Aceclofenac organogels: in vitro and in vivo characterization.

PURPOSE: To develop and evaluate the suitability of lecithin organogels containing aceclofenac for topical application and compare its In vitro and In vivo effects with conventionally used hydrogels. METHODS: The components and their concentration necessary for organogels formation were evaluated using phase diagram. Solubility of aceclofenac was determined. The In vitro skin permeation ability of aceclofenac from ethyl oleate based lecithin organogels [EO/lecithin organogel] and hydrogel was investigated. The In vivo characterization of ethyl oleate based organogel study was compared with that of hydrogel.The alterations in microstructure of organogels during diffusion study were elucidated. Viscosity and micellar size of the organogel sample were estimated. The safety of optimized organogel was determined using histopathological investigation. RESULTS: The flux calculated for skin permeation ability of aceclofenac was in the order EO/lecithin organogel > hydrogel. The In vivo results also demonstrated that organogels are more effective in faster drug release as compared to hydrogels. It was observed that viscosity of gels decreased with increasing stress .The size of micellar aggregation increased with water added and has been revealed in dynamic light scattering (DLS) study. The histopathological data showed that EO/lecithin organogel were safe enough for topical purpose.

N-myristoyltransferase: a novel target.

Myristoyl-CoA:Protein N-myristoyltranferase (NMT) is a cytosolic monomeric enzyme which catalyses the transfer of a rare fatty acid, myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. N-myristoyltransferase is a novel target for anticancer, antiviral and antifungal agents. Recent N-myristoyltransferase inhibitors like benzofurans and benzothiazole derivatives show in vivo antifungal activity and are promising selective fungal N-myristoyltransferase inhibitors.

Solid lipid nanoparticles and nanostructured lipid carriers--innovative generations of solid lipid carriers.

The first generation of solid lipid carrier systems in nanometer range, Solid Lipid Nanoparticles (SLN), was introduced as an alternative to liposomes. SLN are aqueous colloidal dispersions, the matrix of which comprises of solid biodegradable lipids. SLN are manufactured by techniques like high pressure homogenization, solvent diffusion method etc. They exhibit major advantages such as modulated release, improved bioavailability, protection of chemically labile molecules like retinol, peptides from degradation, cost effective excipients, improved drug incorporation and wide application spectrum. However there are certain limitations associated with SLN, like limited drug loading capacity and drug expulsion during storage, which can be minimized by the next generation of solid lipids, Nanostructured lipid carriers (NLC). NLC are lipid particles with a controlled nanostructure that improves drug loading and firmly incorporates the drug during storage. Owing to their properties and advantages, SLN and NLC may find extensive application in topical drug delivery, oral and parenteral administration of cosmetic and pharmaceutical actives. Cosmeceuticals is emerging as the biggest application target of these carriers. Carrier systems like SLN and NLC were developed with a perspective to meet industrial needs like scale up, qualification and validation, simple technology, low cost etc. This paper reviews present status of SLN and NLC as carrier systems with special emphasis on their application in Cosmeceuticals; it also gives an overview about various manufacturing techniques of SLN and NLC.

Formulation and evaluation of flurbiprofen microemulsion.

The purpose of the present study was to investigate the microemulsion formulations for topical delivery of Flurbiprofen (FP) in order to by pass its gastrointestinal adverse effects. The pseudoternary phase diagrams were developed and various microemulsion formulations were prepared using Isopropyl Myristate (IPM), Ethyl Oleate (EO) as oils, Aerosol OT as surfactant and Sorbitan Monooleate as cosurfactant. The transdermal permeability of flurbiprofen from microemulsions containing IPM and EO as two different oil phases was analyzed using Keshary-Chien diffusion cell through excised rat skin. Flurbiprofen showed higher in vitro permeation from IPM as compared to that of from EO microemulsion. Thus microemulsion containing IPM as oil phase were selected for optimization. The optimization was carried out using 2(3) factorial design. The optimized formula was then subjected to in vivo anti-inflammatory study and the performance of flurbiprofen from optimized formulation was compared with that of gel cream. Flurbiprofen from optimized microemulsion formulation was found to be more effective as compared to gel cream in inhibiting the carrageenan induced rat paw edema at all time intervals. Histopathological investigation of rat skin revealed the safety of microemulsion formulation for topical use. Thus the present study indicates that, microemulsion can be a promising vehicle for the topical delivery of flurbiprofen.

In-vitro pediculicidal activity of Hedychium spicatum essential oil.

The essential oil extracted from rhizomes of Hedychium spicatum was evaluated for in-vitro pediculicidal activity. At 5%, 2% and 1% concentration the essential oil showed more significant activity than 1% permethrin based product.

Nutraceuticals--an emerging era in the treatment and prevention of cardiovascular diseases.

Foods and nutrients play a vital role in normal functioning of the body. They are helpful in maintaining the health of the individual and in reducing the risk of various diseases. Worldwide acceptance of this fact formed a recognition link between "nutrition" and "health" and the concept of "nutraceuticals" was evolved. Nutraceuticals are medicinal foods that play a role in maintaining well being, enhancing health, modulating immunity and thereby preventing as well as treating specific diseases. Thus the field of nutraceuticals can be envisioned as one of the missing blocks in the health benefit of an individual. More than any other disease, the etiology of cardiovascular disease reveals many risk factors that are amenable to nutraceutical intervention. The scientific literature shows that several ingredients marketed for use in dietary supplements address each of these. The ability of nutraceuticals to positively influence cardiovascular risk factors should be recognized as an enormous opportunity in the treatment of a highly prevalent disease. Nutraceuticals hold promise in clinical therapy as they have the potential to significantly reduce the risk of side effects associated with chemotherapy along with reducing the global health care cost. In this review, an attempt has been made to summarize some of the recent research findings on garlic, omega-3-fatty acids, soy products, dietary fibres, vitamins, antioxidants, plant sterols, flavonoids, prebiotics and probiotics that have beneficial effects on the heart, in order to update the practising clinician on the benefit of using nutraceuticals for the management of cardiovascular diseases.

Applications of microemulsion based drug delivery system.

The use of microemulsions as drug delivery vehicle has been an exciting and attractive area of research because of its many potential and extraordinary benefits. Microemulsions offer an interesting and potentially quite powerful alternative carrier system for drug delivery because of their high solubilization capacity, transparency, thermodynamic stability, ease of preparation, and high diffusion and absorption rates when compared to solvent without the surfactant system. The oral efficacy of microemulsion has already been proved by cyclosporine formulation (Neoral), but apart from oral route, microemulsions for other routes like dermal, transdermal, ocular, vaginal, rectal, buccal, periodontal, parenteral, and nasal delivery routes have also been developed. The present review focuses on various applications of microemulsions through different above mentioned routes and also gives idea about new application of micro emulsion as oral solid dosage form, as microreactors and as blood substitute.

Topical delivery of aceclofenac from lecithin organogels: preformulation study.

The purpose of this research is to evaluate the suitability of lecithin organogels containing aceclofenac for topical application. The present article focuses on the preformulation part of the whole research work. Thin layer chromatography was carried out to determine lecithin's purity. The excipients for formulating lecithin organogel were screened. Lecithin organogels are thermo reversible in nature and hence gelation temperature study was carried out to determine the temperature where Sol-Gel and Gel-Sol transformation takes place. Partition coefficient of the drug was estimated. Drug solubility in plain oil and organogel containing reverse micelles was estimated. Effect of water added on the properties of lecithin organogels such as X-ray diffraction pattern, conductivity and viscosity were determined. Microscopy of the gel sample has been carried out at different magnifications. The pseudo ternary phase diagram has been constructed to determine the organogel existence region. The permeation study of aceclofenac from different concentrations of lecithin organogels [200 mM, 300 mM and 400 mM] has been determined using cellulose acetate membrane (0.45 micro) and excised rat skin. Lecithin organogel in ethyl oleate has desired stability and consistency. A single spot on the TLC plate confirms the purity of soy lecithin to be used in organogel formation. Aceclofenac solubility was found to be more in lecithin/oil reverse micellar system as compared to its solubility in oil. The X-ray diffraction pattern confirms the incorporation of water in micellar gel network. The physical properties of organogels are affected by water incorporated and concentration of gelator. The permeation of aceclofenac through artificial membrane and excised rat skin demonstrated the same trend and were in the following order 200 mM>300 mM>400 mM. The results showed that organogel exhibits useful pharmaceutical properties.

Risk-based approach for systematic development of gastroretentive drug delivery system.

The research envisioned was the development of diltiazem hydrochloride effervescent floating matrix tablet using a risk-based approach. Preliminarily, the in vitro drug release profile was derived which theoretically simulated the in vivo condition after oral administration. Considering this as a rationale, the formulation development was initiated with defining the quality target product profile (QTPP) and critical quality attributes (CQAs). The preliminary studies were conducted to screen material attributes and process parameters followed by their risk assessment studies to select the plausible factors affecting the drug product CQAs, i.e., floating lag time and drug release profile. A 3(2) full factorial design was used to estimate the effect of the amount of swelling polymer (X 1) and gas-generating agent (X 2) on percent drug release (Q t1h and Q t8h) and floating lag time. Response and interaction plots were generated to examine the variables. Selection of an optimized formulation was done using desirability function and further validated. The model diagnostic plots represent the absence of outliers. The optimized formula obtained by the software was further validated, and the result of drug release and floating lag time was close to the predicted values. In a clear and concise way, the current investigations report the successful development of an effervescent floating matrix tablet for twice daily administration of diltiazem hydrochloride.

Advanced approaches in insulin delivery.

Diabetes is a syndrome of disordered metabolism and inappropriate hyperglycemia resulting from a deficiency of insulin secretion or insulin resistance. Insulin, a pancreatic hormone, helps to lower the blood sugar levels. The structural features of insulin and insulin receptors are summarized. Diabetic patients use insulin in the form of injections, which involves lots of pain, and a need for non-invasive, alternative mode of insulin administration is desired. These challenges have lead to attempts in insulin therapy using oral, nasal, pulmonary, rectal, transdermal, buccal, gene therapy, islet cell transplantation and diabetes vaccine. Among all the approaches pulmonary administration has achieved some clinical significance. Future approaches that can be exploited for insulin therapy in Insulin Dependent Diabetes Mellitus [IDDM] have been summarized. Insulin inhalers or tablets for IDDM are interesting alternatives.

Forced Degradation Studies of Aloe Emodin and Emodin by HPTLC.

Anthraquinones are natural phenolic compounds, which are reported to act as anti-aging, anti-inflammatory, antioxidant, anti-cancer, laxative and antitumor agents. They are abudant in plants like candle bush, aloes, cascara bark and rhubarb. The present work was to observe the effect of different forced degradation conditions by high-performance thin layer chromatography on potential markers i.e. aloe emodin and emodin. Both aloe emodin and emodin were subjected to various forced degradation studies such as oxidation, acid and alkaline hydrolysis, photolysis, hydrolytic and thermal degradation. Aloe emodin, was more susceptible to acid hydrolysis and degradation was found to a lesser extent under thermal degradation whereas significant degradation was observed under acid hydrolysis, lesser extent was observed under alkali hydrolysis for emodin. Forced degradation studies on aloe emodin and emodin gives information about its storage and intrinsic stability conditions considering the advanced pharmaceutical aspects of formulation.

Development and Validation of High-performance Thin Layer Chromatographic Method for Ursolic Acid in Malus domestica Peel.

Ursolic acid, a pentacyclic triterpenoid possess a wide range of pharmacological activities. It shows hypoglycemic, antiandrogenic, antibacterial, antiinflammatory, antioxidant, diuretic and cynogenic activity. It is commonly present in plants especially coating of leaves and fruits, such as apple fruit, vinca leaves, rosemary leaves, and eucalyptus leaves. A simple high-performance thin layer chromatographic method has been developed for the quantification of ursolic acid from apple peel (Malus domestica). The samples dissolved in methanol and linear ascending development was carried out in twin trough glass chamber. The mobile phase was selected as toluene:ethyl acetate:glacial acetic acid (70:30:2). The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.9982 in the concentration range 0.2-7 µg/spot with respect to peak area. According to the ICH guidelines the method was validated for linearity, accuracy, precision, and robustness. Statistical analysis of the data showed that the method is reproducible and selective for the estimation of ursolic acid.

A Validated High-performance Liquid Chromatograhy Method for Estimation of Ferulic Acid in Asafoetida and Polyherbal Preparation.

A high-performance liquid chromatography method was developed for the estimation of ferulic acid from asafoetida and a polyherbal preparation. The separation was carried out on HiQSil ODS C-18 column with a mobile phase of acetonitrile: 10% acetic acid (20:80 v/v). The developed method was validated as per International Conference of Harmonization guidelines for various parameters such as accuracy, precision, linearity, limit of detection, limit of quantification and specificity; and found to be reliable. Linear regression analysis showed a good corelation between peak area and concentration with a corelation coefficient r(2)=0.996 in the range 200-7000 ng/ml. The developed method can be utilized for standardization of herbal formulation comprising asafoetida.

Synthesis, Characterization and In Vitro Antimicrobial Evaluation of Novel Pyrazolothiazol-4(5H)-one Derivatives.

Antimicrobial screening of several novel pyrazolothiazol-4(5H)-one derivatives (3a-3j) has been performed. Reaction of aromatic aldehydes with aromatic ketones yielded starting chalcones (1a-1j) which have been subsequently reacted with thiosemicarbazide for obtaining N-thiocarbamoylpyrazole derivatives (2a-2j). These were further cyclized to pyrazolothiazol-4(5H)-one derivatives (3a-3j) in the presence of ethylbromoacetate. The structures of newly synthesized compounds were confirmed by FTIR and (1)H NMR and/or MS. The in vitro antimicrobial activity of these compounds was evaluated against Gram positive bacteria, Gram negative bacteria and fungi. Their minimum inhibitory concentration was determined by tube dilution method. The results showed that most of the compounds have promising antimicrobial activity as compared to standard drugs. Among the test compounds, 2-[5(4-chlorophenyl)-3-phenyl-4,5-dihydropyrazol-1-yl]-thiazol-4(5H)-one (3e) was found to show the most potent antimicrobial activity.

Direct compression high functionality excipient using coprocessing technique: a brief review.

Tablets are still the most commonly used dosage form because of the ease of manufacturing, convenience in administration, accurate dosing and excellent stability. Direct compression is the preferred method for the preparation of tablets. However, it has been estimated that less than 20 percent of the active pharmaceutical ingredients (API) can be processed into tablets via direct compression since the majority of API lack the flow, cohesion or lubricating properties required for direct compression. Increasing trends toward direct compression suggests the need for development of high functional excipients. High functionality of excipients can be obtained by development of new excipients or by particle engineering of existing excipients. Particle engineering using coprocessing provides a way to obtain an excipient with high functionality. Coprocessed excipients are the mixture of two or more excipients interacting at sub-particle level; that can provide an excipient with improved functionality as well as masking undesirable properties. Coprocessing is very cost effective method of providing high functional excipient. The present review discusses the advantages of coprocessed excipients, role of material science in coprocessing, methods of coprocessing of excipients and properties of various coprocessed excipients available in the market.

Psoralea corylifolia Linn.-"Kushtanashini".

Plants have been the basis of many traditional medicines throughout the world for thousands of years and continue to provide new remedies to mankind. Plants have been one of the important sources of medicines since the beginning of human civilization. The recent resurgence of plant remedies resulted from several factors, such as effectiveness of plant medicines and lesser side effects compared with modern medicines. Psoralea corylifolia, commonly known as babchi, is a popular herb, which has since long been used in traditional Ayurvedic and Chinese medicine for its magical effects to cure various skin diseases. This plant is also pharmacologically studied for its chemoprotective, antioxidant, antimicrobial, and antiinflammatory properties. This review attempts to highlight the available literature on P. corylifolia with respect to its ethnobotany, pharmacognostic characteristics, traditional uses, chemical constituents, and summary of its various pharmacologic activities and clinical effects. Other aspects, such as toxicology and precautions are also discussed. This will be helpful to create interest toward babchi and may be useful in developing new formulations with more therapeutic and economical value.

Enkephalinase inhibitors: potential agents for the management of pain.

Management of acute and chronic pain has always been a key area of clinical research. Enkephalinase inhibitors (EIs) seem to be promising as therapeutic agents having antinociceptive action. They additionally possess anticraving, antidiarrhoeal and antidepressant actions. The antinociceptive action of EIs has been reported for over a decade however, their therapeutic potential is yet to be effectively explored. EIs may be broadly classified as endogenous and those that are obtained synthetically. Endogenous EIs include peptides like spinorphin and opiorphin. And compounds like RB 101, RB 120, RB 3007 constitute the synthetically obtained EIs. Endogenous and synthetic inhibitors enkephalin degrading enzymes have been studied in vivo using standard animal models. The potential EI targets appear to be APN (Aminopeptidase N), NEP (Neutral endopeptidase), DPP-III (Dipeptidyl peptidase). EIs possess the advantage that they lack the opioid side effects. This article reviews the mechanisms by which EIs act and elucidates the pathways involved.

Drug loaded erythrocytes: as novel drug delivery system.

Novel drug delivery systems are one of the widely used delivery systems. In the present scenario, amongst them, "Drug Loaded Erythrocytes" is one of the growing and potential systems for delivery of drugs and enzymes. Erythrocytes are biocompatible, biodegradable, possess long circulation half-life and can be loaded with variety of biologically active substances. Carrier erythrocytes are prepared by collecting blood sample from the organism of interest and separating erythrocytes from plasma. By using various physical and chemical methods the cells are broken and the drug is entrapped into the erythrocytes, finally they are resealed and the resultant carriers are then called "resealed erythrocytes". Surface modification with glutaraldehyde, antibodies, carbohydrates like sialic acid and biotinylation of loaded erythrocytes (biotinylated erythrocytes) is possible to improve their target specificity and to increase their circulation half-life. Upon reinjection the drug loaded erythrocytes serve as slow circulation depots, targets the drug to the reticuloendothelial system (RES), prevents degradation of loaded drug from inactivation by endogenous chemicals, attain steady state concentration of drug and decrease the side-effects of loaded drug. Nowadays, Nanoerythrosomes based drug delivery systems have excellent potential for clinical application.