Advance strategies - Bulk Drug Intermediates for Pharma Industries

Specialty chemicals global sector:

Specialty chemicals and pharmaceutical chemicals, over the decades have gained a lot of popularity in India. Specialty chemicals industry is a very wide and complex segment. It includes variety of products like agrichemicals, elastomers, adhesives, lubricants, oil field chemicals, etc. Worldwide, the specialty chemicals industry has grown into an array of SME’s with their own niche products. The specialty chemicals market has played a significant part in the global chemical sector. The global demand for specialty chemicals is expected to grow at a CAGR of 5.42% from 2015 to 2020.

Various Applications:

Specialty chemicals in Gujarat provide unique materials with unique properties that produce high value custom end products. They have various applications. Specialty chemicals are the chemicals which are used to boast the performance of other chemicals that can be apply in many potential experiments in the chemical industry. One of the most important applications of specialty chemicals is to speed up the manufacturing process of various chemical experiments. They help to get deliverables with less experimental costs and efforts. Some of the specialty chemicals act like value-adders that add value to other chemicals to perform more in less time.

Specialty chemicals Market Range:

North America, Western European, and Japanese firms were always amongst the market leaders in specialty chemicals industry. However, over the last few decades the Asia-Pacific region, especially India and China have globally stated their dominance in the specialty chemicals industry. In India, the speciality chemicals in Gujarat have gained a lot of dominance in this sector and have been providing their end products.

Types of Bulk Drug Intermediates:

Pharmaceutical Chemicals form the most important branch of specialty chemicals. The Pharmaceutical industry in India is the world's third-largest in terms of volume and 10th largest in value terms. . India's drugs and pharmaceuticals industry is expected to grow at a compound annual growth rate (CAGR) of 14 per cent to reach a turnover of $ 47.06 billion by 2018. Indian pharmaceutical industry is gaining rapid popularity owing to the rise in the bulk drug intermediates manufacturers. In India, Gujarat is considered to be the rising hub in the production of pharmaceutical intermediates and bulk drug intermediates. Last ten decades have seen an immense growth in SME niche pharmaceutical intermediates producing companies. Various pharma intermediates like Hexamethyl Disiloxane (HMDSO), Trimethyl Chlorosilane (TMCS), Hexamethyl Disilazane (HMDS / HMDZ) Chloromethyl Isopropyl Carbonate (CMIC) are produced and exported worldwide by these small scale manufacturers in Gujarat.

Applications of Pharmaceutical Intermediates like as lubricants, as adhesion promoter for photoresists, in alkylation agents, in creation of sedatives, medicines, in manufacturing of anhydrous solutions of HCL in alcohols, deactivator for chromatographic support materials, silylating agent in pharmaceuticals, etc.

With all the end products possessing these properties have been exported on a large scale from Gujarat, it is recognized as the upcoming hub in the field of specialty chemicals and bulk pharma intermediates.

Reaction of Hexamethyldisilazane with silica / water

Reaction of Hexamethyldisilazane with silica:

Researchers have been made to study the reaction of Hexamethyldisilazane (HMDS) with OH groups with silica that can be examined by infrared spectroscopy method. This reaction frees the OH groups and results in kinetics. The reaction produces mainly hexamethydisiloxane (HMDSO) and ammonia with a small quantity of nitrogen and methane. When temperature is maintained lower than 300°C no methane is produced. Moreover, ammonia is the first product produced and subsequently HMDSO is produced. As the temperature increases, the amount of nitrogen produces increases and that of ammonia and HMDSO decreases. Reaction of pendant silyl groups with surface acidic hydroxyls to eliminate methane and the concentration of residual silyl moieties on the silica surface both increase with temperature of reaction.

HMDS is used for deactivating materials that support in gas chromatography by many Hexamethyldisilazane Makers. Kinetic studies have been made to get comprehension about the reaction of HMDS with silica and the optimum conditions in which the reactions take place the best.

Study of HMDS:

Four important chemical properties have been deduced from such studies- 1) The freely vibrating hydroxyl groups can occur in either in Si-OH or [Si-(OH)2] configurations, 2) The freely vibrating hydroxyl groups are monoenergetic (i.e. all the OH groups show the same reactivity), 3) Due to the monoenergetic nature of the OH groups, physical absorption results in same fraction of the hydroxyl group being covered for a given pressure and temperature, and 4) The mutually H-bonded OH groups on the surface are essentially nonreactive towards the various bonding agents.

Another such study outlines the kinetics for the reaction of HMDS with silica which is mainly a two-steps process. The first step is a rate determining step that produces trimethylsilylation on the surface of silanol and forms trimethylaminosilane. The second step is where a trimethylaminosilane reactive intermediate reacts to form a trimethylsilyl surface chemical and ammonia. This two step process was mainly applied to analyze the data of the kinetics of HMDS reaction with smoked silica in the field of spectroscopy.

Absorbs Techniques:

Hexamethyldisilazane reacts with many substrate surfaces to enhance their adhesive power. When HMDS reacts with the substrate, it absorbs the excess water in them, reduced surface energy and increases the photoresist adhesion on the surface. The silizane components bond with the oxygen-atoms of the substrates and the methyls offer hydrophobic layers that have good wetting and adhesive characteristics. This dehydration reaction of HMDS on wafers (semiconductor slices) is carried out using two techniques: Liquid Priming and Vapor Priming. It is commonly know that HMDS is very sensitive to the presence of water and degrades in humid air. Studies have been made to understand the reaction of HMDS in dry and humid air in the presence of absorbent surfaces. Studies show that HMDS hydrolyzes in humid air and produces trimethylsilanol (TMS) and ammonia (NH3). Chemcon Speciality Chemicals.Pvt.Ltd is suppliers and Manufacturers of of Speciality Chemicals.

Manufacture of pharmaceutical intermediates in Gujarat

Chemcon Speciality Chemicals Pvt. Ltd. is a pharmaceutical chemicals specialty leading in the manufacturing of pharma intermediates like Hexamethyl Disiloxane (HMDSO) CAS NO. : 107-46-0, Trimethyl Chlorosilane (TMCS) CAS NO. : 75-77-4 and Chloromethyl Isopropyl Carbonate (CMIC ) CAS No. 35180-01-9. Chemcon is the largest manufacturer in India since a decade for Hexamethyldisilazane. The processes for the manufacture of all these products have been developed and engineered in-house by the team of dedicated and expert in-house professionals with in-depth knowledge in the field. We enjoy the highest reputation among Indian as well as Multi-National Companies for being a leading HMDSO, CMIC, and Trimethyl Chlorosilane in India

Three of our most significant products are:

Hexamethyl Disiloxane (HMDSO) CAS NO. : 107-46-0

We specialize in the Manufacture of HMDSO in Gujarat which has many applications like:

•    HMDSO is a pharma intermediate which is very popular in the pharmaceutical industry due to its various applications.

•    It is an organosilicon compound, volatile in nature. It is also used as a reagent and a solvent in various organic syntheses.

•    It is also used as in spectroscopy to standardize the chemical shift.

•    The most important use of HMDSO is in crystallizing of lipophilic compunds.

•    Also used in preparation of liquid bandages.

•    It is manufactured through hydrolysis of trimethlsilyl chloride.

Trimethyl Chlorosilane (TMCS ) CAS NO. : 75-77-4

As India’s leading TMCS Manufacturer in Vadodara, we produce TMCS that has very useful applications in the field of pharmacy like:

•    Trimethyl Chlorosilane is used in the manufacture of all types of silicon compounds.

•    It is widely used in the manufacture of drugs and medicines.

•    It reacts with alcohol to produce anhydrous solutions of hydrogen chloride (HCL) in alcohols that can be used for the synthesis of esters.

•    It has also been used for silylation and as a protection group in the process of various organic syntheses.

•    But the most important application of TMCS is in the preparation of HMDSO.

•    Hydrolysis of TMCS in preparation of HMDSO:

TMCS is reactive toward nucleophiles, resulting in the replacement of the chloride. In a characteristic reaction of TMCS, the nucleophile is water, resulting in hydrolysis to give the Hexamethyl Disiloxane

2(CH3)3SiCl+H2O→ (CH3)3SiO(CH3)3Si+2HCl

Chloromethyl Isopropyl Carbonate (CMIC) CAS No. 35180-01-9

Chemcon prides in its manufacture of CMIC because of its outstanding application to prepare tenofovir. Tenofovir is regarded as a revolutionary drug for curing and preventing AIDS/HIV. Tenofovir disoproxil hemifumarate salt is basically prepared using dealkylating (R)-9-[2-(Diethyl phosphonomethoxy) propyl] adenine. To get a crystallized tenofovir in its stable form, Chloromethyl Isopropyl Carbonate is Used, where it is used to condense tenofovir during the latter’s initial phase of manufacture.

These are some of the importance of pharma intermediates which have revolutionalized the field of specialty chemicals worldwide and Chemcon is one of the world’s leading manufacturers of specialty chemicals and pharma intermediates.

Hexamethyl Disilazane as an Alternative to Critical Point Drying

Critical point drying (CPD) is an established method of dehydrating biological tissue prior to examination in the Scanning Electron Microscope (SEM). This technique was first introduced to preserve three-dimensional structure of biological specimens for transmission electron microscopy, later it was used for obtaining dry specimens for SEM examination. Although CPD is a well-established method for drying specimens, there has been compelling evidence that it can damage soft specimens in two different ways: Structural integrity and Chemical Integrity. Over the years, use of the pharmaintermediate, Hexamethyl Disilazane (HMDS) in critical point drying is an established method of dehydrating biological tissue prior to examination in the SEM. Moreover, use HMDS in the imaging of cells on coal instead of CPD have led to negating the need for expensive equipment.

Studies on the applications of Hexamethyl Disilazane (HMDS) over Critical Point Drying (CPD):

• CPD and HMDS sample preparation techniques were used for testing the effects of both on the cervical cells on field emission scanning electron microscopy and energy dispersive X-ray. The results indicated that SEM imaging, elemental composition, and processing time for sample preparation with the HMDS technique were better than CPD technique for cervical cell preparation technique because in terms of weight percentages of carbon and oxygen element compositions in HMDS technique were higher than the CPD technique.

• CPD and HMDS samples used for preserving biological structures, revealed that samples prepared using CPD had tissue damage in the form of cracking. In addition there was excess amount of debris around the crack openings. Another potential result that placed HMDS as a superior drying agent is the time constraints that can be effective parameters while preparing more specimens; use of the Pharma Intermediate may be preferred over the traditional technique as it allows multiple samples to be dried simultaneously.

Preventing the gas/liquid interface is the main goal of critical point drying (as well as the alternative process of HMDS). Whenever a liquid evaporates into the gaseous phase, large surface tension phenomena occur. These surface tensions can harm fine surface details on the surface of the sample. CPD usually takes up to 3 hours to perform. Using Hexamethyldisilazane instead of CPD is quicker and can yield acceptable results on some samples. When the sample is dehydrated to 100% ethanol, a fifty/fifty mix of ethanol/HMDS can be placed on the sample followed by 2 or 3 exchanges of HMDS. After these exchanges, sample is in a fume hood where HMDS evaporates off. The vapor pressure of HMDS is such that surface damage is minimal.

The pharmaintermediate, Hexamethyl Disilazane is extensively used to replace the critical drying technique in sample preparation of tardigrades for SEM imaging because conventional procedures required CPD apparatus or machines to achieve the suitable temperature/pressure combination to completely dehydrate specimens, but with HMDS, the specimens can be dehydrated by simply bathing them in HMDS, ethanol solution, eliminating the use of any special equipment. All in all, the use of HMDS in SEM instead of CPD is preferred as it is safer, cheaper and more practical.

Calcium Bromide - A Hot Cake Completion Fluid

Calcium Bromide(CaBr2) which is an excellent drilling tool and is a very popular choice in the oilfield industry. With immense increase in drilling activities in petroleum exploration, the demand for clear brine fluids has sky-rocketed. Calcium Bromide, with 14.2 lbs/gal density, is an excellent choice for a completion fluid because of its various properties like non-damaging to the drilling formation, it is very stable chemically and thermally, and it can be used as a single salt clear brine or can be mixed with other bromides and chlorides such as zinc bromide, sodium bromide, calcium chloride, etc; making effective multi-salt compositions that are a formation of balanced high density from 11.7 lbs.gal to almost as high as 19.4 lbs/gal. It is available in powder and liquid forms. In its liquid form, it serves as an excellent drilling mud that helps balance the unstable strata while drilling oil & gas and prevents intrusion of water that may be encountered while drilling on uneven surfaces. In its powder form, it dissolves in water & other brines, and yields completion workover and packer fluids of densities upto 2.3 gm/ml (19.2 lb/gal).

Major Applications of Calcium Bromide as a completion fluid

Calcium Bromide is used as a suspension tool to keep the cuttings from filling the dug holes. While drilling, the hydrocarbons and the rock formations increase the pressure inside the drill holes, CaBr2 is used to control this pressure and even tone it. It is also very useful to seamlessly adjust the characteristics of individual drill holes. Another important use of CaBr2 as a completion fluid in oil well drilling activities is that it stabilizes the rock formation. By aiding in the repair of the individual drill holes, it helps in preventing the collapse of the rock formation. CaBr2is becoming a popular choice in oil and gas drilling, it is in fact preferred over many other fluids because it mixes easily with all the major zinc and calcium based brines and adjusts the density of other brine systems. Calcium Bromide can also be used to drill secondary drill holes from the previously drilled ones, thus increasing the oil well drilling productivity.

This bromide, a highly effective Completion Fluid is used in both offshore and onshore drilling operations. Recent expansion in drilling activity like deep, high pressure wells have contributed to the rapid growth in this market, accounting to an expected growth from $10.86 billion in 2013 to $18.37 billion by 2020, with a CAGR of 7.8 percent.

There are a few comprehensive reports based on the market analysis of CaBr2 as an important agent amongst various drilling chemicals. Such reports give an in-depth study about the current state of CaBr2 across global market. Right from the manufacturing perspective, capacity, production value, and profit to its demand/supply and import/export these reports explore the various aspects and provides a stream-lined guide to the oil field industry players about it.

Hexamethyl Disilazane & Pharma Intermediate

Hexamethyl Disilazane, which is also known as HMDS, is a special organosilicon compound that is a derivative of ammonia. It is different from the traditionally known compound because it has trimethylsilyl groups in place of the two hydrogen atoms. It is a colorless liquid that is a popular reagent and precursor to many bases, making the compound a very popular ingredient in different types of organic synthesis and organometallic chemistry. HMDS has many uses as a chemical intermediate, release agent, lubricant, coupling agent, deactivator for chromatographic support materials, silylating agent in pharmaceuticals, adhesion promoter for photoresists on silicon (electronics), as reagent for temporary protection of reactive sites in manufacture of betalactum antibiotics, etc. Amongst these, the main applications of HMDS are in electron microscopy and in semiconductor electronics industry.

Major Applications of HMDS

HMDS represents an attractive to critical point drying (CPD) in the imaging of cells on coal, negating the need for expensive equipment. Coal, a popular choice in scanning electron microscopy, is easily fragmented into sub-micron particles, which can be problematic in critical point drying procedures.  Alternatively, HMDS was found to be easily used as an ideal substitute to critical point drying that takes place at the time of sample preparation. Even though critical point drying is a popular method of drying up biological specimens that are used for scanning electron microscopy, drying up of specimens by HMDS evaporation is also a very good alternative. Hexamethyldisilazane evaporation is not used frequently however experts have suggested that this is also a great method for drying up of specimens. Hardly any differences are observed during the process and furthermore this method is proved to be much more helpful as far as drying up of whole-mount cells for AFM and TEM are concerned.

Not only this, in the semiconductor industry, with the use of HMDS as semiconductor, companies have been able to enable powerful yet small chips inside computers, tablets and smartphones to work better on a consistent basis. HMDS is used to augment the adhesion of photoresist on silicon and SiO2 surfaces. The effectiveness of HMDS on adhesion is correlated with the reactivity of this compound with surface hydroxyl groups to form a new siloxane end product, i.e. Si-O-Si(CH3)3. This newly formed termination on the substrate renders the surface more hydrophobic in character and leads to greater wettability by photoresist. The latter condition is a crucial factor in good bonding. As a result of these altered characteristics due to the surface chemistry, the treated silicon surfaces become highly compatible with both negative and positive photoresists.

A few experiments were also made to verify the hydrophobicity and adsorption properties of HMDS thin films and the results pointed out that HMDS films can be used: for ultraviolet protection of flexible organic substrates, such as PP, for sensor and/or preconcentrator development, due to their adsorption properties, and in spatial applications due to resistance for O2 attack in hostile conditions, such as plasma etching. Thus, with many applications as described above, HMDS has found its way to be a major player as a Pharma Intermediate.

The Role of Oilfield Chemicals in the Turnaround and Rise of Oilfield Industry

Oilfield chemicals are manufactured on a large scale mainly for their usage in the gas and oil industry. These specialty oilfield chemicals are known to enhance the quality and performance of the production in a manufacturing unit. By delivering apt quality specialty chemicals, oilfield chemicals manufacturers are able to improve the overall recovery rate of the hydrocarbons that are used in the oilfield industry. Consistent advancements in technology and growth in the shale industry has created various positive opportunities for these specialty chemicals. Increased demand for fuel and growth in large scale business activities are also two of the significant driving factors that have contributed to the turnaround and rise of oilfield industry.

The Role of Oilfield Chemicals in The Rise and Turnaround of Oilfield Industry

Utilized in almost all the stages of gas and oil production, ranging from drilling and well exploration, EOR applications to oil production, specialty oilfield chemicals are anticipated to continue to record consistent growth which is driven strongly by increasing demand for energy all over the world. Oilfield Chemicals Manufacturers have identified the fact that they have a huge gap to fill with most of the gas and oil resources in the world drying up. This is where they have been able to provide competent completion and drilling chemicals that have made the work of various industries easier.

Calcium Bromide – A Comprehensive Oilfield Chemical

Calcium bromide available in powder and liquid form, is a comprehensive completion fluid and oilfield chemical. With a CAS number: 7789-41-5 and molecular formula: CaBr2, calcium bromide is one of the best Oilfield Chemicals to be used in the industry because most of the companies in the oil and gas industries opt for CaBr2 for making their applications smoother. Calcium bromide is nothing but the hydrobromic acid of the calcium salt. It can absorb moisture from the air and in its powder form it completely dissolves in common brines and water. It wouldn’t be wrong to say that calcium bromide has played a significant role in boosting the demand for oilfield chemicals and the industry as a whole.

Drivers and Restraints for The Market

As per various industry reports, change in the trend of demand for specialty chemicals is anticipated to create many more opportunities for the manufacturers in the industry. The three main drivers for the market are: improved demand in specialty processes like well stimulation, rise in crude oil production and increase in deep water drilling activities.


It has been observed that powerful rise in the demand for energy and fuel sources is creating a huge demand for chemicals. However political issues across the world are causing some problems for the oilfield chemicals manufacturers, especially in the Middle Eastern regions.

Market Segmentation

For the purpose of deriving ideal forecasting reports, various experts have segment the global oilfield chemicals industry into various types of applications and products. The kinds of products are usually segmented into specialty chemicals and advanced polymers. However, the chemicals on the other hand are sub-categorized into corrosion, biocides and scale inhibitors, pout-point depressants and surfactants. Key applications of all these products comprises in drilling fluid, fracking, cementing, well stimulation, improved oil recovery, production chemicals and completion fluids.

These are some of the interesting things to note about the turnaround and rise of oilfield industry and the role of oilfield chemicals in it.