Bruce Sunderland

An ion pairing approach to increase the loading of hydrophilic and lipophilic drugs into PEGylated PLGA nanoparticles.

The aim of this study was to enhance the loading of dalargin (enkephalin derivatives) a hydrophilic drug and loperamide HCl (non-opiate antidiarrheal agent) a lipophilic drug candidates within PEGylated nanoparticles. A novel nanoencapsulation method based on the concept of s/o/w and ion pairing followed by solvent diffusion was adopted. The copolymers with three different mPEG densities (5%, 12% and 17%) were employed separately in combination with two different grades of dextran sulphate (DS) 5000 and 500,000 MW in the preparations. Nanoparticles prepared from copolymers with increasing mPEG densities, showed an insignificant (p>0.05) increasing trend of drug loading, this was however significantly increased when DS5000 was included in the preparations. The particle size remains unchanged after dalargin loading, with no significant (p>0.05) alteration in the neutral zeta potential compared to that of the preparations without DS5000. Considering that a dalargin ion pair could also have a neutral charge, it was not advisable to conclude its incorporation, as the size remain unchanged, which would otherwise increase if an ion pair was incorporated within the core of nanoparticles. Therefore, it was expected that a dalargin ion pair might be located outside the core as a separate particulate entity or reside in the hydrophilic shell of the nanoparticles. A loperamide HCl ion pair showed significant (p<0.05) increase in size when incorporated; at the same time it provided a neutral zeta potential despite adding negatively charged DS5000 in the preparation, hence it seemed encapsulated. Inclusion of DS500,000 in the preparation further increased the drug loading of dalargin and loperamide HCl. However, a significant (p<0.05) negative zeta potential was noted in both cases which suggested that excess charge was still available on the surface of nanoparticles which could trap further amounts of drug on the surface rather than inside the core of nanoparticles. During in vitro evaluation of drug loaded nanoparticles, dalargin released as quickly as free drug, when loperamide HCl showed almost burst free sustained release profile with respect to the release of their free drug solutions, suggested that ion pairing approach was more pronounced for loperamide HCl formulation.

Pharmacy clients' attitudes to expanded pharmacist prescribing and the role of agency theory on involved stakeholders.

Objective  To examine the views of regular pharmacy clients on pharmacist prescribing and employ agency theory in considering the relationship between the stakeholders involved.

Clinical setting influences off-label and unlicensed prescribing in a paediatric teaching hospital

Purpose To estimate the prevalence of off-label and unlicensed prescribing during 2008 at a major paediatric teaching hospital in Western Australia. Methods A 12-month retrospective study was conducted at Princess Margaret Hospital using medication chart records randomly selected from 145,550 patient encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics. Patient and prescribing data were collected. Drugs were classified as off-label or unlicensed based on Australian registration data. A hierarchical system of age, indication, route of administration and dosage was used. Drugs were classified according to the Anatomical Therapeutic Chemical Code. Results A total of 1,037 paediatric patients were selected where 2,654 prescriptions for 330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%). Inpatients were prescribed more off-label drugs than outpatients or Emergency Department patients (p < 0.0001). Most off-label prescribing occurred in infants and children (31.7% and 35.9% respectively) and the highest percentage of unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7% of off-label and 2.6% of unlicensed medications prescribed across all three settings. Common reasons for off-label prescribing were dosage (47.4%) and age (43.2%). Conclusion This study confirmed off-label and unlicensed use of drugs remains common. Further, that prevalence of both is influenced by the clinical setting, which has implications in regards to medication misadventure, and the need to have systems in place to minimise medication errors. Further, there remains a need for changes in the regulatory system in Australia to ensure that manufacturers incorporate, as it becomes available, evidence regarding efficacy and safety of their drugs in children in the official product information.

Comparison and Validation of Drug Loading Parameters of PEGylated Nanoparticles Purified by a Diafiltration Centrifugal Device and Tangential Flow Filtration

This article describes drug loading validation of nanoparticles. Ultracentrifugation was avoided because of problems arising from small-sized particles. Ultrafiltration was adopted in two different modes followed by monitoring of polyvinyl alcohol (PVA), dextran sulfate (DS), and loperamide HCl contents. Diafiltration centrifugation removed all PVA at the fourth cycle and provided significantly (p = .000, .017) higher drug loading values compared with tangential flow filtration (TFF). This was due to residual PVA associated with the nanoparticles. TFF enabled satisfactory dry weight recovery (101.66 ± 4.45%, n = 3) of nanoparticles during extended purification. Indirect drug loading (from the purification curve) was not significantly different (p = .450, .487) to the direct drug loading values. Encapsulation parameters were obtained from the purification curve once quantitative estimation of the all formulation components was established.

Metal organic frameworks as a drug delivery system for flurbiprofen

Background Metal organic frameworks (MOFs) have attracted more attention in the last decade because of a suitable pore size, large surface area, and high pore volume. Developing biocompatible MOFs such as the MIL family as a drug delivery system is possible. Purpose Flurbiprofen (FBP), a nonsteroidal anti-inflammatory agent, is practically insoluble in aqueous solution, and, therefore, needs suitable drug delivery systems. Different biocompatible MOFs such as Ca-MOF and Fe-MILs (53, 100, and 101) were synthesized and employed for FBP delivery. Patients and methods A sample of 50 mg of each MOF was mixed and stirred for 24 h with 10 mL of 5 mg FBP in acetonitrile (40%) in a sealed container. The supernatant of the mixture after centrifuging was analyzed by high-performance liquid chromatography to determine the loaded quantity of FBP on the MOF. The overnight-dried solid material after centrifuging the mixture was analyzed for loading percent using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, nuclear magnetic resonance, and FBP release profile. Results The loading values of FBP were achieved at 10.0%±1%, 20%±0.8%, 37%±2.3%, and 46%±3.1% on Ca-MOF, Fe-MIL-53, Fe-MIL-101, and Fe-MIL-100, respectively. The FBP release profiles were investigated in a phosphate buffer solution at pH 7.4. The total release of the FBP after 2 days was obtained at 72.9, 75.2, 78.3, and 90.3% for Ca-MOF, Fe-MIL-100, Fe-MIL-53, and Fe-MIL-101, respectively. Conclusion The MOFs are shown to be a promising drug delivery option for FBP with a significant loading percent and relatively prolonged drug release.

An evaluation of prescribing practices for community-acquired pneumonia (CAP) in Mongolia

BackgroundCommunity-acquired pneumonia (CAP) is a significant cause of morbidity and mortality in all age groups worldwide. It may be classified as mild/moderate or severe, the latter usually requiring hospitalisation. Although, there are many studies reported in relation to CAP, there is relatively little known about the treatment of CAP and its antibiotic use in Mongolia. The study aim was to evaluate prescribing practices for the treatment of mild/moderate CAP in Mongolia with respect to national prescribing guidelines.MethodsWritten prescriptions with a written diagnosis of CAP included were collected prospectively and sequentially for ten weeks from a purposefully selected sample of community pharmacies in rural and urban areas of Mongolia. The data collected included the patient’s age, gender, medication details, frequency and number of doses prescribed. Evaluation was with respect to the Mongolian Standard Treatment Guidelines (2005, 2008). Statistical differences between groups were tested using the Chi-squared and Fisher’s exact tests.ResultsPrescriptions were collected from 22 pharmacies and represented the prescribing practices of 118 doctors. The study enrolled 394 (193 adults and 201 children) patients, with a median age for children of 2.0 years (range: 0.03-12) and adults of 33.0 years (range: 13–92).The most commonly prescribed drugs were aminopenicillins, vitamins, and mucolytics, with the median number of drugs being three per prescription. Inappropriate drug selection was similar for adults (57.7%) and children (56.6%), and the major reason for an overall frequency of inappropriate prescribing for adults was 89.0% and for children 78.0%. Doctors in urban areas prescribed more inappropriate drugs than those in rural areas for both children and adults, p = .0014. The proportion of prescribed injections was 28.4% for adults and 9.0% for children, and for adults was significantly higher in urban areas. The prescribing standard for non-hospitalized patients in Mongolia states that injections should not be prescribed.ConclusionsThe high level of inappropriate prescribing for mild/moderate CAP highlights the need to develop comprehensive and reliable procedures nationwide to improve prescribing practices in Mongolia.

Medication supply to residential aged care facilities in Western Australia using a centralized medication chart to replace prescriptions

BackgroundCurrent model of medication supply to R(RACFs) in Australia is dependent on paper-based prescriptions. This study is aimed at assessing the use of a centralized medication chart as a prescription-less model for supplying medications to RACFs.MethodsTwo separate focus groups were conducted with general practitioners (GPs) and pharmacists, and another three with registered nurses (RNs) and carers combined. All focus group participants were working with RACFs. Audio-recorded data were compared with field notes, transcribed and imported into NVivo® where it was thematically analyzed.ResultsA prescription-less medication chart model was supported and it appeared to potentially improve medication supply to RACF residents. Centralization of medication supply, clarification of medication orders and responding in real-time to therapy changes made by GPs were reasons for supporting the medication chart model. Pharmacists preferred an electronic version of this model. All health professionals cautioned against the need for GPs regularly reviewing the medication chart and proposed a time interval of four to six months for this review to occur. Therapy changes during weekends appeared a potential difficulty for RNs and carers whereas pharmacists cautioned about legible writing and claiming of medications dispensed according to a paper-based model. GPs cautioned on the need to monitor the amount of medications dispensed by the pharmacy.ConclusionThe current use of paper prescriptions in nursing homes was identified as burdensome. A prescription-less medication chart model was suggested to potentially improve medication supply to RACF residents. An electronic version of this model could address main potential difficulties raised.

Identifying the perceived training needs for Australian pharmacist prescribers

To explore pharmacists’ perceived needs on training required to undertake an expanded prescribing role taking account of their years of registration, current professional practice area and preferred prescribing model.

Pharmacist and physician perspectives on diabetes service delivery within community pharmacies in Indonesia: a qualitative study

To explore perspectives of physicians and pharmacists on diabetes service delivery within community pharmacies in Indonesia.

Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids

Purpose The purpose of this study was to evaluate the chemical stability of Lincocin® (lincomycin hydrochloride) in commonly used intravenous fluids at room temperature (25°C), at accelerated-degradation temperatures and in selected buffer solutions. Materials and methods The stability of Lincocin® injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25°C±0.1°C in sodium lactate (Hartmann’s), 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin® in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined. Results Lincomycin hydrochloride w as found to maintain its shelf life at 25°C in sodium lactate (Hartmann’s) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days), and was least stable at pH 2 (calculated shelf life of 0.38 days). Conclusion Lincocin® injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann’s) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability.