In-Silico Pharmacology Practice

Traditional pharmacology is the science of drug action in the human/animal body.  We learn how the drug interacts with target molecules, example H2 receptor blockers interact with H2 receptors, and block them so histamine cannot interact with the H2 receptors of the parietal cells of the stomach.  If histamine stimulation does not happen on the H2 receptors, production of HCl in stomach is reduced. This is the pharmacodynamic (what drug does to body) perspective of traditional pharmacology.  Thus, H2 receptors reduce HCl acid production and give relief from pain due to acid peptic disease or stomach ulcers (break in the mucosal lining of stomach).  

We also learn how the body absorbs, distributes, metabolises and gradually excretes the drug from the body (pharmacokinetics or what body does to the drug).  This is the drug action and behaviour inside the body and that sums up the core of pharmacology study.

The advent of computer systems and advanced software is rewriting the study of pharmacology, from acutal living systems to experimenting on drug action in computer systems!  Welcome to the world of in-silico pharmacology!!

In-silico pharmacology refers to the use of computers, advanced software, and artificial intelligence (AI) to simulate, analyze, and predict how drugs interact with biological systems. Derived from the silicon chips that power modern processors, "in silico" complements traditional in vitro (test tube) and in vivo (animal) experiments. This approach allows scientists to evaluate the efficacy, safety, and behavior of thousands of chemical compounds entirely in a virtual environment before stepping into a physical laboratory.

The use of Agentic AI software in the in-silico pharmacology practice, represents a paradigm shift from traditional predictive models and reactive generative AI (like standard chatbots) to autonomous, goal-directed digital entities. While regular generative AI responds to a single user prompt by outputting a fixed text or molecule and then stopping, agentic AI acts as an independent worker equipped with reasoning capabilities, tool integration, and long-term memory. 

For example given a broad strategic goal via a prompt—such as "Find a non-imidazole agonist for the H3 receptor that can cross the blood-brain barrier"—agentic software will independently break the task down into sub-tasks. It actively writes code, queries structural databases (like ChEMBL or UniProt), executes virtual docking simulations, analyzes its own errors, and refines the molecular design continuously without human intervention until the goal is achieved.

The various AI agentic software platforms that are making drug discovery speedier & autonomous: Claude Science (by Anthropic), ChemistryAgent / BioForma Agents, Insilico Medicine Pharma.AI System (Chemistry42 / BioDesign), Schrodinger Glide and NVIDIA BioNeMo Agent Framework.

Learning how to use these agentic AI software systems as part of in-silico pharmacology is the real future of pharmacology, traditional pharmacology is migrating from lab testing of molecules to the state-of-art computer systems and software that do the work faster and more economically.

By - Dr. Sunil S Chiplunkar M Pharm PhD MBA PGDHRM, VP Business Development, Group Pharmaceuticals, Bangalore (17.8.2026).

We are fooling ourselves: India is a sick nation

Indians are definitely unhealthy  

India cannot be called “healthy” in any comfortable sense: it carries a triple burden of unfinished infectious diseases, rapidly rising non-communicable diseases (NCDs), and worsening lifestyle risk factors driven by sedentary work, poor diet, and chronic stress. The country’s disease profile shows both progress and a heavy health load, with NCDs now causing about 60% of deaths and communicable diseases still remaining a major public-health challenge.

Infectious disease burden

India continues to face major communicable disease pressure from tuberculosis, malaria, HIV/AIDS, dengue, acute encephalitis syndrome, and neglected tropical diseases. A public-health review notes that despite progress, these infections remain a serious threat, especially in poorer and more vulnerable populations. India also carries a large burden of neglected tropical diseases; one compiled estimate lists millions of cases for ascariasis, hookworm, trichuriasis, dengue, lymphatic filariasis, and leprosy. This means the infection burden has not disappeared even as the country has developed economically.

NCDs dominate mortality

The bigger shift is toward chronic disease. The Government of India has cited national disease-burden work showing that the share of deaths due to NCDs rose from 37.9% in 1990 to 61.8% in 2016. A major review also states that heart disease, cancer, diabetes, and chronic pulmonary disease together account for nearly 80% of NCD deaths. In addition, a 2026 study on chronic kidney disease found 2023 incidence across Indian states ranging from 226.4 to 316.4 per 100,000, with prevalence as high as 10,452 to 12,539 per 100,000, showing how wide and uneven the chronic-disease burden has become.

Sedentary life and stress

Modern urban and semi-urban life in India is increasingly sedentary: long commutes, desk work, screen time, and low routine physical activity all raise risk for obesity, diabetes, hypertension, and heart disease. The public-health literature links these conditions to lack of physical activity, unhealthy diet, tobacco, and alcohol use. Stress adds another layer, because overwork, financial pressure, traffic, job insecurity, and sleep loss intensify cardiovascular and metabolic risk; even earlier surveys described sedentary but fast-paced lifestyles as a growing driver of heart disease in India.

India is not a nation defined by one disease, but by a health system and social environment under strain. Communicable diseases continue to affect the poor, while NCDs increasingly hit all classes, including younger adults. The real warning is that disease is now shaped not only by microbes, but by how people live, work, eat, travel, and cope with stress every day. 

Post by Dr. Sunil S Chiplunkar M Pharm PhD MBA PGDHRM

Measles epidemic @ Bangladesh (June 2026)

To hear things like a measles epidemic in Asia is quite an eyebrow- raiser.  The turmoil for patients and stigma for a nation due to epidemic is certainly challenging.  Immunization shots are vital to avoid diseases like measles and create individual and herd immunity (resistance to disease).  When health care systems and the general economy go sluggish, there rises the problems of epidemics.  Proactive vigil is as important as prompt action in matters of healthcare to avoid disturbing incidents such as a measles epidemic.

Another vital point to note is that of under-nutrition: a severe risk factor compounding the mortality rate is malnutrition. Additionally, disruptions to public health campaigns in 2025 meant that many children missed their scheduled Vitamin A supplementation rounds. Vitamin A deficiency heavily increases the risk of severe illness, blindness, and death when a child contracts measles.

Why this measles epidemic in Bangladesh?

Before the epidemic, Bangladesh's coverage slipped to roughly 86% for the first dose and 80% for the second dose. This minor-looking percentage drop created a quiet accumulation of completely unvaccinated ("zero-dose") children over 4 to 5 years. Once the virus was reintroduced, this pool of vulnerable children acted as fuel for the explosive outbreak.  Public health requires a strict 95% vaccination coverage rate of both doses of the Measles-Rubella (MR) vaccine to maintain herd immunity.

It is said the trinity of HEALTH, WEALTH AND WISDOM are the real pursuits of humankind.  In the case of current measles epidemic in Bangladesh, health focus has taken a toss.

Why this episode of measles epidemic is dangerous in Bangladesh?

Measles does not just cause a rash and fever; it actively destroys the body's defenses. It induces "immune amnesia," wiping out a child's previously acquired antibodies to other diseases, leaving them vulnerable to other infections for months or years.

Take a lesson from this epidemic measles @ Bangladesh and let us all focus on proper healthcare practices, because ill-health knows no political borders: from Dr. Sunil S Chiplunkar M Pharm PhD MBA PGHDRM 

Momentum @ Community-Led Clinical Influence

There is a new trending that is rolling on like a juggernaut, which many MNCs and other big companies are latching on to very stickily - and experiencing fiery sales growth!  The trending phenomenon is COMMUNITY-LED CLINICAL INFLUENCE.

The concept of community-led clinical influence is based on real-world evidence that clinicians experience daily, thus leading to peer-driven professional advocacy for a therapy or product.  

This "Community-Led Clinical Influence" approach is best illustrated with success of Shy NM toothpaste:

A prime illustration of the COMMUNITY-LED CLINICAL INFLUENCE in modern dentistry is the market trajectory of Shy NM toothpaste. Formulated with Calcium Sodium Phosphosilicate (CSPS), Shy NM is specifically engineered to target dentin sensitivity and facilitate enamel remineralization. The clinical footprint of Shy NM has expanded primarily through the active endorsement of dental professional communities, institutional faculties, and regional practitioner peer groups who actively champion its underlying bioactive glass technology.

The clinical influence for Shy NM operates through decentralized, grass-roots professional circles. Dentists regularly exchange real-world patient outcomes, share case studies in localized forums, and discuss product efficacy on peer-to-peer networks. 

When a respected clinician witnesses how effectively Shy NM occludes open dentinal tubules to offer sustained, long-term relief to dentin sensitive patients, their organic advocacy carries immense credibility within their professional circle. This decentralized validation creates a resilient, high-trust loop that conventional marketing simply cannot replicate.

Pharma companies are going thick into the game of this collective grassroots promotion

GSK is deploying this approach of 'community-led clinical influence' for their antibiotic therapy promotion, DRL is doing it for a wide range of products, and so are Torrent and Glenmark that are knee deep into promoting products through the 'community-led clinical influence' strategy.

Thanks for reading this blogpost by Dr. Sunil S Chiplunkar M Pharm PhD MBA PGDHRM

The big three in trouble

The Middle East conflagration with its world-wide ramifications is slowly & surely affecting health delivery.  The prominent factor of health delivery is accessible and affordable stock of medicines in the pharmacy.  Input costs for manufacturing generics is zooming up, as it is generics have lower margin, and add to the boiling fire there is a dilemma of higher shipping costs.  Hence, contraction of demand leading to negative impact on economies of scale further complicates matters in generic production and distribution, and all countries are affected - Middle East countries and others.

The big three

Manufacturing of generic pharmaceuticals involves using excipients and the big three excipients are: 

a) magnesium stearate that is present in 50% to 60% of oral dosage forms as a lubricant and as an overall excipient of tablets and capsule

b) MCC or microcrystalline cellulose that is used as binder, diluent and filler to hold the tablet matrix together

c) And we have finally, lactose (monohydrate/anhydrous) used as a bulk filler to make up the volume and weight of tablets

The production of magnesium stearate depends heavily on vegetable fats/oils and upstream chemical solvents, while MCC (microcrystalline cellulose) relies on specialized wood pulp and chemical reagents. The escalation of the Middle East war has heavily disrupted global oil, gas, and energy markets. This has translated directly into a 200% to 300% surge in raw chemical material prices within compressed timeframes, directly shrinking the profit margins of generic manufacturers who operate under strict government price controls.  Western Europe (led by companies like DFE Pharma in the Netherlands and Germany) is the central global hub for high-grade pharmaceutical lactose. Severe trade tensions and disruptions around the Persian Gulf and the Strait of Hormuz have heavily penalized input materials for the global dairy industry.  All this has affected generics manufacturing, buffer stocks of 2 to 3 months has saved the situation, however supply constraints, high price of new stocks is squeezing the margins of generic manfacturing - and this will have its toll on medicine availability from the pharmacy of the world: India.  No country will be spared from this ill effect of Middle East war on medicine availability including USA and advanced countries.  

India provides 20% of world's generics, 45% of generics in USA, 25% of all medicines of UK, 50% of medicines in Africa and 50% to 60% of the world's vaccines.  Generics from India are a life line to all the 200 countries of the world.  This high volume of generics production and distribution to the world depends on manageable raw material costs, efficient logistics and judiciously priced energy costs.  Besides, important medicines under price watch of NPPA are called scheduled drugs - and they have heavy margin squeeze.  The answer to all these issues is for the policy makers to keep an eagle eye daily, on the supply and price situation of APIs, intermediates and excipients including the big three (magnesium stearate, MCC and lactose), so India can seamlessly provide affordable generics to its citizens and the world.

As per newspaper reports India’s pharmaceutical exports dropped over 23% by early 2026. Trade bodies estimate that these disruptions could cost Indian drugmakers between $300 million and $600 million.  If there is supply problems there is also a looming danger of widespread factory shutdowns and severe global medicine shortages.  Quelle catastrophe ! (What a catastrophe!)      

 Thanks for reading, written by - Dr. Sunil S Chiplunkar M Pharm PhD MBA PGDHRM

 

The ranitidine conundrum

 

Ranitidine is a unique pharma drug story!  In a way it depicts the age old adage: what goes up must come down!  The ranitidine story is a ride on the giant Ferris wheel, starting in the summer of 1977 at one of the laboratories in UK as AH19065 to becoming the largest prescribed drugs in terms of units in India and the world-over, it seems now ranitidine is seeing a dead end.  Is it control + alt + delete for ranitidine? 

Ranitidine hit national headlines when the NLEM 2022 (National List of Essential Medicines 2022) was released by Dr. Mansukh Mandaviya, Union Health Minister of Govt. of India in September 2022.  Compared to NLEM 2015, the NLEM 2022 that has a total of 384 listed medicines - has dropped 26 drugs, of which one is ranitidine.  And many were wondering why ranitidine was dropped, since ranitidine is traditionally one of the largest prescribed drugs in India in terms of units.  In India, the ranitidine market is about Rs. 700 crores sales per annum. 

Launched first in 1981 in UK, ranitidine had become one of the world’s most prescribed medicines by 1987.  Sales of ranitidine started becoming muted only when omeprazole proton pump inhibitor was launched in 1989.  In 2020, Zinetac was 9% of GSK India’s revenues at about Rs. 200 crores. 

Ranitidine - the cancer connection?

Valisure is an independent laboratory and till 2021 they had a pharmacy in New Haven, Connecticut, USA.  Valisure pharmacy would check the chemicals in a medicine before sending to patients.  Before founding Valisure - one of the founders of Valisure, Clark Joseph used to take generic medicines for his health problem, but continued to feel sick.  He tested the medicine and was shocked to see the generic medicine was not of quality.  When he escalated this problem to his pharmacist, the pharmacist brushed it off saying that it must have been a problem batch.  This stimulated Clark and his colleagues to start Valisure, the pharmacy that tests medicines in its lab before shipping to patients.  It was during one of these testing practices (because Clark’s daughter was taking ranitidine syrup) that Valisure discovered enormous abnormal amounts of NDMA (N-nitrosodimethylamine) in ranitidine tablets/syrup.  Valisure detected 3 million nanograms of NDMA per tablet of ranitidine (due to higher temperature used in their testing procedure).   US FDA states the safe limit of NDMA for human consumption is 96 nanograms per day.  Valisure escalated the problem to US FDA in June 2019.  Thereby, in 2019 after investigation, US FDA also found NDMA (N-nitrosodimethylamine) in ranitidine tablets however it was in much lower levels much less than Valisure.

Similarly, Valisure in the past has shown that certain extended release tablets did not behave as claimed and they even proved that rapid release Tylenol (paracetamol) was dissolving slower than regular paracetamol! 

NDMA is a compound of nitrosamine chemical class, and above 96 ng/day consumption, NDMA is a probable (unproven) human carcinogen and is observed to be a carcinogen in animal studies.  NDMA is described as a genotoxic material.  NDMA is found in nature, plants and food too – in these very tiny amounts, NDMA is not a problem.  NDMA is a problem in larger quantity - if more than 96 ng/day is consumed.    NDMA impurity problem has been seen in various formulations from 2018, due to improper API manufacturing (impurity through solvents) - as in cases of antihypertensive angiotensin 2 receptor blockers (valsartan, irbesartan and losartan) and metformin sustained release products. The problems of excess NDMA are ill effects on liver and abdominal organs, and brain. 

Valisure has a thesis that ranitidine reacts with stomach acid to produce NDMA, however, this view is not accepted by US FDA.  Another theory is that NDMA is produced inside the body by reacting with a specific enzyme in the body’s kidney, brain and prostate. 

Storage of ranitidine tablets at higher temperatures such as 40 degree celsius for 8 weeks and more - causes formation of NDMA inside the ranitidine tablet.  Also, if the active ingredient ranitidine is not properly manufactured, NDMA impurity is created when the ranitidine bulk drug used for manufacturing tablets.  

Consequence of Valisure's findings and US FDA's independent investigation

US FDA pulled out all ranitidine brands including Zantac and ranitidine generics, from USA in April 2020.  Zantac disappeared from pharmacy shelves of UK in October 2019 and ranitidine is not available in UK.  Ranitidine is not allowed to be sold as per EMA (European Medicines Agency).    

Law suits in line!

In USA, normally law suits are filed by aggrieved parties when such problems of medicinal ill effects spring up.  For instance Merck Vioxx (rofecoxib) caused stroke problem, Merck settled its law suits by paying 4.85 billion USD.  Similarly, many law firms in USA are urging Zantac consumers to contact them for filing law suits.  Court proceedings are going on, lawyers are citing a Taiwanese study that ranitidine increases vulnerability to gastric, liver and other cancers. 

Ranitidine in India

Ranitidine is not banned in India nor taken off the shelf by manufacturers.  However, ranitidine is no more in the NLEM 2022.  This is because there is no conclusive and firm evidence that ranitidine tablet loads up dangerous levels of NDMA, which is a probable (not proven) human carcinogen.  Since, the picture is unclear; and court proceedings are still going on in USA, there is no Indian regulatory action on ranitidine.

Zantac – an iconic marketing success brand

The most popular brand of ranitidine across the world is Zantac, from Glaxo Smith Kline, a British company.  In India GSK launched ranitidine as Zinetac.  Zantac global launch was in early 1980s - a sensational market vibration was created since ranitidine had the advantage of lesser side effects compared to earlier H₂ receptor blocker cimetidine.  International speaker experts were flown in to have educational symposia at glitzy hotels.  Glaxo appointed - a daredevil move in India - a separate field force to promote Zinetac, so each of this division medical representative had just one product to promote: Zinetac!  Doctors were pulled to the symposia and drawn by the superiority of ranitidine.  Zinetac was also promoted to primary care physicians giving GSK a large prescriber base.  Abroad, where direct-to-consumer product promotion is allowed, bulletins were distributed on the new novel drug ranitidine, causing patients to ask doctors for prescriptions.  Thereby, a new era in H₂ receptor drug marketing started.

In 1990, Zantac was 50% of GSK’s annual revenues.  The global sales in 1990 fiscal year was 2.40 billion USD.  Zinetac was approved by US FDA in 1983, and Zantac clocked 1 billion USD global sales in 1988.  In India, Zinetac was launched in mid 1980s and again a runaway success in India.

The NDMA ranitidine problem has hit GSK so badly that it sold its Vemegal, Karnataka manufacturing plant to Hetero Drugs as there was a slump in global demand for Zantac.  

Zantac 360

Zantac 360 is a new launch in USA, from GSK, however, this brand contains famotidine and not ranitidine. 

In India, Rantac (J B Chemicals) is a very popular brand of ranitidine.  Interestingly, marketers at J B Chemicals have put on their creative cap and launched RANRAFT antacid suspension in which sodium alginate floats as a raft and the antacid ingredients are on the raft to neutralize excess stomach acid.  The other popular brand of ranitidine is Aciloc (Cadila).

The story is far from over ...

The ranitidine conundrum is far from being solved.  It is in the courts, various theories and assumptions are circulating.  Data from different sources are being compared and debated.  Picture abhi baaki hain!  (the ‘ranitidine movie is not yet ended’.).

THE REALITY IS PRODUCT PROMOTIONAL MESSAGES

Ground level product promotional activity

Ref. for above image: https://www.imd.org/research-knowledge/articles/digital-business-transformation/

Product promotional messaging is the life breath of every business, and finance is the life blood of every business.  Both feed each other. Promotional messages are transmitted through messengers – both animate and non-animate.  From the inception of pharmaceutical industry in India, the medical representatives (MRs) have played a hallmark role of being messengers of product promotional messages to target doctors and pharmacists.  Alongside, they have performed the role of relationship managers too, providing persuasion tools like samples and other knickknacks or sponsorships. 

Marketing myopia is another truism of marketing domain - it happens because marketers like to remain in the comfort zone.  Instead of viewing the product messages as being the pull creator of product sales, companies began to view medical representatives as the product sales pullers.  Yes, the MRs are certainly product sales pullers, but is so only when they push product promotional messages.  Otherwise, they are just mendicant or postman medical representatives.  Hence, the prima donna force providing sales pull is the array of product promotional messages (through MRs or through other means).

There are some pharmaceutical companies who learnt this home truth early on; that the medical representatives are relationship managers, people who handle collaterals in a value added manner, and are product promotional message transmitters.  This is what makes the MRs’ masters of persuasion practice.  The MR based product messaging activity is through the classic modes of visual aid and collateral detailing, extempore detailing and dialogue detailing with yes momentum.  Earlier on the printed visual aid and literatures were main tools for collateral based detailing, today, electronic aids like ipad, smartphone and tablet pc based collateral detailing are being done by MRs to engage the doctors and get them engrossed in the message.  Videos, digital images, gif images, and audio recordings used on these electronic devices have gripped the attention and engaged doctors during in-clinic activity, in-CME product promotion and in-stall or in-booth activity.  So the nub of the matter is that delivery of PRODUCT PROMOTIONAL MESSAGES produces the business outcomes, while other ‘give and take’ transactions, provides a higher level to the business outcome.  For example negotiated sponsorships along with product messaging activity have provided rocket growth to pharmaceutical companies in India.

The digital dimension of product promotional messaging activity

Covid-19 coronaviral infection has upset the apple cart of routine product promotional messaging activity in the pharmaceutical sector.  Doctors have been used to medical representative visits, who provide positive strokes, appreciation, ego massage, informational product points (these are very important to help recapitulate, after all knowledge is volatile) and other inputs that are valued by them (samples, gifts etc).  The virulent pandemic Covid-19 has made people go in for social and physical distancing.  Doctors have seen the horrid of morbidity and mortality with Covid-19 infection from close quarters; hence, they are hesitant to meet up with medical representatives.  This has changed the way pharmaceutical companies transfer product promotional messages and do the relationship management.

Pharmaceutical companies adapt to the market change

There is a saying - IF IT IS IMPORTANT, YOU WILL FIND A WAY - OR YOU WILL FIND AN EXCUSE.  Thus, savvy pharmaceutical marketers have immediately redrawn the blue print of product promotional message transfer, from relying solely on medical representatives to laying focus on the digital route of messaging to target audiences. 

Abbott has found its solution through international Key Opinion Leader (KOL) webinars and focus group discussions involving core doctors.  Micro Labs has started influencing and messaging doctors through zoom based advisory board discussions, and phone talking with core doctors.  Whatsapp has proved a great help to push messages to core doctors and core pharmacies.  So the focus is to find the 20% of doctors, pharmacies and territories (or areas or pincodes) that provide the 80% of the business - and ring-fencing them to protect businesses.

Group Pharmaceuticals, Bangalore is a very innovative and dynamic pharmaceutical company with research based oral care products - this company has focused on digital means of reaching target patients, doctors and pharmacies, through the website route, webinars (for pharmacists and doctors), social cause marketing like Dental Reach and ensuring push messaging of useful nuggets of wisdom to engage doctors and end consumers.  Group Pharmaceuticals has a committed field force with a high morale for ground level activation too.  

The nature of patient-centric reality of the pharmaceutical business especially for OTX (over-the –counter plus prescription products) portfolio has come to the fore due to the Covid-19 disruption.  Many companies are also facilitating or drawing up plans to help doctors provide telemedicine connects to patients.

Conclusion – ‘phygital’ is the way forward

Phygital (physical + digital) is the way forward for ensuring product promotional messages are delivered at the right time, in the right amount of the right quality to the targeted audience, because it is the product promotional messages that actually bring in the business rather than the messenger, -this is the home truth.  The other home truth that has once again hit investors is that cash is king, and businesses survive only when marketing is sharp enough to ensure smooth cash flow into the organization.  And if the business outcomes have to be further improved, then relationship management concepts become important, and here too, ‘phygital ’ is the way forward.