International Journal of Advances in Scientific Research
International Journal of Advances in Scientific Research (IJASR) is monthly online peer-reviewed open access multidisciplinary journal dedicated to publishes articles from the broad field of basic science and scientific research. ISSN: 2395-3616 (Online)
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Immediate release tablet formulations: Formulation strategies, superdisintegrants, and evaluation parameters with special reference to antihypertensive drugs
Immediate-release (IR) tablets represent the most widely utilized solid oral dosage forms owing to their simplicity, cost-effectiveness, and ability to provide rapid therapeutic action. In the management of cardiovascular disorders such as hypertension, prompt drug availability is often essential to achieve effective clinical outcomes. Antihypertensive agents, particularly β-adrenergic blockers, are commonly formulated as immediate-release dosage forms to ensure quick onset of action. Esmolol hydrochloride, a cardioselective β₁-blocker with rapid onset and short duration of action, serves as an ideal model drug for studying immediate-release formulation strategies. This review discusses the principles of immediate-release tablet formulation, selection of excipients with emphasis on superdisintegrants, manufacturing techniques, and evaluation parameters. The role of formulation variables in influencing disintegration and dissolution behavior is highlighted, along with recent advances in immediate-release tablet technology. The review aims to provide a comprehensive overview of formulation approaches for immediate-release tablets of antihypertensive drugs, supporting the development of effective and reliable oral dosage forms.
Copyright (c) 2025 International Journal of Advances in Scientific Research https://creativecommons.org/licenses/by/4.0
Mucoadhesive microspheres are an advanced multiparticulate drug delivery system designed to enhance drug residence time at mucosal surfaces and provide controlled or sustained drug release. By combining the advantages of mucoadhesion and microsphere technology, these systems improve bioavailability, reduce dosing frequency, and enhance patient compliance, particularly for drugs with short half-lives or limited absorption windows. This review discusses the fundamentals of mucoadhesive microspheres, mechanisms of mucoadhesion, polymers used, methods of preparation, evaluation parameters, drug release behavior, applications, challenges, and future perspectives.
Buccal films as an emerging drug delivery platform
Buccal films have emerged as a promising drug delivery platform due to their ability to bypass hepatic first-pass metabolism, improve bioavailability, enhance patient compliance, and provide controlled or rapid drug release. These thin, flexible polymeric films adhere to the buccal mucosa and allow systemic or local delivery of a wide range of therapeutic agents. This review discusses the anatomy and physiology of the buccal mucosa, advantages and challenges of buccal film systems, polymers used for film development, formulation techniques, evaluation parameters, recent advancements, and applications in modern drug delivery. The review concludes that buccal films offer an efficient, patient-friendly, and technologically adaptable platform that will continue to expand in pharmaceutical applications.
A review on Ethogel for topical application
Topical drug delivery remains a challenging field due to the barrier nature of the skin (especially the stratum corneum). Vesicular systems such as ethosomes have emerged as promising nanocarriers for improved dermal/ transdermal delivery. When such ethosomal suspensions are incorporated into gel bases, the resultant formulations are termed “ethogel” (or nano‐ethogel) and offer advantages of enhanced skin permeation, deposition, sustained release and better patient compliance. This review critically examines the formulation science of ethogel, its mechanisms of action, evaluation parameters, applications (especially in dermatology and oncology), formulation challenges, regulatory and translational aspects, and future prospects.
Chemotherapeutic induced neuropathic pain. A review from the literature focusing on its treatments
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of many anticancer agents, presenting with sensory symptoms such as spontaneous pain and mechanical or cold allodynia in a characteristic "stocking and glove" distribution. This neuropathic pain can severely limit the dosage and duration of life-saving chemotherapy, often necessitating treatment modification or cessation, and may persist long after therapy, impairing survivors’ quality of life. Standard pharmacological treatments offer limited efficacy, highlighting the need for alternative therapies. This review summarizes current literature on emerging treatments for CIPN, with a focus on three agents: nabiximols, gabapentin, and phenyl N-tert-butylnitrone (PBN). Nabiximols, a cannabinoid-based oral spray, demonstrated modest efficacy and a favorable safety profile in a small pilot study, suggesting the need for larger clinical trials. Gabapentin, an anticonvulsant, showed potential as an early intervention in patients with mild symptoms, with good tolerability and safety. PBN, a potent free radical scavenger, prevented the development of neuropathic pain in preclinical models of paclitaxel-induced neuropathy, offering promising neuroprotective effects. Collectively, these findings underscore the importance of further clinical and translational research to identify and validate effective therapies for managing CIPN.
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RP-HPLC force degradation profile of antidiabetic drugs
A force degradation profile was developed of Metformin (MET) & Pioglitazone (PIOG) in pharmaceutical combine tablet dosage form on RP-HPLCusing Comosil RP-C18 (4.6 x 150mm, 5µm) in an isocratic mode with mobile phase comprising of Acetonitrile: Pott. Dihydrogen Phosphate (pH 2.5 using OPA). The flow rate was 0.7 mL/ min and effluent was monitored at 254.0 nm. The stress conditions selected on the basis of literature review and the drug profile. For both estimations 99.81%for MET and 99.33% for PIOG mean % recovery was found with % RSD was NMT 2.0 which fully agrees by system suitability in good agreement with labeled claimed of formulation. All the parameters of system suitability were fully obeyed during force degradation profile generation.
Copyright (c) 2015 International Journal of Advances in Scientific Research https://creativecommons.org/licenses/by/4.0
Estimation of ibuprofen and famotidine by (RP-HPLC)
A force degradation profile by RP-HPLC method was developed for Ibuprofen (IBU) & Famotidine (FMT) in combine tablet dosage form using Cosmosil RP-C18 (4.6 x 250mm, 5µm) in an gradient mode with mobile phase comprising of Methanol: Water (pH 2.5 using OPA) The flow rate was 0.7 mL/ min and effluent was monitored at 240 nm. The stress conditions selected on the basis of literature review and drug profile. The analysis of the marketed formulation shows the % RSD of 0.061 and 0.35 for IBU & FMT which fully agrees with system suitability. All the system suitability parameters were fully obeyed during generation of force degradation profile
Copyright (c) 2022 International Journal of Advances in Scientific Research https://creativecommons.org/licenses/by/4.0
Management of vataj type of Shirshula with Goghrit Pratimarsha nasya- A case report
Shira is also known as Uttamanga in Ayurveda. It is the most vital part of our body. In Ayurveda, Shiro rogas are restricted to pain or discomfort seen around cranial vault and not the disorders of brain mostly. Headache is the most frequent and troublesome reason to seek medical help in our daily life. Tension type headache is the most common, primary, most neglected and difficult to treat occurring in about three-quarters of the general population. They can range from the occasional mild headaches to daily disabling headaches in some cases. Current allopathic approach is highly limited in treating the disease with just pain killers, which again have lot of side effects.Holistic Ayurveda approach practically is found to yield very good results in the patients of headache. Vataja Shiroroga can be an apt classical correlation of Tension-type headache. Atiuccha bhashana, Vegadharana, Ratrijagarana, Upavasa and Shoka are the major causes of Vataja shirashula. Classical books of Ayurveda advocate the use of Snehana, Swedana, Navana nasya, Snaihika dhumapana and local Vatahara kriya like Lepa and Parisheka as main mode of treatment. Nasya is a special therapy in all Shalakya disorders and Goghrita is considered as best Vatahara dravya. In this study, Goghrita pratimarsha nasya is done in a 29 year old patient having typical symptoms, to access the overall efficacy. After 1 month of therapy, significant improvement was seen in the symptoms. Mild recurrence was seen post follow-up period.
Copyright (c) 2021 International Journal of Advances in Scientific Research https://creativecommons.org/licenses/by/4.0
In this project, we developed a fuzzy game theory model for Hand Foot Mouth disease (HFMD), a transmissible disease affecting many populations around the world. HFMD is fomented from the genus enteroviruses. Although there are several viruses, coxsackie virus enteroviruses 71 (EV71) and A16 [5] are most probable to produce this disease. Precise estimates of disease transmission rate are critical for epidemiological Game theory model. We considered the transmission co-efficient to be uncertain and described by a fuzzy number which is triangular and symmetric. We defuzzified the fuzzy number by a signed distance method and studied sensitivity analysis.
Systematizing Astrology for Constructive Approach
The research paper presents the hypothesis with the aim to contributes and uplift the standard of accuracy and precision in Astrology. It is an effort to systematize the analysis and prediction of horoscope by briefing the stages of feminine planets, reframing the aspects of Zodiac signs and establishing the subordinating relation between Lagan and Navmansh chart for systematic analysis.
Artificial Intelligence in Orthodontics: Prediction and Planning
Artificial intelligence (AI) with advancement of technology has experienced remarkable growth and development in the field of dentistry. AI is an excellent tool that performs several tasks from diagnosis, treatment planning, predicting the outcome and prognosis particularly in the field of orthodontics based on individual preferences and constructed algorithm models. The present review was carried out to discuss briefly on the role and impact of AI in the field of orthodontics. It was observed that most of the AI models are based on artificial neural networks (ANNs) and convolutional neural networks (CNNs) systems widely used for Cephalometric landmarks identification, image recognition, decision making system to assist treatment planning, prediction of need for extraction and/or orthognathic surgeries, evaluating the cervical vertebrae growth pattern and maturation, predicting the facial attractiveness and post-orthognathic surgery facial profile. Further research on application of AI should be carried out focusing on formulating and establishing cloud-based platforms, integrating large data to improve learning algorithms and construct advanced automated decision making model systems with high specificity, precision, reliability to predict exact outcomes within a short span of time and improve the quality of life.
Association between plasma homocysteine levels and coronary artery disease.
Objectives: Various studies have proposed that increased plasma homocysteine level causes both venous and arterial thrombosis contributing to myocardial Infarction, stroke, and pulmonary embolism, though the results are still debatable. In addition, the homocysteine levels show a genetic and ethnic predisposition. The present study thus aimed to evaluate the association between plasma homocysteine levels and coronary artery disease in Indian patients. Material and Methods: The present study was a hospital-based case-control study, conducted at a tertiary care hospital in North India. The study included 237 diagnosed cases of acute coronary syndrome (ACS) who were compared with 50 age and sex matched apparently healthy controls. Subjects of the two groups were compared for levels of plasma homocysteine, lipid profile and other conventional risk factors of coronary artery disease (CAD). Homocysteine levels were analysed by chemilumniscence immunoassay. Statistical analysis was performed using using SPSS v.21.0. Values were expressed as a mean ± standard deviation or as percentages. Student’s t test and Chi square test was used to evaluate statistical significance. Result: The mean homocysteine levels were found to be significantly higher (p<0.001) in patients of ACS as compared to the healthy controls. (14.34 ± 7.49 µmol/L and 11.34 ± 4.91µmol/L respectively). However, no association was found between homocysteine level and the conventional risk factors. Conclusion: The results suggest that high levels of homocysteine are associated with ACS and may be used for risk assessment of CAD. However, further studies with larger sample size would be required to validate the findings .
Genotoxicity effects of selected alcoholic polyherbal products using Allium cepa
Alcoholic herbal products have been used for years in folk medicine for its believed increase in sexual desire and pleasure. This study is due to the current upsurge in the use of polyherbal products and coupled with loose regulation on public access to these products, to evaluate their biochemical effect, noting also that many of the polyherbal products lack scientific evidence to support their medicinal claims. The objective is to investigate the potential genotoxicity of some commonly consumed polyherbal formulations (Action bitters, Black wood, Jedi-jedi, Agbara, Orijin bitters), using allium cepa. The method involves onion bulbs that were exposed to varied concentrations of herbal alcoholic productsfor microscopic analysis. Tap water has been used as a negative control. All the tested products have been observed to have genotoxic effects on cell division in Allium cepa, with the highest mitotic index as 59% (orijin bitters 25%) and the lowest being 23% (action bitters 75%). The results showed that all tested concentrations of alcoholic herbal products caused decreased mitotic index value and increased chromosomal aberration of Allium cepa root cells. From the findings, alcoholic polyherbal formulations may possess genotoxic effects.
Genotoxicity, meristematic cells, Allium cepa, alcoholic herbal products, cell division
Copyright (c) 2020 International Journal of Advances in Scientific Research https://creativecommons.org/licenses/by/4.0
The Impact of Culture on Scientific Development
Scientific development in societies of the world is not even. Some societies are more developed scientifically than others. There are many possible reasons that could be offered to explain this. This work aimed at unravelling the role cultures play in the growth of science. The research uses creative philosophical analysis to arrive at the conclusion that most countries in spite of parading the same educational curriculum like their counterparts remain dwarfs scientifically. The difference in scientific development as discovered by these researchers is traceable to differences in culture. Though, culture greatly impact on science, it is also discovered that the level of scientific growth also determines how fast a culture would evolve. It implies that the two concepts have impacts on the development of each other.
Astrology is a science based on facts and evidences that has significant accuracy and numerous applications. The paper is an attempt to explore the reasons of its unacceptability and ineffectiveness. There is need to pursue scientific astrological research to utilize its immense potential for human welfare, development, safety, bio-medical use and spiritual awakening.
Challenges of pandemic disease and mental health concern in Ethiopia: A systematic review of literature
Several studies have been carried out on the epidemiological nature, and economic, social, and psychological effects of pandemic diseases. However, little literature has been attempted to comprehensively indicate the psychological challenges of pandemic diseases and strategies utilized to overcome the challenges in the Ethiopian context. Thus, the objective of this comprehensive review of the literature was to assess and organize the literature on the challenges of pandemic diseases in general and COVID-19 in particular, develop guidelines and seek out alternative solutions that have implications for Ethiopia and beyond. The literature has been organized on the history, worldwide challenges of pandemics, Behavioural responses and coping mechanisms, and opportunities motivated by COVID-19. Some criteria were set to review the most relevant local and international studies that are rigorous in design, adequate sample size, relevant sample selection procedures, and those which have used instruments with high validity and reliability. The findings from the literature indicated that there is a high incidence of psychological difficulties (fear, stress, anxiety, and depression) associated with COVID-19 worldwide and in Ethiopia. The problem is attributed to economic, social, psychological, and health-related outcomes of COVID-19 that demand integrated prevention and intervention strategies.
Literature Review on the Bamboo as a Sustainable Material for Interiors with Its Potential and Market Assessment
Bamboo is one of the most fastest growing resources which provides wide opportunities as a cheap raw material to many sectors. Many industries are using bamboo as substitute raw material in different forms and while having a wide chain of demand and supply bamboo does not attain social status in many countries and still been considered as resource for poor class and named as
Bamboo, Sustainability , Bamboo Construction ,Life Cycle Assessment
Is pre vaccination the reason for less morbidity and mortality for COVID-19 in India: an epidemiological study
As we all know the current rapid of the covid-19 in the most of the world has become a pandemic situation. Many research studies have been by various countries to develop a vaccines against the coronavirusSARS-CoV-2. Currently about six vaccine candidates have passed early testing and have entered the clinical trials across the globe, along with more than80 other candidates reported to be in preclinical stages. This state that many different approaches are being moved forward at the same time. However, the destinationis not yet completed and so no vaccines are currently licensed for any of the other coronaviruses affecting humans. If we go in the past few decades, various vaccines were given to geriatrics as well as paediatrics. So if we look the same in other countries the use of the vaccines is very less or instead some countries have no authentic grant to sell or use the vaccines. Here in this present study we are trying to propose that by the early use of the vaccines also reduced the number of reported COVID-19 cases in a country. So is the combination of these vaccines a reason for the reduced morbidity and mortality and can it be a boon to fight against the disaster of COVID-19 in future.
Histopathologic review of ovarian teratoma in Port Harcourt: A multicenter study
Background: Ovarian teratoma are the commonest germ cell tumours of the ovary commonly seen in the young but can occasionally be encountered in the elderly with an increased risk of malignant transformation. Method: This was an 8-year retrospective review of128 histologically confirmed cases of ovarian teratoma in the university of Port Harcourt teaching hospital and Braithwaite memorial specialist hospital both tertiary health facilities in Port Harcourt from 1st January 2009
Copyright (c) 2020 International Journal of Advances in Scientific Research
Artificial neural networks for medical diagnosis: A review of recent trends
Artificial Intelligence systems (especially computer aided diagnosis and artificial neural network)are increasingly finding many uses in the medical diagnosis application in recent times. These methods are known to be adaptive learning algorithms that are capable of handling diverse types of medical data and integrate them into categorized outputs. In this study, we briefly review and discuss the concept, capabilities and applications of artificial neural network techniques to medical diagnosis, through consideration of some selected physical and mental diseases. The study focuses on scholarly researches within the years, 2010 to 2019.Findings show that no electronic online clinical database exist in Nigeria and the Sub-Saharan countries, most review researches in this area focused mainly on physical diseases without considering mental illnesses, the application of ANN in mental and comorbid disorders have not be thoroughly studies, ANN models and algorithms consider mainly homogeneous input data sources and not heterogeneous input data sources, and ANN models on multi-objective output systems are few as compared to single output ANN models.
The environment is fast degrading. Experts believe that in the nearest future, the environment will totally collapse, if the current rate of degradation continues. One of the main drivers of this degradation is believed to be technology. This has led to widespread perception of technology as a curse rather than a blessing to the environment and humanity. This work agrees that technology is one of the main causes of environmental problems but disagrees that technology is a curse. Technology in itself is value neutral; it is its usage that leads to bad or good consequences. It is the contention of these researchers, that technology when well driven could restore the health of the environment. Technology due to its wrong positioning in the past, has caused environmental problems. It could be repositioned to foster environmental health in the future. Technology therefore, has the potential, to restore and heal what it has wounded, when properly driven.
Copyright (c) 2019 International Journal of Advances in Scientific Research
Anti-ulcer potential of the Ethanolic Extract of leavesof Solanum Violaceum in Wistar albino rats
The study evaluates the possible gastro protective of Ethanolic extract of leaves of Solanum violaceum [EESV] using two different gastric ulcer models. Gastric ulcers in Wistar albino rats were induced by Ethanol (1ml/200gm) and Indomethacin (30mg/kg) induced ulcer. Various parameters like Ulcer index, Acid volume, Total acidity, pH, Total protein, Glutathione, Catalase and Superoxide dismutase were evaluated. Omeprazole (20mg/kg) and Ranitidine (60mg/kg) was used as the standard drug. Solanum violaceum was administered at two dose levels, 250 mg/kg and 500 mg/kg body weight. Statistical analysis was done by ANOVA followed by Dunnet
Hepatitis C - Challenges and New Approaches in Vaccine Development
Hepatitis C continues to be the serious global health treat and hundreds of people die every year due to liver failure. Hepatitis C Virus, the virus that that won the battle with no vaccine till date to beat its survival. Despite 15 years of its discovery, no vaccine has come up eradicate the virus. The high genetic diversity and the resistant nature of the virus is halting the progress towards vaccine development however many promising new antiviral drugs are in clinical trials giving a hope that in the coming years a successful vaccine will be developed. Many approaches like inducing neutralising antibody, inducing T cell response, development of Direct Acting Antivirals and drugs targeting host proteins are being tried out for the development of a safe and effective vaccine for Hepatitis C, some of which are discussed in this review.
Sensitivity of various methods (CMT, CE and Indicator Paper) of subclinical cattle mastitis diagnostic in some dairy cows breeding in east of Algeria
The aim of present work is to look for the prevalence of subclinical mastitis in dairy cows of different regions in eastern Algerian ; the prevalence of subclinical mastitis has called for three non-specific methods and by bacteriological analysis. On all teats are 416 ; the first non-specific test is Californiamastitis test (CMT) indicating polymorphonuclear witness infection of the udder. The second test indicates presence of ions (Na Cl) in milk and carries the appellation of the electrical conductivity of milk (EC) and the last test is the one that revealed the pH of milk while using papier pH containing pH indicator and changes color to green or blue if the udder is infected. It is the first component of the study; the second component is to get the bacteriological status of each udder and passing to the study of the sensitivity and specificity of non specifics tests . the present study gave values of mastitis prevalence between 6.7 to 64.7% of cows and 10 to 20% of udders tested by (CMT, pH papers and EC), with an infection rate of 9% of districts and 17% of cows. Bacteriological examination of positive areas showed the prevalence of the following pathogens : 6 species of Staph Saprophyticus= 15%, 6 species staph epidermidis=15%, 4 species staph cohnii=10%, 9 Staph +=22.5%, 2 Micrococcus. Spp=5%, 4 E.Coli=10%, 2 speciesof klebsielle =5%,2Proteus vulgaris=5%, 2Citrobacter freundeii=5%, 1 Streptococcus spp=2.5%, 1Streptococcus uberis=2.5%. et 5% others specie of bacterias. for specificity and sensitivity we have these values r : CMT = 71% and 77%;. For pH paper had values of 15% and 60% .in latter puts the EC with values of 13% and 67% respectively. So the CMT remains the most accessible and reliable tset
Copyright (c) 2018 International Journal of Advances in Scientific Research
Altitudinal Variation in Alkaloid Composition of Hyoscyamus niger: A study with reference to Kashmir region of Himalayas
The present study has been undertaken to understand the impact of altitude on the synthesis of alkaloids in Hyoscyamus niger found in Kashmir valley of Jand K state in India. Given its wide distributional range, the study aimed to quantify the alkaloids (hyoscyamine and scopolamine) in Hyoscyamus niger grown at various altitudes in Kashmir valley. The sampling of populations at varying altitudes allowed assessing the intraspecieac variation and ecological trends of accumulation of alkaloids in the plant. Furthermore the resource allocation in the parts of the plant has also been shown. The four different sites were Gulmarg, Pahalgam, Gurez and Qazigund in Kashmir valley. The study was able to identify the elite genotype and the best suited habitat (altitude) for commercial cultivation of the species with higher quantity of alkaloids.
Comparative studies of NiMnCo3O4 thin film electrodes for super capacitors applications
Present work is devoted to prepareternary NiMnCo3O4 electrodes by electrodeposition method on copper and porous copper substrate. The structural, morphological and electrochemical characterizations of the prepared samples studied and confirmed by using XRD, SEM, EDAX, FTIR and electrochemical measurements. Structural analysis confirms that NiMnCo3O4 film has face centred cubic with polycrystalline nature. Electrochemical measurements prove that NiMnCo3O4 electrode deposited on porous copper substrate has an improved supercapacitive behavior, compared with NiMnCo3O4 electrode deposited on copper substrate.A high specific capacity of 947 F/g at 10 mV/s was observed. Electrochemical performances were investigated atdifferent scan rate range. And it reveals the prepared electrode has excellent capacitance behaviour as well as reversibility. Moreover, stable cycle capability 90.2%inthe capacitance retention was achieved after 3000 cycles. This outstandingelectrochemical properties indicate that the obtained NiMnCo3O4 electrode materials are fairlyideal for supercapacitors.
An updated review on pharmaceutical mini tablets: Formulation and it
The objective of controlled drug delivery systems is to reduce the frequency of the dosing and to increase the effectiveness of the drug. In oral controlled drug delivery system, multiple unit dosage forms (MUDF
The specificity of the quantum metaphysics and a level of entourage and necessity placed over it indicates an essential characteristic of a given research paradigm and its exemplary structure. The interface of the meta-creativity and the cognitive consciousness provides an important impetus to the boon research and ideal innovative program, sometimes implicit. Thence it is a boon to analyse and examine the research contours of any problem from all aspects, imperatives and hypothetical stance.
Peptide Conjugated Lipid Nanoparticles and Cancer Drug Delivery
Peptide Conjugated Lipid Nanoparticles and their role on Cancer Drug Delivery are reviewed here. The benefits of nanotechnology and combination style of medicine delivery are still hindered without the active ligands needed for treatment efficacy. This work analyzes the role of peptide ligands in different forms of cancer treatments targeting cells and tissues.
Study of the effect of intercropping on the physicochemical characteristics of castor bean, soybean, cowpea and common bean seeds after cultured in two agroecological zones of Cameroon
In order to promote the culture of castor bean, soybean, cowpea and d u bean in Cameroon while preserving food safety, the effect of the combination of the crop characteristics physicochemical seeds of this plant are studied in Laboratory after the cultivation of castor in combination with these three field grain legumes in Sudano-Guinean zone of Adamaoua and in the Eastern Bimodal Forest at Cameroon in 2015 and 2016. The physical characteristics such as length, width, thickness, seed mass and weight of one thousand seeds and chemical properties are the s of castor seeds (the moisture content, the content of castor bean, the mass density, the consumer acid, iodine, and saponification of esters) and Leguminous (the protein content, the sugar content and the ash content) are evaluated. The results show that the physico-chemical properties of castor seeds and legumes do not vary, regardless of the study zone, thus showing that these seeds can be grown in different zones without losing their characteristics. Castor bean contents of the grain is varied from 45.27
Copyright (c) 2019 International Journal of Advances in Scientific Research https://creativecommons.org/licenses/by/4.0