin is important a resin with strong acidic or basic functional group provides strong complexation with drug therefore are good candidates for delayed drug release, likewise when early release is intended a weaker acidic or basic functional group resins are useful . Drug resinate is also required to be coated with semipermiable film forming polymers, as drug resinate complex can not be solely relied up on for the intended use. ( ethylcellulose ). In order to maintained the sustained release property of ion exchange resin drug complex it is pretreated with polyethylene glycol so that it do not swell and break open the film coating when it come in contact with gastric juice.
Ion exchange resins are required to be washed with, suitable organic solvent, to remove residual organic or chemical impurities in ion exchange resin, followed by washing with purified water, and regeneration if required, before using for actual process. Ion exchange resin are required to comply with requirements listed in 21 CFR 173.25 by US FDA.
Ion exchange resins have many other applications in pharmaceutical dosage form and drug delivery systems like , localized drug release, stabilization of drug molecule for chemical degradation .
Ion exchange resins are widely used in pharmaceutical industry for purification or raw water and in preparation of water for pharmaceutical use.
-Rajarshi Nareshkumar Patel
USFDA guidelines, GMP guidelines, WHO guidelines, Schedule M, FDA, European guidelines cleaning validation, process validation, water system validation, ICH guidelines, GMP audut compliance, equipment qualification, Installation Qualification, Operational Qualification, Performance Qualification, Calibration, Validation Protocol, SOPs etc.
Sunday, August 12, 2012
Novel Drugs: Cancer Chemotherapy Using Nanoparticles developed with Nanotechnology May Reduce Harmful Side Effects of Antineoplastic Agents.
Chemotherapy for cancer is most of the time associated with one or the other harmful side effect of antineoplastic drugs as these chemotherapeutic drugs themselves are very cytotoxic, i.e. they damage normal cells too.
Antineoplastic drugs bring about their anticancer action by inhibiting cancerour cells growth by virtue of alkylation of nucleotides in cancerous cells or by inhibition of folic acid uptake by cancerous cells or by inhibiting cell division by binding with tubulin and microtubulin in a cancerous cells, it is likely that these drug are also absorbed in to normal tissues, leading to untoward serious cytotoxic effects , like kidney damage and nerve damage in chemotherapy with cisplatin, a drug of choice in most of anticancer chemotherapies.
A new drug delivery technique is being studied which uses Nanotechnology to deliver a cytotoxic drugs specifically directly in to the cancer cells , such drug delivery technique will be able to provide an efficient cancer chemotherapy that do not have much side effects as they pose today , it was observed that with nanoparticle drug delivery system the concentration of drug required to kill the cancerous cell is lesser than required in conventional chemotherapy therapy. As the drug is absorbed efficiently in to targeted cells and also drug is protected from degradation in blood stream , certain class of the anticancerdrugs are very unstable and stay in plasma for a very little time, therefor to achieve the required effect a higher concentration of drug may be required to be administrated.
Nanotechnology drug delivery system involves placing an anticancer drug in to a tiny particles known as nanoparticles which recognize cancerous cells and deliver the drug only to cancerous cells , as nanoparticles are very minute particles (1 nm to 100 nanometer) , the dose of drug required to kill the cancerous cells were also found to be very low as compared to conventional therapy . As the required effective dose it self gets reduced than conventional therapy , the harmful effect of anticancer drug are also likely to be reduced.
A team of scientists from the Massachusetts Institute of Technology and Brigham and Women's Hospital conducted study. They stored an prodrug of cisplatin (which is used in most of cancer chemotherapies) within nanoparticles which they developed to target a specific protein in cancerous cells in prostate gland.
After these prodrug loaded nanoparticles were absorbed by cancerous cells the prodrug was released in to the cancerous cells and was converted in to an active form . The team demonstrated that these prodrug carrying nanoparticles were able to kill cancer cells in culture more efficiently than the drug alone.
Study was conducted by researchers, led by Dr. Omid Farokhzad and Dr. Stephen Lippard, to study nanoparticle drug delivery system for an effective and safer option for chemotherapy in living animals. Their research work is published in Proceedings of the National Academy of Sciences, in Jan 2011 issue of the journal, the study was funded in part by NIH’s National Cancer Institute (NCI) and National Institute for Biomedical Imaging and Bioengineering (NIBIB).
By applying this drug delivery by nanoparticles they were able to shrink tumors in mice with smaller doses of the drug to reduce harmful side effects. Only 30% of the dose of prodrug of cisplatin was required to diminish the tumor by using the drug carrying nanoparticles, than that of standard dose of cisplatin as such.
Researchers initially studied different doses of nanoparticle bound drug in rats and mice, both the types of animals maintained their body weight and survived at higher doses of the drug when drug was delivered using nanoparticles than when injected without nanoparticles. It was also found that the kidney damage was less in rats which received the nanoparticle bound drug.
Also it was found that binding nanoparticles provided greater stability of cisplatin prodrug in blood stream than that of injected alone , after one hour about 77 % of prodrug was found in blood stream when it was delivered using nanoparticles compared to only 16% available drug in case of drug delivered without nanoparticles, cispaltin is very unstable drug and remains in blood for very short time , which calls for more dose to get the desired effect.
Rajarshi Patel
Antineoplastic drugs bring about their anticancer action by inhibiting cancerour cells growth by virtue of alkylation of nucleotides in cancerous cells or by inhibition of folic acid uptake by cancerous cells or by inhibiting cell division by binding with tubulin and microtubulin in a cancerous cells, it is likely that these drug are also absorbed in to normal tissues, leading to untoward serious cytotoxic effects , like kidney damage and nerve damage in chemotherapy with cisplatin, a drug of choice in most of anticancer chemotherapies.
A new drug delivery technique is being studied which uses Nanotechnology to deliver a cytotoxic drugs specifically directly in to the cancer cells , such drug delivery technique will be able to provide an efficient cancer chemotherapy that do not have much side effects as they pose today , it was observed that with nanoparticle drug delivery system the concentration of drug required to kill the cancerous cell is lesser than required in conventional chemotherapy therapy. As the drug is absorbed efficiently in to targeted cells and also drug is protected from degradation in blood stream , certain class of the anticancerdrugs are very unstable and stay in plasma for a very little time, therefor to achieve the required effect a higher concentration of drug may be required to be administrated.
Nanotechnology drug delivery system involves placing an anticancer drug in to a tiny particles known as nanoparticles which recognize cancerous cells and deliver the drug only to cancerous cells , as nanoparticles are very minute particles (1 nm to 100 nanometer) , the dose of drug required to kill the cancerous cells were also found to be very low as compared to conventional therapy . As the required effective dose it self gets reduced than conventional therapy , the harmful effect of anticancer drug are also likely to be reduced.
A team of scientists from the Massachusetts Institute of Technology and Brigham and Women's Hospital conducted study. They stored an prodrug of cisplatin (which is used in most of cancer chemotherapies) within nanoparticles which they developed to target a specific protein in cancerous cells in prostate gland.
After these prodrug loaded nanoparticles were absorbed by cancerous cells the prodrug was released in to the cancerous cells and was converted in to an active form . The team demonstrated that these prodrug carrying nanoparticles were able to kill cancer cells in culture more efficiently than the drug alone.
Study was conducted by researchers, led by Dr. Omid Farokhzad and Dr. Stephen Lippard, to study nanoparticle drug delivery system for an effective and safer option for chemotherapy in living animals. Their research work is published in Proceedings of the National Academy of Sciences, in Jan 2011 issue of the journal, the study was funded in part by NIH’s National Cancer Institute (NCI) and National Institute for Biomedical Imaging and Bioengineering (NIBIB).
By applying this drug delivery by nanoparticles they were able to shrink tumors in mice with smaller doses of the drug to reduce harmful side effects. Only 30% of the dose of prodrug of cisplatin was required to diminish the tumor by using the drug carrying nanoparticles, than that of standard dose of cisplatin as such.
Researchers initially studied different doses of nanoparticle bound drug in rats and mice, both the types of animals maintained their body weight and survived at higher doses of the drug when drug was delivered using nanoparticles than when injected without nanoparticles. It was also found that the kidney damage was less in rats which received the nanoparticle bound drug.
Also it was found that binding nanoparticles provided greater stability of cisplatin prodrug in blood stream than that of injected alone , after one hour about 77 % of prodrug was found in blood stream when it was delivered using nanoparticles compared to only 16% available drug in case of drug delivered without nanoparticles, cispaltin is very unstable drug and remains in blood for very short time , which calls for more dose to get the desired effect.
Rajarshi Patel
Kidney transplant will see more success rate than earlier.
Patients suffering from kidney failure are required to go for treatment like regular dialysis and kidney transplant, and that to be not all kidney transplants are successful , 1 out of every 3 kidney transplants are rejected by patients body (because of patients immune system) , it is because of the human body recognizes difference between its own body tissue and other persons body tissue and human body reject others persons body tissue by producing antibodies against the transplanted tissue , ultimately damaging and rejecting the transplanted kidney.
Dr. Robert A. Montgomery and his team from the Johns Hopkins University School of Medicine have found new technique , which has shown promising method which has greatly lowered the kidney rejection and has done kidney transplants successfully with their method.
They identified that there is an antigen on cells in human called as human leukocyte antigen, a person sensitized by human leukocyte antigen (HLA sensitized ) help human immune system to identify its own body tissue and incoming foreign tissue and trigger antibodies against transplanted kidney transplant and further leads to kidney rejection.
Therefore they developed a method to desensitize patients by filtering out anti-HLA antibodies they removed the anti-HLA antibodies from patient’s body by process of plasmapheresis. Patients were given
Low-dose intravenous immune globulin (antibody preparation made from pooled donor blood) as substitute for anti-HLA antibodies. The procedure of plasmapheresis was repeated several times before the actual kidney transplant was done , these patients were also given other immuno suppressant drugs which are normally given before kidney transplant.
More than 80% of the patients which received kidney transplant and plasmapheresis treatment were still alive after 8 years. Compared to observed lower life period for patients on either dialysis or HLA compatible kidney transplant ad dialysis.
The method is bit costly but is cost effective compared to the total other costs of regular dialysis are considered in kidney failure patients, and success rate.
What is plasmapheresis:
Plasmapheresis is a method of removing toxic or unwanted component from blood , by removing part of blood out of body and processing it in centrifuge to separate blood cells and plasma , the plasma containing toxic or unwanted antibodies is discarded and is replaced with donor plasma , albumin , or 70% albumin and 30% saline , a suitable anticoagulant drug is given to patient before the plasmapheresis procedure .
Dr. Robert A. Montgomery and his team from the Johns Hopkins University School of Medicine have found new technique , which has shown promising method which has greatly lowered the kidney rejection and has done kidney transplants successfully with their method.
They identified that there is an antigen on cells in human called as human leukocyte antigen, a person sensitized by human leukocyte antigen (HLA sensitized ) help human immune system to identify its own body tissue and incoming foreign tissue and trigger antibodies against transplanted kidney transplant and further leads to kidney rejection.
Therefore they developed a method to desensitize patients by filtering out anti-HLA antibodies they removed the anti-HLA antibodies from patient’s body by process of plasmapheresis. Patients were given
Low-dose intravenous immune globulin (antibody preparation made from pooled donor blood) as substitute for anti-HLA antibodies. The procedure of plasmapheresis was repeated several times before the actual kidney transplant was done , these patients were also given other immuno suppressant drugs which are normally given before kidney transplant.
More than 80% of the patients which received kidney transplant and plasmapheresis treatment were still alive after 8 years. Compared to observed lower life period for patients on either dialysis or HLA compatible kidney transplant ad dialysis.
The method is bit costly but is cost effective compared to the total other costs of regular dialysis are considered in kidney failure patients, and success rate.
What is plasmapheresis:
Plasmapheresis is a method of removing toxic or unwanted component from blood , by removing part of blood out of body and processing it in centrifuge to separate blood cells and plasma , the plasma containing toxic or unwanted antibodies is discarded and is replaced with donor plasma , albumin , or 70% albumin and 30% saline , a suitable anticoagulant drug is given to patient before the plasmapheresis procedure .
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