Background A solid dispersion formulation (SD) involves dispersion of poor water soluble active pharmaceutical ingredients (API) in a solubility enhancing polymer with the uttermost goal of improving the oral bioavailability of the API. Objective This study is aimed at production and evaluation of 5- Fluorouracil (5- FU) SD formulations for colon delivery using the hot met technique. Method The solid dispersions of 5-FU were prepared by hot melting method; The SD formulations were characterized using a scanning electron microscopy, USP dissolution apparatus type 2, and MTT assay. Results The SEM revealed that all SD formulations particles were in amorphous state, they rod like shaped with size ranging between 98 -112µm. The FTIR spectral show no chemical interactions between the excipients and 5 FU. The yield (PY), drug entrapment efficiency (DEE) and the drug loading (DL) values were high enough to support commercial scale up of the technique. SD2 had the highest DEE, cumulative drug released and DL values. This may be responsive for its improved cytotoxicity against HT115 cells. The releases of 5 FU in all the formulations follow both Fickian´s and non-Fickian´s kinetics which are also pH responsive with no sign of dose dumping. Conclusion This study demonstrated successful production of pH responsive 5 FU solid dispersions, by hot melt technique. The release follows Korymeyer –Peppas kinetic models and selectively delivered 5 FU to the colon which improved cytotoxicity activity against CRC .
New ideas on controlling the pharmacokinetics, pharmacodynamics, nonspecific toxicity, immunogenicity and efficiency of drugs have generated new strategies, often called as the drug delivery system. Development of an existing drug molecule can significantly improve its performance in terms of patient compliance, safety, and efficacy from a conventional form to a novel delivery system can significantly improve . The variety of dressings based on types of wounds and novel polymers used for the delivery of drugs to acute and chronic wound has resulted in a wide range of new products frequently introduced to target different aspects of the wound healing process. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. Nevertheless, nanofibers with their physicochemical properties and nanotopography display improvements in the fields of tissue engineering, wound therapy and drug delivery systems. At present, there are so many existing drug delivery technologies that a total compilation is not within the scope of this article. Yet an attempt is being made to compile some of the most successfully marketed drug delivery technologies. This review extends the information and hopes to give insight into past, present and future strategies and approaches for wound healing managements.
The skin can be used as the site for drug administration for continuous transdermal drug infusion into the systemic circulation. For the continuous diffusion/penetration of the drugs through the intact skin surface membrane-moderated systems, matrix dispersion type systems, adhesive diffusion controlled systems and micro reservoir systems have been developed. Various penetration enhancers are used for the drug diffusion through skin. In matrix dispersion type systems, the drug is dispersed in the solvent along with the polymers and solvent allowed to evaporate forming a homogeneous drug-polymer matrix. Matrix type systems were developed in the present study. In the present work, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising of Granisetron -HCl with different ratios of hydrophilic and hydrophobic polymeric combinations using solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy. The results obtained showed no physical-chemical incompatibility between the drug and the polymers. The patches were further subjected to various physical evaluations along with the in-vitro permeation studies using rat skin. On the basis of results obtained form the in-vitro study and physical evaluation the patches containing hydrophilic polymers i.e. polyvinyl alcohol and poly vinyl pyrrolidone, with oleic acid as the penetration enhancer(5%) were considered as suitable for large scale manufacturing with a backing layer and a suitable adhesive membrane.
Background & Objective: The objective of the present study was to evaluate the effect of different statins (HMG-CoA reductase inhibitors) on gastric and duodenal ulcer in rats. Methods: The effect of different statins on gastric and duodenal ulcers were evaluated by using different experimental models such as acetic acid induced chronic gastric ulcer, pylorus ligation induced gastric ulcer, ethanol induced gastric ulcer, stress induced gastric ulcer and cysteamine induced duodenal ulcer. Results: The different statins tested in the present showed variable effects in different models of gastric ulcers and cysteamine induced duodenal ulcer. Atorvastain showed anti-ulcer activity in three models; pylorus ligation, ethanol induced gastric ulcer and acetic acid induced chronic gastric ulcers. Simvastatin showed a decrease in free acidity in pylorus ligated rats while lovastatin did not influence gastric and duodenal ulcer formation or healing of gastric ulcers. Interpretation & Conclusion: The atorvastatin showed significant effect on the healing and development of gastric ulcers while other statins did not influence ulcer healing or ulcer formation. It was concluded atorvastatin possess anti-ulcer effect in rats and all the tested statins may be safe for administration to patients suffering from peptic ulcer disease.
Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and heart disease. Although synthetic lipid‑lowering drugs are useful in treating hyperlipidemia, there are number of adverse effects. Therefore, the current interest has stimulated the search for new lipid‑lowering agents with minimal side effects from natural sources. The Purpose of this study was to examine the lipid lowering capability of aqueous: ethanol (1:1) extract of Carissa carandas in high fat diet induced hyperlipidemic rats. A highly significant increase in the weight of high cholesterol diet rats was observed when compared with control group (P<0.01). The extract caused a significant reduction in body weight, Cholesterol, Triglycerides, HDL and LDL in hyperlipidemic rats. Histopathological changes induced by high cholesterol diet were also significantly reduced by the extract. The activity of ethanol and water extract of C. carandas was comparable to that of atorvastatin.
Particle size characterization is one of the key areas involved in quality assurance. The concept of particle size and size characterization acts as a foundation for all the processes involved in theproduction of a formulation; from manufacturing to quality control operations. Particle size characterization dictates many properties of the finished product. Particle size characterization of samples is important to make a better quality product, improve its appearance, taste, texture and shelf-life. There are many instruments for particle size characterization that are available commercially. Each instrument is based on a different technique and each technique is based on a different principle. Selecting the right particle size characterization technique for the given sample is a challenging decision. The choice of technique is made according to the sample. Sometimes even a combination of techniques is used to obtain accurate results. There are several factors upon which choice of technique depends like size range, sample quantity, cost effectiveness etc. To ensure appropriate quality standards in the field of particle sizing and particle size characterization, ICH and US-FDA have recently insisted on including Quality-by-design approach in thepharmaceutical industry. Application of QBD approach to particle size characterization techniques ensures a resilient method which gives reproducible results. It aids in reducing result and method variations and promotes productivity and quality. The main objectives of this review are first, to understand the principle, instrumentation, and working of commercially used techniques and to compare their pros and cons; secondly, to study the factors which govern the choice of technique and lastly, to understand the concept of Quality by design and its role in particle size characterization through some example. Keywords: Particle size characterization; techniques; factors;QBD
Topical application of Itraconazole for the treatment of Basal cell carcinoma represents a new hope in dermatology. Itraconazole for treatment of Basal cell carcinoma is an alternative therapeutic approach for the efficacious treatment of nonmelanoma skin cancer. Itraconazole loaded ethosomes were prepared and characterized by vesicular shape, vesicular size, entrapment efficiency. Ethosomal gel were prepared and characterized by pH, viscosity, washability, spreadibility, drug content, drug release study, stability study, in vivo skin tolerability and antiproliferative activity. Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS) characterise ethosomes as spherical, unilamellar structures having low polydispersity (0.384 ± 0.037) and nanometric size range (169.0 ± 49.0), % Entrapment efficiency of Itraconazole in ethosomal carrier was found to be 82.00 ± 1.78. Ethosomal gel were prepared by using Carbopol. The viscosity was found to be in the range of 1600±1.72 to 1740±1.73 cps. The spreadability was found to be in the range of 6.4g.cm/sec. The drug content of the ethosomal gel formulations ranged from 0.384-0.386 mg/gm. The value of steady-state transdermal flux was observed to be 54.2 ± 1.46 µg/h/cm with a lag time of 1.2 hrs with formulation EG1. Stability studies revealed no noticeable changes in drug release profile occurred. Skin irritation study on rabbit skin suggested that ethosomal gel may offer a suitable approach for transdermal delivery of Itraconazole. The further, antiproliferative study shows that Itraconazole loaded ethosomes is significantly more toxic than the free drug on BCC1/KMC cell line, thus making it a potential alternative to the standard therapy.
Sickle cell disease is a major public health problem. It is the first genetic disease in the world. FACA syrup offers an alternative treatment. It is a dry powder preparation of two components, the roots barks of Zanthoxylum zanthoxyloides Lam. (Rutaceae) Zepernick, Timler and Calotropis procera. Ait. R.B.r. (Asclepiadaceae). The product was developed at Institute for Research in Health Sciences (IRSS) from a traditional recipe used in Burkina Faso for treatment of sickle cell crises. This study aimed to establish physical-chemical, pharmaco technical and microbiological control parameters essential for the standardization of the phytomedicine. This valuation concerned specifications of moisture content, pH, the fingerprint by thin layer chromatography, pesticide residues, heavy metal content, microbial quality, and total ash. These charcteristics were determined by the methods prescribed by the World Health Organization (1998) and the European Pharmacopoeia 6th edition. The results have shown that dry syrups and reconstituted syrups were sweet, slightly spicy with a bitter after taste, a white room color and a faint odor. The density at the preparation was 0.985 and the pH was 5.93. After 2 months of storage in the laboratory, the organoleptic parameters of the reconstituted syrups have not changed. They were mold free, the density remained around 1 and the pH between 5 and 4. These parameters have shown that the quality of plants powders and these medicine comply with the recommendations of the European pharmacopoeia. Faca syrup may contribute to the better management of sickle cell disease in children.
Nebivolol Hydrochloride (NEB) is a lipophilic molecule with low solubility in GI fluid, and high metabolism which leads to its low oral bioavailability 12%. The aim of the present investigation was to develop immediate release self emulsifying tablet (IR-SET) as solid SMEDDS to enhance the solubility and permeability of the drug. Solubility study, pseudo-ternary phase diagrams and 3 2 factorial design were used to select the components of the system and optimize the composition of liquid SMEDDS. Optimal L-SMEDDS contains Kollisolv GTA, Tween 80 and Propylene glycol as oil, surfactant and co-surfactant, respectively in the ratio of 20:26.66:53.34 % w/w, formulates L-SMEDDS with droplet size (55.98 nm), PDI (0.37), emulsification time (16±1.52 sec) and drug content (97.43±0.30 %). The liquid SMEDDS were adsorbed onto Neusilin US2 by adsorbtion technique to form S-SMEDDS. DSC and SEM studies suggested that NEB in the S-SMEDDS may be present in the molecular dispersed state and was sufficiently adsorbed onto solid carrier, respectively. S-SMEDDS was compressed into IR-SET by direct compression method and composition of IR-SET was optimized using 3 2 factorial design. Optimal IR-SET showed disintegration time (92 + 0.57 sec), droplet size (68.57 nm), PDI (0.34) and drug content (96.33±0.15 %). In vitro dissolution studies and ex vivo diffusion studies in rat stomach suggested that SMEDDS played an important role in solubility and permeability enhancing effect. Accelerated stability studies indicated that formulation were stable. Our results illustrated the increase in solubility and permeability of drug from IR-SET.
In this study, ampicillin drug loaded with alginate and nanocellulose film was prepared by solution casting method. Nanocellulose and ampicillin incorporated into alginate to improve both mechanical and swelling properties. Interaction of ampicillin with alginate and nanocellulose was proved by ATR-FTIR spectra. The formulated ampicillin loaded Alg/NC film gave acceptable physicochemical properties compared with Alg-amp film and was able to deliver the drug in a prolonged release pattern. In vitro drug release showed that alginate could provide an immediate release of ampicillin with further enhanced nanocellulose, and followed by a sustained release over 500 min of the remaining drug. The present study exhibited a simple and useful approach to systematically design for providing drug release profiles.
This study was conducted to produce nanosized cyclodextrin (NCD) and assess its effect on bovine spermatozoa during In vitro fertilization (IVF) to optimize the capacitation media for successful IVF. Therefore, Four cyclodextrin formulations were prepared and characterized. Data analysis revealed the best formula (F2) showed a smallest particle size (15 nm), zeta potential (-37 mv), and higher yield percentages (95%) was selected for spem capacitation. Motile spermatozoa were separated from frozen-thawed semen by a swim-up procedure and capacitated in IVF-TALP medium with different formulae of NCD or CD or without treatments (control) and incubated for 3hours(hr) at 38°C and evaluated every one (hr) interval. Data analysis revealed that the formulation of cyclodextrin nanoparticles (F2) after (2hr) incubation in the media gave best effect on sperm capacitation and acrosme reaction (AR) and effect of sperm treated with NCD on fertilization rate was evaluated. The results showed that the proportion of Oocytes fertilized was increased significantly in F2 (60%) than in the control (35%), and cyclodextrin group (50%) groups (p<0.05). It could be inferred from this investigation that cyclodextrin nanoparticles can be used for biomedical interventions in bovine spermatozoa. NCD improve sperm motility, viability, and (AR), also fertilization rate of sperm treated with NCD increase. So NCD gave positive effect on sperm functions during IVF.
Acridone is a unique naturally occurring alkaloid known to associate with several biological activities. 2,3-dimethoxy-10-methyl-10,8a-dihydroacridin-9(8aH)-one (4) and its precursor 2-((3,4-dimethoxyphenyl)methylamino)benzoic acid (3) were synthesized and investigated for potential antioxidant and inhibitory activity against acetylcholinestrase. The synthetic pathway involves reaction of 2-(methylamino) benzoic acid (1) with 4-chloro-1,2-dimethoxybenzene (2) in presence of CuO and K2CO3 to give the precursor 3. Subsequent, cyclcondensation of 3 with Conc. H2SO4 afforded the anticipated acridone 4. Furthermore, the dimethoxyacridone derivative 4 showed potent antiacetylcholinesterase (ACHE) activity at (100 uM) with IC50 = 9.25 uM that is as potent as the reference drug rivastigmine. Assessment of total antioxidant activity of compounds 3 & 4 in comparison to known standard compounds revealed the following order: α-tocopherol > Acridone 4 > trolox > butylated hydroxyl anisole (BHA) > butylated hydroxyl toluene (BHT) > compound 3. Molecular docking characteristics of 3 & 4 within the active site of AChE (PDB: 1ACJ) co-crystallized with 9-amino-tetrahydroacridine (Tacrine) have been studied. Interestingly, the results revealed comparable binding poses to the co-crystallized ligand and demonstrates good correlation of the binding energy (DG) with the observed IC50-values. This finding suggests that compounds 3 & 4 exhibit good antioxidant effect and inhibition of acetylcholinesterase, which might provide profitable candidates in management of Alzheimer’s disease.
Injury to the skin provides a new challenge, as wound healing is a complex and intricate process. Nonhealing wounds represent a significant cause of morbidity and mortality for a large portion of the population. Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Wound healing requires a concerted effort of remodeling of various components of the connective tissue in the presence of appropriate cytokines and growth factors. Unfortunately we still do not understand the actual mechanism of wound healing. This review is an effort to provide information about current challenges of wound healing and their management, recent advances in wound care technology and current management guidelines for the treatment of wounds and ulcers. Various steps like microbial control, subsidence of inflammation, regeneration of connective tissue, angiogenesis and epithelialisation should take place in a time-bound sequence. The development of new and effective interventions in Wound care remains an area of intense research.
Deregulated apoptosis is the hall mark of many cancers, therefore every defect in apoptosis pathway could be a potential target for cancer treatment.The anticancer mechanism of limonene could be multifactorial. However, induction of apoptosis in cancer cells is proposed as the predominant mechanism in several of preclinical studies. Therefore, we determined to investigate the role of apoptosis in the anticancer activity of limonene and BEZ235 combination in COLO-320 and HCT-116 colon cancer cells. Cells after treatments were assessed for apoptosis by DAPI staining for fluorescent microscopic examination of apoptotic cells, estimation of caspases activities, Bcl-2 family proteins in addition to cell cycle analysis by flowcytometry. Results show that both drugs induced apoptosis as demonstrated by increased caspases activity, significant alterations in pro and anti-apoptotic proteins of Bcl-2 family in promoting apoptosis and cell cycle arrest at G1 phase. Over all, it is indicated that limonene and BEZ exerted anticancer activity is mediated through induction of apoptosis involving mitochondria mediated intrinsic death pathway in the selected CRC cells.
Skin is one of the routes for systemic delivery of drugs through various drug delivery system. A transdermal Drug Delivery System (TDDS) is one of the most reliable and useful system to deliver drug systemically through skin. Generally medicated patch is placed on skin for delivery of medication through it into the blood stream. The aim of present study was to formulate and evaluate Palonosetron transdermal patch in vitro that could be used for antiemetic therapy. The incorporation ofPalonosetron a serotonin 5-HT3 antagonist drug was envisaged. The TDDS was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties Thickness, Weight variation, Drug content uniformity, Tensile strength, % Elongation, Folding endurance & Moisture content. The in vitro permeation study of the patch was carried out through KesaryChein diffusion cell as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 10C. The in vitro permeation study of the prepared patch indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 76.25% in 24 hours.The study shows a new approach to work in with Palonosetron.
In this paper we are sketching the chemical structure of suppressor drug for autism spectrum disorder using a computational tool. Here we are designing three molecular compounds like Fluoxetine, Risperidone, Melatonin. Structuring the suppressors, sketching the aromatization and bonding of the functional groups with the elements like Oxygen, Nitrogen, halogens. In our work we are using computational algorithm for drawing the structure of suppressor drug. In this paper we are mentioning the autism spectrum suppressor’s molecular formula as well as structural formula.
In the present work, an attempt has been made to develop gastro retentive floating tablets of Doxofylline . HPMC K4M and carbopol were used as controlled release polymers . All the formulations were prepared by direct compression method on 12 station rotary tablet punching machine. The blend of all the formulations showed god flow properties such as angle of repose, bulk density, tapped density. The prepared tablets were shown good post compression parameters and they passed all the quality control evaluation parameters as per I.P limits. FH 5 was the best optimized floating formulation because it released drug completely in 12hrs.It was also observed that the increasing concentration of polymers had a retarding effect on the drug release from the polymer matrices.
Snakehead fish (Channa striata) has been reported to be used for wound healing by people in South Borneo because it contains albumin. Snakehead fish extract (Channa striata) has hydrophillic property and poor stability. Nanoparticle technology has been started to be developed as an alternative solution to improve drug delivery profile. The purpose of this study was to determine the formulation that obtained best characterization for nanoparticle. Nanoparticles were prepared by ionic gelation method, that was prepared by doing optimize ratio between snakehead fish extract : chitosan and pH of chitosan solvent.Nanoparticles were characterized using Particle Size Analyzer for particle size and particle size distribution, measurement of entrapment efficiency, determined Zeta potential using Particle Size Analyzer, and observation of particle’s morphology using Transmission Electron Microscope. The result showed that the chosen formula was formula 6 which ratio of extract : chitosan 1:2 with chitosan solvent pH 3, particle size 152.3 nm, polidispersity index 0.778, percentage of entrapment efficiency 51.3961 %, Zeta potential +35.9 mV, and round shape of particles.
Today millions of patients depend on medical device based treatment for the management and diagnose of several diseases. Quality and safety of device is depends upon the regulatory guidelines. Medical device manufacturing in India should be taken seriously due to large population and the potential severity of the consequences of introducing inferior and unsafe products to the market-place. Therefore a law containing adequate guidelines of rules and regulations are required for monitoring the entry of such devices into the use in public health. The regulations define requirements of medical device design, development and manufacture to ensure that products reaching market are safe and effective. Presently in India regulatory body CDSCO is governing regulation for regulation of devices which with time, amendment introducing in the law will provide safety assurance to public health. This review provides a study on different regulatory aspects of medical device implemented in India. The present review discuss about the classification of medical devices and regulations aspects in India.
In this present study, Excoecaria agallocha fruit aqueous extract was used to synthesize Silver Nano Particles (Ag NPs/SNPs) which has proven as eco-friendly, nontoxic, less time consuming and energy saving. The synthesized SNPs were characterized by UV-Visible spectroscopy, FTIR and SEM studies. The SNPs were checked for the antibacterial activity against both Gram positive and Gram negative bacteria. The characterization studies clearly revealed the formation and synthesis of SNPs which also showed the inhibitory activity on the tested bacteria. SNPs of Excoecaria agallocha fruit showed higher zone of inhibition against Micrococcus luteus, Arthrobacter protophormiae, Rhodococcus rhodochrous, Bacillus subtilis, Alcaligens faecalis, Enterobacter aerogenes, Proteus mirabilis and Salmonella enterica when compared to that of standard antibiotic, Streptomycin.
