Phospholipid-based self-assembled mesophase systems for light-activated drug delivery.

The manipulation of the structure of phospholipid-based mesophases to induce a slow to fast drug release profile has potential for use in therapeutic situations where continuous absorption of drug is not desirable and reduce the frequency of injection for short acting or rapidly cleared drugs in treatments for diseases such as macular degeneration. This study had two aims; firstly to confirm the phase behaviour of 20 mol% cholesterol in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), which was previously reported to transition from lamellar (slow release) to bicontinuous cubic (fast release) phase with increasing temperature. Contrary to the literature, no bicontinuous cubic phase was observed but a transition to the inverse hexagonal phase occurred at all POPE : cholesterol ratios investigated. The second aim was to render these mesophases responsive to near-infrared laser (NIR) irradiation by incorporation of gold nanorods (GNR) incorporated into the POPE system to induce photothermal heating. The inclusion of 3 nM GNR in POPE systems induced reversible disruption of lipid packing equivalent to increasing the temperature to 55 °C when irradiated for 30 s. This study confirmed that although the previously published phase behavior was not correct, GNR and NIR can be used to manipulate the self-assembled mesophases in phospholipid-based systems and highlights the potential for a phospholipid-based light-activated drug delivery system.

Online teaching and learning of a pharmacy curriculum designed for active learning and professional skills development - A report of students' perceptions and learning experience in two international campuses.

BACKGROUND AND PURPOSE: Pharmacy students' perception of the effectiveness of remote online learning experienced during the pandemic, and their learning expectations post-pandemic were unknown. The main purpose of this study was to examine students' perceived effectiveness of online teaching and learning activities developed for active learning and pharmacy professional skills development, and the feasibility of online assessments. EDUCATIONAL ACTIVITY AND SETTING: A cross-sectional online survey involving second-year pharmacy students of Monash Malaysia (MA) and Monash Australia (PA) campuses was conducted. The survey consisted of 15 Likert-scale multiple-choice questions and an open-ended question. Data were analysed statistically. FINDINGS: Students at both MA and PA campuses were satisfied with the remote online learning experienced during the pandemic but indicated a preference for a blended learning approach. Students at the MA campus felt that on-campus face-to-face classes were more engaging and advantageous for their learning and skills development (P < .05), and on-campus assessments allowed them to engage and perform better (P < .05) compared with students at the PA campus who felt neutral or disagreed. Both student cohorts were happy with some of the lectures being conducted online synchronously or asynchronously. SUMMARY: Differences in cultures, and learning behaviour and preference may influence learners' perceptions and expectations of online learning. This study suggests that blended learning involving both online and face-to-face interactive activities may promote engagement, satisfaction, and outcomes of culturally diverse learner populations post-pandemic.

A mouse model to evaluate the impact of species, sex, and lipid load on lymphatic drug transport.

PURPOSE: To establish a lymph-cannulated mouse model, and use the model to investigate the impact of lipid dose on exogenous and endogenous lipid recruitment, and drug transport, into the lymph of males versus females. Finally, lymphatic transport and drug absorption in the mouse were compared to other pre-clinical models (rats/dogs). METHODS: Animals were orally or intraduodenally administered 1.6 mg/kg halofantrine in low or high (14)C-lipid doses. For bioavailability calculation, animals were intravenuosly administered halofantrine. Lymph or blood samples were taken and halofantrine, triglyceride, phospholipid and (14)C-lipid concentrations measured. RESULTS: Lymphatic lipid transport increased linearly with lipid dose, was similar across species and in male/female animals. In contrast, lymphatic transport of halofantrine differed markedly across species (dogs>rats>mice) and plateaued at higher lipid doses. Lower bioavailability appeared responsible for some species differences in halofantrine lymphatic transport; however other systematic differences were involved. CONCLUSIONS: A contemporary lymph-cannulated mouse model was established which will enable investigation of lymphatic transport in transgenic and disease models. The current study found halofantrine absorption and lymphatic transport are reduced in small animals. Future analyses will investigate mechanisms involved, and if similar trends occur for other drugs, to establish the most relevant model(s) to predict lymphatic transport in humans.

A scoping study of the medication therapy related pharmacist services in the Western Pacific Region.

OBJECTIVES: To identify the preferred terminologies, nature of services, perceived benefits and barriers to medication therapy-related pharmacist services in the Western Pacific region to facilitate the development of a framework for medication therapy management. METHOD: A survey was completed by hospital and community pharmacists purposively selected by the national pharmacist associations. KEY FINDINGS: Pharmaceutical care was the preferred term with services predominantly related to medication safety and public health. The perceived barriers included lack of appropriate facility, time and funding. CONCLUSION: A broader pharmaceutical care framework is a preferred approach to delivery of Good Pharmacy Practice in the region.

A comparison of the academic performance of graduate entry and undergraduate entry pharmacy students at the course exit level.

INTRODUCTION: Graduate entry (GE) pharmacy students are trained in a shorter timeframe than undergraduate entry (UE) students. This study compares the academic performance of GE and UE pharmacy students at the course exit point. METHODS: A retrospective analysis of final exam grades in written and objective structured clinical examination (OSCE) was performed between GE and UE students from three graduating cohorts. Final written examination contained clinical case study questions, whereas OSCE involved role play with simulated patients or doctors. Statistical analyses were performed by t-test and one-way analysis of variance at .05 significance level and Pearson's correlation coefficient. RESULTS: No significant difference in academic performance was seen between GE and UE groups at course exit (P > .05). There was a trend for GE students performing marginally better in OSCE than UE students. Females showed better performances in verbal communication than males. GE males showed significantly lower empathy scores than all other groups. No significant difference was seen in problem-solving scores amongst all groups. Both UE and GE groups scored significantly better in written examinations compared with OSCE. CONCLUSIONS: Graduate entry pharmacy students from accelerated learning pathway and UE students performed similarly at the course exit point, providing empirical support for non-traditional graduate entry pathway as a viable option.

Extemporaneous compounding confidence progression from undergraduate to practice: a pharmacy education perspective.

OBJECTIVE: This study examined how undergraduate students, graduate interns and registered pharmacists perceived their competence in extemporaneous compounding. METHODS: A cross-sectional observational study was conducted using a self-administered survey and participants ranked how confident they felt about compounding certain products using a Likert's scale and free-text responses. KEY FINDINGS: Pharmacy students perceived to be as confident as the interns and pharmacists in preparing 'simple' products, such as solutions, suspensions, creams and ointments. A lack of frequent practice was related to poor confidence by all three groups. CONCLUSION: Integration of theoretical, legal and ethical and patient counselling aspects in extemporaneous compounding curriculum could enhance learning and outcomes.

Comparative assessment of competency frameworks for pharmacists in the Western Pacific region including the potential for a regional framework.

OBJECTIVES: To assess the potential for a regional competency framework for pharmacists in the Western Pacific using the Global Competency Framework (GbCF) as a reference. METHODS: Mixed-methods approach used a self-administered survey and semi-structured interviews of 13 countries to evaluate the perceived benefits, existence and content of competency frameworks. KEY FINDINGS: Variations in structure, components and emphasis of the four frameworks that do exist indicate significant tailoring to local requirements. Based on these four and the GbCF, 32 competencies allocated into four themes has been proposed. CONCLUSION: Varying national requirements mitigate against a single regional competency framework.

Pharmacy Student Challenges and Strategies towards Initial COVID-19 Curriculum Changes.

Due to COVID-19, tertiary institutions were forced to deliver knowledge virtually, which proposed challenges for both institutions and students. In this study, we aimed to characterize pharmacy students' challenges and strategies during COVID-19 curriculum changes, therefore developing a comprehensive understanding of students' learning, wellbeing, and resilience in the ever-changing situation. Data were collected from student written reflections across four year levels at one school of pharmacy from March-May 2020. In addition, data were collected from written responses of second-year pharmacy students responding to prompted questions. The data were qualitatively analyzed inductively by five coders using NVivo 12. For each piece of data, two coders independently coded the data, calculated the inter-rater agreement, and resolved discrepancies. The most coded challenges were 'negative emotional response' and 'communication barrier during virtual learning'. The most coded strategies were 'using new technology' and 'time management'. This study allows researchers and education institutions to gain an overview of pharmacy students' experiences during COVID-19, therefore helping universities to provide students with necessary support and techniques on how to self-cope with COVID-19 as well as stressful events in the future.

Protocol for a randomised controlled trial evaluating the impact of a community pharmacy discharge medication reconciliation service on unplanned hospital readmissions - The DCMedsRec trial.

INTRODUCTION: A substantial proportion of hospital admissions and readmissions are directly attributable to preventable medication-related harm. Interventions that reduce these harms could avert significant suffering and healthcare costs. OBJECTIVES: The Discharge Medications Reconciliation (DCMedsRec) trial will evaluate a structured medication reconciliation service by community pharmacists post hospital discharge on the risk of 30-day unplanned readmission. Electronic access to the Hospital Discharge Summary via My Health Record will underpin this service. METHODS: DCMedsRec is a non-blinded randomised controlled trial of an intervention by community pharmacists within 30 days of hospital discharge in Melbourne, Australia. Patients discharged from hospital will be assessed by a hospital pharmacist for trial eligibility. If eligible, patients will be randomised to either a control or intervention group by sequentially marked sealed envelopes. Intervention patients receive an invitation to the DCMedsRec service at a participating community pharmacy, who will be reimbursed. Control patients will receive usual care. A Number Needed to Treat of 20 will require 293 DCMedsRec interventions to achieve 80% power. With a predicted 30% uptake, a minimum sample of 977 in the intervention arm is required. OUTCOMES: The primary outcome will be the rate of 30-day unplanned hospital readmission in intervention (DCMedsRec) versus usual care groups. Secondary analyses will evaluate the economic impact of the intervention and a qualitative thematic analysis of the experience and value of the service for both patients and service providers (community pharmacists). ANALYSIS: An intention-to-treat analysis will be used to assess intervention efficacy and results will be reported using risk ratios with 95% confidence intervals. Cost-effectiveness analysis will compare within-trial costs and outcomes of the DCMedsRec versus usual care from a health-system perspective. TRIAL REGISTRATION AND FUNDING: This trial is registered with the Australian and New Zealand Clinical Trials Register and funded by the Australian Digital Health Agency.

A global assessment of distance pharmacy education amid COVID-19: teaching, assessment and experiential training.

OBJECTIVES: To explore pharmacy colleges' experiences and challenges worldwide with the transition to online teaching during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: From the six World Health Organization regions, 28 countries with the highest number of COVID-19 cases were identified, and 111 pharmacy colleges were randomly selected from these countries. Two online surveys were sent to faculty members and senior administrators. They assessed changes in teaching and learning, experiential training, assessment, readiness for and challenges with distance e-learning and work-related stress. KEY FINDINGS: Data were collected from 46 colleges. The majority (80.4%) of colleges transitioned to distance e-learning. On-site experiential training was discontinued in 55.5% of colleges and 25.0% redesigned on-site training into remote learning experiences. Assessments were modified in 75.9% of colleges. Assuring the integrity of assessments and delivering practical classes were the most prominent faculty challenges. The majority of faculty (75.0%) and administrators (61.9%) reported moderate work-related stress. Nevertheless, most academics felt that they received adequate support from their institutions and had positive perceptions of the transition to distance e-learning during the pandemic. CONCLUSIONS: The COVID-19 pandemic required drastic changes for most programs' teaching methods. Our results showed that educational institutions were somewhat able to support faculty and the needs of educational programs were largely met. However, academic rigour and provision of experiential training can be improved. Faculty emotional support and training needs were not fully addressed in these difficult times. These results shed light on how the global pharmacy academy has addressed the COVID-19 pandemic and help rethink crisis response models.

Using a collaborative decision-making approach to identify, prioritise and respond to issues influencing Good Pharmacy Practice across countries of the Western Pacific Region.

OBJECTIVES: The Western Pacific Pharmaceutical Forum aims to foster Good Pharmacy Practice (GPP) in the Western Pacific Region (WPR). Our objective in this work was to develop and implement a process that equitably and constructively engaged pharmacy associations from the diverse cultures, languages and models of pharmacy practice in the WPR to identify common issues influencing the implementation of GPP. METHODS: The World Café concept was incorporated into a modified Tuckman's model for group development to conduct a workshop of leaders from the major pharmacy associations of the WPR. Facilitated discussion groups and collaborative decision-making were used to gather opinions and achieve agreement between the regional leaders. KEY FINDINGS: Participants reported the method to be open, systematic and enabled full contribution. Two major issues were identified in relation to each of the four key pharmacist roles associated with GPP. The regional pharmacy leaders agreed the common priority issue for implementing GPP as: 'National competency standards should be established to enable the formulation of professional development framework that lead to enhanced pharmacy practice and patient care' and developed a strategy and work plan to address this issue. CONCLUSIONS: Identification of GPP issues and the common major priority occurred with shared knowledge of the current state of practice across the WPR. The adopted methodology overcame cultural and practice differences to ensure full and equal participation of all delegates. The approach ensured ownership by all participants of the strategy and work plan developed to address competency and professional development in the WPR.

Pharmacy Students' Perceptions and Performance on the Use of an Online Virtual Experience Tool for Practicing Objective Structured Clinical Examinations.

Objective. To examine pharmacy students' performance on and perceptions regarding the use of an interactive online tool for practicing to take objective structured clinical examinations (OSCEs).Methods. The Monash OSCE Virtual Experience (MOVE), an online module consisting of 20 pharmacy case scenarios with virtual patients, was piloted with final-year pharmacy students at Monash University campuses in Australia and Malaysia. A mixed methods approach that included reviewing user attempts and comparing grades, collecting student-administered questionnaires, and holding focus groups was used to examine students' perception and performance.Results. More than 99% of all students attempted at least one online case scenario in preparation for their final in-person OSCE, and 81% attempted all 20 scenarios two or more times. Ninety percent of students at the Malaysia campus and 70% of students at the Australia campus reported that MOVE was a helpful study tool for their OSCE preparation. However, a raw comparison of user attempts and OSCE grades did not find a direct correlation between online module attempts and assessment grades. Self-administered questionnaire and focus group results indicated that MOVE prepared students for targeted and time-restricted history-taking and problem-solving skills. Overall, students perceived MOVE to be a useful learning tool and a less overwhelming learning experience than were face-to-face sessions. Nevertheless, students still preferred face-to-face OSCE practice with simulated patients over online practice with virtual patients.Conclusion. The Monash OSCE Virtual Experience was perceived by our students as a flexible and useful online learning aid in preparing for their final-year OSCE However, there was no direct correlation between online practice attempts and students' exam grades.

Lipid-based drug delivery systems in the treatment of wet age-related macular degeneration.

Recent advances in drug delivery technology have amplified potential opportunities to treat the debilitating diseases that affect the posterior segment of the eye in a less invasive and more efficient manner. Current methods for effective drug delivery to the back of the eye are hindered by many barriers and limitations. As a consequence, considerable efforts have been directed towards developing new materials to selectively deliver drug directly to the target site. This review focuses on lipid-based delivery systems which show promise in improving treatment for the most common disease of the posterior segment of the eye in the developed world, age-related macular degeneration, with an emphasis upon on-demand delivery systems as they have greater potential to overcome the current limitations.

PEGylated interferon displays differences in plasma clearance and bioavailability between male and female mice and between female immunocompetent C57Bl/6J and athymic nude mice.

Gender and immune status can considerably impact on the pharmacokinetics (PK) of macromolecular and small molecule drugs. However, these effects are often not considered in drug development. We aimed to quantitatively evaluate effects of gender and immune status on the PK of PEGylated interferon in frequently used murine models. Chronically cannulated female athymic nude and female and male immunocompetent C57Bl/6J mice (n = 24 in total) received a single intravenous or subcutaneous (s.c.) dose of PEGylated interferon. Serial blood samples were taken for 48 h. Noncompartmental analysis and population PK modeling with covariate analysis were performed to evaluate the data. The PK of PEGylated interferon followed a three compartment disposition model with two sequential compartments for s.c. absorption. Female nude mice had significantly higher plasma clearance than C57Bl/6J mice (0.503 vs. 0.397 mL/h). Male mice had a slower absorption rate constant (0.138 h(-1)) and extent (46.2%) of s.c. absorption than female mice (0.274 in C57Bl/6J and 0.374 h(-1) in nude, 60.8% in both). Thus, gender and immune status significantly impacted on important PK parameters of PEGylated interferon in murine models commonly utilized in drug development. It is critical to take into account these differences when choosing animal models and conducting translational pharmacology research.

The mesenteric lymph duct cannulated rat model: application to the assessment of intestinal lymphatic drug transport.

The intestinal lymphatic system plays key roles in fluid transport, lipid absorption and immune function. Lymph flows directly from the small intestine via a series of lymphatic vessels and nodes that converge at the superior mesenteric lymph duct. Cannulation of the mesenteric lymph duct thus enables the collection of mesenteric lymph flowing from the intestine. Mesenteric lymph consists of a cellular fraction of immune cells (99% lymphocytes), aqueous fraction (fluid, peptides and proteins such as cytokines and gut hormones) and lipoprotein fraction (lipids, lipophilic molecules and apo-proteins). The mesenteric lymph duct cannulation model can therefore be used to measure the concentration and rate of transport of a range of factors from the intestine via the lymphatic system. Changes to these factors in response to different challenges (e.g., diets, antigens, drugs) and in disease (e.g., inflammatory bowel disease, HIV, diabetes) can also be determined. An area of expanding interest is the role of lymphatic transport in the absorption of orally administered lipophilic drugs and prodrugs that associate with intestinal lipid absorption pathways. Here we describe, in detail, a mesenteric lymph duct cannulated rat model which enables evaluation of the rate and extent of lipid and drug transport via the lymphatic system for several hours following intestinal delivery. The method is easily adaptable to the measurement of other parameters in lymph. We provide detailed descriptions of the difficulties that may be encountered when establishing this complex surgical method, as well as representative data from failed and successful experiments to provide instruction on how to confirm experimental success and interpret the data obtained.

Practical lessons in murine thoracic lymph duct cannulations: observations in female and male mice across four different strains that impact on "cannulatability".

Cannulation of the thoracic lymph duct in experimental animals allows direct measurement of the lymphatic exposure of lymph-targeted drugs. When coupled with recent advances in genetically modified and diseased mouse models, this presents further opportunities to define changes in biological processes and disease in response to drug treatment. Although cannulation of the thoracic lymph duct in mice is inherently challenging because of the small size and delicate nature of the duct, it can be further confounded by anatomical variations between animals. In this communication, we present our observations on the anatomical features of the thoracic lymph duct between mice of different strains and genders, and discuss the impact of these features on the "cannulatability" of the duct. We also provide some technical tips to help guide other investigators to deliver higher experimental success rates.

The influence of intestinal lymphatic transport on the systemic exposure and brain deposition of a novel highly lipophilic compound with structural similarity to cholesterol.

OBJECTIVES: To assess the role of intestinal lymphatic transport in the oral bioavailability and brain deposition of a highly lipophilic, centrally acting drug candidate (Org 49209) in comparison to cholesterol, a close structural analogue. METHODS: The intestinal lymphatic transport of Org 49209 and cholesterol was assessed in lymph-cannulated anaesthetised rats and total bioavailability evaluated in non-lymph-cannulated animals. Parallel groups were employed to examine the brain deposition of Org 49209 after intraduodenal and intraperitoneal administrations. KEY FINDINGS: The contribution of intestinal lymphatic transport to total bioavailability was similar for Org 49209 and cholesterol (approximately 40% of the absorbed dose). However, the oral bioavailability of Org 49209 was significantly (fourfold) lower than cholesterol. Brain deposition of Org 49209 was similar after intraduodenal and intraperitoneal administration. Systemic exposure, however, was higher after intraduodenal administration and brain-to-plasma ratios were therefore reduced. CONCLUSION: The oral bioavailability of Org 49209 was significantly lower than that of its structural analogue cholesterol; however, intestinal lymphatic transport played a similar role in oral bioavailability for both compounds. Brain to plasma ratios were lower after intraduodenal versus intraperitoneal administration, suggesting that drug association with intestinal lymph lipoproteins may limit central nervous system access for highly lipophilic drugs.

The impact of lymphatic transport on the systemic disposition of lipophilic drugs.

This work investigates the influence of drug absorption route (intestinal lymphatics vs. blood supply) on drug pharmacokinetics and tissue distribution. To achieve this aim, the pharmacokinetics and tissue distribution of model compounds [1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane, DDT; halofantrine] and lipids were assessed following intravenous delivery in lymph lipoproteins or plasma, and were found to differ significantly. For DDT, the clearance (CL) and volume of distribution (Vd ) were higher, whereas for halofantrine, CL and V(d) were lower, after entry in lymph versus plasma due, in particular, to differences in adipose tissue and liver uptake. In a recent study, halofantrine CL and V(d) were similar following entry in lymph or entry in plasma into the systemic circulation of animals predosed with lymph, whereas in the current study, predosing lymph did not influence DDT CL and V(d). For compounds such as DDT, changes to the route of absorption may thus directly impact on pharmacokinetics and tissue distribution, whereas for halofantrine factors that influence lymphatic transport may, by altering systemic lipoprotein concentrations, indirectly impact pharmacokinetics and tissue distribution. Ultimately, careful control of dosing conditions (formulation, prandial state), and thus the extent of lymphatic transport, may be important in assuring reproducible efficacy and toxicity for lymphatically transported drugs.

Intravenous dosing conditions may affect systemic clearance for highly lipophilic drugs: implications for lymphatic transport and absolute bioavailability studies.

The clearance (Cl) and volume of distribution (V(ss)) of a lipophilic, lymphatically transported drug, halofantrine (Hf) have been evaluated after intravenous delivery to the systemic circulation in ex vivo lymph and plasma, and compared with the data obtained after administration of a lipid-based emulsion and a lipid-free cosolvent formulation. Systemic Cl and V(ss) were significantly lower (approximately twofold) after delivery of Hf in lymph or the emulsion when compared with the administration in plasma or the cosolvent formulation. Preadministration of drug-free lymph, immediately before administration of drug in plasma, however, resulted in plasma profiles consistent with that obtained after administration of drug in lymph/emulsion. Where drug and lipid entered the systemic circulation coincidentally, systemic Cl of Hf, therefore, appeared to be relatively unaffected by the route of entry to the systemic circulation (i.e. via the lymph or the blood), but more significantly altered by total plasma lipid levels. Because temporal changes to plasma lipid levels occur as a result of the absorption of formulation or food-derived lipids and the infusion of intravenous lipid emulsions, the current data suggest that a mismatch in plasma lipid levels after intravenous and oral administrations may lead to differences in drug Cl and errors in bioavailability assessment.

Oral bioavailability assessment and intestinal lymphatic transport of Org 45697 and Org 46035, two highly lipophilic novel immunomodulator analogues.

Org 45697 (MW 600.7, clogP 7.92, soybean oil solubility 50 mg/g) and Org 46035 (MW 601.6, clog P 8.46, soybean oil solubility 40 mg/g) are two poorly water soluble (<0.1 microg/ml), highly lipophilic drug candidates with immunomodulator activity and highly analogous chemical structures. After oral administration to conscious ambulatory rats in an aqueous-based methylcellulose/Tween 80 suspension, the bioavailability of both compounds was low (< 2% of administered dose). However, bioavailability was significantly increased (> 5 fold) after oral administration in a long chain triglyceride lipid (olive oil) formulation. Subsequent studies have explored the potential for solubilising formulations, including lipid-based formulations, to enhance the oral bioavailability of Org 45697 and Org 46035 and secondly to explore the potential contribution of intestinal lymphatic transport to intestinal absorption. The experimental data show that solubilising formulations may provide for significant increases in oral bioavailability for Org 45697 and Org 46035 and that after co-administration with lipid, 35-50% of the absorbed dose may be transported to the systemic circulation via the intestinal lymph. Interestingly, the lymphatic transport of the less lipid soluble analogue, Org 46035 was approximately 40% lower than that of Org 45697 suggesting that relatively subtle differences in lipid solubility can have significant impact on the extent of lymphatic transport.