The research and innovation in the field of excipients of late has been focused on enhancing the drug delivery. As the pharmaceutical industry has emphasized its focus on NDDS (New Drug Delivery Systems) research compared to NCE (New Chemical Entity) due to high impending costs posed by the latter, the excipient industry is thrust with responsibility to work in hand with the former in developing technologies enhancing drug delivery.
As a result global excipient majors like Dow Chemicals, Colorcon, Shimadzu, Daewoo Chemicals, and Roechm-Degussa have stepped up their research focusing on making enhanced drug delivery excipients.
"It costs about $ 1.7 billion in developing a NCE. Compared to this it takes peanuts to develop NDDS. As a result focus of the pharma companies has clearly shifted towards NDDS research. It is a very good opportunity now for excipient manufacturers to work hand in hand with the pharma industry in making excipients enhancing drug delivery," said Devinder Pal, President, Pamdal, who is also an expert on excipients.
Agrees Dr Kamlesh P Oza, managing director, Colorcon Asia Pvt. "From a minor role of diluent for drugs, the role of excipients have become far more significant today. Not only is it playing a key role in the development of NDDS, but also in newer segments of drug development like designer drugs and taste masking," said Dr. Oza.
Colorcon is the only foreign excipient specialist to have set up its manufacturing and R&D base in Goa. The company has a strategic business unit (SBU) dedicated on NDDS research.
Here are some of the recent examples on the growing importance of excipients in NDDS development. Anti-diabetic NDDS metformin went off-patent last year. Metformin is a class 4 drug as it dissolves easily with the body fluids. The problem was with immediate release of the active ingredient, which was tackled by the Hydrophillic Polymer Matrix (HPM) technology developed by Dow Chemicals. HPM, a filler, is put inside the tablet. When it comes in contact with gastric fluids, the gel swells and the resultant diffusion causes a controlled solubility of the active ingredient.
Ranbaxy utilized similar technology to make its Cipro OD (once-a-day), where excipients controlled the solubility of active ingredients in a programmed manner enabling the patients to get more benefits from taking the drug once, compared to twice or thrice.
Colorcon recently developed a patented technology to effectively control the dissolution of proton pump inhibitors or antacids in acidic medium, which would lessen its efficacy. Coating antacid pellet with excipient Acryl-eze enables its dissolution in the alkaline medium and not in the acidic medium, thereby bringing the efficacy of the drug to 100 per cent level.
Gattefosse introduced the Self Micro Emulsifying Drug Delivery System or SMEDDS, which is a technology to raise the solubility of a poorly soluble drug. SMEDDS comprise a surfactant, a co-surfactant, a lipid phase, and an active compound - These systems are custom designed for each active molecule. On dilution, SMEDDS spontaneously convert to optically clear, thermodynamically stable, micro emulsions, which contain the drug in molecular dispersion, thereby raising the solubility of the active ingredients.
'Designer Drugs' is another trend of the day. Here too excipients play a key role. The concept means making the drug attractive and colourful with fancy colours or giving unconventional shapes like that of heart, diamond, polygon, elliptical et al. Blue coloured, diamond shaped Viagra is a good example of a Designer Drug. Recently colours have also being used to indicate a particular illness. For e.g. the red colour is used to indicate drugs for cardiovascular diseases.
"In India too, corporates are preferring to make their tablets more colourful from the conventional white colour," said Sonali Sheth, GM, Commercial, S. Zhaveri & Co.
"Designer Drugs in the form of a different colour or shape enhance brand value of a product. Also it protects from duplication. The trend is more popular in the west and is used widely for OTC brands and some lifestyle products. The trend will not catch up in the country until restrictions like DPCO is removed," said Dr. Oza.
In 2003, Colorcon introduced Brand Enhancement System Tablets or BEST technology, where the company will tailor make designer tablets as per the requirements of the client.
Durorams is the latest patented technology in the field of taste masking introduced by the Swiss company Fermenich. Here either the tablets are coated or filled with flavours masking the bitter taste of the pill and giving the drug a long-lasting taste. Colorcon is the representative of Dow Chemicals, Gattefosse and Ferminich in India.
All the high-end technologies are provided only by MNCs, whose representatives in India source these products to the Indian pharmaceutical companies. There are about 4-5 major Indian representatives for foreign companies in the country. S. Zhaveri & Co is one among them who have aligned with companies abroad like JRS Pharma, Sasol Oleochemicals and Roehm Degussa (Germany) and Sensient Colors (US).
The excipient manufacturing in the country is highly unregulated with small-scale industries playing a major role. However these SSIs can only make low end excipients like sugar and glycerine. Excipients like HPMC are imported from China. "Majority of excipients are polymers. Since there are few polymer making companies in the country, most of it are sourced from abroad," said Sheth.
"Indian drug authorities have to play a key role in regulating the excipient manufacturing in the country and checking the quality of excipients used in drugs for domestic use," she said.