Crisis management in community pharmacies during a pandemic.

BACKGROUND: Although the COVID-19 pandemic required community pharmacies to implement several adaptation strategies to ensure medicines' and services' availability, related empirical research based on crisis management theory is lacking. OBJECTIVE: This study sought to holistically depict crisis management in Finnish community pharmacies and explore whether (1) pre-existing crisis plans, (2) crisis teams, (3) shared decision-making or (4) collaboration and communication with external stakeholders can protect staff resilience, pharmacy owners' resilience, organisational cohesion ('team spirit') and pharmacies' resources or finances during the pandemic. METHODS: A cross-sectional survey was developed based on the crisis management process model and sent to Finnish community pharmacy owners (n = 602) during the pandemic's second wave in October-November 2020. Descriptive statistics were calculated, and logistic regression analysis was performed to explore effects of crisis management efforts. Open-field responses were analysed qualitatively using deductive content analysis. RESULTS: In total, 221 (36.7 %) pharmacy owners participated in the study. Pharmacies responded to the pandemic with increased order volumes and new suppliers, home deliveries and remote consultations, hand sanitiser production and additional customer counselling concerning the COVID-19. Shared decision-making with pharmacy colleagues (p = 0.025) and collaboration with peers or stakeholders in the supply chain (p = 0.015) protected pharmacy owners' resilience during the pandemic. Additionally, shared decision-making protected pharmacies' finances (p = 0.040). Crisis teams or collaboration with social and healthcare operators did not provide advantage to pharmacies. However, pre-existing pandemic plans associated with reduction of pharmacies' resources (p = 0.006). CONCLUSIONS: Community pharmacies responded to the COVID-19 pandemic with several measures to ensure the continuity of pharmaceutical services and care and the availability of medicines, disinfectants and personal protective equipment. Developing shared decision-making in pharmacies and active collaboration with peers and supply-chain stakeholders could improve pharmacies' finances and their owners' resilience in future crises.

Organisation of cross-sector collaboration and its influence on crisis management effectiveness among pharmaceutical supply chain stakeholders during the COVID-19 pandemic.

OBJECTIVES: To investigate the organisation of cross-sector collaboration and how it influenced crisis management effectiveness among pharmaceutical supply chain stakeholders in Finland during the COVID-19 pandemic. STUDY DESIGN: Qualitative semi-structured interview study. METHODS: Purposeful selection was used to obtain the study sample consisting of leaders and specialists from the pharmaceutical industry and wholesalers (n = 9), community pharmacy owners (n = 9), hospital pharmacy heads (n = 6), government agency directors and officials (n = 5) and advocacy organisation representatives (n = 2). Inductive content analysis was performed to examine the data from the semi-structured individual (n = 29) and paired (n = 2) interviews in March-May 2021. RESULTS: A new conceptual model was developed to describe the organisation of collaborative crisis management. Without a predefined crisis management organisation, cross-sector collaboration was organised based on previous collaboration structures, channels and relationships and through the establishment of issue-specific groups by government agencies as per legal mandates. Crisis dynamics and related issues guided the group formation and meeting frequency. Advocacy organisations and government agencies acted in bridging role between stakeholders. Shared knowledge among pharmaceutical supply chain stakeholders enabled anticipation and preparedness during crisis; shared resources fostered maintenance of core functions; and shared problem-solving facilitated cross-sectoral solutions. CONCLUSION: This was the first study exploring cross-sector collaboration among pharmaceutical supply chain stakeholders during a crisis. Sharing knowledge, resources and problem-solving increased the crisis management effectiveness. The study presented a new illustration of organising for collaborative crisis management and added knowledge about private-third sector collaboration and issue-specific groups to the cross-sector collaboration and crisis management literature.

Acceptability of flavoured pharmaceutically non-active mini-tablets in pet cats tested with a rapid 3-portal acceptance test with and without food.

Palatable oral pharmaceuticals are crucial for feline medication. The pharmaceutical industry prefers synthetic flavours over organic ones because of hygiene and regulatory issues. The aim of this study was to find a palatable synthetic flavour for future taste-masking of feline pharmaceuticals. The hypothesis was that synthetic meat aromas and free amino acids would be palatable to cats. The palatability of 18 synthetically flavoured mini-tablets was screened with 10-19 pet cats using a rapid 3-portal acceptance test with and without food. The tested flavours were synthetic amino acids (L-carnitine, l-glutamic acid monosodium salt hydrate, l-leucine, l-methionine, l-phenylalanine, l-proline, and taurine), d-(+)-Maltose monohydrate and thiamine hydrochloride. Furthermore, thiamine hydrochloride was combined with amino acids (l-cysteine, l-leucine, l-methionine and l-proline) and synthetic meat flavours (2-acetylpyridine, 2-acetylthiazole, 2-pentylpyridine and 4-hydroxy-5-methyl-3(2H)-furanone). The negative control was a non-flavoured placebo mini-tablet, while positive controls were an organic yeast-flavoured mini-tablet and a yeast- and fish-based commercial vitamin tablet in mini-tablet form. No significant differences were detected between palatable synthetic flavours and the placebo, nor between the synthetic flavours and the yeast flavour. In general, the mini-tablet seemed to be small enough to be accepted inside a food item. These results differ from the earlier literature about the taste preferences of cats for amino acids, and hence free amino acids should not be considered palatable to cats based purely on previous findings.

Difficulties in administration of oral medication formulations to pet cats: an e-survey of cat owners.

The purpose here was to determine the problems cat owners encounter in medicating their cats with orally administered drugs at home. The study was carried out as an open e-questionnaire survey addressed to cat owners in which the authors focused on the oral administration route. A total of 46 completed questionnaires were included in the survey. In the study, 46 cats received 67 orally administered drugs. Approximately half of the drugs were registered for use in cats by the European Medicines Agency (54 per cent), and there were also off-label drugs registered for human (36 per cent) and canine medication (7.4 per cent) and an ex tempore drug (3.0 per cent). The owners were unable to give the doses as prescribed for their cats for one-fourth of the medications (16/67). Drugs that were registered for feline medication were significantly more palatable than drugs registered for other species (odds ratio (OR) 4.9), and liquid formulations were significantly more palatable than solid formulations (OR 4.8). However, most of the owners (22/38) preferred a solid dosage form, while few (4/38) chose a liquid formulation. The results indicate that there is still a need for more palatable and easily administered oral drugs for cats.

The effect of freeze-drying parameters and formulation composition on IgG stability during drying.

The objective of this study was to explore the effects of freeze-drying parameters and formulation composition on polyclonal IgG stability during processing. Samples were freeze-dried with different primary drying pressures and secondary drying heating rates. After drying, changes in IgG in vitro binding activity, monomer recovery, average particle size, and polydispersity were studied from the rehydrated lyophilizates. Significant trends were not observed in binding activities or monomer recoveries, but increases in particle size and polydispersity were observed when using lower primary drying pressure. This effect could no longer be observed when sodium phosphate buffer was removed from the formulation. Altering the secondary drying heating rates did not result in any measurable changes in protein stability.

Microscale granulation in a fluid bed powder processor using electrostatic atomisation.

The aim of this study was to use the electrostatic atomisation in miniaturised fluid bed granulation process and define the effect of process parameters. The process parameters included in the study were granulation liquid flow rate, atomisation voltage and binder concentration in the granulation liquid. Altogether 22 batches were granulated in Multichamber Microscale Fluid bed powder Processor (MMFP). Granule size distributions were measured with both sieves and image analyses. With these process conditions, the atomisation liquid flow rate had a strong positive correlation with the granule size. Increasing the atomisation voltage increased the granule size, which is contradictory with the expectations. The effect of the binder concentration remained unclear. Although it is challenging to model the fluid bed granulation process in micro-scale, multivariate methods such as principal component analysis (PCA) are helpful in studying the most important phenomena.

A solid-state NMR study of phase structure, molecular interactions, and mobility in blends of citric acid and paracetamol.

Citric acid anhydrate (CAA) and paracetamol (PARA), prepared as crystalline physical mixtures and as amorphous blends, were studied using (13)C solid-state cross polarization magic angle spinning (CPMAS) NMR. Amorphous blends showed significant line broadening from the conformational distribution as compared to the crystalline samples. Also, chemical shift variations were observed between crystalline and amorphous blends, which were attributed to differences in intermolecular interactions. Averaging of proton rotating-frame spin-lattice relaxation times (T(1rho)) probed via different (13)C sites in the amorphous blends confirmed molecular level mixing. For some, initially amorphous, sample compositions the onset of crystallization was evident directly from spectra and from the significantly longer T(1rho) relaxations. Thus, crystallization caused phase separation with properties of the two phases resembling those of pure CAA and PARA, respectively. (13)C spectra of amorphous 50/50 (w/w, %) CAA/PARA recorded from above the glass transition temperature broadened as the temperature increased to a maximum at T approximately T(g) + 33 K. This was the result of a dynamic interference between the line narrowing techniques being applied and the time scale of molecular reorientation in the miscible melt. The derived average correlation time was found to correspond well with previous results from melt rheology. We conclude that the underlying reasons for physical instability (i.e., crystallization from the miscible melt, including molecular interactions and dynamics) of this class of amorphous binary mixtures can be effectively evaluated using NMR spectroscopy.

Characterization of ultrasound extrudated and cut citric acid/paracetamol blends.

The purpose of the present work was to study the effect of ultrasound extrusion and cutting on the physical stability of a viscous and sticky supercooled melt containing (50/50, w/w, %) citric acid anhydrate and paracetamol. Samples were extrudated at temperatures of 50, 60, and 70 degrees C using power levels of 0, 50, 100, and 150 W. Similarly, extrudates prepared at 60 degrees C were cut at temperatures ranging from 25-60 degrees C with an ultrasound knife in the range 0, 50, and 100 W. The characterization methods used were: high performance liquid chromatography, differential scanning calorimetry, Karl Fischer titration, X-ray powder diffraction, Fourier transform infrared microscopy, optical- and stereomicroscopy. There was no physical difference in extrudates or cut surfaces whether processed with or without ultrasound. During 1-year aging time in dry conditions, all the samples were observed to crystallize slowly and ultrasound processing did not enhance the crystallization. Ultrasound thus holds some promise for processing of viscous and sticky pharmaceuticals, provided the material is physically stable enough to withstand mechanical and thermal stress. Processing of sticky and viscous material would be difficult without ultrasound with the methods currently used in pharmaceutical industry.

New processing technique for viscous amorphous materials and characterisation of their stickiness and deformability.

This paper reports on a technique using ultrasound-assisted equipment to characterise and handle stickiness of viscous amorphous blends of citric acid and paracetamol after melt mixing and during processing. Deformability and stickiness were studied using a specially designed sample measurement compartment. An ultrasound-assisted nozzle and knife for pharmaceutical applications were studied. The application of ultrasound was found to increase the mass flow through a nozzle connected to a pressurized tank. This effect was found to be separate from the increased mass transport resulting from the reduced viscosity as the temperature was increased. Ultrasound was also found to have a favourable influence on cutting through melt extrudates. The stickiness and resistance to deformation of samples were observed to be dependent on the amount of paracetamol in the blend and temperature that was in agreement with the glass transition temperature and viscosity. Other influencing factors, such as time-dependent wetting and surface energetics, are discussed. We conclude that it is possible to characterise stickiness and resistance to deformation of viscous amorphous materials with a specially designed probe test, and the stickiness of amorphous material can be handled during processing with ultrasound-assisted equipment.

Mercury porosimetry of mannitol tablets: effect of scanning speed and moisture.

Purpose of the work was to study the effect of the scanning speed of mercury porosimetry and moisture content of the sample on the mercury porosimetry result for mannitol tablets. Tablets were compressed at three different compression pressures from nonhygroscopic mannitol powder and granules. Pore structure of tablets was determined with three different scanning speeds of a high-pressure mercury porosimeter after storage in three different moisture conditions. With low scanning speed, smallest pores of tablets were determined more accurately. Small amounts of moisture, even as low as 1%, before evacuation in nonhygroscopic mannitol tablets decrease the porosity. Decrease in porosity was observed at a pore diameter range of 50-1000 nm, not at the smallest determined pores. Thus, the role of water in pharmaceutical samples appears to be complicated. Reasonably slow scanning is recommended in high-pressure mercury porosimetry. If total pore volume is the only parameter of interest, fast scanning can be used. Pretreatment of the samples by proper drying before mercury porosimetry is important.

Microcrystalline cellulose and its microstructure in pharmaceutical processing.

Mercury porosimetry and nitrogen adsorption methods were used in pore structure and pore surface area characterisation of microcrystalline cellulose powder, granules and tablets. The effect of compression on pore structure and surface area of tablets compressed with three different compression pressures of powder and granules was determined. Densification of MCC in wet granulation led to decreased compactibility in tableting. Effects of granulation on the microstructure of microcrystalline cellulose and plastic deformation of powder during compression were detected with nitrogen adsorption, at the diameter range 3-200 nm. Structure of granules was destroyed during tableting when compression pressures of 196 MPa were used. Fragmentation and deformation of granules were observed from the results determined using both methods. Due to different measurement ranges, different theoretical basis of the methods and behaviour of the samples during analysis, results obtained with mercury porosimetry and nitrogen adsorption methods are not strictly comparable. Results obtained with mercury porosimetry give information on the behaviour of powder and granule particles in granulation or compression, whereas nitrogen adsorption brings out the changes in intraparticular structure of particles. The results obtained using these methods together can be used in the characterisation of behaviour of materials in granulation and tableting.

Rheological characterization of microcrystalline cellulose and silicified microcrystalline cellulose wet masses using a mixer torque rheometer.

The rheological properties of silicified microcrystalline cellulose (Prosolv 50) were compared with those of standard grades of microcrystalline cellulose (Emcocel 50 and Avicel PH 101). Cellulose samples were analyzed using nitrogen adsorption together with particle size, flowability, density and swelling volume studies. The rheological behaviour of the wet powder masses was studied as a function of mixing time using a mixer torque rheometer (MTR). Silicified microcrystalline cellulose exhibited improved flow characteristics and increased specific surface area compared to standard microcrystalline cellulose grades. Although the silicification process affected the swelling properties and, furthermore, the mixing kinetics of microcrystalline cellulose, the source of the microcrystalline cellulose had a stronger influence than silicification on the liquid requirement at peak torque.

Pore structure and surface area of mannitol powder, granules and tablets determined with mercury porosimetry and nitrogen adsorption.

Two methods used in pore structure characterisation, mercury porosimetry and nitrogen adsorption, were compared. Pore structure and surface area of mannitol powder, granules produced in wet granulation and tablets compressed with three compression pressures were studied. Greater surface area, more porous structure and greater number of small pores in granules, when compared with powder, increased the compactibility of mannitol granules in tableting. Plastic deformation and fragmentation of powder and granules in compression were observed in volume pore size distributions and surface areas measured with these methods. Pore volume and volume pore size distribution obtained with mercury porosimetry describe densification of mass better than those obtained with nitrogen adsorption. In spite of differences between the methods, the volume pore size distribution curves of samples in the overlapping pore size range had the same shape. The specific surface area of tablets, measured by the nitrogen gas adsorption method described well the deformation under compression. Fragmentation increased the surface area of powder, and plastic deformation decreased the surface area of granules in the pore size range determined. Surface area values measured with mercury porosimetry were larger than those determined with nitrogen adsorption.

Compression of lactose, glucose and mannitol granules.

The effect of the amount of granulation liquid, compression speed and maximum compression force on then compressibility and compactibility of lactose, glucose and mannitol granules was studied. The porosity based on the geometrical shape and the uniformity of weight of tablets was also studied. Lactose and mannitol granules showed a greater compressibility than glucose granules. Mannitol granules produced the hardest tablets and lactose and glucose the weakest. The change in the amount of granulation liquid caused changes both in the granule porosity and in the amount of binder; this was attributed to differences in tablet strength. All parameters studied were relatively insensitive to changing speeds of compression in the range used, except for the breaking force of mannitol tablets, which was greatest with the lowest speed of compression. All granule masses showed a relatively good continuous flow suitable for table production. Tablets compressed from lactose granules had the best uniformity of weight of the tablets studied.