20PH76 FINAL THESIS (8)

7 ABSTRACT The disposal of expired medications poses a significant challenge, contributing to pharmaceutical waste and environmental pollution while also impacting pharmaceutical company profits. To address this issue, our project focuses on utilizing near to expiry paracetamol tablets as a primary ingredient for synthesizing azo dye, a crucial component that contributes to 50% of the textile industry's total revenue as a colorant. Our research methodology involves extracting the active pharmaceutical ingredient (API) from the near to expiry paracetamol formulation, followed by conversion reactions to obtain the initial reactant necessary for azo dye synthesis. Analytical testing is then conducted to ensure the purity of the obtained compound. By reutilizing expired medications in this innovative manner, our research aims to alleviate both the economic burden and environmental threats associated with pharmaceutical waste. This approach not only offers a sustainable solution to medication disposal but also introduces a novel method of maximizing resources through waste utilization. Keywords: Paracetamol Tablets, Para Aminophenol , Azo Dye, Waste management.8 CONTENTS Chapter No. Contents Page No. 1 Introduction 12 2 Literature review 19 3 Aim and objective 21 4 Plan of work 22 5 Materials and methods 23 6 Result and discussion 30 7 Conclusion 36 8 References 38 9 Appendix 399 LIST OF FIGURES Figure No. Figure Label Page No 1. Scheme reaction for synthesis of Azo dye 13 2. TLC Apparatus 16 3. HPLC machine 17 4. Melting point and Boiling point apparatus 18 5. Structure of Paracetamol 23 6. Structure of Para-aminophenol 24 7. Structure of n-heptane 24 8. Structure of 2-naphthol 25 9. Structure of Iso-propyl alcohol 26 10. Scheme reaction for recovery of Paracetamol from expired tablets 27 11. Hydrolysis pathway for Paracetamol 28 12. Reflux of Para aminophenol 28 13. Para aminophenol obtained through reflux 28 14. Scheme reaction for synthesis of Azo dye 29 15. Melting point of recovered compound 30 16. TLC of Paracetamol 30 17. Melting point of Para-aminophenol 32 18. TLC of Para-aminophenol 32 19. Result of Chemical Test 33 20. Melting point of Azo dye 34 21. Color Fastness Test 34 22. Ph sensitivity Test 34 23. Azo Dye 3410 LIST OF TABLES Table No. Table Title. Page No. 1. Instrumentation detail used in analysis of the compound 16 2. Chemical and Physical properties of Paracetamol 23 3. Chemical and Physical properties of Paraaminophenol 24 4. Chemical and Physical properties of n-heptane 25 5. Chemical and Physical properties of 2-naphthol 25 6. Chemical and Physical properties of iso-propyl alcohol 2610 LIST OF GRAPHS Graph No. Graph Title. Page No. 1. Chromatogram of Standard Paracetamol drug 31 2. Chromatogram of (test) recovered compound 3112 1. INTRODUCTION The exponential growth of the pharmaceutical sector globally is indisputable, with India emerging as a significant player in this landscape. Ranking fifth in global pharmaceutical production, India's industry has contributed substantially to meeting the growing demand for medications while enhancing accessibility and affordability. However, this growth has brought forth a concerning issue: the accumulation of unused or expired pharmaceuticals. Research suggests that nearly half of all medications are not utilized correctly, leading to significant wastage. Improper disposal of these medications not only impacts economic efficiency but also poses environmental risks, exacerbating pollution levels. Despite India's robust pharmaceutical industry, there exists a noticeable gap in regulatory oversight and guidelines for proper medication disposal at the household level, resulting in stockpiling and increasing the risk of misuse or poisoning. The Indian pharmaceutical market stands as a cornerstone of the nation's economy, boasting a domestic value of $42 billion, complemented by robust exports ranging between $30 to $32 billion. This thriving industry, comprised of around 3000 companies, fuels manufacturing activity worth an impressive $75 to $80 billion. However, despite its vitality, the industry faces a notable challenge with approximately $63 million worth of pharmaceutical products expiring annually. This expiration rate, while representing only 1.5% of the domestic market, underscores the importance of efficient inventory management and distribution practices. Nonetheless, India's pharmaceutical prowess remains a significant driver of economic growth and global healthcare provision, reflecting the nation's expertise and contribution to the international pharmaceutical landscape. Among the most pressing concerns is the accumulation of near to expiry paracetamol and similar medications in water systems, posing grave risks to ecosystems and human health. Paracetamol, widely used as a pain reliever and fever reducer, presents an alarming case due to its persistence in water sources and resistance to conventional filtration methods. The transformation of pharmaceuticals in the environment raises serious concerns about their impact on ecosystems and human health, underscoring the urgent need for regulatory measures and assessment frameworks to address the improper use and disposal of pharmaceuticals, including expired medications. Such initiatives are vital not only for mitigating the risks posed by pharmaceutical waste but also for ensuring the continued growth and sustainability of the pharmaceutical sector in India and worldwide. To tackle this multifaceted issue effectively, a comprehensive approach is required. This includes strengthening regulatory frameworks to enforce proper disposal practices at all levels, from manufacturing to end-users. Public awareness campaigns and educational initiatives are also crucial to inform individuals about the importance of correct medication usage and disposal. Additionally, investment in research and development of environmentally friendly pharmaceutical formulations and disposal methods is essential to minimize the environmental footprint of the industry. Collaboration among government, pharma, healthcare, and environmental sectors is vital to tackle pharmaceutical waste, ensuring industry sustainability and protecting human health and the environment.13 Paracetamol, sourced from various outlets like domestic wastewater, hospital effluents, and pharmaceutical manufacturing runoff, enters the environment alongside its degradation byproduct, 4-aminophenol. This contamination poses a significant challenge due to its involvement in the production of azo dyes and photographic materials. Para-aminophenol serves as a crucial component in synthesizing various azo dyes, including mono-azo and disazo types, pivotal in industries like textiles. Recent research has underscored its importance by revealing its role as a coupling component in azo dye synthesis, highlighting its ongoing relevance and versatility in dye chemistry studies. This emphasizes the necessity of addressing its environmental impact while ensuring the sustainability of industries dependent on textile coloration. PARACETAMAOL AZO DYE Fig 1: Scheme reaction for the synthesis of Azo dye14 PARACETAMOL Paracetamol is used as an analgesic and antipyretic drug. It is an widely used OTC drug. The possible side effects of paracetamol are uncommon but can include allergic reactions, flushing, low blood pressure, rapid heartbeat, and blood disorders like thrombocytopenia and leukopenia. Overdosing may result in liver and kidney damage, with severe cases being fatal.  MECHANISM OF ACTION: Paracetamol exhibits COX-2 inhibitor-like effects, reducing inflammation and prostaglandin levels, but doesn't suppress rheumatoid arthritis inflammation. Its selectivity may arise from inhibiting COX-2-dependent pathways at low rates. The analgesic effect potentially involves serotonin pathway activation, while its primary action likely remains prostaglandin synthesis inhibition. COX-3's clinical relevance is doubtful. PARA AMINOPHENOL Para-Aminophenol, also known as Aminophenol or P-Aminophenol, is an organic compound with the chemical formula H2NC6H4OH. It appears as white, reddish, or light brown crystals and is typically found in powder form. While it is insoluble in chloroform, it can dissolve in water, alcohol, and ether. Its significant consumption is noted as an intermediate in the production of various compounds and reagents. Its applications span across several industries including dye manufacturing, pharmaceuticals, cosmetics, and more. The pharmaceutical and cosmetic sectors, in particular, are witnessing a surge in demand for Para-Aminophenol, contributing to market growth. It serves as a crucial ingredient in the production of drugs like Acebutolol, Paracetamol, Ambroxol, and geftinib. In cosmetics, it's favored for its role in producing sulfur red-brown hair dyes. Para-aminophenol indeed serves as a crucial precursor for various azo dyes, including monoazo and dis-azo dyes, which find commercial use in industries such as textiles. While monoazo dyes are more commonly derived from para-aminophenol, dis-azo dyes like CI Disperse Yellow 68 have been synthesized using para-aminophenol, albeit with coupling components like aniline and phenol. Additionally, dis-azo dyes with favorable dyeing properties on polyester and nylon substrates have been successfully prepared from para-aminophenol, showcasing its versatility in dye synthesis. Despite its utility, inhalation of Para-Aminophenol can lead to health issues such as breathing difficulties, skin allergies, and rashes, potentially hindering market growth. AZO DYE Azo dyes are synthetic organic compounds characterized by the presence of the functional group R−N=N−R′, with R and R′ typically representing aryl and substituted aryl groups. They constitute a significant class of azo compounds, featuring the C-N=N-C linkage, and are vital in various industries, including food and textiles. Unlike natural dyes, azo dyes are entirely human-made. While most azo dyes contain a single azo group, there are also diazo dyes with two and tri azo dyes with three azo groups. Azo dyes, constituting a substantial portion (60-70%) of dyes used in food and textile sectors, find extensive application in treating textiles, leather goods, and certain food products. Additionally, derivatives such as azo pigments, which are insoluble in water and other solvents, are chemically related to azo dyes.15 THE AZO DYE ARE CLASSIFIED ARE AS FOLLOW AS: 1. Mono azo dyes: These dyes consist of a single nitrogen-nitrogen bond (𝑁 − 𝑁) within their molecular structure. 2. Diazo dyes: Diazo dyes contain two (𝑁 = 𝑁)bonds, distinguishing them from monoazo dyes. 3. Triazo dyes: Triazo dyes have three (𝑁 ≡ 𝑁)bonds in their chemical composition, setting them apart from both monoazo and diazo dyes. 4. Polyazo dyes: Dyes falling into this category feature more than three (𝑁 ≡ 𝑁) bonds within their molecular structure, representing a higher degree of complexity compared to monoazo, diazo, and triazo dyes.. The different evaluation test for azo dye includes Ph Sensitivity Test, Color Fastness Test, Melting Point and TLC.16 INSTRUMENTATION: 1. THIN LAYER CHROMATOGRAPHY  Preparation of plain silica gel H plates: Silica gel H plates were created by combining silica gel H with double distilled water in a 1:3 ratio (w/v). The mixture was shaken for 10 minutes and then applied to clean glass plates using a TLC applicator, resulting in a layer around 0.25 mm thick. The plates were dried at room temperature and activated by heating at 100 ± 1°C for 1 hour. Following activation, the plates were stored in a desiccator.  Test solution: Five tablets of each drug were powdered and combined with 25 mL of methanol in a 50 mL flask. After sonication for 40 minutes, the solution was filtered and washed with methanol. The filtrate was then diluted to 50 mL with methanol, resulting in a 5 mg/mL (w/v) drug solution.  Detection agent: Iodine vapor served as the detection reagent for the drugs. Different colors were observed for each: Paracetamol exhibited a black-brown spot. Formula: Rf value: Distance travelled by solute front / Distance travelled by the solvent Fig 2: TLC Apparatus