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Background: Coumarins are naturally occurring biologically active heterocyclic molecules endowed with a wide range of biological properties, including antibacterial, antifungal, and antitumor activities. Objective: The present work aimed to synthesize new coumarin-containing compounds and to investigate their cytotoxic activity. Methods: Coumarin peptide and coumarin amino alcohols were prepared by treating epoxidecontaining coumarin derivatives with suitable aromatic amines and peptides in trifluoroethanol as a solvent at 50°C. These derivatives were evaluated for their cytotoxic activity on three different cell lines: HeLa, MDA-MB-231 and L-132. Cell viability was determined by MTT (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results: A new protocol was developed for the synthesis of thirteen novel coumarin peptide and coumarin amino alcohol derivatives. Among the tested compounds, three derivatives showed significant activity against all the tested cell lines. Docking studies indicated favorable interactions of the disubstituted peptide coumarin derivatives with the Asp 351 and Thr 347 amino acids at the active site of the human estrogen receptor. Conclusions: The results suggest that the newly synthesized compounds may be promising candidates in the research of new antitumor compounds.

Aim: This research work was aimed to evaluate Metformin hydrochloride (MH) floating dosage form by In vitro evaluation/In vivo prediction and to evaluate it’s predictability through it’s application during the R&D using Insilico technique in WINONLIN Software. MH was examined as a model drug, which is a biguanide and is an hypoglycemic agent administered orally. The study was aimed to determine the the systemic concentrations of MH using In-vivo prediction. Study Design: Fabrication and assessment of Metformin hydrochloride floating drug delivery system: In Vitro evaluation /In Vivo prediction. Biorelevant media was selected for dissolution profile of 12 units of dosage form. Software assisted program used for data feeding and results output. Methodology: The absorption window for MH is the upper portion of the small gut in which the GI absorption is complete after 6 h. Hence gastroretentive formulation was developed and validity of dissolution study was extended by In vivo pharmacokinetic prediction using WinNonlin Software. A mechanistic oral absorption model was built in Phoenix WinNonlin® software. In the presented work, significant yet crucial, gastrointestinal (GI) variables are considered for biopredictive dissolution testing to account for a valuable input for physiologically-based pharmacokinetic (PBPK) platform programs. While simulations are performed and mechanistic insights are gained from such simulations from the WinNonlin program. Results: These floating tablets were observed for In vitro release and studied for In vivo pharmacokinetic prediction. From the obtained values, a meaningful In vivo prediction was done. interestingly from the results attained floating tablets showed sustained drug release and extended drug absorbed in 24h. Fascinatingly, from the data it was proved that drug formulation resides for desired time. The absorption of MH from the developed CR tablet was 1.4 fold higher than its marketed tablet and it had higher AUC0–t values than the marketed product which indicates superior bioavailability of test product compared to marketed tablet with similar dose in Invivo pharmacokinetic prediction. The mean value of biological half-life (t1/2) and Tmax of MH from test formulation is two times more, Test product has shown higher MRT, showing that the drug is maintained longer in the body in comparison to marketed product indicates controlled absorption. Conclusion: Here we concluded that, a comparative prediction pharmacokinetic evaluation of the fabricated controlled release tablets and the marketed formulation indicates that the fabricated controlled release tablets are well absorbed and the degree of absorption is greater than that of the marketed ER formulation with larger gastric residence time.

Background and Objective: Fluconazole (FLZ) is a novel triazole antifungistatic drug; topical administration of FLZ resulted in systemic absorption and skin inflammation, and thereby failed to achieve mycological eradication, resulting in low patient compliance and undermining therapy effectiveness. The aim of this study was to use the emulsion solvent evaporation technique to create FLZ-loaded nanosponges (NSs) using ethylcellulose (EC) and polyvinyl alcohol (PVA) as a stabiliser. Materials and Method: By varying the drug concentration (FLZ), EC, and PVA, four formulations were developed, each of which was then optimized through particle characterization (polydispersity index (PDI), scanning electron microscopy (SEM), zeta potential (ZP), drug entrapment, and loading efficiency). Results: SEM (Scanning Electron Microscope) analysis showed that the particle sizes of FLZ inclusion complexes ranged from 150 2 to 250 5 nm. The ZP was strong enough to produce stable formulations. FLZ was released from the nano sponges in a regulated manner for 24 hours in both in vitro and in vivo experiments. FTIR and DSC were used to validate the association of the FLZ with the nanosponges. The crystalline nature of FLZ was modified to an amorphous state due to the complexation with the nanosponges, according to an XRPD analysis. The FLZ nanosponges were found to be stable in a stability analysis. Conclusion: Therefore, ethyl cellulose-based nanosponges provide a novel method for controlling the release of FLZ for antifungal effects.

Aim:: To design controlled release topical delivery of mupirocin for the treatment of skin infection. Background:: Mupirocin is an antibacterial drug. Mupirocin works to kill the bacteria, which include strains of Staphylococcus aureus and Streptococcus pyogenes. It is also used for the treatment of inflammation of a hair follicle. The half-life of mupirocin is only 20-40 min. It has very slight solubility in water. Patent literature had shown work on ointment, antibiotic composition, nasal and topical composition. Emulgel is a duel control release system for the topical delivery of hydrophobic drugs. Objective:: The objective was to formulate emulgel with controlled delivery of mupirocin using Sepineo P 600. Methods:: Soya oil, tween 80 and polyethylene glycol 400 (Oil:Surfactant:Cosurfactant) were used for emulsion formulation. Emulgel was optimized by 32 factorial design. Sepineo P 600 and hydroxy propyl methyl cellulose K4M were used as independent variables. Drug excipient compatibility analysis was carried out by FTIR, UV and DSC spectra. Emulgel was evaluated for its physical characterization, in vitro release, ex vivo release, antimicrobial and anti-inflammatory study. Results:: DSC, UV and FTIR analysis confirmed drug excipient compatibility. FE SEM showed a size range between 228-255 nm. Zeta potential was found to be -25.1 mV, which showed good stability of the emulsion. Design expert software showed F2 as an optimized batch. Release studies indicated that the controlled release of drugs forms Sepineo P 600 gel due to its higher gelling capacity. Batch F2 showed comparable results with marketed formulation against Staphylococcus aureus. For batch F2, 40 μg/ml was the minimal inhibitory concentration. Conclusion:: Antimicrobial and anti-inflammatory study proved successful development of stably controlled release mupirocin emulgel.

Objective: The present study aimed to develop a new SR metformin hydrochloride (MH) gastroretentive formulation with novel excipient (NE), which has better floatation and can be prepared with more simple pharmaceutical techniques for the treatment of diabetes Mellitus. Methods: A gastro-retentive floating matrix tablet (GFT) formulation of MH was prepared using various concentrations of PEO (Polyox WSR-303) and hydroxypropyl methylcellulose K100M (HPMC K100 M) and Floating agent (novel excipient) to achieve desirable TFT, FLT and drug release. The wet granulation method was selected using isopropyl alcohol as a binder for the preparation of tablets. D-optimal non-simplex mixture design was used for the selection of suitable polymer concentrations and floating agents. Release kinetics was used to determine the mechanism of drug release. Results: It was observed that GFT with optimum quantities of PEO, HPMC K100M, and the floating agent showed 100 % of drug release in 24h with FT up to 24h and minimum FLT of less than 2 min. Formulation with an in vitro release profile slower to the marketed sample was prepared. Conclusion: A sustained-release (GFT) of MH tablets using PEO-, HPMC K100M, and an effervescent system was successfully prepared. AGFT formulation with an in vitro release profile slower to the marketed sample that releases MH for 24h may suitable for once-daily dosing can be prepared.

Azithromycin (AZT) is a broad-spectrum antibiotic and is found in ocular tissues when administered systemically. AZT inhibits RNA-dependent protein synthesis and hence has effective bactericidal capability against Staphylococcus aureus, Pseudomonas aeruginosa, which are the primary causative organisms for bacterial infection. In situ ophthalmic gels are systems which undergo a sol-to-gel transformation when instilled in eyes. In situ gels overcome the shortcoming of ophthalmic drops as they get washed out and diluted due to tear fluid. The aim and objective of present study was to formulate in situ ophthalmic gelling systems of Azt and determine in vivo ocular residence time in rat eyes of Tc99 labelled Azt by Micro SPECT. The in situ gel was formulated using Poloxamer 407, which is a temperature-induced gelling agent and HPMC K4M, which is known to increases mucosal adhesivity and enhance viscosity to facilitate sustained release of drug. The formulations developed were evaluated for pH, clarity, viscosity, gelling capacity and % drug release. The selected formulation was subjected to isotonicity and In Vivo Bio-distribution studies. Experimental studies on compatibility showed no interaction between polymers and AZT. AZT was found soluble in PB6.8. All formulations were found clear immediately after preparation and after sterilization & pH after gelation was satisfactorily in the range of 6 to 7. Viscosity and Gelation capacity of in situ gel increased with increase in polymer concentration. Formulations F2 showed desired results w.r.t viscosity, gelation capacity, drug release. In Vivo Biodistribution studies of Tc99 labelled AZT by Micro SPECT showed there was a significant increase in ocular residence time of in situ gel when compared with Tc99 labelled marketed solutions.

Aims: To prepare solid lipid nanopaticles (SLNs) of Ketoprofen (KP) using microwave method. Ketoprofen (KP) is 2-(3-benzolphenyl) propionic acid with anti-inflammatory, analgesic and antipyretic property. The drug has a short half-life of 120 mins. It belongs to BCS Class II drug. Gastric irritation is a major limitation for delivery because of acidic nature of the drug. The development of solid lipid nanoparticles with its transdermal drug delivery was the aim of the present work. Methods: Microwave-assisted microemulsion technique was used for the development of solid lipid nanoparticles. Stearic acid was used as lipid and tween 80 was used as a surfactant. By varying the type of lipid and input energy watt, batches were formulated. SLNs were evaluated for zeta potential, drug entrapment, particle size and in-vitro drug release. Crystallinity behaviour was determined by differential scanning calorimetry and powder X-ray diffraction. Anti-inflammatory activity was evaluated for batch M4 of SLNs. The gel was prepared for M4 batch. It was evaluated for viscosity, pH, drug content, in-vitro and ex-vivo diffusion study. Results: SLNs were developed successfully. Based on the size, entrapment efficiency, stability and drug release, batch M4 was selected. SLNs showed 74.8% entrapment efficiency. Forty-fold improvement was observed in the solubility. The particle size was 682.9 nm and average size 1047 nm. PDI was 0.685 and zeta potential was -29.5 mV. M4 SLNs batch of gel showed burst release followed by a controlled release for 8 hrs in in-vitro drug release. Conclusion: SLNs were successfully prepared by Microwave-assisted microemulsion technique. SLNs with anti-inflammatory activity were successfully developed with their transdermal delivery.

Background: An efficient one-pot biocatalysed ultrasound assisted synthesis of dihydropyrimidinones/ thiones has been developed under solvent free conditions. Materials and Methods: The use of biodegradable, non toxic, agar-powder as a catalyst provide advantages like high yield, simple operation, mild reaction condition with short reaction time. 1,2,3,4- tetrahydropyrimidine-2-ones/thiones formed were characterized by mass and 1H NMR spectroscopy. Results: The dihydropyrimidinones substituted with electron donating groups like fluorine, hydroxy along with thienyl groups exhibited good antibacterial activity. The compounds exhibited favorable binding interactions with mycobacterium target protein H37Rv. Conclusion: 4-methoxy substituted dihydropyrimidinones derivative showed significant antituberculosis activity.

Clinical trial is a part of clinical research. It is a systematic experimental biomedical study. They are carried out to evaluate the effectiveness and safety of medications or medical devices or biologics. Trials are conducted to check safety and efficacy of new drug. It includes four phases as phase I, II, III, and IV. The study is carried out according to study protocol and standard operating procedures as per good clinical practices guidelines. The study protocol is developed by the researchers and approved by an independent committee called as Institutional Review Board. Protocol is a roadmap for team of healthcare professionals involved in investigation work. It should explain the significance of research trial, location, detail procedure, methods, activities, time allotment, financial estimate and any other information required. The content of protocol are title, objective, background, eligibility criteria, study methodology, risks or adverse effects, benefits, alternative treatment, data collection, statistical treatment, regulatory guidance, and other information.

Presently, nanoparticles (NPs) technology is a booming business marked by a significantly fast growth rate that covers a wide range of industries. NPs demand increases and they have a potential market value. The nanotoxicity sector has grown significantly for the last 10–15 years, which will pose serious problems in the coming future. Nano-toxicology is an innovative area of toxicological study that assesses the toxicological assets of NPs to decide whether they constitute a risk or an ecological problem and to what degree. To assess the different NPs toxicity, numerous nanotoxicological studies were piloted using different methods. The vital mechanisms of nanomaterial toxicity were recently studied especially in aquatic wildlife. In recent years, nanoparticle toxicity evaluation amplified exponentially by using zebrafish as an animal prototypical system. Zebrafish has been tested as an established model system for experimental biological study and are evolving as a solid nanotoxicity prototype which is progressively used as an in vivo model. It is principally used as a platform for rapid testing and assortment of molecules in the object or phenotype techniques. It offers a number of advantages over other living prototypes by offering prospects to speedily screen nanoparticulate medicines beneath in-vivo environments, also an economical way to link the present gap among in vitro and vertebrate studies. Many researchers have summarized experimental parameters critically used by zebrafish as an animal model for biomedical tests such as sample size, organ, and type wild against transgenic lines. Current chapter will discuss considerable factors of experimentation, advantages, and usage of zebrafish in nanomedicine; different methods of evaluating the nanotoxicity such as hatching exploration; malformation of embryos and organs of development; genetically modified zebrafish by means of living biosensor; disturbance in the endocrine system, skin, and gill; reproductive toxicity; genotoxicity; neurotoxicity; immune-toxicity; and behavioral analysis. Furthermore, it will also discuss an overview of studies about investigation of the toxicity of silver, carbon nanotube, metal oxide, and quantum dots nanoparticles using zebrafish. At the end, future lookouts of zebrafish model are discussed. It is projected that this chapter will update study directed at emerging biocompatible nanoparticulates for a choice of uses and toxicity investigation.

Globally, the zebrafish as an experimental animal has been welcomed, and utilization increased successively. Zebrafish is a common name of Danio rerio fish. It belongs to the Cyprinidae family, within the order of the Cypriniformes. The fish is named for the five uniform, parallel blue-colored long narrow bands on the body side. The stripes are extended up to the tail end of the fish. The successful implementation of zebrafish as a trial animal majorly depends upon the key features like its genotypic and phenotypic similarities to human and their easy maintenance at laboratory scale. There is much similarity between the major organ systems like nervous, cardiovascular, and digestive systems of human and zebrafish. It is possible to identify and study the physiological and pharmacological responses of drugs and other bioactive compounds with therapeutic value. The zebrafish model is a powerful, well-established research platform for the testing of activities of new drug molecules. The nano-sized materials have opened up various possibilities in a variety of industrial issues and scientific endeavors. Nanomedicines are an effective way of drug delivery systems as they enhance drug absorption by improving the solubility characteristics of the drug. Bioactive nanoparticles can be easily and successfully studied on both embryos and adult zebrafish. Nanoparticles having biological activities like anti-convelsant, anti-melanogenic or other activities which affect the cardiovascular system, nervous system, reproduction system, etc. have been successfully studied on zebrafish as an experimental animal model. The zebrafish also plays an important part in toxicological studies of the nanomedicines. The zebrafish has proven its extensive promises as an in vivo animal model for screening of nanomaterials. The zebrafish can be employed in the process of drug development at the stage of pre-clinical testing. Presently, research is focused on the biological activity testing and toxicological testing of newly developed medicines especially chemotherapeutic agents or nanoparticles used in the treatment of cancer.

Background Prochlorperazine maleate (PCM) is a phenothiazine antipsychotic used in the treatment of nausea, vomiting and vertigo. It is BCS class II drug with only 12.5% bioavailability. Patents data on PCM had shown work on conjugation and matrix formulation which suggested idea for the present work design. Objective The objective of this study was to enhance solubility of drug and to optimize gastro retentive floating capsule for controlled drug release at the targeted site for stipulated time. Method The solubility of drug was determined in various vehicles like oils, surfactants and cosurfactants. Pseudo ternary phase diagrams were constructed to identify the efficient self emulsifying region. SMEDDS were tested for micro emulsifying properties. The resultant microemulsions were evaluated and were further selected for the floating drug delivery. Magnesium hydroxide was used as carrier to transform SMEDDS into Solid SMEDD (S-SMEDD). Non-effervescent floating capsule containing S-SMEDD were optimized using factorial design with independent variable HPMC K4M and ethyl cellulose. Results SMEDD consists of PCM, isopropyl myristate, tween 80 and PEG 400 as a drug, oil, surfactant and co-surfactant (1:1 ratio). Optimized formulation F5 showed 10 hrs floating time and percent drug release 91.56±2.7% with controlled drug delivery in stomach. F5 followed Korsmeyer Peppas release kinetics where the drug followed Fickian diffusion transport mechanism due to swelling of polymers in controlled manner. Conclusion It can be concluded that SMEDD enhanced the solubility of drug and floating capsule gave site specific drug release of PCM with the advantages of reduced dosing frequency and better compliance.

Purpose: Ofloxacin is a fluoroquinolone with broad-spectrum antibacterial action, used in treatment of systemic and local infections. Ofloxacin is BCS class II drug having low solubility, high permeability with short half-life. The present work was aimed to design, develop and optimize gellified emulsion of Ofloxacin to provide site targeted drug delivery. Transdermal drug delivery will enhance the bioavailability of the drug giving controlled drug release. Methods: Transdermal drug delivery system was designed with gelling agent (Carbopol 940 and HPMC K100M), oil phase (oleic acid) and emulsifying agent (Tween 80: Span 80). Effect of concentration of gelling agent on release of drug from transdermal delivery was studied by 32 factorial design. Emulgel was evaluated for physical appearance, pH, drug content, viscosity, spreadability, antimicrobial activity, in- vitro diffusion study and ex-vivo diffusion study. Results: FE-SEM study of the emulsion batch B5 has revealed formation of emulsion globules of approximately size 6-8 µm with -11.2 mV zeta potential showing good stability for the emulsion. Carbopol 940 had shown greater linear effect on drug release and viscosity of the formulations due to its high degree of gelling. In-vitro diffusion study through egg membrane had shown 88.58±1.82 % drug release for optimized batch F4. Ex-vivo diffusion study through goat skin indicated 76.68 ± 2.52% drug release. Conclusion: Controlled release Ofloxacin emulgel exhibiting good in-vitro and ex-vivo drug release proving good antimicrobial property was formulated.

Purpose: Inflammatory bowel disease (IBD) is a chronic, relapsing and often life-long disorder. The best way to tackle IBD is to develop a site targeted drug delivery. Methylprednisolone is a potent anti-inflammatory steroid. The relative potency of methylprednisolone to hydrocortisone is at least four is to one. The aim of the present research was to develop a colon targeted drug delivery for treatment of IBD. Methods: Compression coated drug delivery system was designed and optimised. Core tablet contained drug, croscarmellose sodium (CCS-superdisintegrant), avicel (binder) and dicalcium phosphate (diluent). Design of experiment with 32 factorial design was applied for optimization of compression coated delivery. Chitosan and cellulose acetate phthalate were chosen as independent variables. Swelling index, hardness and % drug release were dependant variables. Results: Core tablet (C5 batch) containing 2.15% CCS showed disintegration in less than 10sec. FTIR, UV and DSC study had shown absence of any significant physical and chemical interaction between drug and polymers. F8 was found to be optimised formulation. F8 contained 35% chitosan and 17.5% cellulose acetate phthalate. It showed drug release of 86.3% ± 6.1%, hardness 6.5 ± 1.5 and lag time 7 hrs. Simulated media drug release was 97.51 ± 8.6% with 7.5 hrs lag time. The results confirmed that the lag time was highly affected by the coating of the polymers as well as the concentration of the superdisintegrant used in core tablet. Conclusion: In-vitro and in-vivo results confirmed a potential colon targeted drug therapy for treatment of IBD.

Research is a logical and systematic approach to investigate or find solutions to scientific and social problems. The research is primarily carried out to discover new facts, to verify and test important facts, and to analyze an event or process. Research is carried out with the help of study, experiment, observation, analysis, comparison, and reasoning. Research is important both in scientific and nonscientific fields. There are two types of research: basic and applied. Basic research is an investigation on basic principles and reasons for occurrence of a particular event or process or phenomenon. Applied research solves certain problems employing well-known and accepted theories and principles. The research process is carried out through series of steps. Research methods are the various procedures, schemes, and algorithms used in research. The research methodology is a systematic way to solve a problem. It is a science of studying how research is to be carried out.

The prodrug approach using various carriers has evolved as a significant tool in surmounting different obstacles in relation to drug formulation and targeting. Properties and selection of carriers or promoeities is a very important parameter in successful prodrug design. Carrier would change a drug’s physical attributes in order to increase its fat or water solubility or to allow site-directed delivery. Though several studies have been carried out on various prodrugs, surprisingly very few reviews on different carriers, which can be used for prodrug synthesis were published to date. In this review different types of carriers, which can be used for prodrug synthesis are summarized. Examples of both marketed and investigational prodrugs using several promoieties are discussed with their advantages and future prospects. The present review is expected to be useful for scientists working in the field of drug discovery and development.

Seventeen (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 one derivatives were synthesized via aldol condensation of substituted benzaldehydes with quinoline chalcones starting from 8-hydroxy quinoline. Molecular docking studies were performed on COX-2 protein for analgesic activity and PDE 4 enzyme for anti-asthmatic activity. Docking studies for analgesic activity reveal that the compounds 2 , 4 , 12 , 14 , and 15 showed significant interaction in terms of hydrogen bonding, hydrophobic attachment and van der Waal interaction with COX-2. The docking studies and pharmacological screening indicate that substitution of hydroxyl and conjugated ketone groups on the aldehyde ring and the quinoline ring accelerates analgesia with better binding to active site. Eddy’s hot plate method was used to evaluate analgesic activity of the synthesized compounds. Compounds showed a substantial increase in reaction time when compared with standard pentazocin. Compounds 2 , 4 , 7 , 9 and 13 showed significant binding interactions with PDE 4 enzyme and hence were selected for evaluation of anti-asthmatic activity using the goat tracheal chain method. Studies reveal that substitution of the methoxy group at 4th & 5th positions for compounds 2 , 4 & 7 leads to significant percentage inhibition of histamine induced contraction. The synthesized compounds are thus found to be potent as analgesic and anti-asthmatic agents.

Background:Prochlorperazine maleate is a phenothiazine antipsychotic used principally in the treatment of nausea, vomiting and vertigo. Biological half- life of the drug is about 6 to 8 hrs and oral dose is 5 or 10 mg thrice or four times a day. The mean absolute bioavailability for drug is 12.5%. Due to the solubility of drug in acidic pH, it is mainly absorbed from stomach.Objective:Site specific oral floating delivery of prochlorperazine maleate will prolong the gastric retention time, increases the drug bioavailability, reduces frequency of administration and can result in better patient compliance.Method:The tablets were prepared by direct compression technique. Floating drug delivery was developed using gas forming agent and release retarding agenti.e.hydroxyethyl cellulose HHX (Natrosol HHX) and polymethyl methacrylate (PMMA). 32full factorial design was used for optimization. Prepared tablets were evaluated for pre and post compression parameters.Results:From the factorial batches it was observed that formulation containing 68.5% of hydroxyethyl cellulose HHX and 15% of polymethyl methacrylate had shown a drug release of 91.56 ± 2.7% with floating upto 10 hrs following Korsmeyer Peppas release kinetics.Conclusion:In- vivoplacebo X-ray study for optimized batch F6 had shown good gastroretention ability for 6 ± 0.5 hrs.In- vitroandin- vivostudy confirmed the site specific floating delivery for drug.

Background Inflammatory bowel disease (IBD) is one of the five most prevalent gastrointestinal disease burdens which commonly require lifetime care. Worldwide incidence rate of ulcerative colitis and Crohn's disease is about 16.8% and 13.4% respectively. Colitis is an inflammation of the colon. Colon targeted drug delivery will direct the drug to the colon. The drug will reach at the site of action and hence its side effects as well as dose can be reduced. Recent patent describes treatment of ulcerative colitis using anti CD3 antibodies, with nicotine and anti-depressant drugs, budesonide foam etc. Objective Present study deals with optimization of site targeted methylprednisolone delivery for treatment of colitis. Method Chitosan and Eudragit RS 100 were used as coating polymers. Tablets were prepared by press coated technology. The core tablets contain drug, avicel as binder, croscarmellose sodium as super disintegrant and dicalcium phosphate as diluent. Drug excipient compatibility was carried out using FTIR, UV and DSC. Design of experiment was used to optimize the formulation. Tablets were evaluated for thickness, weight variation, hardness, swelling index, in-vitro drug release and release of drug in simulated media. Results Optimized batch (B2) contained chitosan 40% and eudragit RS 100 17.5%. B2 showed in-vitro drug release 85.65 ± 7.6% in 6.8 pH phosphate buffer and 96.7 ±9.1% in simulated media after 7.5 hours. Conclusion In-vivo x-ray placebo study for formulation B2 had shown that the tablet reached to the ascending colon after 5 hours. This indicated a potential site targeted delivery of optimized batch B2.

Background: Tizanidine hydrochloride acts centrally as a muscle relaxant. It is used for the treatment of painful muscle spasm, spasticity associated with multiple sclerosis or spinal cord injury and treatment of muscle spasticity in spinal cord disease. Tizanidine hydrochloride belongs to BCS class II. It has low oral bioavailability and short halflife. Incorporating this drug in microemulgel is an excellent way to overcome problems associated with the drug. Objective: Present research work was aimed to develop and optimize a microemulsion based gel system for tizanidine hydrochloride. Methods: Screening of oil, surfactant and co-surfactant was carried out. Ternary phase diagram was constructed to obtain concentration range of components. The prepared microemulsion was evaluated for pH, globule size, zeta potential, conductivity, density and viscosity. 32 level factorial design was applied to study the effect of concentration of carbopol 934 and HPMC K15M on % cumulative drug release and viscosity of microemulgel using software Design Expert. Microemulgel was evaluated for pH, spreadability, viscosity, syneresis, drug content, bioadhesive strength, in-vitro as well as ex-vivo diffusion study. Results: Microemulsion was prepared by using isopropyl myristate as oil, tween 80 as a surfactant and transcutol P as cosurfactant. Largest transparent microemulsion region was found with Smix ratio of 1:1. FE-SEM showed globule size 28μm for batch B1 and zeta potential was -1.27mV indicating good stability of the microemulsion. Optimised batch was F6 which showed 92% drug release within 8 hours. It followed the Korsmeyer-Peppas model. Conclusion: A stable, effective and elegant microemulgel formulation, exhibiting good in-vitro and ex-vivo drug release was formulated.

Nanobiotechnology is the combination of nanotechnology and biotechnology. Bioremediation is defined as a waste management technique that involves use of organisms to remove or neutralize pollutants from a contaminated site. This involves no use of chemicals and it allows waste to get recycled; this process has evolved as one of the most important methods. Remediation of contaminants using existing conventional technology is neither effective nor efficient in environmental cleanup. Techniques developed from nanobiotechnology can detect, control, and remediate pollutants by acting as sensors. Use of nanomaterials has less toxic effects and this will not only reduce consumption time but also reduce cost. Nanoparticles developed by using microbial systems provide green nanotechnology and help in keeping the environment clean. Green nanotechnology needs to develop to make cleaner environment with great ecological balance on earth. This chapter deals with traditional methods of bioremediation, methods in nanobiotechnology, and future aspects.

Background Nabumetone is biopharmaceutics classification system (BCS) class II drug, widely used in the treatment of osteoarthritis and rheumatoid arthritis. The most frequently reported adverse reactions for the drug involve disturbance in gastrointestinal tract, diarrhea, dyspepsia and abdominal pain. Microemulgel has advantages of microemulsion for improving solubility for hydrophobic drug. Patent literature had shown that the work for drug has been carried on spray chilling, enteric coated tablet, and topical formulation which gave an idea for present research work for the development of transdermal delivery. Objective The objective of the present research work was to optimize transdermal microemulgel delivery for Nabumetone for the treatment of arthritis. Methods Oil, surfactant and co-surfactant were selected based on solubility study of the drug. Gelling agents used were Carbopol 934 and HPMC K100M. Optimization was carried out using 32 factorial design. Characterization and evaluation were carried out for microemulsion and microemulsion based gel. Results Field emission-scanning electron microscopy (FE-SEM) study of the microemulsion revealed globules of 50-200 nm size. Zeta potential -9.50 mV indicated good stability of microemulsion. Globule size measured by dynamic light scattering (zetasizer) was 160nm. Design expert gave optimized batch as F7 which contain 0.2% w/w drug, 4.3% w/w liquid paraffin, 0.71% w/w tween 80, 0.35% w/w propylene glycol, 0.124% w/w Carbopol 934, 0.187% w/w HPMC K100M and 11.68% w/w water. In-vitro diffusion study for F7 batch showed 99.16±2.10 % drug release through egg membrane and 99.15±2.73% drug release in ex-vivo study. Conclusion Nabumetone microemulgel exhibiting good in-vitro and ex-vivo controlled drug release was optimized.

Floating pulsatile is combined approach designed according to circadian rhythm to deliver the drug at right time, in right quantity and at right site as per pathophysiological need of disease with prolong gastric residence and lag phase followed by burst release. As the migraine follows circadian rhythm in which headache is more painful at the awakening time, the dosage form should be given during night time to release drug when pain get worsen. Present work deals with formulation and optimization of floating pulsatile tablet of sumatriptan succinate. Core tablet containing crospovidone as superdisintegrant (10%) showed burst release. Lag time was maintained using swellable polymer as polyoxN12K and xanthum gum. 3(2) experimental design was carried out. Developed formulations were evaluated for physical characteristics, in vitro and in vivo study. Optimized batch F2 with concentration of polyox N12K (73.43%) and xanthum gum (26.56%) of total polymer weight showed floating lag time 15±2 sec, drug content 99.58±0.2 %, hardness 6±0.2 Kg/cm(2) and drug release 99.54±2% with pulsatile manner followed lag period of 7±0.1h. In vivo x-ray study confirms prolong gastric residence of system. Programmable pulsatile release has been achieved by formulation F2 which meet demand of chronotherapeutic objective of migraine.

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release, with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release, and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.

A novel green approach by photocatalytic oxidative polymerization was developed that addresses and resolves current limitations of chemical polymerization of anilines. This process generates nanoparticles of the conducting polymer poly(N-ethylaniline) (PNETA) and poly-(N-methylaniline) (PNMTA) in a single step by using a catalytic amount of the oxidant in the presence of an organic acid such as DL-(±)-Tartaric acid. Poly(N-ethylaniline) nanoparticles doped with tartaric acid show exceptional antimicrobial activity at low concentration. Five compounds have been synthesized. Of these, two compounds have been found to exhibit significant activity against Klebsiella pneumoniae. The minimum inhibitory concentration value was observed at 50 µg/mL. An extremely simple green approach is described that generates bulk quantities of nanoparticles with average diameter 200 nm size of the conducting polymer PNETA in one-step photochemical method using a catalytic amount of ammonium persulfate as oxidant in the presenc...

Background Triamcinolone is a long acting corticosteroid used in the treatment of arthritis, eczema, psoriasis and similar conditions which cause inflammation. Triamcinolone has half-life of 88min. Prolonged oral use is associated with gastrointestinal adverse effects as peptic ulcer, abdominal distention and ulcerative esophagitis as described in various patents. Microemulgel offers advantage of better stability, better loading capacity and controlled release especially for drug with short half life. Objective Objective of the present study was to optimize microemulgel based transdermal delivery of triamcinolone. Method Saturated solubility of triamcinolone in various oils, surfactants and co-surfactants is estimated. Pseudo-ternary phase diagrams were constructed to determine the region of transparent microemulsion. Microemulsion was evaluated for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity, conductivity etc. Design of experiment was used to optimize microemulsion based gel. Carbopol 971P and HPMC K100M were used as independent variables. Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters. Results Microemulsion was formulated with oleic acid, lauroglycol FCC and propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32 factorial design gave batch F8 as optimized. Design expert suggested drug release; gel viscosity and bio-adhesive strength were three significant dependant factors affecting the transdermal delivery. F8 showed drug release 92.62.16±1.22% through egg membrane, 95.23±1.44% through goat skin after 8hr and Korsmeyer-Peppas release model was followed. Conclusion It can be concluded that a stable, effective controlled release transdermal microemulgel was optimised for triamcinolone. This would be a promising tool to deliver triamcinolone with enhanced bioavailability and reduced dosing frequency.

In this chapter authors have discussed the role of plants to develop contaminant free environment. This concept is also known as Phytoremediation. Phytoremediation is a word formed from the Greek prefix “phyto” meaning plant, and the Latin suffix “remedium” meaning to clean or restore. This technology has been receiving attention lately as an innovative, cost-effective alternative to the more established treatment methods used at hazardous waste sites. Phytoremediation can be classified into different applications, such as phytofiltration or rhizofiltration, phytostabilization, phytovolatilization, phytodegradation and phyto-extraction etc. The chapter will deal with phytoremediation, its advantages, limitations and in detail techniques of classification and application.

Diltiazem hydrochloride is a calcium channel blocker generally indicated for the treatment of angina and hypertension, and it is extensively metabolized due to the hepatic metabolism. Formulation of diltiazem hydrochloride into an oro-dispersible dosage form can provide fast relief with higher bioavailability. The bitter taste of the drug should be masked to formulate it in a palatable form. In the present work, an attempt was made to mask the taste by complexation technique, with a formulation into an oro-dispersible dosage form, using superdisintegrants Doshion P544, crospovidone (CP) and sodium starch glycolate (SSG). The complexes of diltiazem hydrochloride with β-CD (1:1 molar ratio) were prepared by kneading, co-evaporation, co-grounding, freeze-drying and melting methods. Phase solubility showed stability constant 819.13M-1. Prepared inclusion complexes were evaluated for taste masking and characterized by I.R, XRD, DSC. Using the drug β-CD complex, oro-dispersible tablets were prepared and evaluated for hardness, friability, weight variation, thickness, disintegrating time (DT), dissolution rate and taste. Formulations with 4 % Doshion, 8 % CP and 4 % SSG showed DT of 0.54, 0.35 and 1.23 minutes, respectively.O cloridrato de diltiazem é bloqueador do canal de cálcio geralmente indicado para o tratamento de angina e de hipertensão e é extensamente biotransformado devido ao metabolismo hepático. A formulação do cloridrato de diltiazem em orodispersão pode prover rápida liberação com maior biodisponibilidade. O sabor amargo do fármaco deve ser mascarado para ser formulado em forma palatável. No presente trabalho tentou-se mascarar o sabor pela técnica de complexação, com uma orodispersão, usando superdesintegrantes, como Doshio P544, crospivodina (CP) e glicolato de amido sódico (SSG). Os complexos de cloridrato de diltiazem com β-CD (razão molar 1:1) foram preparados por mistura, coevaporação, comoagem, liofilização e métodos de fusão. A solubilidade de fase mostrou estabilidade constante de 819,13 M-1. Os complexos de inclusão preparados foram avaliados com relação ao mascaramento do sabor e caracterizados por IV, Difração de Raios X e DSC. Empregando-se o fármaco complexado com β-CD, prepararam-se comprimidos dispersíveis e avaliaram-se os mesmos quanto à dureza, friabilidade, variação de peso, espessura, tempo de desintegração (DT), taxa de dissolução e sabor. Formulações com 4% de Doshion, 8% de CP e 4% de SSG mostraram DT de 0,54, 0,35 e 1,23 minutos, respectivamente.

The purpose of this research was to formulate and characterize solid dispersion (SD) of metformin hydrochloride using methocel K100M as the carrier by the solvent evaporation and cogrinding method. The influence of drug polymer ratio on drug release was studied by dissolution tests. Characterization was performed by fourier transform spectroscopy (FTIR), ultraviolet, differential scanning calorimetry and X-ray powder diffractometry. The optimized formulation was subjected to accelerated stability testing as per ICH guidelines. Release data were examined kinetically. SD with 1:4 and 1:5 ratio of drug to polymer obtained by solvent evaporation and cogrinding were selected as the best candidates suitable for prolonged-release oral dosage form of metformin.

The rate-limiting step to absorption of drugs from the gastrointestinal tract is often dissolution from the dosage form. Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with leukaemia, radiotherapy, anti-neoplastic agents. One of the major problems with allopurinol is that, it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation method, kneading method, co-precipitation method, co-grinding method and closed melting method to increase its water solubility. In the present study amphiphilic carrier like gelucire 50/13 was used in the ratio of 1:1, 1:2 and 1:4. Prepared solid dispersions were characterized in the liquid state by phase solubility studies and in the solid state by Differential Scanning calorimetric analysis, Powder X-ray diffractometry and Fourier Transform Infrared spectroscopy. The aqueous solubility of allopurinol was preferential by the presence polymer with increasing concentration. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix.Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the current study showed that gelucire 50/13 has a significant solubilizing effect on allopurinol. Keywords: Allopurinol, gelucire 50/13, closed melting-method, co-grinding, dissolution study, powder X-ray diffraction analysis

Nasal route had shown better systemic bioavailability due to its large surface area, porous endothelial membrane, high total blood flow, and avoidance of first-pass metabolism. Timolol maleate is a beta blocker used primarily in the treatment of hypertension. Drug undergoes extensive hepatic first-pass metabolism (80%). The drug has half-life of 4 hrs. Oral bioavailability of timolol maleate is 61%. The aim of the present study was to optimize controlled releasein situnasal delivery for timolol maleate. HPMC and Poloxamer 407 were selected as polymer in formulation of thermoreversiblein situnasal gel. Optimization was carried out using 32factorial design. It was observed that formulations f1 and f4 revealed the highest % drug release, that is, 93.57% and 91.66%, respectively. Factorial design study indicated that the drug release and viscosity were most significant dependent factors.Ex vivodiffusion study through nasal mucosa indicated 67.26 ± 2.10% and 61.07 ± 2.49% drug release for f1 and f4 formulations. f1 was the optimized batch. This batch thus can act as a potential nasal delivery with enhanced bioavailability for the drug.