Category Archives: Drug Discovery

Drug Bioavailability

Drug Bioavailability can be known as the active amount of drug reaches the systemic circulation to the site of action. The Bioavailability of the drug depends on the form of dosage and also its design and the manufacturing. The differences in the bioavailability between the drugs will have the clinical significance so, knowing the equivalence of the formulations is needed.

If the formulations contain the same active compound in the same quantity and also reaches the official standards they are chemically equivalent, however, inactive compounds in the formulation may differ. When the plasma concentrations of two different drugs given to the same patient in same dosage regimen are the same then it’s considered as bioequivalence. If they show the same therapeutic and adverse effects then they are therapeutically equivalent. The bioequivalent products are ought to be therapeutically equivalent. Therapeutic non-equivalence is also observed during the long term treatment of the patient who is stabilized on one formulation is given with the non-equivalent substitute.

Causes of low bioavailability

  • Metabolisation of drugs before reaching adequate plasma concentrations. This usually occurs in the oral dosage forms that are poorly water-soluble and slowly absorbed.
  • Insufficient time of absorption in the GI tract.
  • Age, sex, physical activity, genetic phenotype, stress, disorders
  • Chemical reactions that reduce the absorption. The reactions include complex formation, hydrolysis by gastric acid or digestive enzymes, adsorption to other drugs, metabolism by luminal microflora.

Assessing bioavailability


The assessment of the bioavailability is done by determining the area under the plasma concentration-time curve. AUC is the most reliable measure of the drug bioavailability. If plasma concentration curves are superimposable then drug products may be considered as bioequivalent in extent and rate of absorption. The drugs that are excreted primarily unchanged in urine, bioavailability will be determined by measuring the total amount of drug excreted after every single dose.

Biosimilars will be an industry game-changer?

What are biosimilars?

Biosimilars are organic protein-based substantial atom meds that are exceptionally like existing affirmed biologic medications, known as reference items. They endeavor to duplicate the first innovation, however because of the variable idea of organic meds, it’s difficult to precisely imitate the reference sedate. Clinically however, biosimilars have no important distinction from the first biologic reference regarding wellbeing, viability, virtue or intensity.

How are organic drugs made?

Biologics, and their biosimilar variants, are hereditarily built proteins made by embeddings DNA into living cells, for example, microscopic organisms, yeast or refined creature and human cells, to deliver a specific protein. Biologics are more delicate to contrasts in individual cells and nature they’re made in, so it’s unimaginable for a biologic, or for sure a biosimilar, to be a similar when looked at one next to the other.

Truth be told, the assembling procedure is more perplexing than that for synthetic medications, with many advances and several factors included. So one of a kind are the sythesis and fabricate of biologics that not exclusively do those made by various producers vary, however each bunch contrasts from another.

The medications’ affectability influences how they’re directed as well, with most biologics infused or mixed in light of the fact that their proteins are influenced by our stomach related frameworks whenever taken orally.

Small molecule vs large molecule medicines

Most brand name and nonexclusive medications are little particle, synthetically orchestrated mixes. Natural and biosimilar medications are substantial particle, complex pieces. To give you a thought of the distinction, ibuprofen is comprised of only 21, while the biologic medication.

Biologics versus biosimilar

Biologic medications have upset the treatment of numerous illnesses, including disease, HIV/AIDS, auto-insusceptible and neurological disarranges, offering better results for patients. Be that as it may, the staggering expense of unique biologics makes them less open in a few markets. Biosimilars offer a more reasonable option, with a few nations pitching them at 20 to 30 percent not as much as the first medication.

Regardless of giving comparable clinical results to a reference item, the sub-atomic structure of each biosimilar prescription is special, much like a snowflake. What’s more, similar to the first biologics, each time a biosimilar is produced, it’s somewhat unique.

Amazingly, one more sort of organic medication is the “exchangeable”, which must meet the bio similarity standard, and additionally deliver indistinguishable clinical outcome from the reference item in some random patient. A key contrast between recommending biosimilars and interchangeables is that while a drug specialist can substitute an exchangeable for the reference item without the endorsing specialist’s mediation (regardless of whether the reference was recommended), a biosimilar must be recommended by name, with no substitution allowed.

Generic vs biosimilar

While a conventional drug is a duplicate of its reference item, a biosimilar must be “exceedingly comparative”. What’s more, the tremendous sub-atomic distinction among generics and biosimilars implies there’s extremely no challenge. Assessed cost reserve funds from changing to biosimilars are anticipated throughout the following 10 years.

What’s more, with the licenses for some reference biologics due to terminate in that time, the playing field will extremely open up for biosimilars.

Pharmacovigilance in Drug Discovery

The increased use of novel accelerated regulatory pathways had given a dramatic impact on the role of pharmacovigilance in drug development.

During the past 10 days, there is a decrease in time taken to bring new drugs to market. While this acceleration has increased the detection of the risk of adverse drug reactions only when the product is already in the market, leading to higher demand for post-approval safety surveillance studies and related activities.

The move from paper to electronic formats and with increased vigilance has increased the amount and velocity of safety information in the environment. The evaluation of cases at point of initial entry needs to be undertaken at the highest standard of both quality and timeliness—despite ever-increasing volumes.

The pharmacological science which deals with drug safety including accumulation, detection, assessment, monitoring, and prevention of adverse effects of the drugs is Pharmacovigilance. It focus on detection of unidentified safety issues, identification of risk factors, quantifying risks and preventing patients from being adversely affected unnecessarily. Pharmacovigilance plays a prominent role at various stages of drug discovery and development process. The analysis of all the serious adverse events requires new safety findings from animal studies, and evaluations of benefits and risks. Pharmacovigilance also plays a important role when the drug is commercialized. Safety reviews include Risk Management Plan, Periodic Benefit Risk Evaluation Report, the Development Safety Update Report, Periodic Safety Updates Report, post-marketing surveillance, clinical trials, and pharmacoepidemiological studies.

Introducing a new medicine to the patients is highly time-consuming and expensive process and requires an essential and strict vigilance on the safety and efficacy of the drug. Hence pharmacovigilance plays a key role in drug discovery and development. The drugs  appear to be safe and well-tolerated in preclinical and clinical testing, but their safety in the ‘real world’ may not be distinct, after-effects of the drug when used frequently or in combination with other drugs are generally unknown, safety in vulnerable groups with different metabolic profiles (e.g, pregnant women and breastfeeding mother, elderly person, young children) can be uncertain, and rumors and myths can destroy the integrity, adherence to, and success of a treatment.

Pharmacovigilance is a critical part of the drug discovery and development process. It requires documentation and  monitoring at every phase of drug development including pharmacovigilance inspection and audit, risk management, and reporting of ADR medicinal drugs, periodic safety update report, post-authorization safety studies, additional monitoring, and safety communication. It is essential to establish good pharmacovigilance practices for improving the drug safety issues during the drug development and the patients can be provided with safe and efficacious innovative medicines to meet their prerequisite medical needs.

Medicinal Chemistry Current Approaches to Drug Discovery for Cancer and Tropical Diseases.

4The remarkable changes in technological and scientific developments in the past years have dramatically changed the pharmaceutical innovation process. Well-established strategies, such as high-throughput screening (HTS), have progressively been applied in association with novel techniques founded on genomics and proteomics, molecular and structural biology and molecular modeling. Altogether, these fields have provided outstanding advances for our comprehension of the fundamental cellular and molecular mechanisms of diseases in addition to enabling important progress in the technological arsenal used in drug discovery. Combined with novel methods in organic synthesis, such as combinatorial chemistry, the forefront approaches have built a novel paradigm in the research-based pharmaceutical industry.

Evolving paradigm, which has its roots attached to the recent advances in medicinal chemistry, molecular and structural biology, has unprecedentedly demanded the development of up-to-date computational approaches, such as bio- and chemo-informatics. These tools have been pivotal to catalyzing the ever-increasing amount of data generated by the molecular sciences, and to converting the data into insightful guidelines for use in the research pipeline. ligand- and structure-based drug design have emerged as key pathways to address the pharmaceutical industry’s striking demands for innovation. These approaches depend on a keen integration of experimental and molecular modeling methods to surmount the main challenges faced by drug candidates’ in vivo efficacy, pharmacodynamics, metabolism, pharmacokinetics and safety.

The novel scientific drug discoveries and technological advances are incorporated into the field due to the constant evolving of drug development. More efficient organic synthesis methods, chemical biology approaches and bio- and Chemoinformatics strategies have dramatically changed the process by which an initial hit is converted into a marketable drug. In part, this can be attributed to the expansion of the field towards novel therapeutic areas that are at the limits of the science and technology available today. Indeed, Present Modern strategies are strongly dependent on the high-quality interplay between the basic research originating from research institutions and academia and the Research & Development(R&D) expertise coming from industry.

In this context, multidisciplinary and integrated approaches are indispensable. Research facilities able to perform experimental and computational studies to evaluate pharmacodynamics and pharmacokinetics are greatly needed to identify molecules with a high potential to become drug candidates. This scenario demands a steady input from several areas of the chemical sciences, such as organic, medicinal chemistry, and biological chemistry, which stand at the frontier of the current drug R&D model. The integration of these disciplines in well-structured and consistent research projects is critical for developing promising drug candidates for treating critical conditions such as cancer and other topical diseases.

Scanning of molecules against cancer target

1Scientists have built up a framework to quicken the drug discovery that represses a protein involved in various diseases. The arrangement of apparatuses and strategies, which the specialists used to test in excess of 16,000 mixes has now been detailed. The enzyme, NSD2, is overactive in diseases, for example, intense lymphoblastic leukemia and certain kinds of numerous myelomas, so hindering NSD2 action appears like an encouraging procedure for treating those conditions. In any case, up until this point, scientists have not possessed the capacity to discover any synthetic concoctions that dependably block NSD2 even in a test tube in the research facility, considerably less to test as medication applicants in living models.

Some portion of the reason it’s been hard to find chemical inhibitors of NSD2 is that the catalyst is hard to work within the research center. NSD2 alters histones, the proteins around which DNA is wound. For specialized reasons, researchers conventionally would think about this sort of movement utilizing a part of the compound and a section of histone protein. Be that as it may, NSD2 deals with just entire nucleosomes: units of histone protein in blend with DNA.

Researchers created lab tests including entire nucleosomes that could be utilized to see whether NSD2 could adjust histone proteins within the sight of different mixes. The intensifies the group tried originated from NCATS‘s huge library of bioactive synthetic concoctions. However, finding an aggravate that seems to square NSD2 movement is just the start. To affirm that the synthetic substances recognized in the underlying enormous screen were to be sure real inhibitors that would dependably and reproducibly play out this capacity in future scientists’ examinations, the NCATS group expected to utilize numerous kinds of biochemical strategies to affirm the movement of each compound.

With a few atoms presently having substantiated themselves in this round of screening, Hall’s group plans to proceed with the scan for dependable NSD2 inhibitors that can be utilized as research apparatuses and afterward, additionally not far off, potentially as pharmaceuticals.

Advanced Vision Science in Ophthalmology

Vision science is the logical investigation of vision/Eye. Vision science studies of vision and advanced vision care, for example, human and non-human organisms process visual data, how cognizant visual discernment works in people, how to misuse visual observation for powerful correspondence, and how counterfeit frameworks can do similar errands. Vision science covers with or envelops disciplines, for example, ophthalmology and optometry, neuroscience, brain research, especially in neuropsychology, biopsychology and intellectual brain science, material science, especially optics, ethology, and software engineering (particularly computer vision, artificial intelligence, and computer graphics) and also other building related zones, for example, information perception, UI outline, and human components and ergonomics.

Optometry in vision science:

Optometry is study of health care in vision, which involves examining the eyes and applicable visual systems for defects or characteristics as well as the diagnosing and management of disease of eye. The field of optometry starts with the primary focus of rectifying the refractive error through the use of eye glasses. In Modern-days optometry has evolved in the educational program, in additionally includes with the depth in medical training in the diagnosing and management of eye diseases where ever controlled.

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Optometrists are health care professionals in the primary eye care through including the eye examinations to detected and treat various eye diseases. Being a managed profession, an optometrist’s scope of apply might dissent depending on the situation. Thus, disorders or diseases detected outside the treatment scope of practice in optometry referred out to relevant medical professionals for correct vision care, more commonly to ophthalmologists who are physicians that practiced in triennially medical and surgical care of the eye. Optometrists are works intently beside different eye care professionals such as ophthalmologists and opticians to deliver constitutionally and economical eye care to the overall general public.

New vaccine target for Malaria to control the birth of parasites

Malaria is an illness caused by the transfer of the Plasmodium parasite from bound mosquitos to humans, which is responsible for 429,000 deaths per annum in step with the World Health Organization. The life cycle of this parasite occurs within humans and mosquitos, permitting it to unfold spread at a great rate between the two species. Scientists have noticed that a protein concerned within the life cycle of the protozoal or malarial infection causing parasite is paving the way for a brand-new immunizing agent to scale back illness unfold. Most of the scientific community believe that the key to eliminating the illness is to prevent humans infected with the parasite from passing it on to doubtless dozens of mosquitos, every of which might then continue to infect more people.

On the surface of the reproductive cells of male protozoal infection, parasites may be a small molecule which is a protein referred to as HAP2 and it have discovered that by block it, simply targetable a part of the HAP2 molecule, fertilization between the male and feminine parasites is discontinuous. This ends up in protozoal infection parasites being unable to breed with efficiency, acting as a variety of parasitic birth control. In fertilization process, the male and feminine reproductive cells of the parasites would combine within the abdomen of their mosquito host, grow, then trip the secretion glands of the mosquito able to transmit the protozoal infection inflicting parasite once mosquito next bites an individual’s. Disturbing the method of fertilization prevents that can parasites from travel to the secretion glands of the mosquito, thereby reducing the transmission of the infecting parasite to humans.

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In initial in vitro studies, the team created an antibody that can blocks HAP2 and else it to blood infected with protozoal infection. They then ascertained the amount of winning fertilization events among the parasites that disclosed a big 85.88 percent reduction in comparison with an effect experiment wherever no protein was administered. Finally, the study examined by the scientists however the blocking approach of protein HAP2- affected the transmission of parasites between human blood and mosquitos, victimization blood samples of patient with protozoal infection. The patient blood was combined with antibodies that block HAP2 that resulted in 77 percent reduction in transmission of the parasite from human blood to infected mosquitoes.

It is an inexpensive and straightforward target within the seek for vaccines that may lower the transmission rates of protozoal infection.

Drug Discovery and Development


At initial stage of Drug  Discovery, based on the single molecule disease target, scientist identifies the high specificity compound which modulates and interacts with the target. The approach used by them was “one target and one drug” approach which is the failure one. Thus, result in the intake of series of specific target drugs which reacts in ineffective way to the isolated target. The new drugs are prepared well than the previous generation to increase the life, strength, reduces the pain and suffering. The development of new drugs makes the pharma industry to take risk in cost and time. The new Drugs are discovered in the basis of cheap (to the people) and more effective. The various phase are there for drug discovery and development, at last the drug enters via New Drug Application (NDA) and then launched into the market only by satisfying FDA rules and regulations. The base for the drugs is synthetic molecules, which is directly, or indirectly a natural product or polyconstituents. In future the contemporary drugs and Ayurveda will have win –win relationship. Contemporary Drug discovery and development (DD) process is becoming longer and expensive. Establishing the right balance between efficacy and safety is the crucial part of DD process.

For more specific treatment, genetic engineering applications have been implemented, where targeted diseased gene is treated in more effective way by combination of pharmacology and genetic engineering.

Developments of new rationally designed targeted therapies:: Several recent phase-I trials of molecularly targeted agents have demonstrated remarkable progress when patients were selected based on their molecular profile and subsequently treated with an agent directed against this specific target. The shift from ‘one size fits all’ to molecularly defined subpopulations has been particularly successful in the treatment of patients.