Manufacture Of Medicines Research Articles

Design and performance evaluation of a superabsorbent polymer‐based dryer for medicinal plants

In this study, a superabsorbent polymer-based dryer (Polydryer) was constructed to dry rhizomes and fruits of various medicinal plants (turmeric, greater galangal, lesser galangal, ginger, Curcuma, finger root, and chili) into dried natural ingredients for the manufacture of drugs and medicines (simplisia). The Polydryer mainly consisted of a drying cabinet with three trays, a superabsorbent polymer hydrogel (polygel) cabinet with nine trays, and a blower. Ambient air at different airflow rates was utilized as the drying medium. A polygel based on acrylic acid monomers and cassava starch was employed to absorb the moisture carried by the air flow. Three Polydryer configurations, which included closed-loop or open-loop modes, were investigated to select the optimum dryer configuration. Drying of the rhizomes required 4–5 days to reach the maximum permissible moisture content in simplisia (≤12%). The simplisia exhibited low color change and less structural damage than the commercial simplisia. Practical applications Superabsorbent polymer materials have been known to have outstanding moisture absorption properties. Upon storing in an ambient atmosphere, the material tends to swell in the presence of moisture. These promising properties prompt the development of a superabsorbent polymer-based dryer. The ability of the superabsorbent polymer to absorb moisture in the ambient atmosphere enables a low-temperature operation, retaining material structure and maintaining bioactive compounds in the medicinal plant materials. This study revealed that drying medicinal plants using the Polydryer is time-effective compared with conventional drying techniques, with less structural damage to the materials. This technology is simple, cost-effective, energy-efficient, and highly sustainable for the drying process of medicinal plants that can be implemented in agricultural and pharmaceutical industries. This study is the first to report the application of superabsorbent polymer in the drying process of medicinal plants.

Smartphone-enabled 3D printing of medicines

3D printing is a manufacturing technique that is transforming numerous industrial sectors, particularly where it is key tool in the development and fabrication of medicinees that are personalised to the individual needs of patients. Most 3D printers are relatively large, require trained operators and must be located in a pharmaceutical setting to manufacture dosage forms. In order to realise fully the potential of point-of-care manufacturing of medicines, portable printers that are easy to operate are required. Here, we report the development of a 3D printer that operates using a mobile smartphone. The printer, operating on stereolithographic principles, uses the light from the smartphone’s screen to photopolymerise liquid resins and create solid structures. The shape of the printed dosage form is determined using a custom app on the smartphone. Warfarin-loaded Printlets (3D printed tablets) of various sizes and patient-centred shapes (caplet, triangle, diamond, square, pentagon, torus, and gyroid lattices) were successfully printed to a high resolution and with excellent dimensional precision using different photosensitive resins. The drug was present in an amorphous form, and the Printlets displayed sustained release characterises. The promising proof-of-concept results support the future potential of this compact, user-friendly and interconnected smartphone-based system for point-of-care manufacturing of personalised medications.

A sustainable-resilience healthcare network for handling COVID-19 pandemic.

In this paper, a new production, allocation, location, inventory holding, distribution, and flow problems for a new sustainable-resilient health care network related to the COVID-19 pandemic under uncertainty is developed that also integrated sustainability aspects and resiliency concepts. Then, a multi-period, multi-product, multi-objective, and multi-echelon mixed-integer linear programming model for the current network is formulated and designed. Formulating a new MILP model to design a sustainable-resilience healthcare network during the COVID-19 pandemic and developing three hybrid meta-heuristic algorithms are among the most important contributions of this research. In order to estimate the values of the required demand for medicines, the simulation approach is employed. To cope with uncertain parameters, stochastic chance-constraint programming is proposed. This paper also proposed three meta-heuristic methods including Multi-Objective Teaching–learning-based optimization (TLBO), Particle Swarm Optimization (PSO), and Genetic Algorithm (GA) to find Pareto solutions. Since heuristic approaches are sensitive to input parameters, the Taguchi approach is suggested to control and tune the parameters. A comparison is performed by using eight assessment metrics to validate the quality of the obtained Pareto frontier by the heuristic methods on the experiment problems. To validate the current model, a set of sensitivity analysis on important parameters and a real case study in the United States are provided. Based on the empirical experimental results, computational time and eight assessment metrics proposed methodology seems to work well for the considered problems. The results show that by raising the transportation costs, the total cost and the environmental impacts of sustainability increased steadily and the trend of the social responsibility of staff rose gradually between − 20 and 0%, but, dropped suddenly from 0 to + 20%. Also in terms of the on-resiliency of the proposed network, the trends climbed slightly and steadily. Applications of this paper can be useful for hospitals, pharmacies, distributors, medicine manufacturers and the Ministry of Health.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10479-021-04238-2.

Peculiarities of digging topinambur (Jerusalem artichoke) tubes on the irrigation lands of Uzbekistan

Jerusalem artichoke crops, as a new crop in irrigated agriculture in Uzbekistan, are expanding more and more. Scientists have developed many recipes for using Jerusalem artichoke tubers in the form of food additives that help improve the quality of bakery products, sausages, and various drinks. The pharmaceutical industry uses Jerusalem artichoke for the manufacture of medicines, in the chemical-technological industry, high-quality cellulose is obtained. In agriculture, it is used as a quality animal feed. Therefore, it is required to mechanize the entire cycle of its cultivation. The most time-consuming process is the harvesting of tubers. To dig up Jerusalem artichoke tubers, ordinary potato diggers are used, which are not adapted to dig up the tubers formed under the bottom of the irrigation furrows. The article provides materials on the adaptation of a potato digger for digging up Jerusalem artichoke tubers by installing a special ploughshare on it. Such a share has a complex working surface, adapted for more complete digging of tubers from under the irrigation furrow, reducing losses to 5 percent or less of the grown crop. Such a share must have an increased working width, which makes the process of its operation energy-intensive. Therefore, the authors propose to make a ploughshare from longitudinal strips - grates, when a part of the soil will be separated through their open intervals, facilitating the process of separating the soil from the tubers. Field experiments with such plowshares have shown their effectiveness.

Bioreactor Technology for Cell Therapy Manufacturing in Regenerative Medicine

Bioreactor Technology for Cell Therapy Manufacturing in Regenerative Medicine

Professional burnout and experience in implementing lean manufacturing in medicine

Using the methodology of psychological diagnostics of V.A. Vinokur «Attitude to work and professional burnout» and the original questionnaire «Lean competencies of a medical worker», the manifestations of professional burnout in medical workers of medical organizations in which lean manufacturing technologies were introduced were studied. The study for the first time established an inverse correlation between the severity of professional burnout and involvement in lean manufacturing in medical workers. Based on the results obtained, it is suggested that participation in project activities to improve processes in a medical organization can help reduce the severity of emotional exhaustion and work tension, as well as contribute to professional development and increase the self-esteem of medical workers.

STUDY OF THE EFFECT OF ABAMEKUR ON THE LIFESPAN OF RATS

The article shows the achievements of the last decades, which led to the emergence of new
 directions in the manufacture of medicines, to the revision and reassessment of a number of theoretical
 positions and traditional techniques. The most significant influence on the development of dosage forms
 was the establishment of the dependence of the therapeutic effect of medicinal substances not only on the
 chemical structure and physiological activity, but also on other factors, such as the technology of drug
 manufacture, the degree of dispersion of medicinal substances, their physical condition, the type of
 dosage form, etc. The rational way to find new drugs, namely antiparasitic ones, is still to vary the
 structure of the molecules of known chemical compounds, for example, avermectins, and to optimize
 them-to strengthen the desired and weaken the side effect by creating a dosage form.
 Until recently, the dosage form was considered from the point of view of its compliance with
 purely technological requirements, i.e., as a more or less convenient form of the active substance that has
 the appropriate properties: particle size, consistency, hardness, fusibility, flowability, surface appearance,
 smell, taste, mass. At the same time, the dosage form has a significant effect on the effect of the drug
 substance included in it. It is the whole set of properties, and not only the active substance, affects a
 certain process in the body.

Optimization of Energy-Intensive Process in Ayurvedic Medicine Manufacturing Unit—a Case Study

Optimization of Energy-Intensive Process in Ayurvedic Medicine Manufacturing Unit—a Case Study

Characterization of Potentized (Homeopathic, Anthroposophical and Antihomotoxic) Medicines Registered and Notified In Brazil

Background: Potentized medicines include, according to the Brazilian legislation, homeopathic, anthroposophic, and antihomotoxic medicine and are regulated by the Brazilian Health Surveillance Agency (ANVISA). 
 Aim: This study aims to analyze and describe a profile of potentized medicines manufactured in Brazil, either registered or notified. 
 Methodology: Information was obtained by data analysis related to ANVISA’s electronic medicine registration system. 
 Results: The results, obtained as of September 2012, showed that 106 potentized medicines were registered and 519 were notified. Among the registered medicines, 92.0% were combined and 100.0% of the notified were simple medicines. For registered medicines, there were equivalent manufacturing scales among them, whereas for notified medicines, there was a predominance of centesimal scales. Active pharmaceutical ingredients (API’s) of vegetal origin were the most commonly used for potentized medicine manufacturing processes; the oral route was the most common form of administration. Potentized medicines manufacturing units are more often located in southeast region of Brazil. In addition, homeopathic medicines prevail as registered or notified medicines, followed by anthroposophic medicines.
 Conclusions: The results of the study are expected to be useful as reference material for ANVISA to improve its regulatory activity as well the industry sector and other stakeholders.

Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine.

Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative medicine for over two decades, wherein clinical experience was gathered for safely managing burns and refractory cutaneous ulcers. Inherent FPC advantages include high robustness, optimal adaptability to industrial manufacture, and potential for effective repair stimulation of wounded tissues. Major technical bottlenecks in cell therapy development comprise sustainability, stability, and logistics of biological material sources. Herein, we report stringently optimized and up-scaled processing (i.e., cell biobanking and stabilization by lyophilization) of dermal FPCs, with the objective of addressing potential cell source sustainability and stability issues with regard to active substance manufacturing in cutaneous regenerative medicine. Firstly, multi-tiered FPC banking was optimized in terms of overall quality and efficiency by benchmarking key reagents (e.g., medium supplement source, dissociation reagent), consumables (e.g., culture vessels), and technical specifications. Therein, fetal bovine serum batch identity and culture vessel surface were confirmed, among other parameters, to largely impact harvest cell yields. Secondly, FPC stabilization by lyophilization was undertaken and shown to maintain critical functions for devitalized cells in vitro, potentially enabling high logistical gains. Overall, this study provides the technical basis for the elaboration of next-generation off-the-shelf topical regenerative medicine therapeutic products for wound healing and post-burn care.

A data-driven workflow for evaporation performance degradation analysis: a full-scale case study in the herbal medicine manufacturing industry

A data-driven workflow for evaporation performance degradation analysis: a full-scale case study in the herbal medicine manufacturing industry

Pharmaceutical industry payments and assisted reproduction in Australia: a retrospective observational study

ObjectivesTo investigate the extent and nature of pharmaceutical industry payments related to fertility and assisted reproduction in Australia.Design and settingThis retrospective observational study employed four databases compiled from publicly available...

Combatting Substandard and Counterfeit Medicines in the Nigerian Drug Market: How Industrial Pharmacists Can Rise Up to the Challenge.

Substandard and counterfeit medicines (SCMs) are a major public health threat in Africa. In Nigeria, the manufacture and distribution of substandard and counterfeit medicines in the drug market are booming, despite the efforts of law enforcement agencies to crack down on criminal syndicates over the years. The current situation has been exacerbated due to factors tied to unregulated open drug markets, lack of counterfeit detection technology, poor local pharmaceutical manufacturing capacity, and porous cross-border monitoring and surveillance systems. However, industrial pharmacists have a key role to play in combatting the production and circulation of SCMs in the Nigerian drug market. In this commentary, we examine the prevalence of SCMs in Nigeria and proffer feasible recommendations that industrial pharmacists can leverage to ensure its effective containment.

How have Economic Evaluations in Relapsing Multiple Sclerosis Evolved Over Time? A Systematic Literature Review.

IntroductionThe introduction of disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) over the last two decades has prompted the economic assessments of these treatments by reimbursement authorities. The aim of this systematic literature review was to evaluate the modeling approach and data sources used in economic evaluations of DMTs for RMS, identify differences and similarities, and explore how economic evaluation models have evolved over time.MethodsMEDLINE®, Embase®, and EBM Reviews databases were searched using Ovid® Platform from database inception on 25 December 2019 and subsequently updated on 17 February 2021. In addition, health technology assessment agency websites, key conference proceedings, and gray literature from relevant websites were screened. The quality of included studies was assessed using the Drummond and Philips checklists.ResultsA total 155 publications and 30 Health Technology Assessment (HTA) reports were included. Most of these were cost-utility analysis (73 studies and 25 HTA reports) and funded by medicines manufacturers (n = 65). The top three countries where studies were conducted were the USA (n = 29), the UK (n = 16), and Spain (n = 10). Studies predominantly used Markov cohort models (94 studies; 25 HTAs) structured based on the Expanded Disability Status Scale (EDSS) with 21 health states (20 studies; 12 HTA reports). The London Ontario and British Columbia data sets were commonly used sources for natural history data (n = 33; n = 13). Twelve studies and ten HTAs from the UK assumed a waning of DMT effect over the long term, while this was uncommon in studies from other countries. Nineteen studies adjusted for multiple sclerosis (MS)-specific mortality estimates, while 18 studies used data from the national life table without adjustment. Studies prominently referred to mortality data that were about two decades old. The data on treatment effect was generally obtained from randomized controlled trials (43 studies; 7 HTAs) or from published evidence synthesis (23 studies; 24 HTAs). Utility estimates were derived from either published studies and/or supplemented with data from RCTs. Most of the models used the lifetime horizon (n = 37) with a 1-year cycle length (n = 63).ConclusionAs expected, similarities as well as differences were observed across the different economic models. Available evidence suggests models should continue using the Markov cohort model with 21 EDSS-based states, however, allowing the transition to a lower EDSS state and assuming a sustained treatment effect. With reference to the data sources, models should consider using a contemporary MS-specific mortality data, recent natural history data, and country-specific utility data if available. In case of data unavailability, a sensitivity analysis using multiple sources of data should be conducted. In addition, future models should incorporate other clinically relevant outcomes, such as the cognition, vision, and psychological aspects of RMS, to be able to present the comprehensive value of DMTs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00264-1.

Chemistry behind the Betel Leaves and Betel Quid: Their Health Benefits and Adverse Health Effect-a Review

Piper betle leaves have been used in Indian and Chinese folk medicine for centuries and is well known for its extensive use in Ayurvedic medicine. Recently, it has been used as a chemo-preventive agent because of its anti-oxidant activity. Several biologically active compounds from P. betle have potential for use as medicines, neutraceuticals and industrial compounds. Consumption of betel leaf is usually in the form of betel quid which consists of areca nut, lime and some spices with or without tobacco. Long term consumption of betel quid with tobacco is known to cause adverse health effects, mainly carcinomas. In addition to oral cancer it is also known to induce chromosomal aberrations and tumours in the pharynx and oesophagus. However, consumption of betel leaf alone does not induce cancer and has invaluable health benefits due to its tremendous medicinal properties. Phenol-rich leaves of P. betle show high antioxidant activities and because of its anti-oxidant properties, it has been used as a chemopreventive agent. Its oil is used as an industrial raw material for manufacturing of medicines, perfumes, mouth fresheners, tonics, food additives etc. The leaves are nutritive and contain anti-carcinogens showing promise for manufacturing of a blood cancer drug. It is also playing a vital role in various ceremonies and auspicious occasions as an indicator of goodness. Since the traditional use of P. betle involves chewing, it offers possibilities of use in drug delivery through buccal mucosa bypassing the gastric route.

Incentive alignment for blockchain adoption in medicine supply chains

In recent years, blockchain technology has been increasingly adopted in OTC medicine supply chains, enabling customers to track the entire process from raw material purchasing to finished medicine distribution. This improves the brand image and hence expands the market. With the use of blockchain, information transparency can be achieved because data are stored immutably and safely in a distributed database that is accessible by all supply chain members. However, will the incentives for supply chain members to participate in blockchain for larger-scale demand come at the cost of information disclosure? In this paper, to investigate the supply chain members’ incentive alignment opportunities towards the adoption of blockchain technology, we consider a two-stage supply chain comprising two medicine manufacturers and a common retailer that has more accurate demand information than the manufacturers have. We find that, interestingly, the retailer has incentives to participate in blockchain when the manufacturers’ competition is mild and the demand variance is low. We further investigate the impact of blockchain on total surplus and customer surplus and find that the adoption of blockchain always benefits customers and society; therefore, blockchain can be particularly useful for social goods such as OTC medicine.

Pharmaceutical nationalism as an instrument to ensure the access to medicines

Keywords: pharmaceutical nationalism, access to drugs, compulsory licensing, governmentuse, exclusion from intellectual property rights
 The article concerns the emergence of the phenomena of«pharmaceutical nationalism» in the year of the COVID-19 pandemic. Pharmaceuticalnationalism is manifested in the qualitative and quantitative aspects. In the contextof a qualitative manifestation of pharmaceutical nationalism, we presume the politicalwill on establishing of a new state protectionist policy to local manufacturers ofmedicines, the establishing of preferences, exemptions of the patent monopoly basingon international legal instruments (TRIPS-flex). The quantitative aspect of pharmaceuticalnationalism is the primacy of satisfaction of the needs of the domestic marketof medicines in quantities that could ensure the biological security of individually foreach state, independently of the interests of others. The article also raises the issue ofthe need and means of forming pharmaceutical nationalism in Ukraine.The world community is calling for the demonopolization of research results on theprevention and treatment of COVID-19. WHO invites developers and companies towork together to ensure the disclosure of treatments and methods if they prove effective.International Federation of Library Associations and Institutions also presentedan open letter to WIPO urging WIPO to use all available flexible intellectual propertymechanisms to maximize global access to information (research data) on the treatmentof COVID-19. Canada, Israel and the EU are working to prevent the monopolizationof COVID-19 prevention and treatment.Ukraine should actively work to develop legislation in the field of compulsory licensing,as provided for in Art. 31 TRIPS Agreement. From a political point of view, itis the historical chance of Ukraine to become «he second India» or «the first Ukraine»in Europe in the production of generic medicines and biosimilars.

A micro-extrusion 3D printing platform for fabrication of orodispersible printlets for pediatric use

3D printed pharmaceuticals offers the potential to manufacture personalized medicines for patients. Such technology is of particular benefit to pediatric populations from the offer of increased patient compliance and dose flexibility. With a bench-to-patient approach, this study established and optimized the critical parameters of the semi-solid micro-extrusion 3D printing process to guarantee the quality attributes of the final dosage form. Pediatrics orodispersible printlets of hydrochlorothiazide were manufactured through the modification of printing parameters, as well as printing surfaces materials. The printlets were characterized and the dimensions were measured using a digital caliper and computer vision algorithm. This study identified that the printing surface material and the first printing layer are critical parameters for high-resolution printlets. Following the optimization of 3D printing parameters, high quality orodispersible printlets loaded with hydrochlorothiazide – specifically tailored for pediatric patient’s dosage forms – were obtained (4.62 mm × 1.90 mm). Mass and content uniformity assays demonstrated that the printlets satisfied the requirements for orodispersible printlets set by the European Pharmacopoeia. As such, in order to transition from laboratory research towards the treatment of patients, distinguishing accurate 3D printing parameters is necessary for the manufacture of medicines with key quality attributes that follow Pharmacopoeia requirements.

DIR reform, supply chain security, and more

DIR reform, supply chain security, and more

An Ethnobotanical Study of Tongkat Ali (Eurycoma longifolia Jack) on Malay Ethnic Group in Tanjung Balai, Karimun, Riau Islands

Tongkat ali (Eurycoma longifolia Jack) is one of the tropical forest plants in Indonesia, which is utilized as a raw material in the manufacture of various modern and traditional medicines. However, information regarding the potential and conservation of this plant in indigenous communities in Karimun, Riau Islands has not been well-documented. Therefore, researchers conducted a study in Pongkar Village and Karimun Anak, Tabing, Riau Islands concerning the potential and conservation of tongkat ali for the lives of the people in these research locations. Data were collected through an ethnobotanical approach and interviews with selected respondents, traditional healers, village heads, the representative from Karimun Forestry Conservation Office, and local people who utilize this plant in their daily lives. The results showed that the local community utilized tongkat ali (Eurycoma longifolia Jack) as medicinal ingredients to treat fever caused by malaria, to increase stamina, and to be an alternative source to increase the family’s income. In addition, efforts to conduct in-situ and ex-situ conservation supported by the community, indigenous communities, and government agencies are highly needed so that its utilization can be carried out sustainably.