Kinetics of Tetracaine Solvolysis in Propylene Glycol.

Tetracaine is a potent ester-type local anesthetic. Recent publications describe the use of TC free base in topical anesthetic formulations containing propylene glycol. While solvolysis of tetracaine in propylene glycol solutions has been reported, there are no detailed reports on the kinetics of tetracaine reaction with propylene glycol. The objectives of the study were to characterize the kinetics and temperature dependence of tetracaine solvolysis in PG solutions. In this study, products of tetracaine degradation in propylene glycol solution at 60°C were collected and analyzed by high-performance liquid chromatographymass spectrometry and nuclear magnetic resonance. The kinetics of tetracaine reaction with propylene glycol was studied at 22°C, 30°C, 40°C, and 60°C. The reaction of tetracaine with n-propanol and isopropanol was also studied. Analysis was performed by high-performance liquid chromatography-mass spectrometry with ultraviolet detection using a gradient elution method. Tetracaine concentrations were quantitated using a four-point standard curve. Tetracaine degradation rates were consistent with apparent first order kinetics at all temperatures studied. The data indicated that tetracaine degrades via transesterification with propylene glycol. The rate constants ranged from 2.26 x 10-3 d-1 at 22°C to 7.06 x 10-2 d-1 at 60°C. Arrhenius analysis indicated an activation energy for the reaction of 74.1 kJ/mol, which is similar to published values for the hydrolysis of pharmaceutical esters.

Patient-centered care as value-added service by compounding pharmacists.

The term "value-added" is widely used to describe business and professional services that complement a product or service or that differentiate it from competing products and services. The objective of this study was to determine compounding pharmacists' self-perceptions of the value-added services they provide. A web-based survey method was used. Respondents' perceptions of their most important value-added service frequently fell into one of two categories: (1) enhanced pharmacist contribution to developing and implementing patient therapeutic plans and (2) providing customized medications of high pharmaceutical quality. The results were consistent with a hybrid community clinical practice model for compounding pharmacists wherein personalization of the professional relationship is the value-added characteristic.

The use of extemporaneously compounded 1% tetracaine to improve adherence with clotrimazole 1% topical solution in the treatment of ear infection: a case report.

For most medically amenable conditions, adherence to drug therapy is a necessary condition for a successful outcome. Drug side effects, especially pain, can interfere with the desired outcome. We report a case of non-adherence due to severe pain associated with the topical use of clotrimazole 1% solution in the ear. Instillation of tetracaine 1% solution prior to the administration of the clotrimazole blocked the pain sensation allowing the patient to successfully complete the antifungal therapy.

Assessment of the accuracy of pharmacy students' compounded solutions using vapor pressure osmometry.

OBJECTIVE. To assess the effectiveness of using a vapor pressure osmometer to measure the accuracy of pharmacy students' compounding skills. DESIGN. Students calculated the theoretical osmotic pressure (mmol/kg) of a solution as a pre-laboratory exercise, compared their calculations with actual values, and then attempted to determine the cause of any errors found. ASSESSMENT. After the introduction of the vapor pressure osmometer, the first-time pass rate for solution compounding has varied from 85% to 100%. Approximately 85% of students surveyed reported that the instrument was valuable as a teaching tool because it objectively assessed their work and provided immediate formative assessment. CONCLUSIONS. This simple technique of measuring compounding accuracy using a vapor pressure osmometer allowed students to see the importance of quality control and assessment in practice for both pharmacists and technicians.

Stability of non-aqueous topical tetracaine and clotrimazole solutions in polypropylene droptainer bottles.

Tetracaine topical solution may improve patient adherence with topical clotrimazole therapy for fungal otitis externa. The chemical stability of tetracaine 1% and combination clotrimazole 1% with tetracaine 1% topical solutions was determined using a stability-indicating high-performance liquid chromatography assay. Propylene glycol and polyethylene glycol 400 were used as anhydrous solvents. Standard curves for tetracaine and clotrimazole were linear with r2 > or = 0.999. Clotrimazole did not degrade in either propylene glycol or polyethylene glycol 400 throughout the 90-day study period. Tetracaine degraded significantly in propylene glycol but not in polyethylene glycol 400. A beyond-use date of 90 days is supported for tetracaine and the combination clotrimazole-tetracaine solution in polyethylene glycol 400. A beyond-use date of 60 days is supported for tetracaine and the combination clotrimazole-tetracaine in propylene glycol.

Stability of sodium bicarbonate solutions in polyolefin bags.

PURPOSE: The stability of sodium bicarbonate solutions in sterile water for injection or 5% dextrose injection stored at 21-24 degrees C or 2-4 degrees C was evaluated. METHODS: Sodium bicarbonate injection was obtained in 50-mL vials of 8.4% (1 meq/mL). A total of 50, 100, or 150 meq of sodium bicarbonate was added to each 1-L polyolefin bag of either sterile water for injection or 5% dextrose injection. All solutions were prepared in a laminar-airflow hood using aseptic technique. Bags were punctured once to remove headspace air and once for the addition of each 50 meq of sodium bicarbonate. Six replicates of each test solution were prepared. The solutions were stored at 21-24 degrees C and 2-4 degrees C. Control solutions (50 and 150 meq) were similarly prepared in triplicate. Control solutions were sparged with either nitrogen gas or oxygen gas before storage. Sodium bicarbonate stability was assessed by measuring solution pH. Bicarbonate content was measured utilizing titration. Both pH and bicarbonate concentrations were measured immediately upon preparation and on days 3, 5, and 7 for both test and control solutions. RESULTS: All 95% confidence interval values for sample solution pH remained within 7.0-8.5 for seven days at 2-4 degrees C. CONCLUSION: Sodium bicarbonate solutions of 50, 100, and 150 meq in sterile water for injection or 5% dextrose injection were stable for up to seven days when refrigerated. The 50-meq solution was stable for up to 48 hours when stored at room temperature, and the 100- and 150-meq solutions were stable for up to 30 hours when stored at room temperature.

Independent community pharmacists' perspectives on compounding in contemporary pharmacy education.

OBJECTIVES: To identify compounding practices of independent community pharmacy practitioners in order to make recommendations for the development of curricular objectives for doctor of pharmacy (PharmD) programs. METHODS: Independent community practitioners were asked about compounding regarding their motivations, common activities, educational exposures, and recommendations for PharmD education. RESULTS: Most respondents (69%) accepted compounding as a component of pharmaceutical care and compounded dermatological preparations for local effects, oral solutions, and suspensions at least once a week. Ninety-five percent were exposed to compounding in required pharmacy school courses and most (98%) who identified compounding as a professional service offered in their pharmacy sought additional postgraduate compounding education. Regardless of the extent of compounding emphasis in the practices surveyed, 84% stated that PharmD curricula should include compounding. CONCLUSIONS: Pharmacy schools should define compounding curricular objectives and develop compounding abilities in a required laboratory course to prepare graduates for pharmaceutical care practice.

Perceptions of pharmaceutical care among pharmacists offering compounding services.

OBJECTIVES: To identify and describe pharmaceutical care practices implemented by independent community pharmacists who provide compounding services. DESIGN: Qualitative study. SETTING: Independent community pharmacies in Illinois, Missouri, and Iowa in July 2006. PARTICIPANTS: 12 independent community pharmacists with compounding practices. INTERVENTIONS: Semistructured telephone interviews. MAIN OUTCOME MEASURES: Response themes describing pharmaceutical care in compounding practices. RESULTS: Most participants described having a closer relationship with patients receiving compounded preparations than with patients receiving only manufactured products. Higher compounded prescription volume was associated with a higher level of pharmaceutical care services for patients receiving compounded preparations. Patient health and prescription records, the nature and duration of patient counseling, and interaction with physicians differed depending on the type of preparation (compounded or manufactured) provided. CONCLUSION: Community pharmacists provided descriptions of pharmaceutical care and their satisfaction with patient and pharmacist relationships in the context of providing compounded preparations. Pharmacists, especially those providing compounded hormone replacement therapy, developed a hybrid clinical-community practice.

Prevalence of compounding in independent community pharmacy practice.

OBJECTIVES: To determine the extent of prescription compounding in independent community pharmacies and identify factors that influence the decision of independent pharmacists whether to provide compounding services. DESIGN: Cross-sectional survey. SETTING: Illinois, Missouri, Kansas, and Iowa. PARTICIPANTS: 370 pharmacists in charge. INTERVENTION: Anonymous questionnaire mailed in January 2005. MAIN OUTCOME MEASURES: Percentage of pharmacies that provide compounding; percentage of dispensed prescriptions that require compounding; factors contributing to decisions whether to provide compounding service. RESULTS: Overall, 94% of respondent pharmacies provided compounding services at the time of this survey. Prescriptions that required compounding represented less than 1% of total prescriptions for the majority (58.3%) of respondents. The main reasons for the decision to provide compounding service were wanting to provide full pharmaceutical care to patients (73.8% of compounders) and responding to requests by prescribers (48.7%). Pharmacies that did not provide compounding service cited the main reason as not receiving prescriptions that required compounding (63.6% of noncompounders). CONCLUSION: Compounding remains a component of pharmacy practice in the independent community setting. Prescriptions that required compounding represented 2.3% of all prescriptions dispensed by compounding pharmacies.

Effect of plant stanol tablets on low-density lipoprotein cholesterol lowering in patients on statin drugs.

The objective of this study was to show that plant sterols in tablet form provide additional low-density lipoprotein (LDL) cholesterol lowering for patients on statin therapy. Dispersible phytosterol tablets were tested in a double-blind, placebo-controlled, parallel clinical trial. Twenty-six patients who were following the American Heart Association Heart Healthy Diet and on long-term statin therapy were studied for 9 weeks. After 3 weeks of placebo treatment, the subjects were randomized to receive either 1.8 g of soy stanols or placebo for 6 weeks in addition to their usual statin regimen. Stanol tablets reduced LDL cholesterol 9.1% (p = 0.007) or 12.2 mg/dl. Total cholesterol was reduced by 12.9 mg/dl (p = 0.03). A strong inverse correlation (r(s) = -0.82, p = 0.0007) was found between the baseline LDL cholesterol and the percent change in LDL cholesterol observed after stanol treatment. The additional LDL cholesterol lowering with stanol/lecithin tablets provided a potential adjunctive therapy for patients who have not reached their target LDL cholesterol goal during statin therapy.

Phytostanol tablets reduce human LDL-cholesterol.

The feasibility of using solid dosage forms containing stanol lecithin to lower human LDL-cholesterol was investigated. The particle size distribution of a coarse aqueous dispersion of a stanol lecithin mixture was determined at various weight ratios of the components. At a stanol-to-lecithin weight ratio of 1.00-1.50, dispersions could be spray dried and the solid reconstituted with water to produce a particle size distribution that was similar to that of the aqueous dispersion from which it was derived. Two solid dosage forms containing this spray-dried stanol lecithin preparation had different disintegration times--tablets less than 10 min and capsules greater than 45 min. Each delivery system was then tested for LDL-cholesterol reduction activity in a placebo-controlled, double-blind clinical trial containing a total of 52 subjects. After a six-week treatment period, the group that received rapidly disintegrating stanol lecithin tablets (1.26 g stanols daily) experienced a decrease in both LDL-cholesterol and the ratio of LDL-cholesterol to HDL-cholesterol by 10.4% (P = 0.01) and 11.5% (P = 0.03), respectively, relative to placebo. On the other hand, with slowly disintegrating capsules (1.01 g daily) there was no statistically significant difference in any lipid parameter between the active group and placebo group. Taken together, these studies demonstrate that for maximum LDL-cholesterol reduction activity the stanol lecithin formulation must be delivered in a rapidly dispersible form to reach the site of cholesterol absorption.

Fat-free foods supplemented with soy stanol-lecithin powder reduce cholesterol absorption and LDL cholesterol.

OBJECTIVE: The objective of this work was to show that fat-free, lecithin-formulated soy stanols lower cholesterol absorption and serum LDL cholesterol. DESIGN: Reduction in cholesterol absorption was measured in paired single-meal tests with or without formulated soy stanols (acute test), and changes in serum lipids were investigated in a 10-week, randomized, double-blind parallel trial in which formulated stanols or lecithin vehicle were given three times daily for the last 4 weeks (chronic test). SUBJECTS/SETTING: Forty-five normal or mildly hypercholesterolemic subjects were recruited for both studies. The 21 subjects (16 female, 5 male; mean age 32.5 years) in the absorption studies had the following mean lipid values: LDL cholesterol, 2.79 mmol/L and total cholesterol, 4.73 mmol/L. For the lipid reduction, 24 subjects (16 female, 8 male; mean age 50.6 years) were enrolled with mean LDL cholesterol and total cholesterol of 3.72 mmol/L and 5.66 mmol/L, respectively. INTERVENTION: Reduction in cholesterol absorption was measured using a lemonade beverage or egg whites that contained 625 mg stanols. Throughout the chronic study, subjects followed the American Heart Association Step I diet. During the 4-week treatment phase, subjects consumed daily a lemonade-flavored beverage containing either placebo or formulated soy stanols (1.9 g). MAIN OUTCOME MEASURES: Inhibition of cholesterol absorption was determined from the difference in plasma deuterated cholesterol enrichment after a test meal containing stanol-lecithin and one with lecithin vehicle only. In the chronic study, the primary endpoints were changes in LDL and total cholesterol. STATISTICAL ANALYSES PERFORMED: Paired or unpaired t tests were used to determine statistical significance. RESULTS: Stanol-lecithin reduced cholesterol absorption by 32.1% (P=.0045, n=10) and by 38.2% (P=.0022, n=11) when delivered in a lemonade-flavored beverage and in egg whites, respectively. Reduction in cholesterol absorption was strongly related to the initial level of absorbed cholesterol tracer in serum (r(s)=-0.739). Stanol-lecithin given in a beverage reduced total serum cholesterol by 10.1% (P=.0019, n=24) and LDL cholesterol by 14.3% (P=.0016, n=24). APPLICATIONS/CONCLUSIONS: Powdered soy stanol-lecithin lowers cholesterol absorption and LDL cholesterol when consumed in fat-free foods.

The Th2-restricted immune response to xenogeneic small intestinal submucosa does not influence systemic protective immunity to viral and bacterial pathogens.

Implantation of mice with xenogeneic extracellular matrix (ECM) not only results in tissue remodeling but also elicits a strong Th2 immune response. It is possible that the Th2 cytokines induced by ECM act systemically and result in immune suppression to unrelated antigens. In this case, the recipient would be predisposed to immune dysfunction and have increased susceptibility to various pathogens. The purpose of this study was to determine if ECM implantation does, in fact, influence the immune response to other antigens. Four models were examined to determine the effects of ECM implantation on systemic immunity. In the first model, mice were subcutaneously implanted with porcine small intestinal submucosa (SIS) and immunized with a T-dependent subunit vaccine against influenza virus. The antibody response and protection against lethal infection were then measured. The second model consisted of similar experiments performed using a T-independent polysaccharide vaccine against S. pneumoniae. In the third model, mice were implanted and the cell-mediated response to dinitrofluorobenzene (DNFB) challenge was determined. The fourth model involved examining the influence of SIS implantation on rejection of xenogeneic skin grafts. We found that antibody levels of mice vaccinated against influenza virus or S. pneumoniae were not affected by SIS implantation and these mice did not exhibit increased or decreased susceptibility to either infectious agent. Similarly, mice implanted with ECM showed no cell-mediated immune dysfunction upon challenge with DNFB or xenogeneic skin grafts. The results of this study demonstrate that the Th2-restricted response induced by xenogeneic ECM implantation does not cause generalized immune suppression. Therefore, SIS implantation does not increase susceptibility to viral or bacterial pathogenic agents.