HM Medical Clinic

 

Rsisinternational.org

2nd International Conference on Multidisciplinary Research & Practice P a g e 182

Purification of Chlorzoxazone by Adsorption A Bharucha1*, V Patel1, C Patel1, C Prajapati1, A Parmar1, V Desai1, A Sharma1 1Chemical Engineering Department, Sarvajanik College of Engineering and Technology, Surat, Gujarat Abstract: Chlorzoxazone (C7H4ClNO2) chemically 2-hydroxy
Where X is selected from the group consisting of 5-chloro and aromatic
compound
4-chloro which are known as pharmaceutical carrier. The benzoxazole family which is having benzene fused oxazole ring
compositions of the present compound have been found to structure, is a centrally water insoluble acting muscle relaxant
produce relaxation of the skeletal muscles by a mechanism used to treat muscle spasm and the resulting pain or discomfort.
involving the depression of the polysynaptic, pathways of the It is a white, odorless, crystalline powder mostly soluble in
central nervous system. [2] Benzoxazole is an aromatic organic solvent. Chlorzoxazone is produced from the hydrolysis
of 2-amino-chloro benzoxazole (C
organic compound having benzene fused oxazole ring 6H6ClNO). The undesirable
brown color in downstream of reactor is removing by
structure with a molecular formula C7H5NO molar mass adsorption. This paper reviews selection of solvent and adsorbent
119.12 g/mol, and an odor similar to pyridine with IUPAC for purification.
name 1-Oxa-3-aza-1H-indene, Insoluble in water and melting point 27-30OC. Benzoxazoles can be considered as structural Keywords: Chlorzoxazone, Purification, Adsorption, Solvent,
isosteres of the naturally occurring nucleic bases adenine and Adsorbent
guanine, which allow them to interact easily with polymers of living systems [3]. Chlorzoxazone is having IUPAC name 5- INTRODUCTION hlorzoxazone, chemically 2 hydroxy chlorobenzoxazole properties are shown in Table 1. Can d is a centrally active muscle relaxant for the treatment of painful muscles spasm associated with muscloskeletal disorders, such as fibrositis, bursitis, myositis, spondylitis, Chemical name(IUPAC) sprains, and muscle strains. Chlorzoxazone C7H4ClNO2 is White, odorless, crystalline powder which is soluble in Molecular formula solutions of alkali hydroxides and ammonia; sparingly soluble Chemical structure in alcohol, in isopropyl alcohol, and in methanol.[1] The composition of the present compound comprises a benzoxazole compound selected from the group consisting of 2-hydroxy benzoxazoles having the structural formula shown in fig 1. [2] Molecular weight Heterocyclic Benzoxazole Crystalline solid Water solubility Slightly soluble Other solubility Sparingly soluble in alcohol, isopropanol and methanol; soluble in ammonia and alkaline solutions Figure 1 .Structural formula (a) 2-hydroxy benzoxazoles (b) Volume III Issue I IJRSI ISSN 2321-2705 2nd International Conference on Multidisciplinary Research & Practice P a g e 183

Synonyms
Undesirable brown color is present in downstream of reactor. So it is necessary to purify it according to USP standard. As chlorzoxazone is a pharmaceutical product it has to follow the USP standards and according to USP the chlorzoxazone should be white crystalline solids. 5-chlorobenzoxazolidone PURIFICATION OF CHLORZOXAZONE Chlorzoxazone is a solid substance so there is very limited choice for the purification operation. Another thing in selecting is efficiency & concentration of feed stream. As it is pharmaceutical product it requires very high degree of 2-hydroxybenzoxazole purification. The downstream of reactor contains around 95% of chlorzoxazone so it is required to remove 5% impurities. So for this reason conventional heat driven process can be proved costly. Thus for removing undesirable impurities adsorption is carried out by using activated charcoal [2]. SOLVENT FOR ADSORPTION Chlorzoxazone is water insoluble compound. It is having good solubility in organic solvents like chloroform, methanol, ethanol, ethyl acetate, acetone, etc. The solvent required for this operation should have higher volatility, less cost, uniform crystals, high dissolution rate etc. The study on different properties of solvent like volatility, dissolution rate, crystals are done by Talluri Chandrasekar and his co workers. His Table 1 Properties of Chlorzoxazone [11] results are shown in following Table 1. MANUFACTURING PROCESS Table 1: Dissolution rate of chlorzoxane in different solvent by Talluri et al 2-hydroxy chlorobenzoxazole is prepared by hydrolysis of the corresponding 2-amino-5- or 4-chloro benzoxazole. Percentage of drug release Benzoxazole compound is also water insoluble in nature and an aromatic organic compound having benzene fused oxazole ring structure. So, during the production of this compound it is dissolve in organic solvent like methanol, ethanol, acetone, ethyl acetate and chloroform etc [1]. These organic solvents have been used for solubilization of poorly water-soluble drugs production. Drawbacks of organic solvents include high cost and error in analysis due to volatility [3]. For any pharmaceutical compound the dissolution rate is very important thing. Here in this Table 2 it can see that the highest 2-hydroxy chlorobenzoxazole is produced by reaction dissolution rate is obtained with Chloroform, Methanol and between 2-amino-5- or 4-chloro benzoxazole, HCl and Urea at Ethanol. Another important thing is the crystals formed from 115°C with constant pH of 4.5 – 5. In this reaction HCl is these solvents. This also uniform in case of all three. Here added to solubalise 2-hydroxy chlorobenzoxazole and chloroform is toxic as compared to Ethanol and Methanol so it neutralizes the ammonia released from reaction. Here acetic cannot be selected. [1] acid is added as buffer solution. Further solution is centrifuge for getting crude product which further purified by adsorption Now considering economical factor like cost which is shown (decolorization) and finally crystallization occurs in presence in table. It's high in case of ethanol as compared to methanol. of organic solvent like methanol. [11] Another thing related to ethanol is the legal restriction. Due to less cost, more volatility, less toxicity, and uniformality of product size methanol is selected as best solvent among of all. 6H6CINO +NH2CONH2+ 2HCL
7H4ClNO2+ 2NH4CI
Volume III Issue I IJRSI ISSN 2321-2705 2nd International Conference on Multidisciplinary Research & Practice P a g e 184

Activated carbon has wide range different desired properties are available. The study is also done on the behavior of different activated carbons so the performance can be easily predicted. Activated carbon contains very less amount of ash by Talluri et al [1] and heavy metal. So for these reasons activated carbon is gives good result then above tow adsorbent. This review paper concludes that for purification of chlorzoxazone methanol can be used as solvent as it gives product having good rate of dissolution, volatility, less cost and better crystals uniformality. Activated carbon silica gel Table no: 3 comparisons of different solvent properties and fly ash used as adsorbent. ADSORBENT FOR ADSORPTION OPERATION In adsorption the adsorbent plays very important role. So [1]. Talluri chandrashekar, Bairy padma, Kantham Srinivas Kusuma selection of it is crucial parameter. At present the available praveen Kumar, (2110) Preparation and characteristics of polymer adsorbent in India are Fly ash, Silica gel and Activated of chlorzoxazone, International Journal of Biopharmaceutics. Charcoal. In India as the thermal power station use [2]. U S Patent No: 2895877 [3]. U S Patent No: 2890985 bituminous grade coal as fuel, it contains high amount of SiO2 [4]. U S Patent No: 2780633 & Al2O3. This may affect the product characteristics. It also [5]. Priyanka Lokwani1, B.P. Nagori, Nikhil Batra, Anju Goyal, Stuti required costly pretreatment. [8] Another option is silica gel. Gupta1and Nisha Singh, (2011) Benzoxazole: The molecule of The much research is not done on it for adsorption of solids. It diverse biological activities. [6]. Rajesh Sharma, Pandurang Gaikwad, Rupali Joshi, (2010) A is mostly used for adsorption of vapor from gas mixtures. The Novel Application of Hydrotropic Solubilization for Simultaneous mechanism of adsorption for silica gel involves the making of Estimation and Validation of Acetaminophen, Chlorzoxazone, and hydrogen bond so, to adsorb anything on the silica gel it is Aceclofenac in Tablet Dosage Form. necessary that it makes hydrogen bond and this thing cannot [7]. Preparation and characteristics of polymer of chlorzoxazones [8]. Anjan K. Chatterjee, Indian Fly Ashes, Their Characteristics, and be predict in this case as the compound giving color is Potential for Mechano-Chemical Activation for Enhanced [9]. Mass-Transfer Operation by Robert E. Treybal, Third Edition. [10]. United Volume III Issue I IJRSI ISSN 2321-2705

Source: http://www.rsisinternational.org/2ICMRP2015/182-184.pdf