Doktorarbeit / Dissertation, 2022
257 Seiten
1. Introduction
1.0 Introduction
1.1 Indian agriculture – history
1.2 Agriculturalwaste
1.3 Tobacco
1.3.1 Tobacco consumption
1.3.2 Tobaccocultivation
1.3.3 Genus and species
1.3.4 Production in india
1.3.5 Types of tobacco
1.3.6 Tobacco production in gujarat
1.3.7 Types of tobacco used and their constituent.
1.3.8 Tobacco varieties in gujarat
1.3.9 Traditional Medicinal Usage of tobacco
1.3.10 Tobacco in ayurveda
1.3.11 Tobacco waste
1.3.12 Chemicals present in tobacco
1.4 Nicotine content in indian tobacco
1.4.1 Nicotine
1.4.2 Other source of nicotine
1.4.3 Structure and properties of nicotine
1.4.4 Uses nicotine
1.4.5 Dose of nicotine
1.4.6 Nicotine derivatives from tobacco
1.4.7 Commercially important of nicotine and itsderivatives
1.4.8 Smokingcessation products
1.4.9 Medicinal use ofnicotine
1.4.10 Worldpesticide market and prospects for nicotine sulfate
1.4.11 Nicotine derivatives and its uses
1.4.12 Nicotinic acid (pyridine 3-carboxylic acid)
1.5 Cellulose from tobacco waste
1.5.1 Cellulose and its derivatives
1.5.2 Cellulose ether derivatives
1.5.3 Cellulose ester derivatives
1.5.4 Applications of cellulose and its derivatives in pharmaceutical industries
1.5.5 Application in bio-adhesive and muco-adhesive drug delivery systems
1.5.6 Application as gelling agents
1.5.7 Application as thickening and stabilizing agents
1.5.8 Application in pharmaceutical coating processes
1.5.9 Application as fillers in solid dosage forms
1.5.10 Application as binders in granulation process
1.5.11 Application as disintegrating agents
1.5.12 Application as taste masking agents
1.6 Extraction of nicotine and cellulose from tobacco waste
1.6.1 Extraction of nicotine
1.6.2 Extraction of cellulose
1.7 Extraction
1.7.1 Conventionaltechniques for extraction
1.7.2 Methods Purification of extracted product
1.8 Chemical functionalization of cellulose
1.8.1 Chemical modification of cellulose:
1.9 Grafting of polymers
1.9.1 Pharmaceutical utilities of grafted polymers
1.10 Pharmaceutical chemistry
1.10.1 What is Drug?
1.10.2 What are excipients?
1.10.3 Pharmaceuticalformulation
1.11 Drug delivery route
1.12 Drug delivery systems
1.12.1 Conventionaldrug therapy
1.12.2 Sustainedrelease formulations
1.12.3 Advantages of sustained release dosageforms
1.12.4 Disadvantages of sustained release dosageforms
1.13 Tablets as a dosage form
1.13.1 Typesof tablets
1.13.2 TabletIngredients
1.14 In- vitroDissolutiontesting in pharmaceutical analysis
1.14.1 Dissolutiontesting in pharmaceutical analysis
1.14.2 Dissolution
1.14.3 Dissolution method parameters
1.15 In Vivotesting in pharmaceutical analysis
1.15.1 Phase I clinical trials
1.15.2 Phase II clinical trials
1.15.3 Phase III clinical trials
1.15.4 Phase IV clinical trials
1.15.5 Post-marketing studies
1.15.6 Mathematical models for drug Delivery
1.16 Principles of examination techniques used throughout the present study
1.16.1 Fourier transform infra-red spectroscopy analysis (FTIR)
1.16.2 Powder X–ray diffraction (XRD)
1.16.3 Scanning electron microscope (SEM)
1.16.4 Thermo gravimetric analysis
1.16.5 Nuclear magnetic resonance spectroscopy (NMR)
1.16.6 Mass spectrometry
2. Chapter 2
2.0 Introduction
2.0.1 Nicotine
2.0.2 Chemistry of nicotine
2.0.3 Cellulose
2.0.4 Cellulosechemistry
2.1 Literature review extraction of nicotine and cellulose
2.1.1 Fundamental of extraction of solutes from plant materials
2.2 Objectives of the present chapter
2.3 Part – 1: Extraction of nicotine form tobacco waste
2.3.1 Method and material
2.3.1.1 Chemicals
2.3.1.2 Extraction of nicotine
2.3.1.3 Percentage of nicotine
2.3.1.4 Process for nicotine extraction
2.3.2 Result and discussion
2.3.2.1 Percentage of nicotine
2.3.2.2 Optimization of nicotine
2.3.3 Characterization of the extracted nicotine
2.3.3.1 Mass Spectra of Nicotine
2.3.3.2 FT-IR spectroscopy analysisnicotine
2.3.3.3 NMR of nicotine
2.4 Part – 2: Extraction of cellulose form tobacco waste
2.4.1 Chemicals
2.4.1.1 Extraction of cellulose
2.4.1.2 Process for cellulose extraction
2.4.2 Optimization of cellulose extraction
2.4.3 The characterization of the extracted cellulose
2.4.3.1 FT-IR spectroscopy analysis of cellulose
2.4.3.2 Thermo gravimetric analysis of extractedcellulose
2.5 Conclusions
3. CHAPTER 3
Chemical modification of nicotine and cellulose
3.0 Introduction
3.1 Cellulose reactivity
3.2 Dissolution and regeneration of cellulose
3.2.1 Chemical modification of cellulose
3.3 Esterification of cellulose
3.3.1 Esters of cellulose with organic acids
3.3.2 Esters of cellulose with inorganic acids
3.4 Sodium cellulose sulfate (cellulose sulfate)
3.4.1 Litreture reviwe for cellulose sulphate
3.5 Nicotine structure and reactivity
3.6 Objectives of the present chapter
3.7 Part-1: Synthesis of nicotinic acid and nicotine picrate
3.7.1 Materials and Method
3.7.1.1 Materials
3.7.1.2 Synthesis of nicotinic acid
3.7.1.3 Synthesis of nicotinicpicrate
3.8 Result and Discussion
3.8.1 Optimization of nicotinic acid
3.8.2 Effect of concentration of hydrogen peroxide
3.8.3 Effect of time
3.8.4 Effect of temperature
3.8.5 FT-IR of Nicotinic acid
3.8.6 Mass of Nicotinic acid
3.8.7 NMR of nicotinic acid
3.9 Effect of Picric acid Nicotine
3.9.1 FTIR of nicotine picrate
Part-2: Synthesis sodium cellulose sulfate and cellulose acetate
3.10 Synthesis of sodium cellulose sulfate
3.10.1 Determination sulphuric contain and degree substitution via titration
3.11 Preparation of cellulose acetate
3.11.1 Determination of acetyl contain and degree substitution via titration
3.12 Result and Discussion
3.12.1 Optimization sodium cellulose sulfate
3.12.1.1 Effect of sodium bisulfate
3.12.1.2 Effect of time
3.12.1.3 Effect of temperature
3.12.1.4 FT-IR of sodium cellulose sulfate
3.12.1.5 TGA of sodium cellulose sulfate
3.13 Optimization of cellulose acetate
3.13.1 Effect of acetic acid
3.13.2 Effect of time
3.13.3 Effect of temperature
3.14 Conclusion
4. CHAPTER 4
Polymerization of cellulose derivatives
4.0 Introduction
4.1 Techniques of grafting
4.2 Analytical techniques used in characterization of grafted polymers
4.3 Pharmaceutical utilities of grafted polymers
4.3.1 To alter drug of biological carrying capacity
4.3.2 To achieve tailored physicochemical properties by grafting of polymers
4.3.3 Fro the achievement of desired dosage form characteristics
4.3.4 To attain site specific delivery by grafting of polymers
4.4 Objective of the present work
4.5 Experimental method
4.5.1 Chemicals
4.5.2 Synthesis of amide grfated sodium cellulose sulfate derivatives
4.5.3 Purification of modified sodium cellulose sulphate
4.5.4 Swelling index
4.5.5 % Grafting
4.5.6 FTIR spectroscopy
4.5.7 Scanning electron microscopy
4.5.8 Thermo gravimetric analysis
4.5.9 Powder X-Ray Diffraction
4.6 Result and discussion
4.6.1 Effect of Initiator Concentration
4.6.2 Effect of Monomer Concentration
4.6.3 Effect of reaction Temperature
4.6.4 Effect of Reaction Time
4.6.5 FTIR of grafted sodium cellulose sulfate
4.6.6 TGA of grafted sodium cellulose sulfate
4.6.7 Scanning electron microscopy grafted sodium cellulose sulfate graft
4.6.8 XRD grafted sodium cellulose sulfate graft
4.7 Conclusion
5. CHAPTER 5
Tablet Formulation
5.0 Introduction
5.1 Tablets asa dosage form
5.1.1 Types of tablets
5.1.2 Tabletingredients
5.1.3 Diluents
5.1.4 Binders
5.1.5 Lubricants
5.1.6 Glidants
5.1.7 Disintegrants
5.2 Tablet characteristics
5.2.1 Tablet hardness and friability
5.2.2 Uniformity of dosage forms
5.2.3 Tabletdisintegration
5.2.4 Tabletdissolution
5.2.5 Stability
5.3 Methods of preparation of tablets
5.3.1 Wet granulation
5.3.2 Dry granulation
5.4 Evaluation of granules
5.4.1 Flowproperties of granules
5.4.2 Angle of repose
5.4.3 Bulk density measurements
5.4.4 Carr’sindex
5.4.5 Conventional drug therapy
5.4.6 Sustained release formulations
5.4.7 Advantagesof sustained releasedosageforms
5.4.8 Disadvantages of sustained release dosage forms
5.5 Literaturereview
5.6 Drugprofile
5.7 Polymerprofile
5.7.1 Hydroxypropyl methylcellulose
5.7.2 Magnesiumstearate
5.7.3 Microcrystallinecellulose
5.7.4 Talcpowder
5.7.5 Sodium cellulose sulfate graftedwith acrylic acid, N, N-methylene acrylamide
5.8 Pre-formulation study
5.8.1 Identification of drug by FT-IR spectroscopy.
5.8.2 Drug – excipient compatibility study
5.9 Objective of thepresent work
Part – 1: Tablet formulation
5.10 Experimentalmethod
5.10.1 Materials
5.11 Methods for evolution of binder
5.11.1 Moisture content of the sodium cellulose sulfate grafted with acrylic amide
5.11.2 Bulk density sodium cellulose sulfate grafted with acrylic amide
5.11.3 Angle of repose
5.11.4 Particle size of sodium cellulose sulphate grafted with acrylic amide.
5.11.5 Preparation of granules
5.12 Determination of flow properties of the granules
5.12.1 Bulk density of granules
5.12.2 Angle of repose of granules
5.12.3 Compression of Tablets
5.13 Evaluation of tablets
5.13.1 Uniformity of weight test
5.13.2 Thickness
5.13.3 Crushing strength
5.13.4 Friability test
5.13.5 Swellingindex of tablets
5.14 Dissolutiontest
5.14.1 Preparation of phosphate buffer
5.14.2 Mathematical models for drug release studies
5.15 Results and discussion
5.15.1 Physicalcharacterization of granules
5.15.2 Physicalcharacterization tablet
5.16 Fourier transform infrared spectroscopy (FTIR)
5.17 Particle size of grafted sodium cellulose sulphate
5.17 Invitro drug release study
5.17.1 Thestandard curve ofdiclofenac sodium drug
5.17.2 Mathematical models for drug release studies
5.18 Part – 2: Ointments formulation
5.18.1 Preparation of ointments
5.18.1.1 Physical properties of ointments
5.19 Conclusion
The primary objective of this research is to investigate the potential of using agricultural waste, specifically tobacco waste, as a sustainable source for the extraction of nicotine and cellulose. The study aims to enhance the physicochemical properties of these derivatives through chemical modification, such as grafting, to create value-added pharmaceutical excipients, which are then utilized in the development and evaluation of sustained-release drug delivery systems, specifically diclofenac sodium tablets and therapeutic ointments.
1.2 Agriculturalwaste
Agriculture wastes are the by-product of the agriculture activity, because they are not the primary product. The waste generate are useless for the farmer but it can be used as the most important resources. These waste chiefly take the form of crop residue (residual stalk, straw, leaves, roots, husk, shell) agriculture waste are widely available. Though, many of the agricultural wastes are yetmostlyunder-utilized and left to root or outside burned in the field, particularly in developing countries [8].
The residue of the crops such as corn stalks, straw, tobacco waste, sugarcane leavings, bagasse, nutshells and other such as animal manure from cattle, poultry, and hogs; forestry residues, such as wood chips, bark, sawdust, timber slash, and mill scrap; and municipal waste such as waste paper and yard clippings. Crop residue are now been used as a raw material to many useful product, rather than discarding or burning them they are recycled or processed and used for many purposes such as:-
(1) Heat source
(2) As a fertilizer (nutrient source for crops)
(3) Bio fuels
(4) Also as many useful chemicals by extraction from the waste crop residue. [9]
Chapter 1: Provides an extensive introduction to Indian agriculture, the history of tobacco, and the chemical composition and medicinal uses of tobacco components like nicotine and cellulose.
Chapter 2: Details the methodologies used for the extraction and characterization of nicotine and cellulose from tobacco waste, including the optimization of extraction parameters.
Chapter 3: Explores the chemical modification of nicotine and cellulose, specifically the synthesis of nicotinic acid and sodium cellulose sulfate, including structural confirmation via spectroscopy.
Chapter 4: Focuses on the polymerization and grafting techniques applied to sodium cellulose sulfate to create advanced derivatives for pharmaceutical drug delivery applications.
Chapter 5: Covers the practical formulation and evaluation of sustained-release diclofenac sodium tablets and medicated ointments using the synthesized polymers as excipients.
Tobacco waste, Nicotine extraction, Cellulose extraction, Chemical modification, Graft polymerization, Sodium cellulose sulfate, Sustained-release tablets, Diclofenac sodium, Drug delivery systems, Pharmaceutical excipients, FTIR, TGA, XRD, Polymer characterization, Agricultural biomass.
The research focuses on the valorization of tobacco industry waste by extracting two key high-value components—nicotine and cellulose—and transforming them into useful pharmaceutical chemical derivatives.
The primary fields are pharmaceutical chemistry and drug delivery, specifically the engineering of novel natural polymer-based excipients for controlled drug release.
The goal is to move from waste material to functional drug delivery systems, specifically testing the efficacy of modified cellulose to sustainably deliver diclofenac sodium in oral dosage forms.
The study employs solvent extraction for primary isolation, chemical modification/synthesis routes (grafting, oxidization, sulfonation), and a wide suite of structural characterization methods including FT-IR, NMR, Mass Spectrometry, TGA, and XRD.
The content is partitioned into five distinct chapters: introductory background, extraction experimental methods, chemical modification, polymerization and grafting, and final formulation/evaluation studies.
Tobacco waste, grafting, cellulose derivatives, sustained release, nicotine extraction, pharmaceutical polymers, diclofenac sodium, and biopolymer characterization.
The modification is validated through structural comparison using specialized instrumentation like FTIR (to identify functional group changes) and TGA (to establish thermal stability shifts in the polymer).
Grafted polymers are used because they improve properties like viscosity, mucoadhesiveness, and swelling characteristics, which are essential for controlling the rate of drug release and enhancing the stability of the final tablet formulation.
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