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Mechanofusion is a dry coating method in which the high shear forces cause a mechanochemical reaction between the processed particles. With the approach it is possible to improve flowability of a host cohesive powder when the guest particle forming the coating is magnesium stearate. Applying mechanofusion in tablet formulations could make poor flowing large dose drug substances suitable for direct compression. However, it is well known that magnesium stearate decreases mechanical strength of the tablets and prolongs disintegration and dissolution time of tablets. A previous study, however, showed that it is possible to compress tablets from a formulation dry coated with magnesium stearate without reducing the dissolution rate. Dry coating with magnesium stearate and its effect on a plastic material, known to be sensitive for the negative effects of magnesium stearate, has not been studied previously. The aim of the study was to examine the effect of mechanical dry coating with magnesium stearate on the physical qualities and compression behaviour of a plastic material. The effect was studied by dry coating four grades of microcrystalline cellulose with different magnesium stearatecon centrations. The approach was to find an optimum between the flowability and compressibility of the powders by using different process parameters. Microcrystalline cellulose with median particle size of 23 and 78 µm were also mechanofused without magnesium stearate in order to examine whether mechanofusion itself has an effect on the properties of microcrystalline cellulose. Pure raw materials and Turbula-mixed magnesium stearate and microcrystalline cellulose blends were studied as references. Dry coating with magnesium stearate improved the flow properties of microcrystalline cellulose with D50 value less than 78 µm. Powders with D50 value greater than 144 µm, however, break down under the shear during the process and hence their flow properties were decreased. This suggests, that mechanofusion as a process is more suitable for the small particle size microcrystalline cellulose powders which, based on the results, can withstand the high-shear forces better. Mechanofusion of plain microcrystalline cellulose (D50 78 µm) revealed that the moisture content of the powder increased and stronger tablets could be compressed. Mechanofusion may cause changes to the microstructure of microcrystalline cellulose particles and to its ability to adsorb moisture. Dry coating with magnesium stearate was very effective even with short processing times and relatively low blade speeds, and it was challenging to compress hard tablets from the mechanofused mixtures. Plastic material was found to be sensitive for the negative effects of magnesium stearate, and better flow properties of a mechanofused powder resulted in weaker compressed tablets.

Automated dispensing cabinets can improve patient safety by reducing medication errors, and consequently, the incidence of adverse drug events, as well as reduce the number of outdated drugs and the size of ward inventory. They can reduce the amount of time nurses and other staff spend on distribution and ordering of medicines, and time spent on taking inventory. In conjunction with an electronic narcotics registry, they may significantly reduce the time needed for filling, checking and correcting narcotics registry forms. This study evaluated the impact of automated dispensing cabinets on the amount of time nurses spend on selecting and picking doses for patients, as well as its effect on the size of ward inventory and wastage of drugs. The amount of time nurses, pharmacists, and technical staff spent on narcotics registry related activities in the hospital ward and hospital pharmacy was also measured. No evidence was found to support the conclusion that automated dispensing cabinets speed up selection and picking of doses, and they may in fact slow it down. With current number of narcotics distributed in the hospital annually, the overall time taken by narcotics registry activities can be 10.9 full time equivalents. Most of this time, roughly 8.7 FTE, consists of nurses filling narcotics registry forms while administering drugs, though only a tiny proportion of each nurses’ time is spent on this activity. On average, it the cost of labor needed to fill one form is 9.3 €. An electronic narcotics registry in combination with and ADC could reduce this down to 0.36 € - 1.16 € per narcotics package by removing the need to fill redundant information in different registries.

The Finnish Medicines Agency, Fimea, is the authority responsible for supervision pharmacies in Finland. Recently, there has been more interest in Fimea to improve its supervision of community pharmacies. For this purpose, a questionnaire was made. Prior to the making of the questionnaire, community pharmacy supervision practices were studied in Nordic countries and in the UK. Additionally, faults found in Finnish community pharmacy inspections in 2016–2018 were classified by analysing anonymized fault lists (n=94) separated from inspection reports. When the most common faults were identified, it was possible to include questions concerning these faults into the questionnaire. A modified version of the Delphi method was used when developing the questionnaire. Comments on the applicability of the questions were given by a panel of experts consisting of inspectors of Fimea. The questionnaire was subsequently edited in accordance with the given comments. Separate versions of the questionnaire form were developed for community pharmacies and for their subsidiary pharmacies. At the end of this study, the questionnaire was sent to seven pharmacies and to three subsidiary pharmacies. After the results of the questionnaire were collected, Fimea gave feedback on the questionnaire. 25 categories were created by classifying faults found from pharmacy inspections. The most common inspection observations were faults in storage condition monitoring (97 % of pharmacies), narcotics (86 %), implementation of code of conduct (86 %), product errors (86 %) and preparation of medicines ready for use (81 %). The questionnaire begins by asking basic information about the pharmacy. Following questions concern the personnel and their further adequacy training. The questionnaire also includes several questions on the code of conduct within the pharmacy. Additionally, there are questions about storage condition monitoring, dispensary and accounting of narcotics. At the end of the questionnaire, there are also a few questions about the European Medicines Verification System (EMVS) which will be implemented by February 2019. Support from the inspectors of Fimea and studying regulations of pharmacies helped identify appropriate questions for the questionnaire. However, the perspective of the questionnaire may be limited due to the questionnaire being developed based up on faults found from inspections. The faults observed from inspections across pharmacies in Finland have been very similar with some of them being also alarmingly common. Because many of the observed faults are relatively easy to fix, simple corrective measures could be implemented to improve the situation across several pharmacies. Thus, usage of questionnaires, such as one made in this study, could be considered a feasible way of improving supervision of pharmacies.

The use of different methods of extended reality (xR) as a support in teaching has been under research for a long time. Although the use of various xR-technologies in other fields of healthcare, such as medical and nursing education, is already common, their use in pharmacy education is not yet well established. There is evidence that xR-technology has a positive impact for example on students’ motivation and learning outcomes. On the other hand, there are limiting factors that inhibit the technology becoming widespread, such as costs as well as a lack of knowledge about the technology usability. The aim of the study was to investigate usability and advantages of the augmented reality (AR) in a laboratory course as an educational supportive tool by using AR-glasses. The aim was also to investigate the learning outcomes of the students who participated in the study in three different phases: before carrying out the laboratory work (pre), immediately after the laboratory work (post) and in the course exam (delayed). Furthermore, the motivation of the students to use new technology in their studies was studied. The research was done in a collaboration with the Centre for University Teaching and Learning (HYPE) and with Sciar Company Oy. The researchers of HYPE were responsible for the pedagogical point of view, whilst the experts from the Faculty of Pharmacy were responsible for the study measurements of laboratory work related content knowledge. The research was implemented in two laboratory courses in Bachelor of Science level pharmacy studies: Medicinal product II and Pharmaceutical biology and asepsis in the fall of 2020. The students (n=18) prepared eye drops by using AR-glasses in the Medicinal product II -course and reference group (n=14) without AR-glasses. In the course of Pharmaceutical biology and asepsis, students (n=7) used AR-glasses to study the microbiological purity of the eye drops by utilizing membrane filtration method in cleanroom and reference group (n=9) without AR-glasses. ln addition, a serial dilution method was performed on a 96-well plate using an AR mobile application. The effect on learning outcomes was evaluated by using six open-ended questions measuring the understanding of content knowledge underlying the laboratory work, that were answered by the students at three different stages of the study (pre, post, delayed). To measure the usability of the AR equipment, a five-point Likert scale questionnaire studied the experimental groups students’ opinions on whether the AR mobile application could provide sufficient guidance and feedback while performing the laboratory work. In an open question, the students had the possibility to comment on the overall user experience of the AR mobile application. There were no statistically significant differences in learning outcomes between the AR-group and the reference group in both laboratory courses. The results showed indicative differences in short-term and long-term learning, with the AR-group achieving better learning outcomes in the short-term and the reference group in the long-term. In the course of Pharmaceutical biology and asepsis, the learning outcomes were the opposite. Students’ were found to be receptivity to the new technology that together with motivation supports positively the learning process. The use of AR-hardware increased certainty and reduced nervousness about the use of AR technology. As a conclusion, the study could not demonstrate the benefit of AR-technology in student learning outcomes. The study was limited by the small sample size. However, further studies are encouraged due to students’ positive attitudes and motivation towards AR technology. Regarding further studies, it is important to take into consideration the different backgrounds and learning methods of students. Thereby, the effects of xR-technologies on learning outcomes can be assessed as objectively as possible.

The price competition of biological medicines induced by biosimilars has started slower than expected in Europe. One of the main reasons has been the differences in physicians’ attitudes toward biosimilars. Switching biological medicines to clinically comparable alternatives is an important way to enhance the cost-effectiveness of using biological medicines. The focus of the conversation has shifted from the general similarity of biosimilars and the originators to whether frequent switching involves additional risks. The purpose of this master’s thesis was to investigate factors influencing physicians’ prescribing of biological medicines. In addition, their perceptions of the automatic substitution of biological medicines in Finland were explored. The study was based on structured personal interviews of rheumatologists and gastroenterologists including specialising physicians who work at HUS Helsinki University Hospital in the Hospital District of Helsinki and Uusimaa (n=48). They had a chance to comment on their responses at any time freely. The interview consisted of four sections: demographics, general attitudes toward biosimilars, factors affecting prescribing biological medicines, and perceptions of the automatic substitution of biological medicines. Study participants had a chance to comment on their structured responses during the interview. The interviews were recorded for further analysis of the comments. The results are based on a descriptive quantitative analysis and an inductive analysis of the comments. The interviewed physicians’ (n=27, response rate 56,3%) attitudes toward biosimilars were highly positive. Most of the physicians (21/27, 78%) also strive to motivate patients to switch biological medicines to clinically comparable but lower-cost options despite the challenges associated with switching, for example the differences in the administration devices. Of the previously determined factors, the ones affecting prescribing biological medicines the most were the willingness to support the price competition between the biological medicines, reimbursement status, and the hospital’s drug formulary when initiating the biological treatment in the hospital. The attitudes toward the automatic substitution of the biological medicines were positive among 13/27 (48 %) physicians. Our study results are in line with the results of earlier studies, but the open responses especially to the automatic substitution of biological medicines might indicate more positive perceptions on the subject among physicians in Finland.

Biopharmaceutical Classification System (BCS) is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability. When combined with dissolution of the drug product, the BCS takes into account three major factors that govern the rate and extent of drug absorption. For a BCS biowaiver, the in vitro dissolution study may be used as a surrogate for in vivo bioequivalence studies. Currently, BCS I drugs are accepted as biowaiver candidates by EMEA, FDA and WHO. EMEA and WHO also accept class III drugs in some conditions. The main difficulty in classifying drugs according to BCS is the determination of permeability. Biopharmaceutics Drug Distribution Classification System (BDDCS) was introduced to provide a surrogate for permeability. If the major route of elimination is metabolism, then the drug exhibites high permeability. There are two parts in this master thesis. BCS and BDDCS are discussed and evaluated in the literature part. The focus is in the BCS III drugs. The purpose of the experimental part is to evaluate BCS III drug, hydrochlorothiazide as a biowaiver candidate. Solubility of the drug substance and dissolution of the drug product was determined. Aim of the permeability studies with Caco-2 cells were to study if hydrochlorothiazide permeates by passive diffusion across the monolayer. Importance of paracellular diffusion was evaluated by opening tight junctions with EDTA. Influence of dissolution rate was evaluated by theoretical simulation. According to the results of this study, hydrochlorothiazide has good solubility in aqueous buffer. It has been reported to diffuse passively across the epithelial cells but in this study permeability increased when concentration decreased. This may be due to active transport. Hydrochlorothiazide diffuses partially through the tight junctions. Dissolution of the hydrochlrothiazide tablet was very rapid. Drug eliminates almost entirely by metabolism, it is also BDDCS class III drug. EMEA and WHO accept BCS III drugs as biowaiver candidate if dissolution rate is very rapid. According to this, hydrochlorothiazide could be suggested as a biowaiver candidate. There are also other issues to be considered, for example excipients used in tablets. Since hydrochlorothiazide has been discovered to be absorbed in the upper part of the small intestine, the influence of excipients is especially important. This possible influence should be evaluated before the final decision of biowaiver.

The liver is the major site of drug metabolism and excretion. Within the liver endogenous and exogenous compounds are eliminated through many metabolizing enzymes. Drug removal is not only dependent on metabolic enzymes, but also on transporters. Before cellular metabolism can occur, a drug must first enter the hepatocyte. Very lipophilic drugs enter the cell membrane through passive diffusion, but polar or ionized organic compounds can enter the cell membrane only by transporters. Transporters in the basolateral membrane of the hepatocyte facilitate drug entry and access to drug metabolizing enzymes. Transporters in the canalicular domain (apical) of the hepatocyte faclitate removal of drugs or metabolites from the cell interior. Recent studies have shown that transporters can mediate drug-drug interactions, and transporter genes are subject to genetic polymorphism which may affect pharmacokinetic parameters of a drug, such as absorption, distribution, and excretion. This Master's thesis consists of two parts, a literature review and an experimental section. In the literature review two transporters, OATP1B1 and MRP2, are discussed in detail. OATP1B1 is expressed on the basolateral and MRP2 on the apical membrane of the hepatocyte. These transporters are responsible for the vectorial transcellular hepatobiliary transport of various organic anions in humans. The experimental section aims at modelling vectorial hepatobiliary transport of three compounds in a double-transfected (OATP1B1/MRP2) MDCKII cell line. All three compounds studied, rosuvastatin, estrone sulphate, and estradiol glucuronide, are substrates of both transporters. Wild type (WT) MDCKII cells were used as a control. Tight junctions form a barrier between cells. This barrier regulates the paracellular passage of, for example, water, ions, large molecules, and drugs. In the experimental section the tight junctions were reversibely opened to distinguish between trans- and paracelluar routs of transport of the three compounds studied. Permeation of rosuvastatin and estradiol glucuronide in the basolateral to apical direction was faster in the double-transfected cell line compared to the MDCKII-WT cell line. Permeation of estrone sulphate, however, behaved unexpectedly in the double-transfected cell line. The permeation of this compound was almost equal in the apical to basolateral and basolateral to apical direction. The reason for this unexpected finding remains unclear. By opening the tight junctions the permeation of all compounds in both cell lines was increased, indicating that the compounds studied preferred the paracellular route and the importance of transporters were reduced. The double-transfected MDCKII cell line is a useful in vitro model of hepatic vectorial transport of organic anions in humans.

Medication reviews can be used to assess the appropriateness of a patient’s medication and to identify and resolve clinically significant drug-related problems. Medication reviews have been highlighted in several health and medicines policy documents as ways to improve medication safety in older adults. Collaborative practices and their development are key strategies in promoting the coordinated care of patients. Medication reviews have been previously defined from a multi-professional perspective but no definition based on multi-professional consensus has been established. The aim of this study was to harmonize the definition of medication review from a multi-professional perspective to suit various healthcare contexts in Finland. The goal was to create a shared understanding for physicians, nurses, pharmacists, information management professionals for their collaboration in reviewing medications. Furthermore, the aim was to define the tasks and responsibilities of different professional groups in collaborative medication reviews in order to support its implementation. The study was conducted as a 3-round survey using the Delphi method. The Delphi method is a qualitative consensus method based on the views of experts aiming at reaching consensus on the studied subject. The Delphi rounds were conducted as electronic surveys in September-December 2020. Expert panelists assessed the proposed definition of a collaborative medication review and the tasks and responsibilities of health care professionals involved in conducting it. The expert panel consisted of 41 participants: 12 physicians, 13 pharmacists, 10 nurses, and 6 information management professionals. The results of the study were analyzed both quantitatively and qualitatively. Consensus was reached on the definition of medication review from a multi-professional perspective, while no consensus was reached on most of the responsibilities and tasks of different healthcare professionals involved. Most challenging was to define patient groups benefiting from medication reviews and the situations in which medication reviews should be performed. Therefore, further research is needed to define the division of responsibilities between care team members, for example by defining separately the responsibilities and tasks in different healthcare contexts. This is the most comprehensive attempt taken in Finland to define medication review as a concept from a multi-professional perspective. The results of the study imply to the development and harmonizing of medication review practices and standardizing patient data documentation. The expected outcomes relate to enhanced patient and medication safety, improved coordination in medication management with integrated medication reviews.

Different kind of medication reviews have been developed in different countries. In Finland comprehensive medication review was developed in the late 2000th. Only few researches of medication review exist in Finland. In other countries more studies on the subject have been done. This Master's thesis's aim in the literature review was to examine what kind of outcome measurements were used in medication review studies and what kind of results were obtained from these measurements. In many medication review studies different kind of drug related parameters were used to evaluate the effectiveness of medication review. These parameters are Drug Related Problems (DRP), Medication Appropriateness Index (MAI) and different kind of criteria's for potentially inappropriate medication for elderly. Medication reviews have showed a positive effect on these parameters. To the health-related quality of life medication reviews have not shown any statistical effect. Physical performance meters have not been used a lot in medication review studies. And results have been controversial. Omahoitosuunnitelma 2100 (OMA21) research project, that examines the effectiveness of the comprehensive medication review in Finnish health care, could potentially due to its long follow-up time produce results also from the quality of life and physical performance instruments. In the Master's thesis's experimental part the aim was to evaluate unity of the medication reviews in OMA21 research project. For four intervention patients in the OMA21 research project parallel medication reviews were done. From these reviews were examined how many of the problems found in the reviews were the same with different reviewers. There was a lot of dispersion in the problems found in the reviews. Only 17.5 % of the 40 different problems found in the reviews were the same with all the reviewers. From 12 patients medication reviews drug related problems were categorized by PCNE classification V6.2. 69 drug related problems were found from the medication reviews. Most common problem was the treatment effectiveness (P1) (37.7 %). For the problems 92 potential causes were found and the most common of them was drug selection (C1) (39.1 %). The aim was also examine whether Evidence-Based Medicine electronic Decision Support (EBMeDS) tool, developed by Duodecim Medical Publications Ltd, could be useful in the OMA21 research project. It was shown that EBMeDS have limited advantage if patients' information has not been reported right in the electronic health records. Only 30 % of the examined drugs had indication. In the future if the patients' information was reported right in the electronic health records the EBMeDS tools could be useful help in medication reviews, because EBMeDS contains many electronic databases that are often used in medication reviews.P50O48

Family caregiving refers to the organization of home care for an older adult, disabled or sick person with the assistance of a relative or other close person. The number of elderly carers (> 65 years) of all family garegivers is significant. There are challenges concerning family caregiving for the older adults, due to increased age is in connection with decreased physical performance and increased number of medications and polypharmacy. Despite these factors, there has been little research on the medication safety in the family caregiving among older adults. The aim of this Master's thesis was to identify factors influencing the ability of a caregiver to cope with the medication management of the older adults. These factors were divided into subgategories: factors associated a family caregiver, associated a care recipient and system-oriented factors. The research was conducted as a method triangulation, in which the data were collected through two interviews with home visits (n = 21) and related questionnaires. The questionnaire data were quantitatively analyzed by calculating the frequencies and relative frequencies. The transcribed interviews were analyzed by abductive content analysis, combining both deductive and inductive approach. James Reason's theory of human error was used as the theoretical framework. Caregiving families participating in this research were very different compared with each other. Some family caregivers and care recipients were in good physical condition while others were severely disabled. However, the situation of the families was not individually considered when considering appropriate support services for the families. The workload of family caregivers due to the pain and the absence of days off contributed to the difficulty of medication management. The foremost system-oriented challenges in the management of the medications were: 1) difficult for the families to reach the physician and 2) for those families where assisted home care helped the caregiver, the families were not satisfied with its functioning. Due to the poor availability of physicians and the lack of a family physician, there was no one in control of the medication as a whole and there was inadequate monitoring of the medication. In the assisted home care, challenges were caused by the fact that home care visits were conducted over a wide period of time, which created challenges for giving the medications. Carers do not receive sufficient support from the society for the management of the medications. The medication safety of the older adults in the family caregiving is particularly affected by the difficulty of reaching a physician, the inadequacy of support from the assisted home care, the failure to recognize the individuality of caregiving families, and the caregivers’ burden due to pain and lack of days off. Support for caregivers must be at the forefront of society in the future, so that caregivers can cope with heavy nursing care and complicated medications, even without excessive self-activity.