Nonsterile Drugs Research Articles

[Translated article] Compounding training programme for pharmacy technicians using a digital platform and simulation techniques

ObjectiveTo describe a compounding training plan in a tertiary hospital pharmacy service. The project aimed pharmacy assistant technicians to use a digital training platform and simulation techniques. MethodsTwo training programs were designed, one for sterile and the other for non-sterile drugs. Each programme consists of several phases: a basic online training course (digital e-learning platform), a practical simulation workshop, a supervised practice in real conditions, and a final verification by the pharmacist to qualify the technician. Both programs include continuous and accredited evaluation by the hospital's Continued Education Commission.A satisfaction survey on training (e-lerning platform) was designed and conducted for pharmacy technicians (sterile and non-sterile). ResultsThe project has been running for 3 years. Six specialist pharmacists from different areas involved in compounding are responsible for training and continuous evaluation. Twenty-one technicians have been trained, and nineteen have obtained qualifications. Two of them were found to be unfit. Currently, we employ13 pharmacy technicians who were initially trained.The participation rate in the satisfaction survey on training (e-learning platform) was 61.5% (n=8) out of a total number of current developers (n=13). Overall, 62.5% of technicians reported being satisfied or very satisfied, while the remaining 37.5% were indifferent. ConclusionsCompounding training program is currently in its third year. It has been crucial in delegating tasks to pharmacy technicians. The use of digital technology is essential in this training. We consider that, specific training in compounding, is indispensable and should be included in the academic plan for pharmacy technicians.

Analysis of time costs in the manufacture of non-sterile drugs in the form of liquid dosage forms in a production pharmacy

AIM: to determine the time spent on pharmaceutical manufacturing of non-sterile medicines in the form of liquid dosage forms and assess their compliance with current standards. MATERIALS AND METHODS: the objects of the study were the technological pro- cesses of manufacturing non-sterile liquid dosage forms in pharmacies of the State Unitary Enterprise “Tattechmedpharm” No. 57 and No. 361 (Kazan), No. 277 (central district pharmacy of Almetyevsk), performing a manufacturing function (license L042-01181-16/00269222 dated 16/09/2020). During the study, methods of grouping, systematization, structural and logical analysis, comparative analysis, direct observation method, measurement method, time-study method, methods of statistical data processing using the SPSS Statis- tics program were used. RESULTS AND DISCUSSION: during the study, the time-study of technological operations in the manufacturing of non-sterile liquid dosage forms was used by direct measurement using a stopwatch. Time measurements were carried out for dosage forms, which were prepared daily, with different numbers of components (from 1 to 6). The most labor-intensive operations were identified, namely: weigh- ing of pharmaceutical substances, filtration of a water solution, and performing calculations in a written control passport. The obtained results were also compared with current standards. During the pro- cess, it was revealed that the time spent was compliant with the use of concen- trated solutions, as well as when preparing glycerin solutions that don’t require filtration. However, when performing such technological operations as weighing of ingredients, dissolving and filtering the dosage form, the results exceeded the recommended standards. CONCLUSION: in modern conditions, the time spent on manufacturing of liquid dosage forms according to individual prescriptions, exceeds established stan- dards, due to the lack of burette systems in pharmacies and the reduction of the practice of using concentrated solutions. Based on the results of the study, re- serves were identified for increasing the productivity of pharmaceutical employees in the manufacture of liquid dosage forms: the use of electronic scales, concen- trated solutions and the development of standard operating procedures for the pharmaceutical manufacturing of liquid dosage forms.

Programa de formación en elaboración de medicamentos para técnicos de farmacia utilizando una plataforma digital de formación y técnicas de simulación

ObjectiveTo describe a compounding training plan in a tertiary hospital Pharmacy Service. The project aimed to train Pharmacy Assistant Technicians using a digital training platform and simulation techniques. MethodsTwo training programmes were designed, one for sterile and the other for non-sterile drugs. Each programme consists of several phases: a basic online training course (digital e-learning platform), a practical simulation workshop, a supervised practice in real conditions and a final examination by the pharmacist to qualify the technician. Both programmes include a continuous and accredited evaluation by the hospital's Continuing Education Commission.A satisfaction survey on training (e-learning platform) was designed and conducted for pharmacy technicians (sterile and non-sterile). ResultsThe project has been running for three years. Six specialist pharmacists from the different areas involved in compounding are responsible for training and continuous evaluation. Twenty-one technicians were trained, 19 were qualified, and two of them were unsuccessful. Nowadays, we have 13 pharmacy technicians out of those who were originally trained.Participation in the training satisfaction survey (e-learning platform) was 61.5% (n = 8) of the total number of current developers (n = 13). Overall satisfaction was good with 62.5% of technicians satisfied or very satisfied and the remainder were indifferent (37.5%). ConclusionsThe compounding training program is now in its third year. It has been crucial in delegating tasks to Pharmacy technicians. The use of digital technology is essential in training. We believe that specific training in compounding, is essential and should be included in the pharmacy technician curriculum.

On the Possibility of Reducing the Sample Size for Microbiological Examination of Some Pharmaceutical Substances

The possibility of reducing the sample size for microbiological examination of some pharmaceutical substances is considered. Trypticase-soy agar was evaluated for the ability to detect yeast and mold fungi and to isolate the minimal amount of certain types of microorganisms. The minimal sample size for microbiological examination was 0.2 g (mL) for synthetic substances intended for the production of non-sterile drugs and 1.2 g (mL), for sterile drugs. Based on the experimental results, a scheme has been developed for microbiological examination of particular pharmaceutical substances using a reduced sample size

Objectionable microorganisms in pharmaceutical production: Validation of a decision tree

The release of quality, safe, and effective non-sterile drugs needs to exclude the presence of objectionable microorganisms, which include microorganisms potentially involved in product degradation, or considered as poor hygiene indicator during manufacturing, or causing adverse effect on patient's health. In this paper, a method allowing objective and verifiable evaluations has been investigated through the development of a suitable decision tree with a template for data collection.The decision tree has been used to establish which microorganisms were objectionables, using several hypothetical scenarios in which 24 different biological agents, both harmless microorganisms and opportunistic pathogens, were combined with 9 different products, representing each type of administration route for non-sterile drugs. The results showed that the use of aforementioned approach makes the microorganisms evaluation easy and verifiable and highlighted that even the microbes initially considered harmless could be objectionable.

The study of the stability of pessaries, designed to prepare the birth canal before childbirth

An urgent problem in obstetrics and gynecology is the prevention of soft tissue ruptures during childbirth. In addition to various physical exercises aimed at increasing elasticity and muscle tone, it is necessary to use aids designed to minimize perineal injuries. For this purpose, pessaries with hyaluronic acid and phytocomplex of CO2-extracts of aloe, calendula and green tea were created.
 The aim of the work – study of the stability of the proposed extemporaneous pessaries in accordance with the requirements of the article «Suppositories and pessaries manufactured in pharmacies» of the State Pharmacopoeia of Ukraine (SPU) 2.0 and Guidelines ST-N MPH 42-4.5:2015 «Requirements for the manufacture of non-sterile drugs in pharmacies».
 Quality control of pessaries was carried out on the following indicators: description, homogeneity, pH, average weight, time of deformation, decay time, melting point, acid number, microbiological purity. To detect falsified samples, a test was performed to check the base. Biopharmaceutical studies were also performed to evaluate the release of API of phytoextracts of calendula and aloe by the method of «diffusion into agar».
 When assessing the appearance and homogeneity of pessaries, it was found that they have a yellowish color and a specific odor of cocoa butter and green tea extract. There were no patches on the longitudinal section. The pH values ranged from 3.80 to 4.50, which corresponds to the normal pH value of a woman's vagina. According to other quality indicators, such as average weight, melting point, time of complete deformation, decay time, acid number and microbiological purity, the investigated drug also fully satisfies the requirements of SPU 2.0 and Guidelines ST-N 42-4.5:2015. To detect falsified samples, a test was performed to check the base. Biopharmaceutical studies were performed to evaluate the release of API of phytoextracts of calendula and aloe by the method of «diffusion into agar». The research was conducted immediately after the manufacture of pessaries and in the process of their storage.
 The stability of extemporaneous pessaries containing hyaluronic acid and phytocomplex of CO2-extracts of aloe, calendula and green tea, intended for the preparation of the birth canal before childbirth, was studied. The main quality indicators of pessaries immediately after their manufacture and during storage have been studied. It is shown that the samples of studied pessaries fully meet the requirements of the article «Suppositories and pessaries manufactured in pharmacies» of the State Pharmacopoeia of Ukraine 2.0 and Guidelines ST-N MPH 42-4.5:2015 «Requirements for the manufacture of non-sterile drugs in pharmacies».

Rapid identification of microbial contaminants in pharmaceutical products using a PCA/LDA-based FTIR-ATR method

Microbiological quality of pharmaceuticals is fundamental in ensuring efficacy and safety of medicines. Conventional methods for microbial identification in non-sterile drugs are widely used; however they can be time-consuming and laborious. The aim of this paper was to develop a chemometric-based rapid microbiological method (RMM) for identifying contaminants in pharmaceutical products using Fourier transform infrared with attenuated total reflectance spectrometry (FTIR-ATR). Principal components analysis (PCA) and linear discriminant analysis (LDA) were used to obtain a predictive model capable of distinguishing Bacillus subtilis (ATCC 6633), Candida albicans (ATCC 10231), Enterococcus faecium (ATCC 8459), Escherichia coli (ATCC 8739), Micrococcus luteus (ATCC 10240), Pseudomonas aeruginosa (ATCC 9027), Salmonella typhimurium (ATCC 14028), Staphylococcus aureus (ATCC 6538), and Staphylococcus epidermidis (ATCC 12228) microbial growth. FTIR-ATR spectra provide data on proteins, DNA/RNA, lipids, and carbohydrates constitution of microbial growth. Microbial identification provided by PCA/LDA based on FTIR-ATR method were compatible with those obtained using traditional microbiological methods. The chemometric-based FTIR-ATR method for rapid identification of microbial contaminants in pharmaceutical products was validated by assessing the sensitivity (93.5%), specificity (83.3%), and limit of detection (17-23 CFU/mL of sample). Therefore, we propose that FTIR-ATR spectroscopy may be used for rapid identification of microbial contaminants in pharmaceutical products and taking into account the samples studied

Trends of ex tempore drug preparation in Ukraine. Ways of their introduction into the practice

Background. Advantages of the ex tempore formulation include the ability to provide the drug in the form and dosage, not available on the pharmaceutical market, but necessary for a particular patient; the ability to include the required ingredient in any desired form; the option of combining drugs; the manufacture of drugs without flavorings, preservatives and stabilizers; the possibility of adjusting of the drug taste; the possibility of manufacturing drugs that are in short supply on the market; no possibility of counterfeiting; production of specific drugs.
 Objective. Assess the current situation and trends in the preparation of oncological drugs ex tempore.
 Materials and methods. Analysis of the literature on this topic.
 Results and discussion. In oncology the possibilities of ex tempore preparation include the manufacture of chemotherapeutic agents with individual dosage, of any adjuvant agents without excipients, of radiopharmaceuticals, combined and orphan drugs. In Ukraine, ex tempore formulation is not widespread: as of 2017, the percentage of drugs prepared in such way was 1.7 %, in 2018 – 1.43 %, in 2019 – 1.41 %. The situation is different in the European Union. For instance, in Poland the pharmacy receives a license only after creating the conditions for the manufacture of drugs, in Estonia any pharmacy must be able to produce non-sterile drugs, in Latvia 50 % of pharmacies have a license to manufacture drugs. The popularity of ex tempore preparation is also growing in the other countries (Australia, USA, Brazil, Jordan). The main areas of application of ex tempore drugs include hormone replacement therapy, analgesia, dermatology, chemotherapy, ophthalmology, treatment of orphan diseases, parenteral nutrition. Civilized countries often choose to develop the hospital pharmacy. However, there are a number of problems, including the lack of well-trained staff, the high cost of equipment and maintenance of sterile facilities, the constant changes in regulatory requirements and the need to gain the consumers’ respect.
 Conclusions. 1. Ex tempore drug preparation has a number of advantages, in particular, the ability to provide the drug in the individual form and dosage, the ability to combine drugs and the manufacture of specific drugs. 2. Extemporaneous preparation of drugs is especially important for oncology. 3. In contrast to European Union countries, ex tempore drug preparation is not widespread in Ukraine. 4. Problems of ex tempore drug preparation include lack of the staff, high equipment costs, and constant changes in regulatory requirements.

Validation Parameters as Applied to Methods for Quantification of Microorganisms in Medicinal Products

Validation/verification of microbiological methods is a prerequisite for quality control of non-sterile drugs. However, the use of existing procedures for validation/verification of analytical methods is challenging, since a number of factors, such as microorganism distribution in the sample, cell morphology, and metabolic activity of microorganisms contribute to the error in microbiological testing.The aim of the study was to assess the feasibility of using the microbiological method validation parameters for validation/verification of the agar plate method.Materials and methods: 18 non-sterile medicinal products were used in the study. Experiments included determination of antimicrobial activity. The quantification of viable bacteria, yeasts and moulds was performed using the modified pour plate method. The statistical processing of the obtained results was performed using Microsoft Excel 7.0 and Statistica 8.0.Results: the paper provides the results of quantitative determination of test microorganisms inoculated into non-sterile drugs. The results were obtained as part of validation/verification of the agar plate method of the State Pharmacopoeia of the Russian Federation, XIV ed.Conclusions: the validation/verification of the test method for isolation and quantification of microorganisms revealed no deviations of the study results from the established acceptance criteria. This proves the feasibility of using the following validation parameters: accuracy, precision, robustness, and limit of quantitation when validating new methods for quantitative determination of microorganisms or verification of previously validated methods.

The study of microbiological purity of ointment “Fitolan” during storage

Topicality. Mastopathy is a benign disease of the mammary glands, and it belongs to a number of hormone-dependent pathologies. The danger of mastopathy is not only in that it significantly reduces the quality of life of a woman, but also in the possibility of its rebirth and masking of the initial stage of breast cancer.Aim. Studies of microbiological purity of the developed semi-solid medicine for epicutaneous application on the basis of phytooils of sea buckthorn, amaranth, parsley and tea tree under the conditional name “Fitolan”.Materials and methods. The testing samples of semi-solid dosage form under the conditional name “Fitolan” was carried out at the Department of Biotechnology of NUPh in accordance with the requirements of the SPhU 2 ed. To test and eliminate the antimicrobial activity of the drug samples, dilutions 1 : 10 of the dosage form were used.Results and discussion. Determination of the microbiological purity of the samples of the medicine “Fitolan” for epicutaneous application using the two-layer seeding method showed that the total number of viable aerobic microorganisms (TAMC) is 20 CFU/g and the total number of yeast and mold fungi (TYMC) does not exceed 10 CFU/g within 27 months of storage, it meets the requirements of SPhU [1].Conclusions. According to the results of microbiological purity research of the studied samples of the semi-solid dosage form “Fitolan” using the double-layer agar method the ointment fully complies with the requirements of SPhU on the indicator “Microbiological purity of non-sterile drugs” within 27 months of storage.

Effect of primary packaging on microbiological status of oral solid dosage form

The emergence of microbial contaminants in non-sterile drugs caused not only the degradation of many products, but also proved to be a potential risk to consumer health. The aim of this study was to test microbial load of non sterile solid pharmaceutical product and investigate the effects of different packaging system on microbial status of pharmaceutical product. A total of 18 sample of solid dosage form packaged in different packaging were procured from market. All samples have been tested for the presence of specific microorganisms, Total aerobic microbial counts (TAMC) and Total yeast and mold counts (TYMC) using compendial procedures. Out of 18 sample 72.22 % (n=13) had shown microbial growth and only 16 % (n=3) of samples were non-compliant. Sample containing herbal ingredients, were the most heavily contaminated, showing a bacterial load > 104 CFU/g. The result showed that all the tested samples were free from E. coli. There was no significant difference (p>0.05) in microbial load of product packaged in different primary packaging.

Эффективность антимикробных консервантов некоторых нестерильных лекарственных препаратов для приема внутрь

Определена эффективность антимикробных консервантов некоторых нестерильных лекарственных препаратов для приема внутрь в виде сиропов и растворов: Кларисенс®, сироп 1 мг/мл, Элькар®, раствор для приема внутрь 300 мг/мл, Лазолван®, сироп 15 мг/5 мл и др. Установлено, что качество 7 исследованных образцов, содержащих в составе такие консерванты, как бензойная кислота, метилпарабен, пропилпарабен, натрия бензоат, спирт этиловый, соответствует требованиям ОФС 42-0069-07 «Определение эффективности антимикробных консервантов лекарственных средств». Представленные результаты испытаний получены с помощью модифицированного глубинного чашечного метода посева, рекомендованного ГФ РФ XII издания при определении микробиологической чистоты лекарственных средств. Возможность применения модифицированного глубинного чашечного метода целесообразно внести как дополнение к методике и в дальнейшем включить в следующее издание Государственной фармакопеи РФ.

Microbiological quality of non-sterile pharmaceutical products

In microbiological terms, pharmaceutical products can be divided into two groups: sterile and non-sterile. Non-sterile drugs must satisfy the appropriate microbiological purity criteria which are included in pharmacopoeial monographs. Pharmacopoeial studies are prepared specifically with a view to ensuring that the medicinal product is therapeutically effective and safe for the patient. The analysis comprised the results of microbiological purity tests performed before the products are marketed. Total of 1285 samples of non-sterile drugs manufactured by different pharmaceutical plants in Polish were taken into study. The microbiological quality of drugs was assessed in accordance with the criteria included in the European Pharmacopoeia (EP). An analysis of test results demonstrated that the percentage of non-compliant samples was 1.87%. The groups of drugs, which the most often did not satisfy EPs’ requirements, were drugs containing raw materials of natural origin (5.7%). The samples of studied drugs that did not meet the criteria contained in EP, exceed the maximum allowable microbiological count limits and contained microbes whose presence is prohibited. The most common non-compliance was the excessive levels of the maximum acceptable fungal count (n=12) and the excessive the maximum acceptable aerobic microbial count (n=10).

Aspects of investigating microflora contamination of drugs (A Review)

Various aspects of investigating microorganisms present in drugs are considered. Sources of contamination in nonsterile drugs are indicated. Problems related to changes in the organoleptic properties and therapeutic quality of contaminated drugs and the hazard of microorganisms for human health are analyzed. Data on the qualitative and quantitative composition of contaminant microflora isolated from various drugs are presented. Effective methods of contaminant isolation are described. Modern culture media and methods for the identification of bacteria and fungi during the microbiological quality control of drugs are presented.

American Society of Health-System Pharmacists' Pain Management Network

The American Society of Health-System Pharmacists' (ASHP) Pain Management Network is one of several informal networking groups of pharmacist practitioners who specialize in a clinical practice area. Pharmacy practitioners are showing an increased interest in the management of pain because of expanding clinical roles, the Joint Commission on Accreditation of Health Care Organizations' development of pain management standards, and involvement with performance improvement and quality initiatives. The Pain Management Network is one of the American Society of Health-system Pharmacists (ASHP) Section of Clinical Specialists and Scientists specialty practice networks. The Network serves as an informal venue for practitioners interested in pain management to gather and share information. Pain Management Network Assemblies are held at each ASHP national meeting. Practitioners communicate between meetings via the Section's e-mail list server. Pharmacists who participate in the Pain Management Network have a variety of roles in both acute and chronic pain management. Their roles may be consultative in nature or they may be involved in the actual medication management as part of a collaborative drug therapy management agreement with a physician.Pharmacists are involved with acute pain, cancer-related pain, and chronic nonmalignant pain management. Current issues involve education of pharmacy students and practicing pharmacists as well as the use of meperidine as an analgesic agent. Compounding of non-sterile drugs for intraspinal use is another current issue. Access to evidence-based pain management resources may be difficult to locate and access but is essential to good pain management. The ASHP Pain Management Network has proven to be a valuable way for participants to gather and exchange new information and share in their clinical practice experiences.

American Society of Health-System Pharmacists' Pain Management Network

The American Society of Health-System Pharmacists' (ASHP) Pain Management Network is one of several informal networking groups of pharmacist practitioners who specialize in a clinical practice area. Pharmacy practitioners are showing an increased interest in the management of pain because of expanding clinical roles, the Joint Commission on Accreditation of Health Care Organizations' development of pain management standards, and involvement with performance improvement and quality initiatives. The Pain Management Network is one of the American Society of Health-system Pharmacists (ASHP) Section of Clinical Specialists and Scientists specialty practice networks. The Network serves as an informal venue for practitioners interested in pain management to gather and share information. Pain Management Network Assemblies are held at each ASHP national meeting. Practitioners communicate between meetings via the Section's e-mail list server. Pharmacists who participate in the Pain Management Network have a variety of roles in both acute and chronic pain management. Their roles may be consultative in nature or they may be involved in the actual medication management as part of a collaborative drug therapy management agreement with a physician.Pharmacists are involved with acute pain, cancer-related pain, and chronic nonmalignant pain management. Current issues involve education of pharmacy students and practicing pharmacists as well as the use of meperidine as an analgesic agent. Compounding of non-sterile drugs for intraspinal use is another current issue. Access to evidence-based pain management resources may be difficult to locate and access but is essential to good pain management. The ASHP Pain Management Network has proven to be a valuable way for participants to gather and exchange new information and share in their clinical practice experiences.

Numerical taxonomy of Bacillus isolated from orally administered drugs.

Numerical taxonomy procedures were used to study 118 strains of Bacillus isolated from non-sterile drugs prepared for oral administration. Similarities between pairs of strains were calculated by the simple matching coefficient of Sokal and Michener (SSM). Each strain was tested for 60 unit characters and three clusters were defined. The strains in each cluster presented a similarity level of at least 60%. Cluster A comprised the strains identified as Bacillus cereus (SSM = 93.13%), cluster B contained three subgroups corresponding to the species B. pumilus, B. subtilis and B. licheniformis (SSM = 84.35%) and cluster C also included three subgroups that belonged to the species B. firmus, B. lentus and B. badius (SSM = 80.14%). The most discriminating tests were selected to differentiate the clusters from the subgroups. The feature with the highest discriminating power between clusters A and B was the lack of acid production from arabinose and mannitol. The Voges-Proskauer, methyl red tests and sensitivity to polymyxin B clearly distinguished cluster A from C. The Voges-Proskauer test and acid production from arabinose were the best to differentiate between B and C. Bacillus pumilus and B. subtilis differed in starch hydrolysis and B. licheniformis in growing anaerobically. To discriminate B. firmus from B. lentus the most important tests were the acid production from glucose and sucrose; intermediate strains were found. Bacillus badius was differentiated from B. firmus by 10 tests, and from B. lentus by the production of urease.

Selection of a method for quantitative determination of bacteria in nonsterile drugs

Selection of a method for quantitative determination of bacteria in nonsterile drugs

Problems and methods of estimation of microbial contamination of nonsterile drugs (Review)

Problems and methods of estimation of microbial contamination of nonsterile drugs (Review)

Isolation and identification of microorganisms in nonsterile drugs

Isolation and identification of microorganisms in nonsterile drugs