Genuine Medicines Research Articles

Demonstration of an End-To-End Workflow Using Atmospheric Solids Analysis Probe-Mass Spectrometry (ASAP-MS) With Real-Time Sample Recognition Software for the Identification of Falsified and Substandard Pharmaceutical Tablets.

Counterfeit pharmaceuticals are a subclass of falsified and substandard medicines. They are illicit products, purporting to be genuine medicines, that are made and sold by criminal organisations. They represent a significant risk to patient safety, as well as a financial and reputational threat to the companies who make the genuine medicines. It is essential to have analytical methods to determine if suspect samples seized by law enforcement agencies are counterfeit, with mass spectrometry (MS) being a commonly used technique in forensic cases. Speed-to-answer is vital to enable law enforcement agencies to progress investigations, as well as for pharmaceutical companies so that they can notify health authorities of the circulation of counterfeit medicines. In this work, an atmospheric solids analysis probe (ASAP)-MS was assessed as a fast and simple-to-use approach to analyse tablets on a commercially available instrument. Complementing the analytics with real-time sample recognition software demonstrated that the classification of tablets as authentic or counterfeit could be achieved quickly (< 2 min) and without the need for MS interpretation skills. Authentication of five tablets (two authentic pharmaceuticals, one placebo and two counterfeits containing the correct active pharmaceutical ingredient [API] but at lower quantities than in the genuine medicine and with different excipient contents) of unknown origin was achieved with 100% success. This creates the opportunity to deploy the end-to-end workflow as a tool for non-scientists, such as law enforcement officers and border control staff, for use in-territory to obtain fast answers and make data-led decisions to control the illegal trading of medicines.

Experiences of Consumers on the Health Effects of Fake and Adulterated Medicines in Nigeria

Medicines are used to cure and treat ailments, relieve or eliminate disease symptoms, and slow down the disease process. Any attempt to disrupt this natural medicine process, using falsified medications, spells doom to a consumer of such medication. The challenge of fake medicines is a global one and affects developing and developed nations and currently assumes great significance as a result of globalization challenges, which have flattened the entire world, hence removing barriers to the movement of products and services. The cross-sectional survey was conducted, using six local government areas of Anambra State in South-East Nigeria, namely Awka, Nnewi, Onitsha, Aguata, Ogbaru, and Anaocha, among adults aged 18 years and above. A minimum sample size of 500 was calculated and stratified sampling was employed to select respondents in order to ensure that various population groups, the upper class, middle class, and lower class were represented. This research has shown that falsified medicine is an evil wind that blows nobody any good. It negatively affects every aspect of the citizen’s livelihood, ranging from their health, which manifests as treatment failures, deformities, loss of life to death, to loss of confidence in the healthcare providers, revenue losses to individuals, healthcare providers, manufacturers, and finally corruption of the genuine medicines supply chain with fake and adulterated medicines. The study has clearly shown the experiences of residents of Anambra State, South-East Nigeria with fake and adulterated medicines and also services as a wake-up call to medicines regulators like NAFDAC, PCN, the PSN, and Federal Ministry of Health to declare a state of emergency on the fight against fake and adulterated medicines and make enabling laws that are punitive enough towards the fight against this scourge, so that the healthcare and well-being of Nigerians would be assured at all times.

Counterfeit Medicine Detection using Blockchain

The healthcare industry has grappled with the challenge of monitoring genuine medicines while counterfeit drugs continue to proliferate, posing significant risks to patient safety. These fraudulent pharmaceuticals not only have detri- mental effects on health but also result in substantial financial losses, with reports indicating annual losses of approximately 200 billion dollars for US pharmaceutical companies. Particu- larly concerning is the World Health Organization’s revelation that in underdeveloped nations, one in every ten medicines consumed by patients is counterfeit and of low quality. To address this critical issue, we use blockchain technology to track the supply chain, from the manufacturing stage to the end- user. Leveraging blockchain technology, our system enhances reliability, transparency, and security in healthcare data. This paper focuses on bolstering transaction security, safeguarding medicine quality, and fortifying data protection through the utilization of blockchain technology.

Study of Fake Medicine Detection using Blockchain

The healthcare industry has grappled with the challenge of monitoring genuine medicines while counterfeit drugs continue to proliferate, posing significant risks to patient safety. These fraudulent pharmaceuticals not only have detri-mental effects on health but also result in substantial financial losses, with reports indicating annual losses of approximately 200 billion dollars for US pharmaceutical companies. Particu-larly concerning is the World Health Organization’s revelation that in underdeveloped nations, one in every ten medicines consumed by patients is counterfeit and of low quality. To address this critical issue, we use blockchain technology to track the supply chain, from the manufacturing stage to the end-user. Leveraging blockchain technology, our system enhances reliability, transparency, and security in healthcare data. This paper focuses on bolstering transaction security, safeguarding medicine quality, and fortifying data protection through the utilization of blockchain technology.

Perception of Consumers, Stakeholders, and Policy Makers on NAFDAC Anti-counterfeit Technologies and Interventions Regarding Counterfeit Drugs in Nigeria

Counterfeiting medicines is a global phenomenon affecting developed and less developed countries. The World Health Organization, in its report, describes counterfeit medicines as becoming “a global public health crisis. This study examines consumers, stakeholders, and policymakers' perceptions of NAFDAC anti-counterfeit technologies and interventions regarding counterfeit drugs in Nigeria. This study uses a qualitative research method to examine consumers, stakeholders, and policymakers' perceptions of NAFDAC anti-counterfeit technologies and interventions regarding counterfeit drugs in Nigeria. Participants were selected using convenience sampling, and data was collected through an online interview. Data were analysed using thematic analysis. Stakeholders emphasised the importance of NAFDAC having a comprehensive anti-counterfeiting strategy and implementing measures such as checking for NAFDAC registration numbers, inspecting packaging, and requesting seller receipts to identify genuine medicines. Policymakers at NAFDAC acknowledge the seriousness of the problem and recognise the roles of stakeholders in implementing anti-counterfeiting interventions. They emphasise the need for effective communication, engagement, and collaboration with healthcare professionals. Consumers express concerns about the accessibility to good quality medicines and the prevalence of substandard and counterfeit drugs. However, consumers also demonstrate a willingness to support NAFDAC's efforts and show a preference for quality medicines, which is a positive indicator for the Nigerian pharmaceutical industry. The findings underscore the importance of continuous efforts to raise awareness and implement effective anti-counterfeiting strategies to safeguard public health and combat the growing threat of fake drugs. Keywords: Falsified, Substandard, Counterfeit, Knowledge.

Determination of the Genomic DNA Degradation Rate of the Chinese Herb Gentianae crassicaulis Radix During Processing and Storage

Background Accurate identification of Chinese herbal medicines is the basis for their research and utilization. Molecular identification can effectively differentiate original plants from counterfeit plants. The quality of genomic DNA is an important factor affecting molecular identification. However, the processing can lead to DNA degradation of the herbal medicines, which can make it difficult for their molecular identification. Objectives To establish a genomic DNA degradation model of Gentiana crassicaulis Radix to evaluate the effects of processing methods and storage times on genomic DNA integrity. Materials and Methods A genomic DNA degradation model of G. crassicaulis—the original plant source of the Chinese herbal medicine G. crassicaulis Radix—was established using a steam heating method. Genomic DNA integrity of G. crassicaulis Radix was evaluated using capillary electrochromatography (CEC) fingerprinting and polymerase chain reaction (PCR) of DNA barcoding markers following different processing and drying methods, including slicing (sliced roots), no slicing (whole roots), stoving, air drying, and sweating. Results CEC fingerprinting and DNA barcoding PCR effectively evaluated genomic DNA integrity. Compared to whole roots, sliced roots better helped maintain genomic DNA integrity. As the storage time increased, the integrity of the genomic DNA reduced; the integrity of the genomic DNA of sliced roots was greater than that of whole roots. Furthermore, the interactions between slicing and drying methods possibly reduced the genomic DNA integrity. Conclusion A genomic DNA degradation model and an evaluation system for herbal medicines were established. Our findings can help optimize the method for processing G. crassicaulis Radix and establish the traceability of genuine herbal medicines. Key Message The quality of genomic DNA is an important factor affecting molecular identification, which is essential to determine original plants. The results of our study can help develop a method for processing G. crassicaulis Radix and enable the traceability of genuine herbal medicines.

Combating Counterfeit and Substandard Medicines in India: Legal Framework and the Way Ahead

India has witnessed an exponential rise in markets of counterfeit medicines. Public health and well-being have suffered drastically due to these nefarious enterprises that are engaged in the trade of fake and substandard drugs for making illegal profits. As per WHO, the global market of fake drugs amount to 200 billion USD and 67% of these counterfeit drugs were categorized as dangerous to human health. Perpetrators have targeted Indian markets because it is a lucrative avenue for them and India doesn’t have a stringent regime or legal framework to tackle the menace of counterfeit drugs. India is the fourth largest export-import market for counterfeit and substandard medicines. In addition to people, ethical companies manufacturing genuine medicines have also endured heavy losses due to the booming counterfeit medicine market. Though India has certain administrative bodies in place to combat the challenge, criminals keep coming up with new methods to defraud the public as well as the government. The authors, in this article, have attempted to conduct a comprehensive analysis of the contemporary trends and challenges pertaining to counterfeit and substandard drugs racket. The author has also analyzed the legislative and policy framework and its efficacy against the menace of fake and substandard drugs.

Digital Transformation in Pharmaceutical Supply Chain: An African Case

Abstract Background: The pharmaceutical supply chain, pivotal in ensuring timely and efficient delivery of medical goods, has experienced significant challenges in the African context. Infrastructure deficiencies, fragmented distribution networks, and limited transparency have historically been obstacles in ensuring the consistent flow of essential drugs and treatments. Materials and Methods: The transformative power of digital technologies in reconfiguring the pharmaceutical supply chain across Africa. Drawing on multiple case studies, this paper presents evidence of how technologies such as blockchain, artificial intelligence, and the Internet of Things (IoT) are being employed to enhance traceability, improve inventory management, and optimize distribution routes. These digital innovations are not only ensuring the integrity of medicines by reducing counterfeit products but are also enhancing the agility of the supply chain to respond to sudden market and health demands. Results: Executed in a thorough data analysis strategy to interpret the results and extract significant insights by investigating the challenges faced in this digital transformation, which include the need for skills development, infrastructure investment, and the creation of supportive regulatory environments. The study underscores the role of partnerships between governments, international organizations, and private enterprises in driving these innovations. Conclusion: While the journey of digital transformation in Africa’s pharmaceutical supply chain is ongoing, there are promising strides being made. By embracing digital solutions, Africa is positioning itself to better tackle health challenges and ensuring that its populace has access to genuine and essential medicines. This research contributes to a deeper understanding of digital transition strategies and offers actionable insights for stakeholders involved in global health and supply chain management.

Counterfeit medicines: relevance, consequences and strategies to combat the global crisis

Counterfeiting of medicines, also known as “falsification” or “adulteration”, is the process in which the identity, origin, or history of genuine medicines are intentionally modified. Currently, counterfeit medicines are a global crisis that affects and is mostly caused by developing countries in Asia, Africa and Latin America. These countries lack strict law enforcement against this practice and have low-income populations with medicinal needs. Lately, the crisis has escalated, impacting developed countries as well, e.g., the US and the EU, mainly via the Internet. Despite this extension, some current laws aim to control and minimize the crisis’ magnitude. Falsification of medicines maintains an illegitimate supply chain that is connected to the legitimate one, both of which are extremely complex, making such falsification difficult to control. Furthermore, political and economic causes are related to the crisis’ hasty growth, causing serious consequences for individuals and public health, as well as for the economy of different countries. Recently, organizations, technologies and initiatives have been created to overcome the situation. Nevertheless, the development of more effective measures that could aggregate all the existing strategies into a large functioning network could help prevent the acquisition of counterfeit medicines and create awareness among the general population.

Falsified and substandard medicines trafficking: A wakeup call for the African continent

While great effort is being placed on reducing disease burdens in Africa, the circulation of falsified and substandard medicines in the continent are reversing the hard-won gains. This commentary provides insights on the high (and increasing) burden, impact and threat that falsified and substandard medicines pose to the region's development. The proposed recommendations, such as a coherent multi-sectorial and government-led strategy, call for a fundamental rethink of approaches towards strong regulations, policies, legislations, community-based approaches, collaborations and investments, which all must be scaled up before this the situation gets out of control. These recommendations are of paramount importance and have the potential to ensure access to genuine medicines and also to avert therapeutic failure and intoxication from dangerous substances. In addition, there will be added benefits to the economic, social, health and well-being of the region. Concerted efforts towards medicine regulations have enormous potential to contribute towards averting many preventable deaths and reducing disease burden in the region. A paradigm shift is necessary to ensure quality medicines reach patients at community and healthcare facilities to prevent this silent epidemic in Africa.

Benchtop NIR data standardization on handheld spectrometers to identify paracetamol tablets

AbstractNear‐infrared spectroscopy (NIRS) allows innovative applications in terms of quality control, for example, in raw materials verification, in process analytical technology (PAT), and in discrimination between genuine and falsified medicines. The development of small and cheap handheld devices is expanding in the field, while trying to keep similar performances as benchtop instruments have. Considering traceability and quality control of drug compounds, this work is intended to identify 13 different paracetamol tablets on the Belgian market by using NIRS. The performances of a Fourier‐transform near‐infrared spectroscopy (FT‐NIR) benchtop and two handheld NIR spectrometers were investigated comparatively. All spectra were collected through the blister in the reflectance diffuse mode. NIR spectral fingerprints were pretreated and analyzed using principal component analysis (PCA) and classified with soft independent modeling of class analogy (SIMCA). The performances of the spectrometers were evaluated after standardization of the reference benchtop database to the handheld spectrometers. The instrumental response of the benchtop spectrometer was standardized towards the handheld device using the piecewise direct standardization (PDS) algorithm. These investigations permitted the advantages and limitations of NIR data standardization on predictive models to be pointed out. The SIMCA models based on the spectral data of the benchtop (B), handheld 1 (H1), and handheld 2 (H2) instruments had an accuracy of 99.2%, 97.7%, and 96.2%, respectively. The same accuracy was obtained with the models of the transferred benchtop spectra for the H1 and H2 devices. However, adding handheld spectra to the transferred benchtop spectra resulted in models with improved accuracy: from 97.7% to 98.5% for the H1 instrument and from 96.2% to 97.7% for the H2 instrument. The proposed strategy highlights the potential of using a reference database collected by NIRS for pharmaceutical analyses by handheld NIR spectrometers in terms of traceability.

Sounding out falsified medicines from genuine medicines using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)

The trade in falsified medicine has increased significantly and it is estimated that global falsified sales have reached $100 billion in 2020. The EU Falsified Medicines Directive states that falsified medicines do not only reach patients through illegal routes but also via the legal supply chain. Falsified medicines can contain harmful ingredients. They can also contain too little or too much active ingredient or no active ingredient at all. BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy) harnesses an acoustic phenomenon associated with the dissolution of a sample (tablet or powder). The resulting acoustic spectrum is unique and intrinsic to the sample and can be used as an identifier or signature profile. BARDS was evaluated in this study to determine whether a product is falsified or genuine in a rapid manner and at lower cost than many existing technologies. A range of genuine and falsified medicines, including falsified antimalarial tablets from south-east Asia, were tested, and compared to their counterpart genuine products. Significant differences between genuine and falsified doses were found in their acoustic signatures as they disintegrate and dissolve. Principal component analysis was employed to differentiate between the genuine and falsified medicines. This demonstrates that the tablets and capsules included here have intrinsic acoustic signatures which could be used to screen the quality of medicines.

UHPLC for quality evaluation of genuine and illegal medicines containing sildenafil citrate and tadalafil.

One of the highest incidences of illegal drug products is related to phosphodiesterase-5 inhibitors, used in treatment of erectile dysfunction, including those containing sildenafil citrate and tadalafil. In this context, comprehensive evaluation of the quality of genuine and illegal medicines was performed. A simple and rapid ultra-high performance liquid chromatography (UHPLC-UV) method to quantify sildenafil and tadalafil in the presence of six degradation products was developed and validated. Sildenafil and tadalafil were submitted to forced degradation. The separation was carried out on a Kinetex C18 (50 × 2.1 mm; 1.7 μm) column with mobile phase composed of acetonitrile and aqueous triethylamine solution. The calibration curves were linear in the range of 14-126 μg mL-1 for sildenafil citrate and 4-36 μg mL-1 for tadalafil and the method proved to be selective, precise, accurate and robust. Sildenafil degraded in oxidative media, whereas tadalafil degraded in acidic, alkaline and oxidative environment. The chemical structures and the mechanisms for the formation of the main degradation products were proposed by UHPLC coupled to tandem mass spectrometry. The UHPLC-UV method was applied in the pharmaceutical analysis of genuine and seized medicines. Some of them did not meet quality standards, mainly due to contents below specifications and the large variation on contents between units within a batch.

Detection of counterfeit and substandard tablets using non-invasive NIR and chemometrics - A conceptual framework for a big screening system

A detailed step-by-step procedure for revealing counterfeit and substandard tablets is presented. Non-invasive NIR measurements are used for data collection. The entire complex multi-layer object as the “packaging -coating-core” system requires special treatment at all stages of model development and validation. The influence of each layer is studied. A procedure that covers data collection, construction of the model, as well as special internal and external validation is advocated here. A special set of objects called ‘nearest of kin’ (NoK) collection, which consists of generic medications nearest to the target objects, assists in reliable assessment of the model specificity. The whole procedure summarizes the results obtained for over a thousand different dosage forms of tablets. Two real-world examples of genuine and counterfeit medicines are considered. The first example presents uncoated tablets with high concentration of active ingredient and fairly simple set excipients. Its NoK collection consists of six different manufacturers. The second example presents coated tablets with low concentration of active ingredient and rather complex set of excipients. Its NoK collection is presented by seven different manufacturers.

The use of microtomographic imaging in the identification of counterfeit medicines

The practice of drug counterfeiting is an important challenge due to the extremely rapid growth rate of this disturbing trend and its immense potential harmfulness. According to WHO even 10% of counterfeit medicines can be exact copies of genuine medicines: they have exactly the same quantitative and qualitative composition in terms of both API and excipients. Thus, the identification of such drugs using chemical analysis methods can be very difficult or even impossible. The aim of this study was to verify the effectiveness of using computed microtomography in the identification of counterfeit medicines.The General Electric v|tome|x s microtomography system was used in the study. The recorded microtomographic scans were subjected to analysis and image processing. The following parameters of image analysis and processing were identified: mean brightness, homogeneity, contrast, quadratic tree decomposition.The original and falsified 100-mg Viagra® tablets (Pfizer) were compared. 8 original Viagra® tablets (hereinafter referred to as T) and 8 falsified tablets (hereinafter referred to as F1-F8) were tested.The range of variation for the genuine medicines against fake products was: brightness: 90.9–117.1 vs 33.8, 50.1, homogeneity: 0.84–0.92 vs 0.94–1.01 and quadratic tree decomposition for the 1 × 1 mask: 55768–58792 vs 0–439.The proposed method of microtomographic image analysis and processing enables to identify solid dosage forms, including those that are an accurate chemical copy, with high sensitivity and specificity, 94.5% and 97%, respectively. The advantage of the μCT method is its high efficiency and speed, whereas the disadvantages include the possibility of using only solid dosage forms and high equipment costs.

Medicine discrimination of NIRS based on a regularized collaborative representation identification with the gabor optimizer

Counterfeit medicines, which adversely affect patients’ health and lives, are widespread. Therefore, discriminating between genuine and counterfeit medication is becoming a critical concern. Near-infrared spectroscopy (NIRS) is a popular and effective technique that has nondestructive characteristics and is used for medicine identification. To discriminate between genuine and counterfeit medicines, a sparse signal representation model is established in the presence of spectrum crossover and overlapping. However, the sparsity of nonzero representation coefficients is low when solving L2 -norm in the representation model. To overcome this problem, a novel identification model, called regularized collaborative representation identification with the Gabor optimizer (RCRCG), is proposed in this paper. A Gabor filter is adopted to control L2 -norm for the more relevant factor vectors. Then, Lasso regulation on local identification is used to improve the accuracy of medicine discrimination. The results of experiments using NIRS samples from three datasets (with the use of erythromycin ethylsuccinate and domperidone as active substances) show that the proposed method is more effective and robust than the existing methods and its speed is twice that of the Sparse Representation-based Classification (SRC) and Class L1 -optimizer classifier with the closeness rule (C_CL1C).

Triboelectric Nanogenerator (TENG) Mass Spectrometry of Falsified Antimalarials.

RationaleAn epidemic of low‐quality medicines continues to endanger patients worldwide. Detection of such ‘medicines’ requires low cost, ambient ionization sources coupled to fieldable mass spectrometers for optimum sensitivity and specificity. With the use of triboelectric nanogenerators (TENGs), the charge required to produce gas‐phase ions for mass analysis can be obtained without the need for high‐voltage electrical circuitry, simplifying and lowering the cost of next‐generation mass spectrometry instruments.MethodsA sliding freestanding (SF) TENG was coupled to a toothpick electrospray setup for the purposes of testing if falsified medicines could be fingerprinted by this approach. Extracts from both genuine and falsified medicines were deposited on the toothpick and the SF TENG actuated to generate electrical charges, resulting in gas‐phase ions for both active pharmaceutical ingredients and excipients.ResultsOur previous work had shown that direct analysis in real time (DART) ambient mass spectrometry can identify the components of multiple classes of falsified antimalarial medicines. Experiments performed in this study show that a simple extraction into methanol along with the use of a SF TENG‐powered toothpick electrospray can provide similar detection capabilities, but with much simpler and rugged instrumentation, and without the need for compressed gases or high‐voltage ion source power supplies.ConclusionsTENG toothpick MS allows for rapid analyte ion detection in a safe and low‐cost manner, providing robust sampling and ionization capabilities.

Chiroptical and vibrational spectroscopic study of genuine and counterfeit medicines containing tadalafil.

The production and distribution of counterfeit pharmaceuticals present a serious problem worldwide. This is true especially in case of phosphodiesterase type 5 inhibitors for treating erectile dysfunction, where consumers often prefer buying them anonymously from unverified sources. In this study, genuine and counterfeit Cialis® 20mg tablets were analyzed by electronic circular dichroism, vibrational circular dichroism, and infrared spectroscopy. The characteristic spectral patterns were identified by comparison with the spectra of tadalafil standard as an active pharmaceutical ingredient, and its presence was confirmed in all samples. The amount of tadalafil, however, was markedly lower in the case of counterfeit tablet as the observed band intensities were considerably lower. No other significant differences between the genuine and counterfeit tablets were revealed. Ab initio density functional theory calculations provided a detailed description of the stable conformers of tadalafil in a solution and enabled thorough interpretation of the experimental spectra.

휴대형 근적외선/가시광선 분광기를 이용한 의약품 분류기법

It is important to prescribe and take medicines that are appropriate for symptoms, since medicines are closely related to human health and life. Moreover, it becomes more important to accurately classify genuine medicines with counterfeit, since the number of counterfeit increases worldwide. However, the number of high-quality experts who have enough experience to properly classify them is limited and there exists a need for the automatic technique to classify medicine tablets. In this paper, we propose a method to classify the tablets by using a handheld spectrometer which provides both Near Infra-Red (NIR) and visible light spectrums. We adopted Support Vector Machine(SVM) as a machine learning algorithm for tablet classification. As a result of the simulation, we could obtain the classification accuracy of 99.9 % on average by using both NIR and visible light spectrums. Also, we proposed a two-step SVM approach to discriminate the counterfeit tablets from the genuine ones. This method could improve both the accuracy and the processing time.

Pharmaceutical Evaluation of Mrityunjaya Rasa w.s.r. to preparatory method of Rasendra Sara Sangraha

Mrityunjaya Rasa is a herbo-mineral formulation mentioned under Jwarachikitsa in Rasendra Sara Sangraha along with different Anupana. It is having ingredients like Shuddha Hingula, Shuddha Gandhaka, Shuddha Vatsanabha, Shuddha Tankana, Pippali and Maricha which show significant result on various types of fever. All drugs of Mrityunjaya Rasa are having properties like Katu Rasa, Teekshna Guna and Jwaraghana action. Rasaushadhis given in smaller dosage restore the individual’s health immediately. In preparation of Rasaushadhis, precaution must be taken throughout the whole procedure. Now-a-days quality assured drugs are not formulated because Standard operative procedure (SOPs) is not followed properly so chances of adverse drug reaction also increase. By following SOP genuine medicines can be prepared. The purpose of standardizing traditional remedies is obviously to ensure therapeutic efficacy. To establish the efficacy along with safety of Rasaushadhis, precaution must be taken throughout the whole procedure to formulate the medicine. So here an effort is placed to validate the process of Shodhana of Hingula, Gandhaka, Vatsanabha and Tankana and to develop a Standard operative procedure for preparation of Mrityunjaya Rasa.