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.

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.

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.