Hydrogels are presently under investigation as a delivery system for bioactive molecules, because of their similar physical properties as that of living tissue, which is due to their high water content, soft and rubbery consistency, and low interfacial tension with water or biological fluids. Anionic hydrogels are used in the design of intelligent controlled release devices for site-specific drug delivery of therapeutic proteins to the large intestine, where the biological activity of the proteins are prolonged, and cationic hydrogels are studied for the development of self-regulated insulin delivery system, which releases the insulin in response to changing glucose concentration. The different methods of preparation of hydrogels, novel methods of crosslinking used in the preparation of hydrogels, the mechanism of water transport through the ionic hydrogels, and the release mechanism of the solute from the hydrogels, are discussed in the present article.

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Monolithic matrix tablets of ambroxol hydrochloride were formulated as sustained release tablets employing hydroxypropyl methylcellulose polymer, and the sustained release behaviour of the fabricated tablets was investigated. Sustained release matrix tablets containing 75 mg ambroxol hydrochloride were developed using different drug polymer ratios of hydroxypropyl methylcellulose. Tablets were prepared by direct compression. Formulation was optimized on the basis of acceptable tablet properties and in vitro drug release. The resulting formulation produced robust tablets with optimum hardness, consistent weight uniformity and low friability. All tablets but one exhibited gradual and near-completion sustained release for ambroxol hydrochloride, and 98-101% released at the end of 12 h. The results of dissolution studies indicated that formulation F-V (drug to polymer 1:1.47), the most successful of the study, exhibited drug release pattern very close to theoretical release profile. A decrease in release kinetics of the drug was observed on increasing polymer ratio. Applying exponential equation, all the formulation tablets (except F-V) showed diffusion-dominated drug release. The mechanism of drug release from F-V was diffusion coupled with erosion (anomalous).

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Pulsatile systems are gaining a lot of interest as they deliver the drug at the right site of action at the right time and in the right amount, thus providing spatial and temporal delivery and increasing patient compliance. These systems are designed according to the circadian rhythm of the body. The principle rationale for the use of pulsatile release is for the drugs where a constant drug release, i.e., a zero-order release is not desired. The release of the drug as a pulse after a lag time has to be designed in such a way that a complete and rapid drug release follows the lag time. Various systems like capsular systems, osmotic systems, single- and multiple-unit systems based on the use of soluble or erodible polymer coating and use of rupturable membranes have been dealt with in the article. It summarizes the latest technological developments, formulation parameters, and release profiles of these systems. Products available as once-a-daily formulation based on Pulsatile release like Pulsincap®, Ritalin®, and Pulsys® are also covered in the review. These systems are beneficial for the drugs having chronopharmacological behaviour where night time dosing is required and for the drugs having high first-pass effect and having specific site of absorption in GIT. Drugs used in asthmatic patients and patients suffering from rheumatoid arthritis are also discussed along with many other examples.

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In the last two decades, proteins and peptides have become an important class of potent therapeutic drugs. However, their susceptibility to chemical and physical degradation presents a challenge to formulation scientists, for the development of stable pharmaceutical preparations. This is in part, due to the unique physicochemical and biological properties of the proteins and peptide drugs. The insight into the fundamental understanding of the mechanism, by which protein stabilizes, will help in the formulation of protein based pharmaceuticals.

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There has been keen interest in the development of a novel drug delivery system. Novel drug delivery system aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and channel the active entity to the site of action. At present, no available drug delivery system behaves ideally achieving all the lofty goals, but sincere attempts have been made to achieve them through novel approaches in drug delivery. A number of novel drug delivery systems have emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery. Encapsulation of the drug in vesicular structures is one such system, which can be predicted to prolong the existence of the drug in systemic circulation, and reduce the toxicity, if selective uptake can be achieved. Consequently a number of vesicular drug delivery systems such as liposomes, niosomes, transfersomes, and pharmacosomes were developed. Advances have since been made in the area of vesicular drug delivery, leading to the development of systems that allow drug targeting, and the sustained or controlled release of conventional medicines. The focus of this review is to bring out the application, advantages, and drawbacks of vesicular systems.

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Transdermal dosage forms, though a costly alternative to the conventional formulations, are becoming popular because of some unique advantages. Controlled zero-order absorption, simple administration mode and the option of easy removal in case of adverse manifestations make them particularly desirable in cardiovascular therapy. Nitroglycerin and isosorbide dinitrate, the two antiischaemic drugs; and clonidine, an antihypertensive molecule, are being extensively used in the transdermal form. Studies that compared these patches with the established dosage forms had shown that though patches were costlier than conventional prescription products, they reduced the occurrence of hospitalization and diagnostic costs. Currently a number of antihypertensive drugs are being developed for transdermal administration. This article reviews the research on cardiovascular patches as well as the marketed products.

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A simple, specific and accurate reverse phase high performance liquid chromatographic method was developed for the simultaneous determination of atorvastatin calcium and aspirin in capsule dosage forms. A phenomenex Gemini C-18, 5 mm column having 250 x 4.6 mm i.d. in isocratic mode, with mobile phase containing 0.02 M potassiumdihydrogen phosphate: methanol (20:80) adjusted to pH 4 using ortho phosphoric acid was used. The flow rate was 1.0 ml/ min and effluents were monitored at 240 nm. The retention times of atorvastatin calcium and aspirin were 5.4 min and 3.4 min, respectively. The linearity for atorvastatin calcium and aspirin were in the range of 0.5-4 mg/ml and 5-25 mg/ml, respectively. The recoveries of atorvastatin calcium and aspirin were found to be in the range of 98.02-100.68% and 98.38-101.42%, respectively. The proposed method was validated and successfully applied to the estimation of atorvastatin calcium and aspirin in combined capsule dosage forms.

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The nonsteroidal antiinflammatory drugs are among the most widely prescribed and used drugs in the community for rheumatologic as well as nonrheumatologic conditions, which include acute and chronic pain; biliary, ureteric colic; dysmenorrhoea; fever; and other applications that derive from the suppression of prostaglandin synthesis. Almost all nonsteroidal antiinflammatory drugs irritate gastric mucosa and enhance ulceration by blocking protective action of the prostaglandins on gastric mucosa, causing ulcer formation not only in stomach but also in lower part of oesophagus and in duodenum too. This review focuses on the adverse effects of nonsteroidal antiinflammatory drugs, severity of these adverse effects and attempts made to reduce the side effects through the concomitant use of other drugs.

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A therapeutically significant drug may have limited utilization in clinical practice because of poor organoleptic properties, poor bioavailability, short duration of action, nonspecificity, incomplete absorption, poor aqueous solubility, high first-pass metabolism or other adverse effects. There is a great emphasis on research to discover methods aimed at improving their therapeutic efficacy by minimizing or eliminating these undesirable properties. Sometimes, an adequate pharmaceutical formulation can overcome these drawbacks, but often the galenic formulation is inoperant and a chemical modification of active molecule is necessary to correct its pharmacokinetic insufficiencies. This chemical formulation process, whose objective is to convert an interesting active molecule into a clinically acceptable drug, often involves the so-called 'Prodrug design.' Mutual prodrug is a type of carrier-linked prodrug, where the carrier used is another biologically active drug instead of some inert molecule. A mutual prodrug consists of two pharmacologically active agents coupled together so that each acts as a promoiety for the other agent and vice versa. Mutual prodrug design is really no different from the general drug discovery process, in which a unique substance is observed to have desirable pharmacological effects, and studies of its properties lead to the design of better drugs. It is a very fruitful area of research, and its introduction in human therapy has given successful results in improving the clinical and therapeutic effectiveness of drugs suffering from some undesirable properties that otherwise hinder their clinical usefulness. The present article takes a review of various applications of mutual prodrugs and the developments in this field during the last few decades.

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In the present investigation, an attempt has been made to increase therapeutic efficacy, reduce frequency of administration, and improve patient compliance, by developing sustained release matrix tablets of diclofenac sodium. Sustained release matrix tablets of diclofenac sodium, were developed by using different drug: polymer ratios, such as F1 (1:0.12), F2 (1:0.16), F3 (1:0.20), F4 (1:0.24) and F5 (1:0.28). Xanthan gum was used as matrix former, and microcrystalline cellulose as diluent. All the lubricated formulations were compressed using 8 mm flat faced punches. Compressed tablets were evaluated for uniformity of weight, content of active ingredient, friability, hardness, thickness, in vitro dissolution using basket method, and swelling index. All the formulations showed compliance with pharmacopoeial standards. Among different formulations, F1 showed sustained release of drug for 12 hours with 89.67% release. The effect of other parameters like addition of release modifier (PEG 6000), gum concentration, pH of dissolution medium, rotation speed and dissolution by paddle method, were also studied. Selected formulation (F1) was subjected to stability studies for three months at 0-4°, room temperature (28°), and 45° with RH 75±5%, and showed stability with respect to release pattern. The kinetic treatment showed that the release of drug follows zero order kinetic (R ² = 0.9758). Korsmeyer and Peppas equation gave value of n = 0.9409 which was close to one, indicating that the drug was released by zero order kinetic. Thus, Xanthan gum can be used as an effective matrix former, to extend the release of diclofenac sodium.

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Asthma is an inflammatory disorder that results in the obstruction of air pathways and causes difficulty in breathing. Amongst the currently available means of treatment, oral dosage forms are associated with lag time and delayed onset of action. However, aerosols and parenterals have rapid onset of action but strongly affect patient compliance. Thus, an attempt was made to improve the onset of action of bronchodilator used commonly in the treatment of asthma. Fast dissolving tablets of salbutamol sulphate were prepared using sublimable ingredients. Selection of the filler also had an important role in deciding the disintegration time. Evaluation of the tablets showed that all the tablets were found to be within official limits and the disintegration time for the formulations ranged from 5 s to 40 s. Amongst all, the formulation containing microcrystalline cellulose and ammonium bicarbonate showed the least disintegration time of 5 s.

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The plethora of drug therapies and types of drugs demand different formulations, fabrications conditions and release kinetics. No single polymer can satisfy all the requirements. Therefore there have been tremendous advances in area of biodegradable copolymers over the last 30 years. This article reviews current research on biodegradable polymers, focusing their potential as drug carries. The major classes of polymers are briefly discussed with regard to synthesis, properties and biodegradability, and known degradation modes and products are indicated based on studies reported in the literature. A vast majority of biodegradable polymers studied belongs to the polyester family, which includes polyglycolides and polylactides. Other degradable polymers such as polyorthoesters, polyanhydrides and polyphosphazenes are also discussed and their advantages and disadvantages are summarized.

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The human immunodeficiency virus has been shown to be the causative agent for acquired immunodeficiency syndrome (AIDS). The human immunodeficiency virus encodes for unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors act by preventing the formation of functional proteins from precursor proteins, which are vital for production of mature infectious viral particles. This review summarizes the data documenting the pharmacology and chemistry of non-peptide protease inhibitors that may be used as therapeutic agents against the human immunodeficiency virus infection. These agents are structural mimics of peptides with little or no peptidic character, thus overcoming various pharmacological problems of peptidic protease inhibitors. Structure-based drug designs of potent protease inhibitors, discovered through broad screening, have been developed into various clinical candidates for the treatment of AIDS. Non-peptide protease inhibitors could provide a useful model in the further search for novel compounds with even more pertinent pharmacological and pharmacokinetic profiles.

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Mitochondrial sodium calcium exchange inhibitors are novel agents in the treatment of type-II diabetes due to their glucose dependent efficacy. While the compounds of this class are expected to correct hyperglycemia, they do not lower basal blood glucose level, thus avoiding the serious consequences of hypoglycemia. The 3DQSAR analysis of benzothiazepines and their derivatives as mitochondrial sodium calcium exchange inhibitors was performed by comparative molecular field analysis to determine the structural factors required for the activity of these compounds. After performing a leave one out cross validation study, satisfactory results were obtained, with cross-validated q ² and conventional r ² values of 0.711 and 0.970, respectively. The results provided the tools for predicting the affinity of the related compounds, and guidance for the designing and synthesis of novel and potent mitochondrial sodium calcium exchange inhibitors as antidiabetic agents.

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The small and simple benzothiazole nucleus is present in compounds involved in research aimed at evaluating new products that possess interesting biological activities, such as antitumor, antimicrobial, anthelmintic, antileishmanial, anticonvulsant and antiinflammatory. The present review focuses on the benzothiazoles with potential activities that are now in development.

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Aceclofenac, a non-steroidal antiinflammatory drug, is used for posttraumatic pain and rheumatoid arthritis. Aceclofenac fast-dispersible tablets have been prepared by direct compression method. Effect of superdisintegrants (such as, croscarmellose sodium, sodium starch glycolate and crospovidone) on wetting time, disintegration time, drug content, in vitro release and stability parameters has been studied. Disintegration time and dissolution parameters (t _50% and t _80% ) decreased with increase in the level of croscarmellose sodium. Where as, disintegration time and dissolution parameters increased with increase in the level of sodium starch glycolate in tablets. However, the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium. Stability studies indicated that tablets containing superdisintegrants were sensitive to high humidity conditions. It is concluded that fast-dispersible aceclofenac tablets could be prepared by direct compression using superdisintegrants.

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DNA triple helices offer new perspectives towards oligonucleotide-directed gene regulation. Triple helix forming oligonucleotides, which bind to double-stranded DNA, are of special interest since they are targeted to the gene itself rather than to its mRNA product (as in the antisense strategy). However, the poor stability of some of these structures might limit their use under physiological conditions. Specific ligands can intercalate into DNA triple helices and stabilize them. This review summarizes recent advances in this field while also highlighting major obstacles that remain to be overcome, before the application of triplex technology to therapeutic gene repair can be achieved.

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For most patients with type 1 diabetes, the worst part of the disease is to tolerate needle after needle, both for glucose measurement and to deliver insulin. In the last two decades, concept of insulin therapy by multiple-dose injection has undergone a miraculous change. Needle-free insulin delivery appeared to be a wonderful approach, and its allure rested in being comfortable and safe. In today's era, insulin delivery by alternative route is a topic of current interest in the design of drug delivery system. Major global pharmaceutical companies are showing encouraging progress in their attempts to develop alternative insulin delivery technologies. Many such drug delivery systems have been developed for oral, buccal and nasal route. This review article discusses, in brief, the novel and emerging technologies that are in pipeline, including insulin inhalers, insulin spray, insulin pill, insulin analogues, insulin complement, islet cell transplant, implantable insulin pumps and guardian continuous glucose monitoring system.

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Treating central nervous system diseases is very challenging because of the presence of a variety of formidable obstacles that impede drug delivery. Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid barrier as well as various efflux transporter proteins make the entry of drugs into the central nervous system very difficult. The present review provides a brief account of the blood brain barrier, the P-glycoprotein efflux and various strategies for enhancing drug delivery to the central nervous system.

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Till recent, injections remained the most common means for administering therapeutic proteins and peptides because of their poor oral bioavailability. However, oral route would be preferred to any other route because of its high levels of patient acceptance and long term compliance, which increases the therapeutic value of the drug. Designing and formulating a polypeptide drug delivery through the gastro intestinal tract has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size. The main challenge is to improve the oral bioavailability from less than 1% to at least 30-50%. Consequently, efforts have intensified over the past few decades, where every oral dosage form used for the conventional small molecule drugs has been used to explore oral protein and peptide delivery. Various strategies currently under investigation include chemical modification, formulation vehicles and use of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. This review summarizes different pharmaceutical approaches which overcome various physiological barriers that help to improve oral bioavailability that ultimately achieve formulation goals for oral delivery.

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The ability to deliver therapeutic agents to a patient in a pulsatile or staggered release profile has been a major goal in drug delivery research recently. This review will cover methods that have been developed to control drug delivery profile with different polymeric systems. Externally and internally controlled systems will be considered, including a range of technologies like preprogrammed systems as well as systems that are sensitive to modulated enzymatic or hydrolytic degradation, pH, magnetic fields, ultrasounds, electric fields, temperature, light and mechanical stimulation. These systems have the potential to improve the quality of life for patients undergoing therapy with a variable dosing regime.

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Microspheres of diltiazem hydrochloride were formulated using combination of polyethylene glycol 6000 and Eudragit RS 100 and Eudragit RS 100 alone by solvent evaporation and non-solvent addition methods with an aim to prolong its release. Six formulations prepared by using different drug to polymer ratios, were evaluated for relevant parameters and compared with marketed SR capsules. Depending upon the drug to polymer ratio, the entrapment, loading and encapsulation were found to range between 77.45±0.22 to 91.08±0.62% , 34.76±0.15 to 52.46±0.25% and 66.09±0.19 to 82.7 ±0.57%, respectively. The microspheres were spherical, discrete and compact and size distribution was between 4 to 24 µm. In vitro studies were carried out at different pH for a period of 12 h and compared with marketed formulation. As similarity factor f2 was 92.8 for FVI, it was subjected to further study. Formulations prepared using the combination of the retardants exhibited first order of drug release and zero order for preparations containing Eudragit RS 100 alone. The analysis of regression values of Higuchi plot and Korsmeyer-Peppas plot and "n" values of Korsmeyer-Peppas model suggested a combination of diffusional and dissolutional mechanism indicating the drug release from the formulations was controlled by more than one process. Drug polymer interaction was absent as evidenced by FT-IR and DSC thermograms. In vivo pharmacokinetic study of the formulation proved that prolongation of drug release was obtained by formulating as microspheres.

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The present research paper introduces Indion 414, an ion exchange resin, as a new superdisintegrant for pharmaceutical dosage forms. Indion 414 is a pharmaceutical grade weak acid cation exchange resin. Model drugs belonging to various classes were taste masked and formulated into palatable mouth dissolve tablets. Experiments were carried out to evaluate the disintegrant property of Indion 414 by incorporating Indion 414 in fast disintegrating dosage form like mouth dissolve tablets. Indion 414 was compared with the conventional disintegrants to determine its relative efficacy.

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Ever since their experimental discovery in 1985, fullerenes have attracted considerable attention in different fields of sciences. Investigations of chemical, physical and biological properties of fullerenes have yielded promising information. Their unique carbon cage structure coupled with immense scope for derivatization makes fullerenes a potential therapeutic agent. Henceforth various potential therapeutic applications of fullerenes have been reviewed in the present paper. These include antiHIV- protease activity, photodynamic DNA cleavage, free radical scavenger, antimicrobial action and use of fullerenes as diagnostic agents.

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The main purpose of this research was to study the mechanism of drug release from solid dispersions of albendazole, giving special emphasis to particle size of the drug in solid dispersions. Solid dispersions were prepared using three different carriers, mixing ratios and methods in an attempt to improve the solubility and dissolution rate of albendazole. The mechanism of enhanced dissolution was investigated by a novel dissolution technique as an adjunct to phase solubility study, wettability test, differential scanning calorimetry, X-ray diffractometry, infrared spectroscopy and scanning electron microscopy. The solubility of albendazole was greater with albendazole-poloxamer 407 system, while polyethylene glycol dispersions showed predominant wettability. Physical mixtures showed enhanced dissolution compared with the pure drug, due to improved wetting and solubilization of drug in the diffusion layer offering carrier-rich microenvironment. Preparation of solid dispersion further improved the dissolution compared to the physical mixture, owing to increased surface area for mass transfer, thermodynamically enhanced dissolution of a higher energy amorphous form from the carrier, in addition to improved wetting and solubilization. All carriers showed comparable degree of drug particle size reduction, whereas mixing ratio and method of preparation substantially affected the particle size. Intermolecular association of drug with the carrier led to inhibition of drug recrystallization.

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