Modern Instrumental Methods in Solid Dosage Form Analysis

The book “Modern Instrumental Methods in Solid Dosage Form Analysis” is focused on the description of selected modern instrumental methods widely used in the evaluation of dosage forms. It explains their main principles, provides a brief description of the instrumentation and offers numerous examples of practical applications in both the pharmaceutical research and development as well as the commercial pharmaceutical manufacture where these methods are used as valuable tools of quality assurance and quality control (QA/QC) of incoming raw materials, final medicinal products and manufacturing processes.

pplication of Beekeeping Products, their Standardized Substances and Apipreparations in Medicine, Pharmacy and Cosmetology

The monograph covers issues related to the use of bee products and their standardized substances in medicine, pharmacy and cosmetology. The publication describes the products of beekeeping, in particular (honey, propolis, flower pollen (bee pollen), bee venom, perga) as natural raw materials for production based on them in industrial conditions and in the conditions of pharmaceutical manufacture of pharmaceuticals and cosmetics. in order to provide the population with effective domestic natural medicines as an alternative method of treatment of various diseases. Characteristics, chemical composition and features of use of biologically active standardized substances on the basis of beekeeping products developed in Ukraine are presented: propolis phenolic hydrophobic drug, aqueous extract of propolis, honey, powdered honey, liphophilic extract of bee stalk, fermentation, substances of bee venom, perga, big bee larva biomass. The technology of production of extemporaneous medicinal apipreparations of different direction of action in the conditions of pharmacies is given. The publication is intended for a wide range of specialists of pharmacies in Ukraine, scientists and practitioners of pharmacy, medicine, apitherapy, beekeeping and cosmetology.

Manufacturing chemicals with light: any role in the circular economy?

We outline how recent developments in photochemistry can contribute to the realization of the 1912 vision of the pioneering Italian scientist Giacomo Ciamician, namely world-wide chemical-using industry-based chemical plants fuelled solely by the Sun. We then show how a combination of organic photochemistry and flow chemistry could contribute to the circular economy by harnessing the ability of light to provide the energy to promote reactions without the need for some of the added reagents that are necessary in more traditional chemical routes, so-called 'reagentless' chemistry. Photochemistry has a long history but recently it has undergone a renaissance, particularly with the rise in interest in photoredox chemistry. Continuous photoreactors offer a route to scaling up such reactions to a productivity needed for smaller scale pharmaceutical manufacture. We describe some reactor designs from our own laboratory and outline some of their applications. We then relate these to the requirements of the circular economy and the need to conserve the stocks of the less abundant chemical elements. This article is part of a discussion meeting issue ‘Science to enable the circular economy'.

Parallel Interconnected Kinetic Asymmetric Transformation (PIKAT) with an Immobilized ω-Transaminase in Neat Organic Solvent

Comprising approximately 40% of the commercially available optically active drugs, α-chiral amines are pivotal for pharmaceutical manufacture. In this context, the enzymatic asymmetric amination of ketones represents a more sustainable alternative than traditional chemical procedures for chiral amine synthesis. Notable advantages are higher atom-economy and selectivity, shorter synthesis routes, milder reaction conditions and the elimination of toxic catalysts. A parallel interconnected kinetic asymmetric transformation (PIKAT) is a cascade in which one or two enzymes use the same cofactor to convert two reagents into more useful products. Herein, we describe a PIKAT catalyzed by an immobilized ω-transaminase (ωTA) in neat toluene, which concurrently combines an asymmetric transamination of a ketone with an anti-parallel kinetic resolution of an amine racemate. The applicability of the PIKAT was tested on a set of prochiral ketones and racemic α-chiral amines in a 1:2 molar ratio, which yielded elevated conversions (up to >99%) and enantiomeric excess (ee, up to >99%) for the desired products. The progress of the conversion and ee was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.

Improving production of Streptomyces griseus trypsin for its application in processing insulin precursor

Background: Trypsin has a plenty application in food and pharmaceutical manufacture. While, the commercial trypsin is usually extracted from pork pancreas, which has the risk of infectious and immunogenicity. Therefore, the microbial Streptomyces griseus trypsin (SGT) is a prior alternation because it processes efficient hydrolysis activity without the aforementioned risk. The remarkable hydrolysis efficiency of SGT caused its autolysis, and five autolysis sites R21, R32, K122, R153, and R201 were identified from its' autolysate. Results: The tbcf (K101A, R201V) mutant was screened by directed selection approach for improved activity in flask culture (60.85 ± 3.42 U·mL -1 , increased 1.5-fold). From the molecular dynamics simulation, the K101A/R201V mutation shortened the distant between catalytical residues D102 and H57 from 6.5 Å vs 7.0 Å, which afforded the improved specific activity 1527.96 ± 62.81 U·mg -1 . Further, the production of trypsin was increased 302.8% (689.47 ± 6.78 U·mL −1 ) in 3-L bio-reactor, with co-overexpression of chaperones SSO2 and UBC1 in Pichia pastoris. Conclusions: The SGT protein could be an adequate trypsin for insulin production. When working with hydrolysates analysis and direction selection, the tbcf (K101A, R201V) mutant increased 1.5-fold activity. Further, the production of trypsin was improved 3-fold by overexpressing chaperone protein in Pichia pastoris . The future study should be emphasized on the application of SGT in insulin manufacture and pharmaceutical.

The way of the pharmaceutical ingredients to the finished pharmaceutical form

The modern pharmaceutical industry is a strictly controlled area. Both national and international rules apply, but none of these deals with logistical issues arising from the manufacture of the product. Following the path of a drug, it is possible to get acquainted with the problems that arise and their solution. The drug is much more than a common product. The drug is a product of confidence, which is provided with information. It defines its quality as well, to comply with the relevant directives and standards in the manufacture of, and that the enclosed information is sent to the user. This requires the manufacturer, the distributor and the user to comply with it. There is no production without material handling, but GMP (Good Manufacturing Practice) does not yet have a chapter on logistics. References to handling raw materials and finished products can be found in the corresponding GMP chapters, the responsibility of the correct execution are borne by the manufacturer. In this case, the effect of the common sense prevails exponentially, keep the medicine in mind and it has to be done, that no loss, no quality deterioration is not caused by the transport, handling of such loads, storage. It is typical that the raw material and the finished product are going through the entire site during the pharmaceutical manufacture. Starting from the warehouse, it runs through the manufacturing facilities, on the packaging, and some units go to the lab, so that eventually, in medicine form returns to the warehouse, from where it goes further in the supply chain through the pharmacies to the patients. In our study we examine the logistics activity and problems of a small pharmaceutical company and tasks to be solved presented in the light of the theory.

MODERN REQUIREMENTS TO INDUSTRIAL PRODUCTION AND PHARMACEUTICAL MANUFACTURE OF INFUSION MEDICINAL PREPARATIONS IN THE RUSSIAN FEDERATION: SIMILARITIES AND DIFFERENCES

The quantitative reduction of the manufacturing pharmaceutical organizations significantly lowers public accessibility to medicinal preparations manufactured by pharmacies. The aim of this research has is the analysis of the normative legal standards regulating the industrial production and the pharmaceutical manufacture of infusion medicinal preparations in the territory of the Russian Federation. Materials and methods: The research has been carried out by the analysis of the current legislative and normative acts by means of documentary observation and content analysis. Results and discussion. Hereby the review has been done of the main acts along with normativelegal documentation regulating the industrial production and the pharmaceutical manufacture of infusion medicines such as federal laws, regulations of the Government of the Russian Federation, the State Pharmacopeia (Editions XI and XIII), orders of the Ministry of Health of the Russian Federation, etc. It has been established that in the Russian Federation there has been developed and currently functioning the system of mandatory requirements to industrial production and quality control of infusion medicinal preparations produced by manufacturing enterprises. At the same time, despite the restrictions on the pharmaceutical manufacture of the aseptic medicines registered in the Russian Federation, the pharmaceutical organizations implement manufacture of the medicines which are not produced industrially. That makes it possible to provide an individual dosage of ingredients and take into account patients’ individual characteristics. The normative legal regulation system for the pharmaceutical manufacture significantly differs from the similar system for the industrial production. The scientific discussion on the implementation of the international Rules of Good Manufacturing Practices (GMP) into pharmaceutical activities has not arrived at a unanimous organizational and technological opinion because of essentially different purposes, a diverse range of the undertaken tasks and dissimilar economic opportunities of pharmaceutical organizations and manufacturing enterprises. Conclusion: The currently existing normative legal regulation system for the industrial production and the pharmaceutical manufacture of infusion medicines in the Russian Federation is aimed at providing the national health services’ needs of necessary remedies for infusion therapy. At the same time, the pharmaceutical manufacture does not oppose the industrial production, but quite the contrary, expands public accessibility to such preparations for treatment in emergency or urgent cases and also during routine treatment of patients.

VALIDATION OF WATER PURIFICATION SYSTEM

Objective: Validation of water treatment systems is required to achieve water with all preferred quality attributes. This also delivers a circumstantial to establish a total control over the process which screens efficacy, safety, and ultimately, the process outcomes. The goal of steering validation is to establish that a process when operated within established limits, yields a product of reliable and definite quality with a high degree of assurance.Methods: The current work is an effort to deliberate several aspects of validation comprising different approaches, machineries of water purification systems, equipment qualifications, performance testing phases, microbial and chemical analysis of water samples, documentation, and post-validationmonitoring. Mainly the validation is done for new water plants in pharmaceutical industry.Results and Discussion: Sampling of water was carried out after each step in the purification process, and the results were found within limits.Conclusion: Water purification systems must be operated in the interior regulatory guidelines as with pharmaceutical manufacture facilities.Successful achievement of validation is confirmed by various testing phases. Usually, a three-phase testing approach is recommended over an extendedperiod to prove reliability and robustness of the system for producing water of specified quality with a high degree of assurance.Keywords: Validation, Water purification systems, Quality attributes, Pharmaceutical manufacture facilities, Microbial and chemical analysis.

Hacking nature: genetic tools for reprograming enzymes

Enzymes have many modern industrial applications, from biomass decomposition in the production of biofuels to highly stereospecific biotransformations in pharmaceutical manufacture. The capacity to find or engineer enzymes with activities pertinent to specific applications has been essential for the growth of a multibillion dollar enzyme industry. Over the course of the past 50–60 years our capacity to address this issue has become increasingly sophisticated, supported by innumerable advances, from early discoveries such as the co-linearity of DNA and protein sequence1 to modern computational technologies for enzyme design. The design of enzyme function is an exciting nexus of fundamental biochemical understanding and applied engineering. Herein, we will cover some of the methods used in discovery and design, including some ‘next generation’ tools.