Analysis of enhanced pharmacy services in rural community pharmacies in Western Australia.

INTRODUCTION: Enhanced pharmacy services (EPS) are health related services above those normally available with the supply of medicines. Rural pharmacies could provide a diversity of EPS in response to the limited access and reduced health services available in rural areas. The objective of this study was to evaluate the provision of EPS in rural Western Australian (WA) pharmacies in 2006, compared with findings extracted from a national survey conducted in 2002. Barriers to and facilitators for the provision of ETS in rural settings were also analysed. METHODS: The survey was conducted in 2006, using a questionnaire developed from a 2002 Australian national survey questionnaire. The questionnaires were mailed to all 103 pharmacies in rural WA and 51 were returned (49.5%). Chi-squared tests were used to test associations between year of survey and provision of each EPS. Where significant associations were reported, logistic regression analyses that controlled for sex, age, PhARIA location (remoteness), and inclusion of a forward pharmacy area were performed. RESULTS: The WA rural pharmacies offered a range of EPS. There were marked increases in weight testing and weight management services. The availability of smoking cessation services increased from 52% of rural pharmacies in 2002 to 63% in 2006. Other EPS (asthma, diabetes, hypertension, hyperlipidaemia), which correspond to the Australian Government National Health Priorities Areas were offered by 20% to 50% of pharmacies and had not increased between surveys. A continued shortage in the pharmacist workforce was a major barrier to EPS provision. CONCLUSIONS: Provision of EPS in rural pharmacies is more important than in metropolitan pharmacies because there is often a lack of other sources for these services in rural and remote locations. A range of defined EPS were provided by 25% to 60% of rural and remote pharmacies, with other services offered in lower percentages. Significant increases were found in some important EPS, such as weight management. Additional support for EPS provision in rural and remote communities is required to increase uptake among pharmacists. Government and pharmacy bodies need to implement rural practice models to address identified pharmacist workforce barriers and improve access to EPS to rural communities.

Kinetics of amoxicillin and clavulanate degradation alone and in combination in aqueous solution under frozen conditions.

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.

Kinetic study of the reaction of sulfamethoxazole and glucose under acidic conditions: I. Effect of pH and temperature.

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.

Failure-mode and effects analysis in improving a drug distribution system.

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.

Fluctuations in syringe-pump infusions: association with blood pressure variations in infants.

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.

A high-performance liquid-chromatographic assay for amphotericin B in a hydrophilic colloidal paste base.

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).

Chemical incompatibility between procainamide hydrochloride and glucose following intravenous admixture.

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.

Solubilities and intrinsic dissolution rates of sulphamethoxazole and trimethoprim.

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.

Influence of hydroxypropyl beta-cyclodextrin on the stability of benzylpenicillin in chloroacetate buffer.

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 effect of media and other variables on the BP solution rate test for slow lithium carbonate tablets.

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.

Intrinsic dissolution of lithium carbonate in aqueous solutions.

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 effect on syringe performance of fluid storage and repeated use: implications for syringe pumps.

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.

Impact of pharmacist intervention on oral theophylline therapy in adult inpatients.

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 amoxycillin sodium in normal saline and glucose (5%) solutions in the liquid and frozen states.

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.

An alternative aerosol delivery system for amiloride.

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.

Stability of aqueous solutions of amoxicillin sodium in the frozen and liquid states.

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.

Trends in licit opioid use in Australia, 1984-1998: comparative analysis of international and jurisdictional data.

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.