Background: Solid medication dosage forms are regularly modified to aid medication delivery to patients that are unable to swallow them. Aim: To identify medications that are commonly modified in Queensland hospitals at the bedside and in the pharmacy and to identify how these modifications are made. Method: A self-report survey was sent to 97 hospitals of varying sizes in metropolitan and rural areas across Queensland.

Although the world’s population is ageing and as a result of this an increasing number of patients are experiencing difficulty in swallowing, there remains a lack of commercially available oral liquids for both these older and paediatric patients. This presents a problem to health care professionals, especially the pharmacist in practice, who is often required to provide a solution for these patients by preparing oral liquids extemporaneously from commercially available products. Preparation of these oral liquids is challenging, both due to the lack of pharmacopoeial and stability-indicating formulae and the fact that their stability is not only determined by the active pharmaceutical ingredient, but also the ability of excipients from the commercial product to interact with each other and the active pharmaceutical ingredient. This increases the complexity of the stability considerations to be taken into account within these oral liquids, highlighting the number of parameters to be considered in the extemporaneous preparation of oral liquids. This paper presents new evidence on the stability of 42 oral liquids prepared from commercially available products, reported on in the literature since the previous review published in 2006. However, unlike the previous review where the stability concerns in 7.2% of the extemporaneously prepared oral liquids were mainly due to interaction between the active pharmaceutical ingredients and the excipients in the commercial product, most of these stability considerations have been recognised and this has resulted in the authors proposing solutions to these problems prior to the extemporaneous preparation of the oral liquid. As such this paper also focuses on the increased level of research that has been undertaken to solve previous issues related to stability, especially in terms of the use of commercial products, which is common practice in the extemporaneous preparation of oral liquids. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

BackgroundDespite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.Methods and designThis study is a multicentre, randomised, placebo controlled, two arm, parallel trial of escalating doses of oral CBD. It will compare efficacy and safety outcomes of a titrated dose of CBD (100 mg/mL formulation, dose range 50 mg to 600 mg per day) against placebo. There is a 2-week patient determined titration phase, using escalating doses of CBD or placebo to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians.DiscussionA major strength of this study is that it will target symptom burden as a whole, rather than just individual symptoms, in an attempt to describe the general improvement in wellbeing previously reported by some patients in open label, non controlled trials of medicinal cannabis. Randomisation with placebo is essential because of the well-documented over reporting of benefit in uncontrolled trials and high placebo response rates in cancer pain trials. This will be the first placebo controlled clinical trial to evaluate rigorously the efficacy, safety and acceptability of CBD for symptom relief in advanced cancer patients. This study will provide the medical community with evidence to present to patients wishing to access medicinal cannabis for their cancer related symptoms.Trial registration numberALCTRN12618001220257 Registered 20/07/2018.

The evidence for the efficacy of corticosteroids for pain control in cancer patients is weak. Significant pain relief was noted in some studies, albeit only for a short period of time. This could be important for patients with poor clinical status. Further trials, with increased numbers of participants, are needed to evaluate the safety and effectiveness of corticosteroids for the management cancer pain in adults, and to establish an ideal dose, duration of therapy and route of administration.

Four practical concepts that could be implemented in the clinical setting are proposed. These include: role preparation for managers, understanding internal and external motivation, fostering internal motivation in nursing staff, and the importance of attitude when investing in relationships.

Monitoring fentanyl concentration in saliva and plasma may be useful in pharmacokinetic/pharmacodynamic studies. Salivettes(®) have been used widely for collecting saliva samples. However due to its lipophilicity, fentanyl adsorbs to the cotton dental bud (CDB) used in this device. Furthermore, due to dry mouth being a common adverse effect seen in patients treated with opioids, obtaining enough saliva for analysis is often a challenge. Hence, a simple simultaneous method to quantify fentanyl and its metabolite in both human plasma and saliva was developed and validated. A novel extraction method was also developed and validated to recover fentanyl in saliva directly from the CDB. This extraction method utilises acetonitrile to recover the fentanyl directly from the CDB rather than recovery by centrifugation, which is not always possible. Reverse phase chromatographic separation was performed on a Shimadzu LC 20A HPLC system using gradient elution. The electrospray ion source (ESI) was operated in positive ion mode using an Applied Biosystems API 3200 LC/MS/MS as detector. Deuterated fentanyl (D5) and nor-fentanyl (D5) were used as internal standards (IS). The retention times for fentanyl and nor-fentanyl were 3.70 min and 3.20 min respectively. The lower limit of quantitation (LLOQ) was determined to be 0.030 μg/L in plasma and 0.045 in saliva for fentanyl and nor-fentanyl. Acceptable linearity for fentanyl and nor-fentanyl in both plasma and saliva was demonstrated from 0.02 to 10 μg/L (R(2) 0.9988-0.9994). Accuracy for fentanyl and nor-fentanyl in both plasma and saliva samples was between 96% and 108%. Total imprecision expressed as the co-efficient of variation was between 1.0 and 15.5% for both analytes in both matrices. The validated method was applied successfully in 11 paired plasma and saliva samples obtained from patients with cancer pain receiving transdermal fentanyl (Duragesic(®)) at doses from 25 μg to 100 μg.

Background: Despite the widespread use of dose administration aids (DAAs) there is little available data on the stability of drugs during repackaging or storage in these devices. Aim: To investigate the physicochemical stability of paracetamol tablets repackaged in DAAs. Method: Physicochemical stability studies were performed on a commonly used paracetamol tablet directly after heat-sealing in a DAA frequently employed in practice, then at ambient (25 ºC; 60% relative humidity) and accelerated (40 ºC; 75% relative humidity) conditions, over a 3-month period. Physical characteristics of the tablets (weight uniformity, physical appearance, thickness, hardness, friability, disintegration, dissolution rates) were evaluated at time = 0, directly after heatsealing, 1 month and 3 months. Chemical stability was confirmed by high performance liquid chromatography (HPLC). The results were compared to control samples stored in the original packaging at the various environmental conditions studied. Results: All compendial requirements for physicochemical stability were met for both ambient and accelerated conditions over the 3-month period. Chemical stability of paracetamol content fell within the required range of 95-105% of the labelled amount, for all environmental conditions. Conclusion: This study provides evidence on the stability of paracetamol tablets in a DAA, to support pharmacists in making sound clinical and operational decisions regarding the repackaging of paracetamol in these devices. J Pharm Pract Res 2006; 36: 25-8.

The proven therapeutic efficacy of methadone in cancer pain is hindered by a challenging pharmacokinetic-pharmacodynamic profile, considerable interpatient variation, and increasing concern about the complexities of dosing. The objective of this study was to assess the evidence for the use of methadone in cancer pain management. The authors conducted a systematic literature search for randomized controlled trials (RCTs) published post the 2007 Cochrane review of methadone in cancer pain. Trial quality was assessed using the Oxford Quality Scoring System and Cochrane Handbook for Systematic Reviews of Interventions. Of the 152 abstracts found, 4 were RCTs (272 participants). Two RCTs compared the efficacy and safety of methadone with placebo or active control and two investigated rotation to methadone from other opioids. The studies used different routes of administration, dosing, initiation, and titration of methadone and distinct pain scoring tools and did not address the issues raised by the Cochrane review. Methadone has an important role in the management of cancer pain, with many advantages including low cost, high oral bioavailability, rapid onset of action, once-daily dosing, and postulated benefits in difficult pain control scenarios. However, due to limited research in this area, methadone dosing remains a challenge, with vigilant dose initiation, adjustment, and monitoring required. There is a need for further studies using standardized methodology to evaluate the optimal dosing strategy of methadone, the effect on different types of pain, and the role of pharmacokinetics and pharmacogenomics in clinical outcomes.