Use Of Hexamethyldisilazane As A Pharmaceutical Chemical

Pharmaceutical chemicals are used for benefitting human as well as animal health. They may be discharged into the environment, even if in the minutest levels, through their manufacture, use and disposal. Many scientists all over the world are trying to discuss the effects of this release on the environment. We already have a large array of pharmaceutical products and every year newer products are being added. The active ingredient in every drug or medicine is a pharmaceutical chemical. They have a separate biochemical mode of action and therefore one has to strictly consider the effects of these active ingredients on the flora and fauna.

Manufacture of pharmaceutical chemicals

Manufacture of the pharmaceutical chemicals normally takes place in two stages. It is either manufacturing them in bulk or manufacturing the finished drug product. Good manufacturing practices or cGMPs are responsible for minimizing any kind of unnecessary excipient into the environment. All pharmaceutical manufacturing facilities are subject to various kinds of restrictions or schedules, compliant to the rules and regulations pertaining to processed or non processed effluent discharge. There are restrictions on rates, quantities and concentrations of physical, biological and other constituents.

The Use Of Hexamethyldisilazane As An Alternative In The Analysis Of Ambers

Amber’s physical properties can be used for production of tools, ornaments and various works of art. If derivatisation techniques are used for the transformation of the polar pyrolysis products into less polar and more volatile compounds, Tetramethyl ammonium hydroxide can be used. This improves the analytical performance and the detection limits of the technique. It allows for the hydrolysis and the methylation to be done simultaneously. Very recent developments silylating reactions are done with the help of Hexamethyl Disilazane or HMDS which has also been proposed to be the alternative of amber. HMDS comes with great potentials as compared to the strongly alkaline TMAH reagent. The main limitations of this derivatizing reaction are related to the occurrence of the secondary reactions. These secondary reactions include decarboxylation reactions which are undergone by carboxylic acids as well as the formation of the dehydration products and other by products. These reactions produce pyrogams which are very tough to interpret.

Other Uses Of Hexamethyldisilazane

The use of HMDS as a drying agent was beneficial in the specimen preparation for scanning electron microscopy imaging of bacterial surface colonization on sub bituminous coal. The ability of the microbes to biofragment, ferment and generate methane from coal is where HMDS comes to use. It acts as a very good alternative to critical point drying in the imaging of cells on coal. Thus there is no need for very expensive equipments. Coal can be easily fragmented into sub-micron particles which can create a problem in critical point drying procedures. Both individual and aggregated cells appear in good shape with the least occurrence of the flat cells. This is the importance of the use of HMDS in cell attachment studies on sub-bituminous coal. The use of HMDS drying is a much preferred technology over the most commonly used CPD method as it is not only safer and cheaper but also more practical as method.

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.

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.

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.

An Overview of the Chemical Manufacturing Industry and HMDS Manufacturers

HMDS manufacturers

Chemicals like HMDS and Chloromethyl Isopropyl Carbonate play a crucial role in the pharmaceutical industries because they act as great intermediates that power important manufacturing processes. The pharma intermediate industry is becoming bigger and better due to the emergence of companies like Chemcon Specialty Chemicals. Chemcon is one of the most prominent HMDS Manufacturers that have changed the market significantly. Besides HMDS, the company also specializes in manufacturing Chloromethyl Isopropyl Carbonate which is a colorless and clear liquid with a molecular formula C5H9ClO3.

Performance of HMDS

For understanding the role and significance of these chemicals better, it is important to go through an entire overview of the industry and the top HMDS manufacturers, which have regained pace after a long period of recession. Various manufacturers are responsible for producing complex chemicals like HMDS in this interlinked yet self-sufficient industry. These specialty chemicals are nothing but chemical products which are sold not on the basis of their composition but their function or performance. These can be chemical formulations or single entities based on their requirements. Due to the fact that manufacturing complex chemicals like CMIC and HMDS requires special innovation and technology, the emergence of players like Chemcon has proved to be a boon for the industry.

Even though this industry is undergoing a huge transition, one important fact which has emerged is that several Japanese, Western European and North American companies are dominating the market. However, with several economic barriers being broken down, the growth of technology and presence of trade liberalization, more and more companies are entering the market to break the monopoly. As a result, specialty chemicals like Chloromethyl Isopropyl Carbonate and HMDS are now being sold at affordable rates. In Asia too, several Indian and Chinese HMDS manufacturers have entered the industry and are doing exceedingly well. As more and more competition increases, it seems that the clients will be in a win-win situation because the costs will be lower and the quality of these specialty chemicals will keep on improving.

In the last decade or so, the growth in the specialty chemical industry has been particularly low, however the profitability has been decent considering the fact that there has been a very competitive environment. The growth, which has been predicted for the upcoming future, looks to be somewhere around 2.0% which is not bad at all. The fact that all the new manufacturing firms are coming up with better technology and tools such as driers, reactors and condensers, the growth is surely going to be better by the next decade.

Uses of HMDS in Different Section

Various segments in the specialty chemicals industry are predicted to grow faster than the average growth speed. Some of these segments include: electronic chemicals, oil field chemicals, radiation curable coatings and specialty polymers. Popular chemical manufacturer like Chemcon also specializes in oil field chemicals and therefore the prospects of the company look really good from the onset.

It wouldn’t be wrong to say that the prospects of the specialty chemicals industry growing look very good not just in certain parts of the world, but the growth seems to be equally divided across the world. In no time, the world will see many more HMDS manufacturers coming up and giving tough competition to the firms having a monopoly in the market.