Synthetic Excipients Research Articles

Moringa oleifera as a multifunctional excipient: Transforming pharmaceutical drug delivery

Moringa oleifera, a multifaceted plant species indigenous to tropical and subtropical climates, has garnered considerable interest in the pharmaceutical sector as a natural excipient. This abstract examines the significance of Moringa oleifera in pharmaceutical formulations, emphasizing its ability to tackle critical difficulties in medication transport and formulation. The plant's many components, such as leaves, seeds, and bark, possess bioactive chemicals with distinct characteristics that render them appropriate for use as excipients. These features include binding, disintegration, film formation, as well as antioxidant and antibacterial activity. The use of excipients generated from Moringa oleifera has several benefits, including increased bioavailability, greater stability, and less toxicity in pharmaceutical formulations. Moreover, the plant's extensive availability, economic viability, and environmentally sustainable characteristics make it a compelling substitute for synthetic excipients. This study consolidates contemporary research on the uses of Moringa oleifera in pharmaceutical formulations, examining its potential to transform drug delivery methods and aid in the creation of more sustainable and effective treatments. The results highlight the need for more research into the pharmaceutical uses of Moringa oleifera, facilitating the development of novel medication formulations and enhanced patient outcomes.

Systematic Review of Plant-Based Excipients in Topical Drug Delivery

AbstractThis review explores the use of plant-based excipients in topical drug delivery. The review examines the advantages and challenges of using plant-based excipients, as well as case studies that demonstrate their effectiveness in delivering drugs through the skin. The review also discusses future perspectives on the use of plant-based excipients, including the potential for developing new formulations and improving drug delivery efficiency. The findings of this review suggest that plant-based excipients have significant potential in topical drug delivery and could offer a more sustainable and natural alternative to synthetic excipients. Overall, this review provides valuable insights for researchers and practitioners in the pharmaceutical industry who are interested in developing new and innovative drug delivery systems.

Sustainable Alternatives to Petroleum-Derived Excipients in Pharmaceutical Oil-in-Water Creams.

Recently, vast efforts towards sustainability have been made in the pharmaceutical industry. In conventional oil-in-water (O/W) cream formulations, various petroleum-based excipients, namely mineral oil and petrolatum, are commonly used. Natural or synthetic excipients, derived from vegetable sources, were explored as alternatives to petroleum-based excipients in prototype topical creams, with 1% (w/w) lidocaine. A conventional cream comprised of petroleum-derived excipients was compared to creams containing sustainable excipients in terms of key quality and performance attributes, physicochemical properties, and formulation performance. The petrolatum-based control formulation had the highest viscosity of 248.0 Pa·s, a melting point of 42.7°C, a low separation index at 25°C of 0.031, and an IVRT flux of 52.9 µg/cm2/h. Formulation SUS-4 was the least viscous formulation at 86.9 Pa·s, hadthe lowest melting point of 33.6°C, the highest separation index of 0.120, and the highest IVRT flux of 139.4 µg/cm2/h. Alternatively, SUS-5 had a higher viscosity of 131.3 Pa·s, a melting point of 43.6°C, a low separation index of 0.046, and the lowest IVRT flux of 25.2 µg/cm2/h. The cumulative drug permeation after 12 h from SUS-4, SUS-5, and the control were 126.2 µg/cm2, 113.8 µg/cm2, and 108.1 µg/cm2, respectively. The composition of the oil-in-water creams had influence on physicochemical properties and drug release; however, skin permeation was not impacted. Sustainable natural or synthetic excipients in topical cream formulations were found to be suitable alternatives to petroleum-based excipients with comparable key quality attributes and performance attributes and should be considered during formulation development.

Polysaccharides Obtained from Vegetables: an effective source of alternative excipient.

Polymers are the major constructive material of pharmaceutical formulations that play a prime role in designing effective drug-delivery systems and releasing drugs at their sites of application. Polymers are composed of multiple repeating units of high molecular mass components with attendant properties. Most synthetic polymers are non-biocompatible, expensive, and extremely inclined to deliver adverse impacts. Meanwhile, edible polymers obtained from natural sources have gained remarkable recognition for their promising use in modern medicine. Moreover, polymers derived from natural sources are generally preferred due to certain of their unique features such as abundant availability, biocompatibility, nontoxicity, economical, safe, and effective functions that fit the purpose. Polysaccharides including starch, cellulose, hemicellulose, pectin, and mucilage are identified as a major class of naturally obtained molecules that have a substantial role as functional polymers. This review summarizes the potential role of polysaccharides derived from vegetable sources such as adhesives, anticaking agents, binders, disintegrants, emulsifiers, film-framing agents, and thickeners. This is simply an opportunity to abandon synthetic excipients that hurt our bodies and think back to nature from where we originate.

AN OVERVIEW ON PHARMACEUTICAL EXCIPIENTS- THEIR ROLES AND APPLICATIONS

Excipients play an important role in formulating a dosage form. These are the ingredients which along with Active Pharmaceutical Ingredients make up the dosage forms. Excipients act as protective agents, bulking agents and can also be used to improve bioavailability of drugs in some instances; the following review discusses the various types of excipients along with their uses. The objective of this paper is to indicate the ingredients that possess health effect that can be found in cosmetics and personal care products. The related paper was reviewed in terms of the chemicals that commonly identified in the cosmetic and personal care product. This paper also highlighted the health risk possesses by such ingredients in the products. As we know that dosage form is a combination of active pharmaceutical ingredient (API) and excipients therefore it is clear that any pharmaceutical dosage forms cannot be formulated without the use of excipients. Excipients are the major part of formulation. They do not show any adverse effect but promotes the therapeutic activity of pharmaceutical product. Synthetic excipients have some toxic properties so the uses of natural excipients are coming in the picture. This review shows the uses of natural excipients in modern time and in medicinal sciences.

A Metronidazole-Modeled Central Composite Design Strategy for Plantago ovata Seed Mucilage-Supported Floating Microspheres for Helicobacter pylori Eradication

Background of the research and the purpose: Instead of using costly synthetic excipients or polymers, the authors were in search of an economical, easily available, and plant-based excipient for making microspheres. Plantago ovata seeds have already been proven to have anti-ulcer and gastro-protective activity. The same mucilage is used in this study as a polymer that can aid in floating the microspheres. In this study, mucilage from Plantago ovata seeds was added to sodium alginate and used with Metronidazole as a treatment to eradicate Helicobacter pylori. Methodology: Plantago ovata seed mucilage (POSM) and sodium alginate were used to make microspheres. To check the effects of independent variables (POSM and SA levels) on entrapment efficiency (EE) and floating time (FT) as responses, this paper used a central composite design with a design expert.11 software. The microspheres were investigated for Metronidazole (MNZ) content, size, yield, buoyancy, and release during congeniality studies. Results: As POSM content increased in the microspheres, MNZ entrapment increased, and the floating time (FT) was greater in microspheres with more POSM. MNZ release was slightly reduced in microspheres with higher levels of POSM. Conclusion: According to the investigation, MNZ can be retained in the stomach for extended periods of time in order to eradicate H. pylori, and the floating assets were enhanced by POSM.

Formulation and evaluation of herbal lipstick using beta vulgaris and lawsonia inermis as natural colorants

This study sought to formulate and evaluate herbal lipstick using Beta vulgaris and Lawsonia inermis as natural colorants. Lipsticks contribute to 60 per cent of the world's commonly used cosmetics to enhance appearance, emblem a woman's strength, power, and ambition and give the first impression. However, 75 per cent of available lipsticks are made up of synthetic excipients, including colorants that pose health hazards and safety concerns; hence need to use natural excipients that are safe and readily available. A moulding process successfully formulated the herbal lipstick. The formulated lipstick had uniform dark red colour, with a good force of application and spread ability. It had a melting point of 60 degrees Celcius and a breaking point of 55. The project was an experimental based study and analytical in nature. The area of study was in the Pharmacognosy lab from the initial steps of extraction. Formulation and evaluation of the lipstick samples were done in the Pharmaceutics laboratory. The study concluded that Herbal excipients are safe and readily available and hence should be exploited in the formulation of cosmetic products. This study recommends further evaluation of lipstick for safety and efficacy. In addition, the stability of the formulated lipstick under different storage conditions should be performed.

Structural Modifications and Strategies for Native Starch for Applications in Advanced Drug Delivery.

Pharmaceutical excipients are compounds or substances other than API which are added to a dosage form, these excipients basically act as carriers, binders, bulk forming agents, colorants, and flavouring agents, and few excipients are even used to enhance the activity of active pharmaceutical ingredient (API) and various more properties. However, despite of these properties, there are problems with the synthetic excipients such as the possibility of causing toxicity, inflammation, autoimmune responses, lack of intrinsic bioactivity and biocompatibility, expensive procedures for synthesis, and water solubility. However, starch as an excipient can overcome all these problems in one go. It is inexpensive, there is no toxicity or immune response, and it is biocompatible in nature. It is very less used as an excipient because of its high digestibility and swelling index, high glycemic index, paste clarity, film-forming property, crystalline properties, etc. All these properties of starch can be altered by a few modification processes such as physical modification, genetic modification, and chemical modification, which can be used to reduce its digestibility and glycemic index of starch, improve its film-forming properties, and increase its paste clarity. Changes in some of the molecular bonds which improve its properties such as binding, crystalline structure, and retrogradation make starch perfect to be used as a pharmaceutical excipient. This research work provides the structural modifications of native starch which can be applicable in advanced drug delivery. The major contributions of the paper are advances in the modification of native starch molecules such as physically, chemically, enzymatically, and genetically traditional crop modification to yield a novel molecule with significant potential for use in the pharmaceutical industry for targeted drug delivery systems.

Hydrogel for topical drug delivery based on Mimosa pudica seed mucilage: Development and characterization

A Large number of existing excipients had become common place in today's pharmaceutical formulations as additives but had certain drawbacks such as lack of biodegradability, biocompatibility, toxicity, side effects, high cost as well as environmental pollution during synthesis. As the establishment of toxicity and side effects poses a problem with synthetic excipients for the recognition as safe use from regulatory authorities, more interest is attracted towards the development of natural excipients. In the present study, attempts were made to explore mucilaginous polysaccharides isolated from seeds of Mimosa pudica as a hydro-gelling agent as mucilaginous materials obtained from plant sources could be an effective gelling agent. The isolated mucilaginous polysaccharides material was tested for its physicochemical, spectrophotometric, thermal, mechanical, biodegradation, micromeritics properties (like particle size, density, flow properties of powder) and oral toxicity study. The results reveal that isolated mucilaginous polysaccharides had slightly acidic pH, low moisture and ash content and a good swelling index with good micromeritics properties. Rheological properties showed non-Newtonian shear thinning behavior. Biodegradation study confirms its easily biodegradable nature at a reasonable rate. The FTIR and NMR spectrum showed its characteristic as polysaccharide moiety. Oral toxicity studies report of M pudica mucilaginous polysaccharide confirms it as GRAS material. Isolated mucilaginous polysaccharide exhibits hydrogel-forming ability at 1% w/w concentration. Diclofenac loaded hydrogel exhibited persistent drug release. These findings demonstrated that the Mimosa pudica mucilaginous polysaccharide could be a suitable excipient as a hydrogel-forming agent not only in drug delivery applications but also in cosmetic industries.

Synthesis and evaluation of grafted xanthan gum as a drug carrier in developing lornoxicam gel formulations

Background: In the medical and pharmaceutical fields, man has successfully used natural-origin things for millennia. Polymers obtained from plant sources have flashed much consideration in current eras owing to their various pharmaceutical properties, such as gelling agents in gels. Also incorporated in cosmo products, fabrics, dyes, and paper manufacture as binders, diluents, disintegrating agents, thickeners in oral fluids, protective colloids in suspensions, and bases in a suppository. Objectives: Natural polymers are chosen over semisynthetic and synthetic excipients due to their lack of toxicity, low cost, availability, soothing action, and nonirritant nature, as well as their ability to undergo a variety of chemical modifications. However, they have some drawbacks, including microbial contamination, lot to lot variation, reduced viscosity throughout storage, inappropriate mechanical properties, low storage, and an uninhibited rate of hydration. Current research work aims to chemically modify xanthan gum and study its impact on the formulation of topical gels. Materials and Methods: Chemical modification of xanthan gum is conceded by using a thiol-esterification reaction with thioglycolic acid (TGA) in the presence of hydrochloric acid. Microwave irradiated thiolated xanthan gum was also willing by further irradiation of thiolated xanthan gum by microwave using 750 W frequency. Topical drug delivery of lornoxicam release applications of thiolated and microwave irradiated xanthan gum are comparatively evaluated with pure xanthan gum polymer by formulating gel incorporated lornoxicam as a drug. Results: The physical properties of gel-like physical evaluation and viscosity results are within official limits. Formation of gel with idyllic properties. Determination of drug content, spreadability, and extrudability of modified xanthan gum was high compared with native xanthan gum. In vitro drug release study showed that prepared gel sustains the drug release for 24 h. Conclusion: Thiolation and irradiated xanthan gum sustain the release of lornoxicam over a prolonged period and might be a promising lornoxicam carrier in topical drug delivery to enhance antinociceptive and anti-inflammatory efficiency.

Production and Analysis of Lip Balm using Herbal Resources

Lip care products are an integral part of a day-to-day lifestyle. These impart the colour and protect the lips from the external environment. The major function of lip balm is to protect and moisturize the lips. A variety of lip care products are available in the market. The main concern with this product is that these contain synthetic colourant and flavouring agents that may have adverse effects such as darkening of lips. Besides, these may contain heavy metals that adversely affect various body organs. The current research work deals with preparation lip balm by using maximum possible natural ingredients and evaluation of the formulation. Various natural ingredients used were beetroot extract, Cocoa powder, Almond oil and Vitamin E. The physicochemical properties such as colour, odour, consistency, spreadability, melting point, pH and stability were studied. It was found that the formulation possesses red colour due to the addition of beetroot pigments, it had a typical flavour of cocoa powder, uniform in consistency and good spreadability. The melting point and pH of formulation were found to be 58-60°C ± 0.62 and 6.9 ± 0.25 respectively. The stability study indicated that formulation is stable at room temperature and refrigeration temperature. It can be concluded that lip balm formulation was successfully prepared by using these natural additives and better alternatives to synthetic excipients.

FORMULATION AND EVALUATION OF BUDESONIDE PELLETS CONTAINING NATURAL GUMS FOR COLON TARGETING

Pellets formulation with natural gums. The formulation of an enzyme as well as pH dependant pellets containing natural gums such as Mornings oleifera gum Lam. (MOG) and Cyamopsis tetragonolobus gum Taub. (CTG) were used for enzyme dependant release and further coating is provided to shows colon-specific delivery. Extrusion and spheronization techniques were used for the preparation of pellets. Pellets of budesonide evaluated for various properties such as flow behavior, physical properties such as sphericity, roundness, aspect ratio, hardness, and friability also investigated in vitro and in vivo targeting in rabbit. Preparation of pellets was done by using extrusion and spheronization method with the use of optimized concentration of gums those were 7.5% and 10% for CTG and MOG respectively and proportion of solvent mixture of water and Isopropyl alcohol in the ratio of 80:20. Pellets of budesonide evaluated for various properties includes flow behavior, physical properties such as sphericity, roundness, aspect ratio, hardness, and friability and found that all properties as per official limit also in vitro release study found that release of uncoated pellets in a sustained manner in 0.1N HCl for 2h due to swelling of natural gum, therefore further step of the coating was done in fluidized bed coater to prevent the release of drug in the upper part of GIT and after coating found that In vitro release of drug at the colonic environment and it confirmed with in vivo investigation in rabbit with X-ray examination of targeting and found that pellets reach at colonic part without disintegration. The use of natural gums for preparation of pellets in optimized concentration and wetting agent produce a formulation with all required chemical and physical properties and it gives effective in vitro release and also shows In vivo targeting in rabbit and due to use of natural gum for preparation of pellets also reduce some problems of metabolism of synthetic excipients.

Bio-mediated synthesis of 5-FU based nanoparticles employing orange fruit juice: a novel drug delivery system to treat skin fibrosarcoma in model animals

Nano-sized drug delivery systems (NDDS) have been widely exploited to achieve targeted delivery of pharmaco-materials. Traditional pharmaceutical approaches, implied in the synthesis of nano-formulations, are obscure owing to the incompatible physico-chemical properties of the core drug as well as some other factors crucial in development of NDDS. Infact, most of the existing methods used in development of NDDS rely on usage of additives or excipients, a special class of chemicals. Barring few exceptions, the usage of synthetic excipients ought to be curtailed because of several associated undesirable features. Such issues necessitate strategies that lead to development of the synthetic excipient free drug delivery system. Plant based extracts have great potential to induce synthesis of nano-sized particles. Considering this fact, here we propose a prototype employing orange fruit juice (OJ) to facilitate bio-mediated synthesis of nano-sized supra-molecular assemblies of 5-fluorouracil (5-FU), a potent anticancer drug. The as-synthesized 5-FU Nanoparticles (NPs) retained the anti-neoplastic efficacy of the parent compound and induced apoptosis in cancer cells. The novel 5-FU NPs formulation demonstrated enhanced efficacy against DMBA induced experimental fibrosarcoma in the mouse model when compared to the micro-sized crystals of parent 5-FU drug.

Development and Gamma Scintigraphy Study of Trigonella foenum-graecum (Fenugreek) Polysaccharide-Based Colon Tablet.

The major concern with the use of some synthetic excipients is their safety towards biological tissues, hence influencing the reliability of products. With the aim to minimize dependency on highly toxic synthetic excipients, the present study was designed to deliver metronidazole (MNZ) into thecolonic region for localized treatment of amoebiasis using natural polysaccharide-based drug delivery. Compression-coated tablets wereprepared using water extractable natural polysaccharide from Trigonella foenum-graecum (FG). Physical properties of the tablets were evaluated and dissolution study was performed at pH1.2, 6.8, and 7.4 with rat cecal material. Results indicate that all batches demonstrated pH-dependent drug release and prevented release into the stomach, allowing traces into the intestine and highest availability into the colon. A significant correlation (r2 = 0.975) was found between the coating levels of extracted polysaccharide and lag time release of drug. Gamma scintigraphy images of in vivo study conducted on human volunteers showed a small intestinal transit time, i.e., 3-5 (4.2 ± 0.4)h and confirmed that thetablets reached the colon within 6-8h. The present study revealed that theFG polysaccharide-based double compression tablets may be promising colon-specific drug carriers withreduced toxic effects of commonly used synthetic excipients.

MORINGA OLEIFERA AS A PHARMACEUTICAL EXCIPIENT

Plant gums and mucilages are being used due to their abundance in nature, safety and economy. Additives play an important role in pharmaceutical preparations like tablet, lotions, suspensions, syrups and ointments. Recent trends towards the use of the natural and nontoxic products which demand the replacement of synthetic excipients with natural ones. Moringaoleifera gum has good mucoadhesive polymer, disintegrating agent and binder. Moringa Oleiferagum show that it has high potential for industrial application especially in the food, textile and pharmaceutical industries.

Design and Evaluation of Sustained Release Matrix Tablets of Etodolac

In recent years, plant derived polymers have evoked tremendous interest due to their diverse pharmaceutical applications such as diluent, binder, disintegrant in tablets, thickeners in oral liquids, protective colloids in suspensions, gelling agents in gels and bases in suppository. These polymers such as natural gums and mucilage are biocompatible, cheap and easily available and are preferred to semi synthetic and synthetic excipients. The main objective of the present work was to develop sustained release matrix tablets of water insoluble drug etodolac using natural polymers and gums like tamarind xyloglucan, gellan gum, sodium CMC and xanthan gum. Tablets were prepared by wet granulation method and evaluated for various physical parameters. The granules prepared were free flowing with good compressibility. FTIR and DSC studies revealed that there was no chemical interaction between the drug and the excipients. The hardness of all the formulated tablets were in the range of 6–7 kg/cm2 and friability test was found to be less than 0.1% in all the cases and swelling index studies shown that increase in the concentration of polymer increases the swelling index of tablet. Tablets containing xanthan gum and sodium CMC showed highest swelling index. Drug release was faster from tablets prepared with gellan gum and sodium CMC as matrix forming material. However, tablets formulated with xanthan gum and tamarind xyloglucan it sustained drug release effectively for 12 hrs. And it is reveals that increase i n the polymer concentration decrease the release of Etodolac from matrix tablet. Among the formulation studied, formulation F16 containing xanthan gum (1: 0.25) showed release of drug more than 12hrs was found to be the optimized combination. Optimized formulation F16 followed higuchi kinetics. The release co-efficient values ‘n’ indicated that the drug release followed non fickian anomalous mechanism based on formulation factors. Stability studies were carried out at 40°C±2°C/75%±5% RH for formulation F16 for 90 days. The results of stability studies indicated no significant changes with respect to physicochemical properties and in vitro drug release.

Herbal gums and mucilage as excipients for Pharmaceutical Products

There are number of synthetic polymers are available in market for pharmaceutical formulation, but these synthetic polymers have certain disadvantages such as high cost, toxicity, environmental pollution during synthesis, non-renewable sources, side effects, and poor patient compliance. Because of these disadvantages natural polymers such as natural gums and mucilage are preferred to semi synthetic and synthetic excipients because of the following advantages: such as: low cost and natural origin, free from side effects, biocompatible and bio-acceptable, renewable source, environmental friendly processing, local availability etc. Natural gums and mucilages are available in nature freely. These natural gums and mucilages were successfully used in various dosage forms.

Myriad Molecules to Overcome Efflux Drug Transporters and Drug-Metabolizing Enzymes: A Journey from Synthetic to Natural.

A vast range of prescribed drugs suffers from low and variable bioavailability mainly because of metabolism and permeation complications. This issue of bioavailability is a key problem that has been ongoing for many years. Various tactics have been introduced that have been quite beneficial for improving the bioavailability of poorly bioavailable drugs. Some of these tactics are targeted on cytochrome-P450 (CYP) enzymes and the permeability-glycoprotein (P-gp) efflux pump. Strategies include small-molecule inhibitors, novel drug-delivery systems, pharmaceutical synthetic excipients, and natural bioenhancers. This review discusses the role of synthetic excipients and natural bioenhancers in potentiating the activity of poorly bioavailable drugs, including their pharmacological background and their future applicability to health care. The molecules of synthetic origin such as Gelucire and those of natural origin such as quercetin and silibinin can provide noteworthy benefits to patients and the health care system by helping to reduce dosing and drug side effects.

Natural gums and its pharmaceutical application

Gums are widely used natural excipients for conventional and novel dosage forms. With the increasing interest in polymers of natural origin, the pharmaceutical world has compliance to use most of them in the formulations. In recent years, there has been a tremendous development in natural products, which are needed to be used for a variety of purposes. Nature has provided us a wide variety of materials to help improves and sustains the health of all living things either directly or indirectly. These natural materials have advantages over synthetic ones since they are chemically inert, nontoxic, less expensive, biodegradable and widely available. They can also be modified in different ways to obtain tailor made materials for drug-delivery systems and thus can compete with the available synthetic excipients. Moreover, the tremendous orientation of Pharma world towards these naturally derived polymers has become a subject of increasing interest to discover, extract and purify such compounds from the natural origin. Gums are the potent candidates to be used in various pharmaceutical formulations as a potential candidate for novel drug delivery system (NDDS). In this review, we describe the developments in natural gums for use in the pharmaceutical sciences.

Preliminary Investigation on Sodium Alginate Extracted from <i>Sargassum Subrepandum</i> of Red Sea of Eritrea as Tablet Binder

Natural polysaccharides hold advantages over synthetic polymers for conventional and novel dosage forms, because these are non-toxic, less expensive, and biodegradable. These can also be modified to tailor-made materials and thus can compete with the available synthetic excipients. Therefore, the aim of present work is to extract sodium alginate from the seaweed S. subrepandum to assess its binding property using propranolol as model drug. Sodium alginate was extracted by room-temperature alkaline extraction and high-temperature (80°C) alkaline extraction methods. Binding strength was evaluated by using two different formulations i.e., formulation 1 with sodium alginate as a binder and formulation 2 with hydroxypropylmethylcellulose (HPMC) as reference standard. The two tablet formulations were evaluated and compared for parameters such as friability, hardness and disintegration. The percentage yield was found to be 17.5% w/w by room-temperature alkaline extraction and 21%w/w by high-temperature extraction method. The results obtained for all tested parameters for tablets with sodium alginate were found within acceptable range of USP standards. It was also founded that both sodium alginate and HPMC have similar binding strength at similar concentration. So, it can be concluded that sodium alginate of S. subrepandum can be used as suitable alternative binder in tablet formulations.Keywords: Sargassum subrepandum; Sodium alginate; Hydroxypropyl methylcellulose; Friability; Hardness; Disintegration.© 2011 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi:10.3329/jsr.v3i3.6770 J. Sci. Res. 3 (3), 619-628 (2011)