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Background: Reviewing pharmacist diabetes intervention studies revealed a lack of structured process in providing diabetes care, leading to varied results from increased to minimal improvements. The aim of this study was to determine the effectiveness of the Simpler tool, a structured clinical guidelines tool, in the delivery of diabetes care. The primary outcome was significant improvement in HbA1c. Secondary outcomes were improved lipid profiles and blood pressure (BP)., Methods: A 6-month parallel multicenter two-arm, single-blind randomized controlled trial involving 14 pharmacists at seven primary care clinics was conducted in Johor, Malaysia. Pharmacists without prior specialized diabetes training were trained to use the tool. Patients were randomized within each center to either Simpler care (SC), receiving care from pharmacists who used the tool (n =55), or usual care (UC), receiving usual care and dispensing services (n = 69)., Results: Compared with UC, SC significantly reduced HbA1c (mean reduction 1.59% [95% confidence interval {CI} -2.2, -0.9] vs 0.25% [95% CI -0.62, 0.11], respectively; P ≤ 0.001), and significantly improved systolic BP (-6.28 mmHg [95% CI -10.5, 2.0] vs 0.26 mmHg [95% CI -3.74, 0.43], respectively; P = 0.005). A significantly higher proportion of patients in the SC than UC arm reached the Malaysian guideline treatment goals for HbA1c (14.3% vs 1.5%; P = 0.020), systolic BP (80% vs 42%; P = 0.001), and low-density lipoprotein cholesterol (60.5% vs 40.4%; P = 0.046)., Conclusions: Using the Simpler tool facilitated the delivery of comprehensive evidence-based diabetes management and significantly improved clinical outcomes. The Simpler tool supported pharmacists in providing enhanced structured diabetes care., (© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Studies on a structured method used by pharmacists to provide comprehensive, evidence-based diabetes care are lacking. The aim of this study was to prioritise, rank and construct validate indicators categorised as seven treatment factors utilised in the management of type 2 diabetes namely: Cholesterol, blood pressure and glycaemia control; medication and lifestyle management; cardiovascular risk management and patient education using the Delphi process., Methods: A Delphi questionnaire consisted of 29 Part 1 and nine Part 2 indicators which were incorporated into a tool called Simpler™. The indicators were mainly sourced from American, Australian and Malaysian diabetes management guidelines. Diabetes experts were asked to rank indicators in the order of importance in Part 1. In Part 2, indicators had to be chosen for inclusion into Simpler™ using a fivepoint Likert scale. The consensus level was pre-set at 60%., Results: A three round Delphi process was used to validate all 38 indicators by 12 experts from Australia and Malaysia: five pharmacists, four doctors, two endocrinologists and a diabetes nurse. Consensus was reached for 93.1% (27/29) of the Part 1 indicators and all nine Part 2 indicators (100%). Five out of nine indicators in Part 2 questionnaire obtained consensus disagreement for inclusion into the Simpler ™ tool., Conclusion: The Simpler™ tool is the first structured diabetes multifactorial tool to address all seven evidence-based factors. The tool was refined and validated by multi-disciplinary health professionals from Australia and Malaysia. Pharmacists can use the Simpler™ tool to facilitate evidence-based comprehensive individualised care among type 2 diabetes patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objective: The study aims to evaluate factors influencing pharmacists' management of eye infections following the reclassification of ophthalmic chloramphenicol to pharmacist supply., Methods: Data were collected using a self-administered questionnaire posted to a random sample of community pharmacies in urban and rural areas in Western Australia. Data were entered into Excel and analysed using SPSS v17 (SPSS Inc., Chicago, IL, USA) and SAS v9.2 (SAS Institute Inc., Cary, NC, USA). Descriptive statistics were used to summarise the responses and demographics of respondents. Regression analysis was used to identify relationships between variables. Factor analysis was conducted to pool variables and the derived factors were subjected to regression analysis., Key Findings: Of the 240 community pharmacies surveyed, 119 (49.5%) responded (79% urban and 21% rural pharmacies). Urban and rural pharmacies provided ophthalmic chloramphenicol over-the-counter (OTC) 3-4 and 1-2 times weekly, respectively (P = 0.021), with some pharmacies providing 12 or more per week. Over 82% of respondents claimed that sales of other OTC products used for acute bacterial conjunctivitis had 'decreased/decreased markedly'. A majority of respondents (59%) claimed that there was no change in the number of prescriptions received for ophthalmic chloramphenicol. Most respondents (76.4%) agreed/strongly agreed that pharmacist's current level of training was adequate to provide ophthalmic chloramphenicol. However, approximately one-fifth (21.8%) responded that pharmacists required some additional training., Conclusions: Down-scheduling of ophthalmic chloramphenicol has improved pharmacists' capability to treat acute bacterial conjunctivitis, largely as a replacement for products previously available OTC, rather than fewer general practitioner consultations. Pharmacists showed overall support for the reclassification as it enabled better use of professional skills and patient access to improved treatment options., (© 2014 Royal Pharmaceutical Society.)

Objective: The objective of this study was to evaluate the level of appropriateness of prescribing to outpatients in selected healthcare facilities in Papua New Guinea (PNG), using health department guidelines as the benchmark., Methods: A prospective study was carried out at Losuia Health Centre (LHC), Alotau Provincial Hospital (APH) and Port Moresby General Hospital (PMGH) in PNG. At each setting >300 consecutive prescriptions were evaluated in 2010. Diagnosis and prescribing data were collected from written prescription orders, patient health books and by patient interview. The appropriateness of prescribing was evaluated with respect to the relevant PNG Health Department guidelines. Differences in prescribing indices were evaluated using chi-squared tests as appropriate., Results: There were 1090 patients (748 adults; 341 children) enrolled in the study with 356 at LHC, 318 at APH and 416 at PMGH. A total of 2495 medicines were prescribed. The most common were amoxicillins (355), paracetamol (344), artemether/artesunate (186) and chloroquine (162). The average number of drugs prescribed per patient was 2.3 (range: 1-7). The most common diseases treated were malaria (23.2%), acute soft tissue injuries (10.4%), anaemia (8.9%), respiratory problems (8.7%) and cough (5.9%). Overall, inappropriate prescribing was 33.4% in adults and 39.9% in children, the difference mainly arising from inappropriate drug dosage. There were statistically significant differences observed for the level of inappropriate prescribing by prescriber category on drug selection (P < 0.0001), drug dosage (P < 0.0001) and drug duration (P < 0.0001)., Conclusion: The level of inappropriate prescribing was as high as 53.8% in the selected locations in PNG, which is of great concern with respect to the quality of PNG healthcare delivery. Appropriate interventions such as review/upgrade of the guidelines, supervision/oversight of compliance to guidelines and/or publication of ongoing supervision/audit oversight reports need to occur to address the underlying causes.

Background: Partial thickness skin graft wounds are painful. Topically applied lidocaine has been used for analgesia in several clinical trials. This study compared the effectiveness of two different formulations of topical local anaesthetic for dressing changes of partial thickness skin graft donor sites., Methods: A double-blind randomised controlled, pilot trial was conducted in 29 patients undergoing split thickness skin graft surgery. Subjects were randomised to either a 3% lidocaine emulsion formulation "Treatment E" (NOPAYNE™) or a 4% aqueous solution "Treatment A" (Xylocaine™). Subjects received one spray per 3 cm(2) of donor site area followed by up to two further spays as required. Endpoints included pain intensity measured by the numerical rating scale (NRS) up to 1h after dressing change commencement, sting sensation, overall satisfaction and lidocaine plasma concentration., Results: The 60 min pain scores for E and A were 1.3 ± 0.3 (mean ± SEM) and 1.8 ± 0.4 (p=0.98) respectively. Nearly 90% of patients were very satisfied with their treatment. The mean plasma concentrations of lidocaine for A and E were 0.132 mg/l and 0.040 mg/l respectively (p=0.069)., Conclusion: The topical local anaesthetic formulations achieved low pain scores during dressing changes. The safety profile was potentially improved with the emulsion formulation of lidocaine., (Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.)

Background: The sublingual administration of opioids is a simple and noninvasive method that provides rapid analgesia. In this phase I study we investigated the pharmacokinetics and bioavailability of a fentanyl wafer in healthy volunteers. The principal study objective was to investigate the pharmacokinetic profile of a new sublingual fentanyl wafer and to establish its absolute bioavailability., Methods: Twenty-four healthy volunteers, mean age 23 years, were randomly assigned to receive the equivalent of fentanyl 100 μg by both the sublingual and IV routes. Blood samples were collected in sterile polypropylene tubes for 24 hours after each fentanyl administration. The pharmacokinetic parameters were determined by model-independent pharmacokinetic analyses of the plasma fentanyl concentration-time profiles., Results: The mean absolute bioavailability of the sublingual fentanyl wafer was 78.9% (90% confidence interval [CI] 51.1% to 121.7%). The first detectable plasma fentanyl concentration time ranged from 2 to 10 minutes in all volunteers, and the mean (±SD) time to peak plasma concentration at 0.91 (±0.73) hours after administration., Conclusion: Sublingual administration of fentanyl as a wafer product resulted in rapidly detectable plasma fentanyl concentrations. The absolute bioavailability of 78.9% indicated a high systemic availability of fentanyl and suggests that further development of this wafer is justified.

Objective: To evaluate the prescribing practices of Australian dispensing doctors (DDs) and to explore their interpretations of the findings., Design, Participants and Setting: Sequential explanatory mixed methods. The quantitative phase comprised analysis of Pharmaceutical Benefits Scheme (PBS) claims data of DDs and non-DDs, 1 July 2005-30 June 2007. The qualitative phase involved semi-structured interviews with DDs in rural and remote general practice across Australian states, August 2009-February 2010., Main Outcome Measures: The number of PBS prescriptions per 1000 patients and use of Regulation 24 of the National Health (Pharmaceutical Benefits) Regulations 1960 (r. 24); DDs' interpretation of the findings., Results: 72 DDs' and 1080 non-DDs' PBS claims data were analysed quantitatively. DDs issued fewer prescriptions per 1000 patients (9452 v 15 057; P = 0.003), even with a similar proportion of concessional patients and patients aged > 65 years in their populations. DDs issued significantly more r. 24 prescriptions per 1000 prescriptions than non-DDs (314 v 67; P = 0.008). Interviews with 22 DDs explained that the fewer prescriptions were due to perceived expectation from their peers regarding prescribing norms and the need to generate less administrative paperwork in small practices., Conclusions: Contrary to overseas findings, we found no evidence that Australian DDs overprescribed because of their additional dispensing role.

Dihydroartemisinin (DHA) is a poorly water-soluble drug that displays low bioavailability after oral administration. Attempts have been made to improve the solubility of DHA. Yet, no information is available concerning improved bioavailability. This study aimed to improve the water solubility of DHA by two systems: solid dispersions with polyvinylpyrrolidone (PVPK30, PVPK25, PVPK15) and inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD), as well as improving the bioavailability of both systems. The phase transition of DHA with hydrophilic polymers was evaluated by X-ray diffraction (XRD) and differential scanning calorimetery (DSC). DHA became amorphous in DHA-HPβCD complexes and showed more amorphous behavior in XRD analyses with rise in molecular weight of PVP. Melting onset temperature of DHA decreased, while DSC thermograms revealed the peak area and enhanced enthalpy change (DH) in solid dispersions as well as inclusion complexes. DHA solubility was enhanced 84-fold in DHA-HPβCD complexes and 50-times in DHA-PVPK30. The improved solubility using the four polymers was in the following order: HPβCD > PVPK30 > PVPK25 > PVPK15. Values of area under curve (AUC) and half life (t(1/2)) of DHA-PVPK30 were highest followed by DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25. V(d)/f of DHA-PVPK30 was 7-fold. DHA-HPβCD, DHA-PVPK15 and DHA-PVPK25 showed significantly different pharmacokinetic parameters compared with DHA solutions. The 95% confidence interval was meaningful in AUC and t(1/2). Pharmacokinetic parameters revealed that all four-test preparations were significantly more bioavailable than DHA alone.

Introduction and Aims: Pseudoephedrine is a precursor often diverted into the illegal manufacture of amphetamine type substances (ATS). The aim of this study was to evaluate the effectiveness of a linked electronic medication recording system (LEMS) established in Australian pharmacies in 2005 for preventing the diversion of pseudoephedrine., Design and Methods: The number of illegal ATS laboratories detected in each jurisdiction of Australia from 1996-1997 to 2004-2005 were analysed by linear regression nationally and by each jurisdiction. The statistical significance of seizures in 2005-2006 was based on the comparison of the observed value to the 95% prediction confidence intervals calculated from the historical data for each jurisdiction and nationally., Results: Pharmacies in Queensland commenced an LEMS in late 2005 to minimise retail pseudoephedrine diversion. The number of ATS laboratories seized in 2005-2006 in Queensland was significantly lower (P < 0.05) than predicted by historical data. For all other jurisdictions and nationally the totals of laboratories seized in 2005-2006 were not significantly different from predicted values., Discussion and Conclusions: The significant decline in ATS illegal laboratories seized in Queensland in 2005-2006 suggests the effective use of LEMS in pharmacies to minimise pseudoephedrine diversion. In order to evaluate a national LEMS, more frequent data on numbers of linked pharmacies, ATS laboratories seized and indicators of pseudoephedrine sales and misuse are required. Testing the use of LEMS by pharmacies for preventing the diversion of other medicines seems appropriate.

Objectives: Some doctors perform the dual roles of prescribing and dispensing pharmaceuticals. The dispensing doctors (DDs) role may give rise to prescribing behaviours that vary from those of non-DDs. The aim of this review was to systematically and comparatively appraise the research evidence related to the practices of DDs., Methods: A systematic search of bibliographic databases and reference lists from selected papers were the sources of the data. Inclusion criteria were papers published in English, between 1970 and 2008 that provided quantitative data comparing the practices of DDs and non-DDs. At least two of the authors abstracted data from all eligible papers using a purpose-made data extraction form., Results: Twenty-one papers were included in this review. Evidence indicated that DDs prescribed more pharmaceutical items and less often generically than non-DDs. There was limited evidence to suggest that DDs prescribed less judiciously and were associated with poor dispensing standards. Patient convenience and access to pharmaceuticals were main reasons for doctors to dispense., Conclusion: DDs can fill an important gap in the provision of pharmaceuticals for their patients especially where health workforce shortages exist. There was evidence the dispensing role influenced prescribing. Patient convenience should be balanced against scarce medical resources, being utilised for dispensing.

Dihydroartemisinin (DHA) is a major metabolite of artemisinin and its derivatives, including arteether, artemether, and artesunate. To improve the solubility and stability of poorly soluble DHA, we prepared inclusion complexes with hydroxypropyl-beta-cyclodextrin (HPbetaCD) and recrystalized DHA to study its thermal stability. The complexes were characterized by differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), thermal stability, phase, and equilibrium solubility studies. Pure DHA was crystalline and remained crystalline after recrystallization, but its unit cell dimensions changed as exhibited by XRD. DHA-HPbetaCD complexes showed a phase transitions towards amorphous in DSC thermograms, FTIR spectra, and XRD patterns. The phase solubility profiles of complexes prepared in water, acetate buffer, and phosphate buffers were classified as A(L)-type, indicating the formation of a 1:1 stoichiometric inclusion complex. The equilibrium solubility of DHA was enhanced as a function of HPbetaCD concentration. DHA-HPbetaCD complexes showed an 89-fold increase in solubility compared to DHA. Solubilities of complexes containing 275.1 mM HPbetaCD in water, acetate buffer (pH 3.0), and phosphate buffer (pH 3.0 and 7.4) were 10.04, 7.96, 6.30, and 11.61 mg/ml, respectively. Hydrogen bonding was found between DHA and HPbetaCD, and it was stronger in complexes prepared in water than in buffers. However, the AH values were higher in buffer than water. DHA-HPbetaCD complexes prepared using commercial (untreated) or recrystallized DHA (no detectable impurity) showed a 40% increase in thermal stability (50 degrees C) and a 29-fold decrease in hydrolysis rates compared with DHA. The rank order of stability constants (K(s)) was: water, acetate buffer (pH 3.0), phosphate buffer (pH 3.0), and phosphate buffer (pH 7.4). Thus, HPbetaCD complexation with recrystalized DHA increases DHA solubility and stability.

In the present study the physicochemical characteristics of dihydroartemisinin, polyvinylpyrrolidone and their solid dispersions were evaluated at various proportions of drug and polyvinylpyrrolidone. These properties were investigated with X-ray diffraction, fourier transform infrared spectrophotometry, differential scanning calorimetry, equilibrium solubility at twenty five and thirty seven degree centigrade. X-ray diffraction analysis detected that dihydroartemisinin became more amorphous as drug carrier ratio was enhanced in solid dispersions. Fourier transform infrared spectra suggested that there was a hydrogen bonding interaction between dihydroartemisinin and polyvinylpyrrolidone in all solid dispersions. These interactions reflected the changes in crystalline structures of dihydroartemisinin. The thermal behavior of dihydroartemisinin was unusual as it exhibited melting exotherm instead of endotherm. In solid dispersions containing varying contents of polyvinylpyrrolidone, enthalpy change and peak area were enhanced while melting onset temperature decreased with increase in polyvinylpyrrolidone proportion. This was attributed to a solid-state interaction. Equilibrium solubility of dihydroartemisinin increased sixty-fold due to induction of polyvinylpyrrolidone. When this solubility was compared among thirty-seven and twenty five degree centigrade in solid dispersions, it was up to seven times more at higher temperature. Physicochemical characteristics of solid dispersions containing drug carrier ratio of one: nine prepared in acetonitrile, ethanol, methanol and tetrahydrofuran showed differences which indicated that properties of medium i.e. dielectric constant, dipole moment and structure, influenced the amount of amorphousness and related properties of dihydroartemisinin.

Objective: To analyse the prevalence and factors associated with the provision of primary preventive services for cardiovascular disease (CVD) in Australia's community pharmacies., Methods: The data were from the 2002 Australia's National Pharmacy Database Project. Questionnaires were completed by a nationally representative 1,131 out of a possible 1,391 pharmacies (81.3% response rate), stratified into PhARIA (remoteness) zones. Preventive services for CVD were analysed by frequency of provision of services. Ordinal analysis and logistic regression analysis were used to ascertain predictors of services., Results: Most community pharmacies initiated nicotine replacement therapies, 58.1% provided blood pressure screening, 11.6% anthropometric tests and 7.6% blood cholesterol screening. Pharmacies in promotional groups, having high customer numbers, an enclosed counselling area, or forward pharmacy area, were significantly associated with providing preventive services for CVD., Conclusions and Implication: The configuration and size of Australia's community pharmacies were associated with providing primary preventive services for CVD.

Kinetics of the reactions of amoxicillin sodium and potassium clavulanate alone and in combination were investigated in the frozen state at selected pH values of 2.0, 4.6 and 7.0. Extrapolation of the rate constant values to the frozen state from the liquid state data indicated marked acceleration of the rates of amoxicillin and clavulanate degradation for the pH values investigated. The highest acceleration in rate recorded was 15.0-fold for clavulanate and the lowest value was 4.6-fold for amoxicillin at -7.3 degrees C in the hydrochloric acid system. The rate constant values obtained were interpreted in terms of the concentration model [Pincock, R.E., Kiovsky, T.E., 1966. Kinetics of reactions in frozen solution. J. Chem. Educ. 43, 358-360], phase-temperature relationship of the solutes, buffer catalysis, pH change and polymerization reactions. A kinetic model was deduced for the hydrochloric acid system providing adequate explanation of the experimental results. A large stabilizing effect of sodium chloride used for maintaining constant ionic strength (micro=0.5) was evident in this system. The shelf-life of amoxicillin was increased from 2.2 to 58.7h at -7.3 degrees C when sodium chloride was included in the hydrochloric acid system.

A tangential flow filtration system was evaluated to purify PEGylated nanoparticles. Two widely used surfactants, PVA and sodium cholate were efficiently removed from an empty nanoparticles suspension using the proposed system. During drug loading, surfactant (PVA) was observed to be entrapped within the core of the nanoparticle to a higher extent, hence was purified at a comparatively slower rate. The presence of dextran sulfate enhanced the drug loading but also resulted in reduced purification rate; this was described by the hypothesis of PVA inclusion within the core of the nanoparticles. Practically, it was possible to correlate the slow purification rate of PVA to its reduced filtration flow during the purification of the empty and loaded nanoparticles containing dextran sulfate. Indirectly, this system was capable of revealing the influence of an excipient and drug on the nanoparticle surface.

Background: Recent attention has focused on access of communities to pharmacy services in rural areas. To increase access to pharmacy services in rural Western Australia some doctors have been granted a licence to dispense medication on the rationale that a pharmacy would not be economically viable in that community. However, there have been no studies conducted on whether a doctor dispensing service adequately provides a pharmacy service with respect to access and quality., Method: Residents of seven single pharmacy towns and seven non-pharmacy rural towns were surveyed to evaluate pharmacy services delivered by a pharmacist and doctor. The towns were chosen to match closely on key demographic features, with an average population of 1,246 and 1,263 respectively. A random sample of 150 households from each town was sent the questionnaire on pharmacy services (1050 in each group). Data was also collected from the Health Insurance Commission (HIC) on dispensing locations for the residents of the two groups of towns., Results: There was a significant difference in access to pharmacy services with 82.4% of participants from pharmacy towns accessing medications within their town compared to 51.3% of non-pharmacy town participants. The HIC data supported these trends with pharmacy town residents having relatively higher prescription rates within their town compared to non-pharmacy town residents where they were more likely to access prescriptions out of their town., Conclusion: Pharmacy town participants were more satisfied with access to health and pharmacy services within their town. Continuation of the doctor dispensing policy requires a greater consideration of the pharmacy needs of rural residents.

The aim of this study was to prepare poly(d, l-lactide) (PLA) microspheres containing naltrexone (NTX) by a solvent evaporation method, and to evaluate both in vitro and in vivo release characteristics and histopathological findings of tissue surrounding an implant formulation in rats. This method enabled the preparation of microspheres of regular shape and relatively narrow particle size distribution. The in vitro release profiles of NTX from PLA microspheres showed the release of NTX did not follow zero-order kinetics. An initial burst release was observed, subsequently followed by a nearly constant rate of 0.4% per day after ten days. The cumulative amount of NTX released at the end of 60 days was 80%. Compressed microspheres showed near zero-order sustained release of NTX for 360 days. The plasma NTX levels in rats showed that for compressed microspheres NTX concentrations were constant and exceeded 2 ng/mL for 28 days. Throughout the 28 days of study, the implantations cause a minor inflammatory response, which can be regarded as a normal defence mechanism. The sustained release performance of NTX from the biodegradable depot systems may provide a reliable, convenient, and safe mechanism for the administration of NTX for the long-term treatment of opioid dependence.

An isocratic ion exchange high performance liquid chromatography method was developed for the simultaneous determination of flucloxacillin and amoxicillin in pharmaceutical formulations for injections. The separation was made by a ZORBAX 300-SCX column using 0.025 M ammonium dihydrogen phosphate (adjusted to pH 2.6 with phosphoric acid)-acetonitrile (95:5) as mobile phase. The validation of the method was performed, and specificity, reproducibility, precision and accuracy were confirmed. The limits of quantification were approximately 0.2 microg/ml for each drug. Due to its simplicity and accuracy the method is particularly suitable for routine pharmaceutical quality control.

Objectives: To examine trends in the licit consumption of the psychostimulants dexamphetamine and methylphenidate in Australia and nine other countries from 1994 to 2000 and in each State and Territory of Australia from 1984 to 2000., Design: Annual rates of consumption of psychostimulants were compared using Poisson regression models. All drug consumption was standardised to defined daily doses per 1000 population per day., Main Outcome Measures: Rates of consumption of each psychostimulant in each country and in each Australian State and Territory., Results: For the 10 countries from 1994 to 2000, total psychostimulant consumption increased by an average 12% per year, with the highest increase from 1998 to 2000. Australia and New Zealand ranked third in total psychostimulant use after the United States and Canada. Australia consumed significantly more than the United Kingdom, Sweden, Spain, the Netherlands, France or Denmark. In Australia, from 1984 to 2000, the rate of consumption of licit psychostimulants increased by 26% per year, with an 8.46-fold increase from 1994 to 2000. Western Australia ranked first, with nearly twice the consumption rate of total psychostimulants as New South Wales, which ranked second. Methylphenidate is the main psychostimulant consumed in the US and Canada, and dexamphetamine in Australia., Conclusions: The consumption of psychostimulants in Australia is high internationally and varies significantly between States and Territories. The results imply varied jurisdictional prescribing determinants and supply processes throughout Australia, which may require new national prescribing standards and access to online patient data for prescribers and dispensers.

Objectives: To examine trends from 1984 to 1998 in licit opioids used in Australia compared with nine other developed countries, and in New South Wales compared with other Australian jurisdictions., Design: Poisson regression analysis of annual rates of national and jurisdictional consumption of methadone, morphine and pethidine., Main Outcome Measures: All drug data were standardised to defined daily doses per 1000 population per day., Results: Methadone consumption increased by, on average, 12% per year (RR, 1.12; 95% CI, 1.08-1.17), with Australia in the first rank of countries. Morphine use increased by 5% per year (RR, 1.05; 95% CI, 1.02-1.09), with Australia ranking equal second with three other countries behind Denmark. Consumption of pethidine in all 10 countries was unchanged (RR, 0.99; 95% CI, 0.97-1.00), with Australia equal first. In Australia, use of methadone syrup increased by 17% per year (RR, 1.17; 95% CI, 1.16-1.17) and by 11% per year for methadone tablets (RR, 1.11; 95% CI, 1.10-1.12). Consumption of methadone syrup in NSW was more than double that of any other jurisdiction. Consumption of methadone tablets was 2.4 times higher in South Australia (RR, 2.35; 95% CI, 2.09-2.65) than NSW. The Northern Territory, Tasmania and Queensland also had significantly higher consumption than NSW. From 1991 to 1998, controlled-release morphine consumption increased by 27% per year nationally (RR, 1.27; 95% CI, 1.24-1.30). The NT had 2.6 times more supply of morphine (RR, 2.63; 95% CI, 1.71-4.03) and Tasmania 58% more supply than NSW (RR, 1.58; 95% CI, 1.11-2.25)., Conclusions: Australia's consumption of licit opioids ranked high internationally. There were diverse trends in the supply of licit opioids to Australia's jurisdictions, resulting in a heterogeneous pattern throughout the country.

The kinetics of the reaction of sulfamethoxazole (SMX) in 5% w/v glucose to form the corresponding alpha- and beta-glucosylamines over the pH range of 0.80-6.88 at 37 degrees C has been investigated. The identity of the glucosylamines was determined by 1H-nuclear magnetic resonance spectroscopy of an authentic sample of the alpha-glucosylamine (USP) and the reaction products, and by interconversion of this compound to the corresponding beta-anomer. The reaction followed pseudo first-order reversible kinetics and involved specific acid and general acid-base catalysis. The pH-rate profile demonstrated that over the pH range of 0.80-2.90 and 5.50-6. 88 the reactions were dependent on H(+) concentration but pH independent between pH 3.00-5.45, which reflects the influence of ionization of SMX and the glucosylamines on the reversible reaction. Interpretation of the data with respect to kinetic models and rate equations for the formation and hydrolysis of the glucosylamines was investigated. Temperature dependence studies followed the Arrhenius equation with an Ea of 49.28 kJ mol(-1) for the forward and 63.46 kJ mol(-1) for the reverse reaction at pH 2.89 respectively.

A stability-indicating high-performance liquid-chromatographic (HPLC) assay has been developed for amphotericin B (AmB) in a paste, containing AmB, tobramycin (or gentamicin) sulphate, colistin sulphate, liquid paraffin and Orabase. Extraction of AmB was performed by partitioning the antibiotic between N,N-dimethylformamide (DMF) and cyclohexane, which led to precipitation of the polymeric materials and extraction of the liquid paraffin into the cyclohexane and AmB into the DMF. Analysis by HPLC of the latter layer gave a linear relationship between concentration and peak area response for the AmB over the range 5.0 x 10(-4) to 7.5 x 10(-3)% (w/v) (r = 0.9995) with a relative standard deviation of +/- 1.46% (n = 8). The efficiency of extraction was 1006 +/- 2.4% (n = 5).

Hydroxypropyl beta-cyclodextrin (HP beta CyD) has been shown to stabilize a wide variety of chemically distinct pharmaceutical entities through inclusion-complex formation between drug and cyclodextrin. The effect of HP beta CyD on the acid-catalysed hydrolysis of benzylpenicillin (penicillin G) was evaluated in chloroacetate buffer at pH 2.20. At penicillin G: cyclodextrin molar concentration ratios from 1:1 to 1:10, HP beta CyD effected stabilization of penicillin G by 1.56- to 5.21-fold. At all temperatures, the observed first-order rate constant (kobs) values assumed a non-linear, Michaelis-Menten type decrease as a function of increasing HP beta CyD concentration. Degradation of penicillin G complexed with HP beta CyD (penicillin G-HP beta CyD), was approximately ninefold slower than uncomplexed penicillin G. The proportion of penicillin G degrading in either of these forms was, in turn, determined by the equilibrium constant for the complexation. The apparent thermodynamic and activation parameters for the complexation between penicillin G and HP beta CyD have also been evaluated. The negative standard enthalpy change (delta H degrees) for the complexation implied that the penicillin G-HP beta CyD complex would be predisposed towards enhanced stability, and thus the kobs value for the hydrolysis of penicillin G decreased with reduction of temperature in these systems. The lack of difference between the enthalpies of activation (delta H ++) for the hydrolysis of uncomplexed and complexed penicillin G seemed to be compensated by the significant difference between the entropies of activation (delta S ++) for these hydrolytic reactions. The results indicate that HP beta CyD represents a viable means of stabilization of penicillin G solutions at the pH employed in this study.

The medication error rate in an existing ward stock drug distribution system and in an alternative system developed after failure-mode and effects analysis (FMEA) was applied to the ward stock system was studied. In the ward stock system of a large teaching hospital in Western Australia, bulk drug packs were stored in cupboards on the wards, and drug products were transferred to drug trolleys before dose administration by nurses. A pharmacist used the disguised-observer technique to determine the error rate in the ward stock system for a medical ward and a surgical ward. The errors and each step in the system were studied by FMEA. A unit supply individual-patient dispensing (USIPD) system was formulated to respond to the failure modes identified. In this system, a five-day supply of medication was dispensed for each patient from a satellite pharmacy close to the ward. Medication charts were reviewed by a pharmacist, and drugs were dispensed in labeled vials that were placed in a locked drawer at the patient's bedside. The error rate under the USIPD system was determined. Problem areas in the ward stock system identified by FMEA included drug availability, review of orders, drug selection, patient-related issues, and use of nurses' time. The percentage of opportunities during which any error occurred was significantly lower under the USIPD system on both wards. FMEA was used to identify deficiencies in the ward stock system that led to medication errors in an Australian hospital. An alternative drug distribution system designed to address the problems identified was associated with fewer errors.

Syringe stiction has been reported to cause syringe pump malfunction, hence the effect on syringe performance of syringe use and the formulations used in the syringe were investigated. The force required for syringe plunger motion (at 2.5 mm min-1), when filled with soybean oil emulsion (SBOE) and with water, and the extraction of silicone oil from syringes by these fluids, were measured for Primo, Talus and Terumo 10 mL, and Terumo 50 mL syringes. The breakloose, average extrusion and maximum force required to maintain plunger motion increased after storage of SBOE for 7 days in all syringes tested (p < 0.05). The storage of water increased the breakloose force of all syringes, but only increased the maximum force of Talus syringes, and both the average extrusion and maximum forces of Terumo 10 mL syringes. The mechanism for this is most likely swelling of the elastomer of the piston due to sorption of fluid. The force was found to increase logarithmically with repeated syringe use. Electrothermal atomization atomic absorption spectroscopy was used to measure the silicone oil content of syringe extractions. Three extractions were performed: repeated flushing, vigorous washing, and storage for 7 days with occasional agitation. Up to 69.4% of the silicone oil present in the syringes was extracted with both water and SBOE when they were stored or washed. In contrast to water, SBOE also extracted the lubricant when the syringe was filled and flushed immediately. If syringes are refilled, stored filled before use, or used over a prolonged period, particularly with a SBOE formulation, syringe striction may occur during infusion with a syringe pump.

Flow continuity of two brands of syringe pumps and four brands of syringes was studied as a possible cause of hemodynamic fluctuations observed in neonates. Cyclical fluctuations were observed in the blood pressure of 14 neonates receiving dopamine infusions by syringe pump at flow rates from 0.2 to 1 mL/hr. Atom 235 and IVAC 770 pumps and various sizes of Terumo, Becton Dickinson, Omnifix, and IVAC syringes were evaluated. Flow continuity was assessed by using a gravimetric technique. The force needed to initiate and maintain syringe plunger motion was also measured. Noncontinuous flow was encountered most commonly with Terumo syringes, which delivered boluses at regular intervals at flow rates up to 5 mL/hr. The interval was dependent on flow rate and was similar to the time between the blood pressure fluctuations observed clinically. The syringe plunger force exhibited regular fluctuations indicative of the plunger sticking, and simultaneous measurement of flow established a direct temporal relationship with boluses. The other syringes tested did not exhibit such fluctuations. No differences were found between the two syringe pumps. Syringe plunger sticking, resulting in intermittent boluses and potential blood pressure fluctuations, may occur at low flow rates and with certain syringe brands. This appeared to be the cause of hemodynamic fluctuations in neonates receiving dopamine infusions.

Background: The advent of novel treatments such as aerosolized amiloride are potentially useful additions to the therapeutic options available for the treatment of cystic fibrosis. Unfortunately, amiloride and other aerosolized drugs such as antibiotics are generally administered via jet nebulisers which are time consuming to use, and thus limit the acceptance and efficacy of these forms of treatment. In vitro experiments were performed in order to determine whether amiloride could be administered in dry powder form using a Turbohaler., Methods: Amiloride was micronised and loaded into 200 micrograms Turbohalers. The dose delivered per actuation and particle size distribution of the generated aerosol were assessed using a flow of 60 l/min through the Turbohaler. The dose of amiloride delivered was measured by collecting the aerosol on a filter and the quantity of drug was assayed by an ultraviolet spectrophotometric method. The particle size distribution was assessed using a Malvern MasterSizer laser particle sizer and compared with that generated by a commercially available 200 micrograms budesonide Turbohaler., Results: The mean (SD) dose delivered per actuation was 246.3 (40.4) micrograms. The volume median diameter of the amiloride aerosol was 3.80 (0.68) micron compared with 3.07 (1.47) microns for budesonide., Conclusions: These results suggest that therapeutic doses of micronised amiloride could be delivered effectively and conveniently as a dry powder aerosol using a Turbohaler.

The chemical reaction between procainamide hydrochloride and glucose following admixture to glucose infusion has been investigated. Substantial amounts (10-15% after 10 h at room temperature) of the procainamide is lost with the formation of a mixture of the corresponding alpha- and beta-glucosylamines. The chemical identity of the latter compounds was confirmed by 13C and 1H nuclear magnetic resonance spectroscopy.

Intrinsic dissolution rate studies were carried out on lithium carbonate discs that were prepared with the disc in a component on the final support. This overcame the problem of further handling of the fragile discs. Dissolution media employed were similar to those used for the routine evaluation of lithium carbonate dosage forms. Linear dissolution rate profiles were found in simulated gastric fluid (SGF), Tris buffer and water. Data in SGF and water showed positive intercepts with the Levich model. The dissolution process of lithium carbonate was considered to be complex. Dissolution profiles in simulated intestinal fluid (SIF) containing phosphate showed a marked initial curvature and a subsequent reduced dissolution rate. This was due to the precipitation of trilithium phosphate onto the disc. Dissolution rate studies on lithium carbonate dosage forms could be invalidated where a phosphate buffer system has been used.

The stability of aqueous admixtures of amoxicillin sodium in both the liquid and frozen (solid) states was studied. Admixtures of amoxicillin sodium were prepared in sterile water for injection to a theoretical concentration of 10 mg/mL. For each experimental run, 2-mL aliquots of the admixture were placed in stoppered glass volumetric flasks and stored at temperatures ranging from 19.5 degrees C to -30 degrees C; 16 flasks were stored at each temperature. After equilibration for approximately 20 minutes, duplicate flasks at each temperature were removed from storage conditions for time-zero assay. Subsequently, duplicate flasks were assayed at various times, depending on the storage temperature, for up to 13 days or until more than 80% of the drug had degraded. All samples were assayed at least in duplicate using high-performance liquid chromatography. When amoxicillin solutions were in the liquid state (at temperatures between 19.5 and 0 degrees C), the time required for the amoxicillin concentration to decrease to 90% of its initial value (t90) increased as temperature decreased. However, between 0 degree C and -7 degrees C, the t90 of frozen solutions decreased from two days to 1.08 hours. As temperature declined further, the rate of degradation decreased until the solution was completely frozen; at -30 degrees C, the t90 had increased to 13 days. Amoxicillin sodium is unstable in aqueous solutions stored between 0 degrees C and -20 degrees C. If admixtures of this drug are to be frozen for later use, the storage temperature should be below -30 degrees C.

The impact of clinical pharmacy services on the utilization of oral theophylline therapy was evaluated in a ten-week study involving 138 adult inpatients. The study initially involved an independent prospective five-week audit of theophylline use, in which clinical pharmacists monitored theophylline therapy and any interventions were designed so as not to influence future actions taken by medical officers with regard to oral theophylline therapy. The second part of the study involved active intervention by clinical pharmacists and a concurrent five-week audit of theophylline use. The study has demonstrated that clinical pharmacist intervention significantly increased the number of patients receiving a theophylline assay when indicated, from 43 to 83 percent; the number of assays appropriately sampled, from 58 to 85 percent; the number of appropriate dosage adjustments, from 63 to 86 percent; and the number of patients with a measured serum theophylline concentration in the therapeutic range, from 17 to 47 percent. These results show that clinical pharmacists can have a significant impact on patient care by efficient monitoring and individualizing theophylline therapy.

The stability of a 1% w/v solution of amoxycillin sodium in normal saline and in glucose (5%) solutions was examined in the liquid and frozen states over the temperature range -26-60 degrees C. It was found that under all conditions amoxycillin sodium was much less stable in glucose (5%) solution. Freezing the solutions markedly reduced amoxycillin sodium stability. Maximum degradation rates in the frozen state occurred over the temperature range -7.5 degrees C to -6.5 degrees C in normal saline and at -8.9 degrees C in glucose (5%) solutions. For example, in normal saline the liquid state t90 (time for the concentration to decrease to 90% of its initial value) at 0 degree C of 252 h, was reduced to 8 h at -6.5 degrees C and increased to 14 h at -19.2 degrees C. In glucose (5%) solution comparative values of 12.5 h at 0 degree C, 2.5 h at -6.5 degrees C and 8.4 h at -19.2 degrees C were found. Amoxycillin sodium is very unstable in these solutions even at -26 degrees C. Maximum stability of the solutions examined in this study was at 0 degree C in normal saline and at -26 degrees C in glucose (5%) where the t90 value was 25.5 h.

The British Pharmacopoeial test for assessing the solution rate of slow lithium carbonate tablets has been evaluated using 'controlled release' tablets containing 400 mg of lithium carbonate. No significant differences in lithium release were found when the volume of media used in the test was reduced from 250 ml to 200 ml, the final stage of the test in pH 6.8 phosphate buffer reduced from 5 to 3 h, the number of tablets in each thimble reduced from three to one, or the prescribed phosphate buffers replaced with phthalate and Tris, respectively. A four-fold increased concentration of phosphate in the phosphate buffers used resulted in a significant retardation in lithium solution rate. This was not attributable to an ionic strength effect but possibly to the formation of trilithium phosphate at the interface. Dissolution studies using the USP Basket Method showed a significantly slower release rate of one tablet into 900 ml of phosphate buffer compared with Tris buffer. This difference was markedly increased when three tablets were investigated in 200 ml of similar media. These differences were considered to be due to the formation of the much less soluble trilithium phosphate in the phosphate buffers.

The influence of pH on the dissolution rates and solubilities of sulphamethoxazole and trimethoprim have been examined. Sulphamethoxazole was evaluated in buffers of ionic strength 0.5 mol dm-3 over the pH range 0.45-7.8 and at 25, 32 and 37 degrees C. The minimum solubility of sulphamethoxazole was 28.1 mg/100 mL at pH 3.22 and 25 degrees C. Solubilities increased significantly with both increased and decreased pH. Intrinsic dissolution rates demonstrated a linear relationship with the solubility data. Trimethoprim solubility was both buffer- and pH-dependent. In both water and hydrochloric acid solution at 32 degrees C the solubility of trimethoprim increased from 50 mg/100 mL in water at pH 8.54 to a maximum of 1550 mg/100 mL at pH 5.5. This maximum solubility was in excess of that predicted theoretically and may be due to supersaturation. Below pH 2 the solubility of protonated trimethoprim diminished from 1125 mg/100 mL with decreasing pH. This was due to the common ion effect. Intrinsic dissolution rates increased as pH was decreased with hydrochloric acid from 6.00 to 1.78, but decreased at pH 1.48 due to the common ion effect. Dissolution profiles of trimethoprim showed complex patterns dependent upon pH. The profile was zero-order at pH 6.00 and became distinctly stepwise at pH 5.5, this effect becoming less pronounced at lower pH values. This was reconciled in terms of the rate of formation of trimethoprim hydrochloride on the surface of the disc and the differing dissolution rates of this species and trimethoprim. A simple relationship between solubility and dissolution rate was not observed.