Biomedical subjects

V R Sinha

Publications and source records attributed to V R Sinha.

At least 19 recordsLinked to original sources

PubMed2005

Complexation of celecoxib with beta-cyclodextrin: characterization of the interaction in solution and in solid state.

Inclusion complexation between celecoxib, a specific cyclooxygenase II inhibitor, and beta-cyclodextrin (beta-CD) was studied in solution and solid state. Drug cyclodextrin complexes were prepared by spray drying while physical mixtures were obtained by simple blending. Inclusion complexes were characterized by nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), and polarimetry. Phase solubility analysis was carried out to determine the stability constant. Solubility studies revealed the existence of a 1:1 complex between celecoxib and beta-CD. NMR studies suggested a strong interaction between celecoxib and beta-CD prepared by spray drying. XRD and SEM analysis illustrated that celecoxib existed as an amorphous complexed form in spray-dried complexes. Dissolution studies showed that the celecoxib entrapped in spray-dried complexes dissolved much faster than the uncomplexed drug and physical mixtures. The data obtained suggest that celecoxib forms an inclusion complex with beta-CD in solution and solid state, which was confirmed by various analytical techniques. A shorter t50% of dissolution is found for the formulation prepared by spray drying when compared on a weight basis in a USP II apparatus.

Calorimetry, Differential Scanning↗

PubMed2005

Biodegradable microspheres for parenteral delivery.

Nowadays, emphasis is being laid to development of controlled release dosage forms. Interest in this technology has increased steadily over the past few years. Although oral administration of drugs is a widely accepted route of drug delivery, bioavailability of drug often varies as a result of gastrointestinal absorption, degradation by first-pass effect, and hostile environment of gastrointestinal tract. Transdermal administration for percutaneous absorption of drug is limited by the impermeable nature of the stratum corneum. Ocular and nasal delivery is also unfavorable because of degradation by enzymes present in eye tissues and nasal mucosa. Hence, the parenteral route is the most viable approach in such cases. Of the various ways of achieving long-term parenteral drug delivery, biodegradable microspheres are one of the better means of controlling the release of drug over a long time. Because of the lipidic nature of liposomes, problems such as limited physical stability and difficulty of freeze-drying are encountered. Similarly, for emulsions, stability on long-term basis and in suspensions, rheological changes during filling, injecting, and storage poses limitation. Also, in all these systems, the release rate cannot be tailored to the needs of the patient. Parenteral controlled-release formulations based on biodegradable microspheres can overcome these problems and can control the release of drug over a predetermined time span, usually in the order of days to weeks to months. Various FDA-approved controlled-release parenteral formulations based on these biodegradable microspheres are available on the market, including Lupron Depot Nutropin Depot and Zoladex. This review covers various molecules encapsulated in biodegradable microspheres for parenteral delivery.

Biodegradation, Environmental↗

PubMed2005

Influence of formulation and excipient variables on the pellet properties prepared by extrusion spheronization.

Four commercial grades of microcrystalline cellulose, Avicel PH 101, Avicel PH 102, Avicel PH 112 and Avicel PH 302 were compared for extrusion spheronization. Model mixes containing Avicel PH 101 with different proportions of fillers like lactose and dicalcium phosphate dihydrate (DCPD) were also compared to observe the influence of these fillers on the pellet properties. The amount of water used for granulation of Avicel/ Avicel mixes was kept constant so as to evaluate and quantitate the influence of these excipients/fillers on the pellet properties. The various pellet properties evaluated included, drug release, size and size distribution, shape, density, friability and flow. Mean pellet diameter did not vary among the Avicel grades. Pellets prepared with different proportions of Avicel PH 101 and lactose were more or less similar in mean diameter. The same phenomena were observed in case of DCPD as well. Plain lactose pellets were the largest in size. Therefore, it can be inferred that the presence of Avicel suppressed the change in pellet size. Circularity was found to be significantly linear function of log of bulk density of Avicel powders. As revealed by the SEM photographs, pellets of Avicel PH 101 were fairly round where as those containing Avicel PH 302 were dumbbell shaped. Formulations containing DCPD showed the highest circularity. Drug release rate varied in all the formulations. Among the Avicel grades, Avicel PH 302 showed the highest drug release rate where as Avicel PH 101 showed the least. Drug release also varied as a function of the type of filler and their proportion in the pellets. For both the fillers, the drug release increased with an increase in their proportion. Less water was required for formulations containing higher amounts of lactose and DCPD. Plain DCPD failed to spheronize, although pellets of plain lactose could be formed at the investigated level of water.

Cellulose↗

PubMed2004

In vivo evaluation of time and site of disintegration of polysaccharide tablet prepared for colon-specific drug delivery.

Compression coating has been found to be useful for colonic drug delivery. The aim of the present investigation was to evaluate a formulation with a considerably reduced coat weight and gum concentration for colonic drug delivery in vivo using gamma scintigraphy. In vitro studies have found this formulation to be useful for delivery of 5-fluorouracil to the colon. Rapidly disintegrating core tablets containing (99m)Tc-DTPA were prepared and compression coating with 150 mg of granules containing a mixture of xanthan (XG), guar gum (GG) and starch. The ratios of the two gums XG:GG in the coat was kept 10:20. In vitro dissolution studies on XG:GG::10:20 tablets containing (99m)Tc-DTPA were carried out in simulated upper GIT conditions and also in presence of colonic contents. Cumulative percent release of technetium in the upper GIT conditions and transit time amounted to 4%. The total amount of technetium released in the 24 h of the dissolution study was 53+/-3.23%. Upon introduction of cecal content into the dissolution medium (4%), the release of technetium from the compression-coated tablet increased to 78.34+/-5.34%. Gamma scintigraphy studies carried out in six healthy human volunteers showed that the tablet remained intact during its transit through the upper GIT. The anatomical site of disintegration was found to be the ascending colon/hepatic flexure and the disintegration of the tablet started between 4 and 6 h post-dose in all the volunteers with a further spread of tracer into the ascending, transverse, descending and sigmoidal colon.

Adult↗

PubMed2004

Poly-epsilon-caprolactone microspheres and nanospheres: an overview.

Poly-epsilon-caprolactone (PCL) is a biodegradable, biocompatible and semicrystalline polymer having a very low glass transition temperature. Due to its slow degradation, PCL is ideally suitable for long-term delivery extending over a period of more than one year. This has led to its application in the preparation of different delivery systems in the form of microspheres, nanospheres and implants. Various categories of drugs have been encapsulated in PCL for targeted drug delivery and for controlled drug release. Microspheres of PCL either alone or of PCL copolymers have been prepared to obtain the drug release characteristics. This article reviews the advancements made in PCL-based microspheres and nanospheres with special reference to the method of preparation of these and their suitability in developing effective delivery systems.

Animals↗

PubMed2004

Chitosan microspheres as a potential carrier for drugs.

Chitosan is a biodegradable natural polymer with great potential for pharmaceutical applications due to its biocompatibility, high charge density, non-toxicity and mucoadhesion. It has been shown that it not only improves the dissolution of poorly soluble drugs but also exerts a significant effect on fat metabolism in the body. Gel formation can be obtained by interactions of chitosans with low molecular counterions such as polyphosphates, sulphates and crosslinking with glutaraldehyde. This gelling property of chitosan allows a wide range of applications such as coating of pharmaceuticals and food products, gel entrapment of biochemicals, plant embryo, whole cells, microorganism and algae. This review is an insight into the exploitation of the various properties of chitosan to microencapsulate drugs. Various techniques used for preparing chitosan microspheres and evaluation of these microspheres have also been reviewed. This review also includes the factors that affect the entrapment efficiency and release kinetics of drugs from chitosan microspheres.

Animals↗

PubMed2004

Colonic drug delivery of 5-fluorouracil: an in vitro evaluation.

Compression coating has been found to be useful for colonic drug delivery. The aim of the present investigation was to design a formulation with a considerably reduced coat weight and gum concentration for colonic delivery of 5-fluorouracil for the treatment of colorectal cancer. Rapidly disintegrating core tablets containing 50 mg of 5-fluorouracil were prepared and compression coating with 175 mg of granules containing a mixture of xanthan gum (XG) and guar gum (GG) in varying proportions was done. With this coat weight, a highly retarded drug release was observed. After 24h of dissolution the mean percent drug release from the compression coated XG:GG 20:20, 20:10 and 10:20 tablets were found to be around 18+/-1.23%, 20+/-1.54% and 30+/-1.77%, respectively. So, the coat weight was further reduced to 150 mg. It was observed that reduction of coat weight did not affect the initial drug release rate in simulated upper gastrointestinal tract (GIT) conditions. At the end of 24h of dissolution the amount of drug released increased to 25+/-1.22%, 36.6+/-1.89% and 42.6+/-2.22%, respectively in XG:GG 20:20, 20:10 and 10:20 tablets. Studies of XG:GG (10:20) tablets in presence of colonic contents showed an increased cumulative percent drug release of 67.2+/-5.23% in presence of 2% cecal content and 80.34+/-3.89% in presence of 4% cecal content after 19 h of incubation.

Administration, Oral↗

PubMed2004

Polysaccharide matrices for microbially triggered drug delivery to the colon.

Matrix tablets were prepared using xanthan gum (XG) and guar gum (GG) in varying proportions, and the suitability of the prepared tablets was evaluated for colon specific drug delivery. Indomethacin was used as a model drug. The ability of the prepared matrices to retard drug release in the upper gastrointestinal tract (GIT) and to undergo enzymatic hydrolysis by the colonic bacteria was evaluated. For this, drug release studies were carried out in the presence of rat cecal content. Further cecal content of rats with induced enzymatic activity were used. To ascertain the role of bacterial flora in carrying out the hydrolysis of the tablet, cecal content of rats treated with antibiotics were used in the dissolution media. Presence of XG in combination with GG in the tablets could retard drug release in the conditions of the upper GIT. However, the presence of GG and starch made these matrices microbially degradable. Guar gum alone as a drug release-retarding excipient in the matrices does not achieve the desired retardation. Presence of XG in the tablets not only retards the initial drug release from the tablets, but due to high swelling, makes them more vulnerable to digestion by the microbial enzymes in the colon.

Animals↗

PubMed2004

Radioactive microspheres in therapeutics.

Microspheres as a drug delivery system hold great promise in reaching the goal of controlled drug delivery as well as site specific delivery. In the last few decades, scientific and technological advancements have been made in the research and development of radiolabeled microspheres. These are used successfully for the treatment of various cancers and tumors. Since response to chemotherapy and external radiotherapy is not so effective and hazardous too, so an alternative to this is internal radiation therapy. These radiolabeled microspheres are very stable and have a proven efficacy in the field of primary as well as metastatic cancers. Radioactive microspheres can be selectively targeted to various tumors without undue radiation to the nontumorous tissues. The radioactive microspheres are injected to halt tumor growth via the blood supply, thereby enabling surgical removal once the tumor size decreases. This review provides an outlook to various aspects of radioactive microspheres and their role in treatment of various tumors and cancers.

Albumins↗

PubMed2003

Biodegradable microspheres for protein delivery.

In a very short time, since their emergence, the field of controlled delivery of proteins has grown immensely. Because of their relatively large size, they have low transdermal bioavailabilities. Oral bioavailability is generally poor since they are poorly absorbed and easily degraded by proteolytic enzymes in the gastrointestinal tract. Ocular and nasal delivery is also unfavorable due to degradation by enzymes present in eye tissues and nasal mucosa. Thus parenteral delivery is currently most demanding and suitable for delivery of such molecules. In systemic delivery of proteins, biodegradable microspheres as parenteral depot formulation occupy an important place because of several aspects like protection of sensitive proteins from degradation, prolonged or modified release, pulsatile release patterns. The main objective in developing controlled release protein injectables is avoidance of regular invasive doses which in turn provide patient compliance, comfort as well as control over blood levels. This review presents the outstanding contributions in field of biodegradable microspheres as protein delivery systems, their methods of preparation, drug release, stability, interaction with immune system and regulatory considerations.

Biodegradation, Environmental↗

PubMed2003

Microbially triggered drug delivery to the colon.

Increasing acceptance of protein- and peptide-based drugs necessitates an investigation into the suitability of various sites for their administration. Colon is being investigated for delivery of such molecules. Colon-specific drug delivery is designed to target drug molecules specifically to this area. Development of site-specific delivery systems may exploit a specific property of the target site for drug activation/release. The gastrointestinal tract is inhabited by over 400 bacterial species, each having a specific niche in the tract. Colon, the distal part of the intestine is inhabited by a large variety of gram negative microflora. This flora produces a vast number of enzymes which are being exploited for formulation of colon-specific drug delivery systems. A number of microbially activated systems for colon-specific drug delivery are being evaluated. These include prodrugs and synthetic or natural polymer-based delivery systems. This article aims at reviewing the various microbially activated drug delivery systems for colon-specific drug delivery with specific reference to the microflora of the various segments of the gastrointestinal tract and their role in targeting drug delivery to the colon.

Administration, Oral↗

PubMed2003

Diagnostic microspheres: an overview.

Diagnostic methods have become increasingly complex and frequently involve the use of agents that must meet the same approval criteria as drugs. The search for diagnostic contrast agents has spread from X-ray to other imaging modalities, especially to magnetic resonance imaging (MRI) and ultrasound. A wide variety of methods have been used to develop microencapsulated agents, from liposomal entrapment to use of biodegradable polymers. Various scientific and technological advancements have been made in the research and development of diagnostic microspheres. Diagnostic microspheres can be used to understand the human body functions in both healthy and sick people. For example, they allow the detection of malignancies vs. benign tissue changes. Diagnostic microspheres give useful clinical information for various diseases, are very stable, and have proven efficacy in the quantitative measurement of blood flow to an organ. This review discusses various aspects of diagnostic microspheres, such as the choice of contrast agents and radioactive molecules, and their applications in blood flow measurements and organ imaging.

Animals↗

PubMed2002

Binders for colon specific drug delivery: an in vitro evaluation.

The aim of the present study was to develop a single unit, site-specific drug formulation allowing targeted drug release in the colon. Tablets were prepared using polysaccharides or synthetic polymer as binders. These included xanthan gum, guar gum, chitosan and Eudragit E. Indomethacin was used as a model drug. The prepared tablets were enteric coated with Eudragit-L 100 to give protection in the stomach. The coated tablets were tested in-vitro for their suitability as colon specific drug delivery systems. The drug release studies were carried out in simulated stomach environment (pH 1.2) for 2 h followed by small intestinal environment at pH 6.8. The dissolution data obtained from tablets demonstrates that the dissolution rate of the tablet is dependent upon the type and concentration of polysaccharide/polymer used as binder. The results demonstrate that enteric coated tablets containing 3% chitosan as a binder, showed only 12.5% drug release in the first 5 h, which is the usual upper gastrointestinal transit time, whereas, tablets prepared using guar gum as binder, were unable to protect drug release under similar conditions. Preparations with xanthan gum as a binder formed time-dependent release formulations. When used in a concentration of 5.92% in the tablets, 28% drug release was observed in the usual upper gastrointestinal tract conditions. It was also found that enteric coated preparation formulated with 8.88% of Eudragit E as binder could be used to carry water insoluble drug molecules to the colon especially in IBD. The above study shows that chitosan could be successfully used as a binder, for colon targeting of water insoluble drugs in preference to guar gum when used in the same concentration. Additionally, formulations developed with chitosan and Eudragit E would be highly site specific since drug release would be at a retarded rate till microbial degradation or polymer solubilization takes place in the colon.

Chemistry, Pharmaceutical↗

PubMed2001

Polysaccharides in colon-specific drug delivery.

Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

Administration, Oral↗

PubMed2001

Colonic drug delivery: prodrug approach.

The colon is largely being investigated as a site for administration of protein and peptides, which are degraded by digestive enzymes in the upper GIT. Also for local diseases of the colon, drug administration to the site of action can not only reduce the dose to be administered, but also decrease the side effects. One of the approaches used for colon specific drug delivery is the formation of a prodrug which optimizes drug delivery and improves drug efficacy. Many prodrugs have been evaluated for colon drug delivery. These prodrugs are designed to pass intact and unabsorbed from the upper GIT and undergo biotransformation in the colon releasing the active drug molecule. This biotransformation is carried out by a variety of enzymes, mainly of bacterial origin present in the colon (e.g. azoreductase, glucuronidase, glycosidase, dextranase, esterase, nitroreductase, cyclodextranase, etc.). The present review includes varius prodrug approaches investigated for colon drug delivery and their site specificity.

Animals↗

PubMed2000

Permeation enhancers for transdermal drug delivery.

The transdermal route has been recognized as one of the highly potential routes of systemic drug delivery and provides the advantage of avoidance of the first-pass effect, ease of use and withdrawal (in case of side effects), and better patient compliance. However, the major limitation of this route is the difficulty of permeation of drug through the skin. Studies have been carried out to find safe and suitable permeation enhancers to promote the percutaneous absorption of a number of drugs. The present review includes the classification of permeation enhancers and their mechanism of action; thus, it will help in the selection of a suitable enhancer(s) for improving the transdermal permeation of poorly absorbed drugs.

Administration, Cutaneous↗

PubMed1999

Novel oral colon-specific drug delivery systems for pharmacotherapy of peptide and nonpeptide drugs.

The increasing number of peptide and protein drugs being investigated demands the development of dosage forms which exhibit site-specific release. Delivery of drugs into systemic circulation through colonic absorption represents a novel mode of introducing peptide and protein drug molecules and drugs that are poorly absorbed from the upper gastrointestinal (GI) tract. Oral colon-specific drug delivery systems offer obvious advantages over parenteral administration. Colon targeting is naturally of value for the topical treatment of diseases of the colon such as Crohn's disease, ulcerative colitis and colorectal cancer. Sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Peptides, proteins, oligonucleotides and vaccines are the potential candidates of interest for colon-specific drug delivery. Sulfasalazine, ipsalazide and olsalazine have been developed as colon-specific delivery systems for the treatment of inflammatory bowel disease (IBD). The vast microflora and distinct enzymes present in the colon are being increasingly exploited to release drugs in the colon. Although the large intestine is a potential site for absorption of drugs, some difficulties are involved in the effective local delivery of drugs to the colon bypassing the stomach and small intestine. Furthermore, differential pH conditions and long transit time during the passage of drug formulations from mouth to colon create numerous technical difficulties in the safe delivery of drugs to the colon. However, recent developments in pharmaceutical technology, including coating drugs with pH-sensitive and bacterial degradable polymers, embedding in bacterial degradable matrices and designing into prodrugs, have provided renewed hope to effectively target drugs to the colon. The use of pH changes is analogous to the more common enteric coating and consists of employing a polymer with an appropriate pH solubility profile. The concept of using pH as a trigger to release a drug in the colon is based on the pH conditions that vary continuously down the GI tract. Polysaccharide and azopolymer coating, which is refractory in the stomach and small intestine yet degraded by the colonic bacteria, have been used as carriers for colon-specific targeting. Finally, the availability of optimal preclinical models and clinical methods fueled the rapid development and evaluation of colon-specific drug delivery systems for clinical use. Future studies may hopefully lead to further refinements in the technology of colon-specific drug delivery systems and improve the pharmacotherapy of peptide drugs.

Journal Article↗

PubMed1998

Bioabsorbable polymers for implantable therapeutic systems.

For a long time, subcutaneous implantable drug pellets using nondegradable polymers have been used for long-term, continuous drug administration. The procedure requires surgical implantation and removal of the drug-containing devices or polymeric matrices, which has a significant negative impact on the acceptability of the product candidate. In addition, the release profile from such devices is neither constant nor readily controlled in terms of precision of rate of release and duration of action. These facts have led to the research and development of novel, controllable, nonirritating, noncarcinogenic, biocompatible, and bioabsorbable drug delivery systems for overcoming the drawbacks of nondegradable implantable pellets for prolonged continuous release. Biodegradable implantable systems release the drug over a long period of time with simultaneous or subsequent degradation in the tissue of the polymer to harmless constituents, thus avoiding removal once the therapy is complete. This approach has considerably improved patient acceptability and patient compliance. Various bioabsorbable polymers have been evaluated for controlled implantable drug delivery, including hydrogels, copolymers of polylactic and polyglycolic acids, polylactic acid, poly(orthoesters), polyanhydrides, poly(E-caprolactone), and polyurethanes. Their characteristics have been studied using a variety of drugs, like anticancer agents, hormone agonists and antagonists, nonsteroidal anti-inflammatory agents, neuroleptics, contraceptives, and others. The present paper describes the current research on implantable therapeutic systems, the bioabsorbable polymers, and the biologically active agents being used in this approach.

Absorption↗