Imagine an orally disintegrating tablet, which disintegrates in the mouth in less than 30 seconds and is ideal for use by children, adults as well as the elderly. The tablet can also be used in synergy with taste masking technology for bitter drug substances. Or think of an extended release tablet, which releases a drug over an eight-hour span, ideal for a once-a-day system. The release profile can be tailored to give a combination of instant and sustained release profiles. Won?t such ?wonder? drugs come to the rescue of harried patients suffering from a host of diseases? metabolic, respiratory, inflammatory and cancer? For instance, a blood pressure medication usually administered three times a day may be formulated as a once-a-day product with better control over symptoms and lesser side effects.
That?s not all. Think of dry powder inhalers (DPI), which could be used by patients of asthma and other respiratory diseases for systematic delivery of drugs to lungs. These easy to operate inhalers?just three steps of open, inhale and close?are designed to deliver uniform dose, irrespective of patient inhalation effort. Besides, they eliminate double dosing or dose wastage by children and adults alike.
Do not be surprised but excitement seems to be brewing at the research and development (R&D) centres of leading drug makers?Ranbaxy, Biocon, Cipla, Sun Pharma, Dr Reddy?s Laboratories, Nicholas Piramal and Wockhardt?to bring to the market novel drug delivery system (NDDS) products, particularly in the oral-controlled release systems segment, where business opportunity is estimated at $50 billion alone. ?The oral -controlled release formulations provide better control of drug concentrations in blood, and minimise the toxic effects,? says Venkat Jasti, chairman, Suven Life Sciences.
Globally, it is estimated that NDDS products constitute 17% of the world?s pharmaceutical market?$104 billion out of $643 billion. The same robust trends are visible in the Indian pharmaceutical market as well. Currently, NDDS products? sale in India is to the tune of Rs 1,480 crore, with an annual growth of 30%, which is well ahead of the domestic pharmaceutical market growth rate of 17% a year. NDDS products currently represent 5.6% of the total market in India.
Globally, the market is expected to double within 2010 with increased opportunities in almost all therapeutic segments. Indian drug companies couldn?t ask for more as NDDS products give them an opportunity to create intellectual property (IP), sell differentiated products with unique technologies and operate in an area where there is superior growth. Companies are buoyed by the fact that there is a strong possibility of the NDDS-based formulations introduced after 2005 getting ?patented? in India, under the provisions of the 2005 Patent Act enactment.
That?s not all. Indian companies have strong product development skills and a record of successfully being able to make ?copies? of internationally available delivery systems-based products in areas such as controlled release. Novel and complex drug delivery systems are ways of modifying delivery of a medication in order to make it simpler to administer, easier for the patient to take, or make it more effective or safer, says Amit Patel, vice-president (corporate development and strategic planning), Dr Reddy?s Laboratories. They could also help Indian drug companies evolve to the next stage by creating delivery systems that can be licensed out or used to bring products to the market.
?It is a win-win situation for all the stakeholders?patients, industry and the clinicians,? says Sanjeev Dani, senior vice-president and regional director (Asia & CIS), Ranbaxy Ltd. NDDS products represent the first significant step towards innovation. They can improve therapy by increasing the efficacy and duration of drug activity. Some can increase patient compliance through decreased dosing frequency and convenient routes of administration. Others can improve targeting for a specific site to reduce unwanted side effects. Ultimately, the product life cycle gets extended, Dani insists.
Ranbaxy occupies a leading market position in the NDDS arena with a basket of over 30 products already on the shelves in the country. It?s technological breakthrough came in 1999, when Bayer AG of Germany, signed an agreement with Ranbaxy to obtain exclusive development and worldwide marketing rights to an oral, once-daily formulation of Ciprofloxacin, originally developed by Ranbaxy. Cipro has been Bayer AG?s blockbuster drug and one of the world?s leading antibiotics. This new once-daily or extended-release oral formulation of Ciprofloxacin, developed by Ranbaxy, offers the twin benefits of improved patient convenience and enhanced compliance.
Similarly, Biocon?s research focus in this space is anchored on the premise that it has a new molecular entity that allows for a novel route of administration, namely, oral, compared to the existing injectable medium.
?Our focus is currently on a molecule, IN105, which is an insulin-conjugate optimised for oral delivery as a tablet. We have already completed Phase I trials of IN-105 in India,? says Arun Chandavarkar, chief operating officer, Biocon Ltd.
According to him, in an NDDS strategy, the active pharmaceutical ingredient (API) is the same and by varying the formulation, one can modify the pharmacokinetics without necessarily altering the route of administration. This allows for extended release or reduced frequency of dosing. This strategy is often used by innovator companies as part of their life cycle management for existing products and also by generic companies who wish to find a niche for entering with differentiated formulation, using an abbreviated regulatory pathway.
Numerous studies conducted by various drug companies on the medical fraternity?s experience suggest that there is high level of poor compliance to the medications by patients. One such study based on daily dosage frequency in Indian patients has shown that those who fail to comply with prescribed treatment usually range from 30% to 60%, with some figures as high as 90%. In other words, non-compliance is fast becoming the most significant reason for failed therapy. Also, studies show that a better compliance is there with medications having once-a-day or twice-a-day dosage guideline.
No wonder, getting a suitable drug delivery form is almost as important as the drug itself. And, the true significance of drug delivery technologies lies in their ability to improve the safety, efficacy and medical utility of several drugs.
The NDDS segment is being driven by the twin trends of declining number of approvals of innovative drugs along with blockbusters going off-patent, says Utkarsh Palnitkar, head of life sciences practice, Ernst & Young (India). Pharma companies are able to give ?newness? to the product by introducing a new technology into old products. This fetches them a higher price valuation. Furthermore, companies are ?tinkering around? with the structure of the original drug, by extending the structure to a NDDS platform, to try to arrive at ?new molecules?, sometimes targeted at newer indications.
Uday Baldota, vice-president (investor relations, Sun Pharmaceuticals Ltd, says, ?We have to evolve to the next stage, that is, create ?new to the world? delivery systems that can be licensed out or used to bring products to market. Once these ?novel? technologies are patented in India, then copying even these will become difficult,? he insists.
However, NDDS need not always be the succour that the industry is looking for. Sensational failures?inhaled insulin is a case in point?highlight the need for successful technology platforms as an enabler of commercial success.
According to Baldota, delivery system-based products are highly technology intensive, and use knowledge across a number of areas. For instance, a safer anti-cancer drug may be based on better purification methods, use the principles of lipid chemistry as well as polymers to deliver tiny microgram doses to the tumour site.
In the present scenario, some
Indian firms are developing novel drug delivery systems for the existing molecules?to control the rate at which a drug dissolves in the blood?and out-license the same to the original patent holders. NDDS help the originators extend the life of the existing product patents and in return, more money to the company that develops the same. Perhaps, Baldota best summarises the mood in the marketplace, ?In the future, one would likely see many new delivery systems, based on interesting technologies in the international market, where the IP is owned by an Indian company.?
