Chandrakant Ramkrishna Malwade

Purification of artemisinin from quercetin by anti-solvent crystallization

In the present work, anti-solvent crystallization of artemisinin from four different organic solvents (methanol, ethanol, acetonitrile, and acetone) was studied. Water was used as anti-solvent. The effect of an impurity (quercetin) on the performance of anti-solvent crystallization of artemisinin was investigated. The fundamental process data such as solubility of artemisinin in pure organic solvents and their binary mixtures with varying composition water were measured at room temperature. The solubility of quercetin was measured only in pure organic solvents at room temperature. Anti-solvent crystallization experiments were designed based on the fundamental process data determined. Firstly, the anti-solvent crystallization of artemisinin without impurity was performed from all four organic solvents and then the experiments were repeated with addition of an impurity (quercetin) while keeping all other process parameters constant. Two different concentrations of impurity, i.e., 10% and 50% of its solubility, in the respective organic solvents at room temperature were used. The effect of impurity on performance of anti-solvent crystallization was evaluated by comparing the yield and purity of the artemisinin obtained with those in the absence of impurity. Results of the present work demonstrated that the presence of quercetin in the solution does not affect the final yield of artemisinin from the solution of each of four organic solvents used. However, the purity of artemisinin crystals were reduced when quercetin concentration was 50% of its solubility in all solvents studied.

Chemometrics for Analytical Data Mining in Separation Process Design for Recovery of Artemisinin from Artemisia annua

The separation process for recovery of natural products from plants very often employs multiple separation techniques, and key to the success of such processes is to find the synergy between different separation techniques. Molecular level understanding of process streams is highly required in order to determine the synergy between unit operations, which can be attained through analysis of process streams using advanced process analyzers such as high performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC-MS), etc. Very often use of such process analyzers generates an enormous amount of data making it difficult to extract useful information. Therefore, application of chemometrics for extracting process information from analytical data of process streams is demonstrated in this work. The multivariate data analysis technique PARAFAC is used to extract chemical information such as number of impurities, their relative concentrations, and finally their identification from rather complex analytical chromatograms of flash column chromatography (flash CC) fractions during purification of artemisinin from the crude extract of Artemisia annua. Crude extract of A. annua leaves obtained from dichloromethane is used in this work. Prior to the application of PARAFAC, the data set is preprocessed to remove baseline drift and peak misalignment caused by retention time shifts due to matrix effects. The process information extracted from analytical chromatograms by using the PARAFAC technique indicated the presence of impurities ranging from coumarins, polyacetylenes, and flavonoids to artemisinin related compounds in the flash CC fractions.

Conceptual process synthesis for isolation and purification of natural products from plants - A case study of artemisinin from Artemisia annua

Abstract A systematic method based on conceptual process synthesis for recovery of natural products from their biological sources is presented. The proposed methodology divides the task into two major subtasks namely, isolation of target compound from a chemically complex solid matrix of biological source and purification of the target compound from the crude extract. This methodology consists of three major separation techniques to achieve the task and provides a platform to generate different process alternatives by employing different combinations of separation units and with different set of key process variables. Decision making about the different combinations of separation units as well as key process variables is based upon the process information collected at every step with the help of process analytical techniques (PAT) and heuristics. The optimal combination of different separation units and set of key process variables is determined in an iterative approach. In the present work, this methodology is applied to isolate and purify artemisinin, an anti-malarial drug from the plant Artemisia annua.

Process Analytical Technology for Crystallization of Active Pharmaceutical Ingredients

BACKGROUND Pharmaceutical industry is witnessing increased pressure to introduce innovative and efficient processes for manufacturing Active Pharmaceutical Ingredients (APIs) in order to be competitive as well as to meet the stringent product quality requirements set by regulatory authorities. Crystallization with its ability to engineer the final product to the desired qualities such as purity, polymorphic form, particle size and shape is one of the most important steps involved in the manufacturing of APIs. Therefore, development of crystallization processes with better understanding of process parameters and their impact on quality of APIs and subsequently the drug products assume great significance for the pharmaceutical industry. METHODS This review paper focuses on the application of PAT tools, an integral part of Quality by Design (QbD) approach, for better understanding, control, and design of crystallization processes in the manufacturing of APIs. RESULTS Firstly, various steps involved in the drug development process are introduced briefly with emphasis on crystallization as one of the most important steps in manufacturing of drug products. Secondly, Critical Quality Attributes (CQAs) of drug products, their dependence on material attributes of APIs and role of crystallization in manipulating material attributes of APIs has been discussed. Finally, application of PAT tools such as advanced process analyzers for continuous monitoring, chemometric methods for multivariate data analysis, and control strategy for APIs crystallization processes has been reviewed along with some examples. CONCLUSION Application of PAT in crystallization of APIs facilitates development of robust processes that works within the design space to produce the drug products of consistent quality. Furthermore, it opens up the opportunities for continuous improvement of the process by generating knowledge base of existing processes.

Chemometrics for analytical data mining in separation process design for recovery of artemisinin from Artemisia annua

The separation process for recovery of natural products from plants very often employs multiple separation techniques, and key to the success of such processes is to find the synergy between different separation techniques. Molecular level understanding of process streams is highly required in order to determine the synergy between unit operations, which can be attained through analysis of process streams using advanced process analyzers such as high performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC-MS), etc. Very often use of such process analyzers generates an enormous amount of data making it difficult to extract useful information. Therefore, application of chemometrics for extracting process information from analytical data of process streams is demonstrated in this work. The multivariate data analysis technique PARAFAC is used to extract chemical information such as number of impurities, their relative concentrations, and finally their identification from rather c...