Cost comparison of oral, nasogastric, and intramuscular cimetidine drug delivery systems

Under diagnosis-related group prospective payment, the role of the hospital pharmacy department is to develop and promote cost effective and rational drug therapy. This study, conducted in a simulated fashion, evaluated the cost effectiveness of various cimetidine drug delivery systems: oral, nasogastric, and intramuscular. The evaluation was also extended to compare time efficacy between different dosage forms for each route of administration with the exception of the intramuscular route. Each of four nurses and four pharmacy technicians conducted 10 trials for each system to detect a statistical significance difference in pharmacy preparation and nursing administration time with at least 80% statistical power. The results showed no statistically significant difference (P > 0.1) between the total oral administration time of a unit-dose tablet or liquid. A significant difference was detected among the pharmacy-prepared liquids, and unit-dose liquid administered nasogastrically (P < 0.01). The most cost-effective system is the orally administered unit-dose tablet and the most expensive system is the unit-dose liquid administered nasogastrically.     

A cost benefit comparison of two antibiotic delivery systems in a children's hospital.

A comparative trial was undertaken in a 301 bed pediatric hospital to determine the feasibility and cost benefit of converting from a minibag intravenous admixture system to one using polypropylene syringes, prefilled with undiluted medication, for the administration of antibiotics. Technical and therapeutic problems unique to a pediatric hospital and the stability of antibiotics in polypropylene syringes were concurrent considerations. The cost of materials and total time involved were measured for each system for a one month period. It was concluded that the prefilled syringe system as a method of dispensing selected parenteral antibiotics, although requiring more time, is more cost effective than the minibag system.     

A cost comparison of intramuscular versus intravenous imipenem.

Previously reported clinical trials of imipenem-cilastatin 500 mg given intravenously every 6 hours (intravenous group) and imipenem-cilastatin 750 mg given intramuscularly every 12 hours (intramuscular group) were analyzed for relative cost savings. Acquisition costs were significantly higher for the intravenous group for intravenous supplies (30.6 +/- 7.9 dollars) when compared to the intramuscular group (0.98 +/- 0.03 dollars) (p less than 0.05). Also, significantly higher cost (p less than 0.05) was noted for salaries of pharmacists and technicians for manufacturing in the intravenous group (5.8 +/- 1.5 dollars) as compared to the intramuscular group (2.4 +/- 0.7 dollars). Nursing administration costs were greater for the intramuscular group (15.6 +/- 4.8 dollars) when compared to the intravenous group (11.7 +/- 3.0 dollars). Incorporating all appropriate costs, the mean total drug therapy costs (TRX$) were significantly greater (p less than 0.01) for the intravenous group (458.17 +/- 175.17 dollars) as compared to the intramuscular group (298.0 +/- 114.76 dollars). Thus, the dosing of imipenem-cilastatin 750 mg intramuscularly every 12 hours is a more cost effective method of drug delivery with equal efficacy and safety when compared to imipenem-cilastatin 500 mg given intravenously every 6 hours.     

An update on ready-to-use intravenous delivery systems

The advent of ready-to-use intravenous (IV) delivery systems, particularly small-volume parenterals less than 250 mL has contributed greatly to pharmacy and patient care. Since their introduction in the late 1970s, the availability and variety of systems have increased. The purpose of this article is to update practitioners on small-volume parenterals systems that have a large product availability requiring little manipulation to make the system patient-specific. Additional benefits such as extended stability, potential for decreasing waste of products, as well improved end-quality are also discussed. With the benefits described that these systems have over the traditional method of preparing small-volume parenterals, there is still hesitation to fully utilize these systems. The primary reason for this seems to be the issue of cost. With various rebate incentive programs offered by manufacturers as well as the benefits that the systems provide, ready-to-use IV delivery systems are comparable in price to the traditional method of preparing small-volume parenteral agents.     

The sorption of isosorbide dinitrate to intravenous delivery systems

The sorption of isosorbide dinitrate from 0.9% sodium chloride and 10% glucose solutions, by intravenous delivery systems has been investigated under simulated infusion conditions. Isosorbide dinitrate was stable in both 0.9% sodium chloride and 10% glucose solutions. Intravenous fluid containers, burettes, a syringe, infusion sets and end-line filters were evaluated. Glass containers, methacrylate butadiene styrene burettes and polybutadiene giving sets did not sorb isosorbide dinitrate. Neither did polypropylene syringes when a 10% glucose solution was used. The sorption of isosorbide dinitrate to end-line filters was unimportant but there was a significant loss to the PVC tubing used to connect the filter housing to the catheter.     

A comparison of anionic nanoparticles and microparticles as vaccine delivery systems

The objective of this work was to conduct an in vivo comparison of nanoparticles and microparticles as vaccine delivery systems. Poly (lactide-co-glycolide) (PLG) polymers were used to create nanoparticles size 110 nm and microparticles of size 800-900 nm. Protein antigens were then adsorbed to these particles. The efficacy of these delivery systems was tested with two protein antigens. A recombinant antigen from Neisseria meningitides type B (MenB) was administered intramuscularly (i.m.) or intraperitonealy (i.p.). An antigen from HIV-1, env glycoprotein gp140 was administered intranasally (i.n.) followed by an i.m. boost. From three studies, there were no differences between the nanoparticles and micro-particles formulations. Both particles led to comparable immune responses in mice. The immune responses for MenB (serum bactericidal activity and antibody titers) were equivalent to the control of aluminum hydroxide. For the gp140, the LTK63 was necessary for high titers. Both nanoparticles and microparticles are promising delivery systems.     

The sorption of isosorbide-5-mononitrate to intravenous delivery systems

The sorption of isosorbide-5-mononitrate, diluted in 0.9% NaCl or 10% glucose solutions, to intravenous delivery systems was investigated. Infusion bags, burettes, a syringe, infusion tubings and end-line filters were tested in static and in dynamic experiments. No clinically significant sorption was detected during those experiments. The use of PVC tubings of different hardness did not influence the results.     

Effects of intravenous delivery systems on infused red blood cells

The effects of various intravenous delivery systems on the integrity of infused red blood cells (RBCs) were studied. Using a factorial design, whole blood and packed RBCs were infused through i.v. delivery systems employing various combinations of i.v. tubing diameter and length, needle gauge, infusion rate (5 and 50 ml/hr), type of infusion pump (piston, diaphragm, or peristaltic operation), and type of blood product. The age and temperature of the blood filter used were held constant. A 5-ml sample of the blood product obtained during each experimental run was analyzed for plasma free-hemoglobin to assess the degree of hemolysis. Osmotic fragility of the RBCs was evaluated by measuring the percentage of hemolysis in the blood products in various concentrations of sodium chloride solution. Type of blood product and i.v. pump were the only variables significantly influencing RBC hemolysis. In both blood products, a greater degree of hemolysis occurred with the peristaltic-type pump than with the other types of pumps. In packed RBCs, the diaphragm-type pump produced greater hemolysis than the piston-type pump, but hemolysis was similar in whole-blood samples. Regardless of the type of pump, more hemolysis occurred in whole blood at the 5-ml/hr infusion rate than at the 50-ml/hr rate, but the converse was true in packed RBCs. Samples of both blood products were less osmotically fragile than their respective controls at sodium chloride concentrations ranging from 0.30 to 0.50%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transdermal testosterone delivery: comparison between scrotal and nonscrotal delivery systems.

The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs). Testoderm, designed to deliver testosterone through scrotal skin, and Androderm, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is approximately 13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration-time curve (AUC0-28)[665 versus 3208 (ng/dl) x hr] between these T-TDSs. However, there is no difference in time to reach Cmax mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (approximately 13-fold) between the nonscrotal and scrotal T-TDSs.     

Prolactin response to TRH after intravenous cimetidine.

Cimetidine administered intravenously to six healthy volunteers caused a significant increase in plasma prolactin response to TRH. The meaning of these results and their relation with the physiological role of histamine H2-receptors in the control of prolactin secretion is discussed.     

Loss of nitroglycerin from aqueous solution into plastic intravenous delivery systems.

The mechanism of potential loss of nitroglycerin stored in plastic and glass containers was studied from an equilibrium and kinetic approach. Plastic strips equilibrated with dilute aqueous solutions of neat nitroglycerin showed that the drug was lost by absorption. Drug loss was followed by an electron-capture GLC assay. The same assay of control solutions in glass showed no drug loss in 48 hr at pH 5.7. The kinetics of nitroglycerin absorption and desorption were determined using synthesized 14C-labeled drug. Absorption can be quantified using a diffusion model, where the concentration in the aqueous phase falls with time. Curve fitting yielded an average diffusion coefficient in plastic of 2.05 x 10(-9) cm2/sec and a partition coefficient of 104 (plastic-water) at 30 degrees. Temperature-dependence studies of absorption showed that the diffusion coefficient followed an Arrhenius relationship with an energy requirement of 19.6 kcal/mole, whereas effects on the partition coefficient were negligible. Nitroglycerin desorption from plastic disks under sink conditions into water can be quantified by assuming a diffusion model where the concentration at the surface of a plane sheet remains constant. Nonlinear least-squares curve fitting generated a diffusion coefficient of 1.14 x 10(-9) cm2/sec for the desorption process at 30 degrees.     

布托啡诺经鼻腔给药和静脉注射用于无痛肠镜的效果比较

目的比较布托啡诺经鼻腔给药和静脉注射用于无痛肠镜检查的效果。方法行无痛肠镜检查的患者90例,随机分为A组和B组各45例,A组经鼻滴入布托啡诺,B组静脉注射布托啡诺。比较2组用药前(T0)、用药后1min(T1)、静脉注射丙泊酚后1min(T2)、2min(T3)、3min(T4)、4min(T5)、术毕(T6)、清醒(T7)时的MAP、HR、SpO2以及诱导时间、苏醒时间、检查持续时间、OAA/S、肢动情况、丙泊酚总量、麻醉效果。结果 2组MAP、HR在T1～T7较T0低,差异有统计学意义(P<0.05),而组间比较差异无统计学意义(P>0.05)。2组SpO2在T2～T6较T0、T1、T7低,差异有统计学意义(P<0.05),且A组高于B组(P<0.05)。2组诱导时间、苏醒时间、检查持续时间、术中镇静评分(OAA/S)、丙泊酚总量比较差异无统计学意义(P>0.05)。2组均无肢动情况。A组麻醉效果优于B组,差异有统计学意义(P<0.05),A组术者满意度明显高于B组,差异有统计学意义(P<0.05)。2组患者舒适度差异无统计学意义(P>0.05)。结论布托啡诺经鼻腔给药用于无痛肠镜检查效果优于静脉注射。     

布托啡诺经鼻腔给药和静脉注射用于无痛肠镜的效果比较

目的 比较布托啡诺经鼻腔给药和静脉注射用于无痛肠镜检查的效果.方法 行无痛肠镜检查的患者90例,随机分为A组和B组各45例,A组经鼻滴入布托啡诺,B组静脉注射布托啡诺.比较2组用药前(T0)、用药后1min(T1)、静脉注射丙泊酚后1min(T2)、2min(T3)、3min(T4)、4min(T5)、术毕(T6)、清醒(T7)时的MAP、HR、SpO2以及诱导时间、苏醒时间、检查持续时间、OAA/S、肢动情况、丙泊酚总量、麻醉效果.结果 2组MAP、HR在T1～T7较T0低,差异有统计学意义(P<0.05),而组间比较差异无统计学意义(P>0.05).2组SpO2在T2～T6较T0、T1、T7低,差异有统计学意义(P<0.05),且A组高于B组(P<0.05).2组诱导时间、苏醒时间、检查持续时间、术中镇静评分(OAA/S)、丙泊酚总量比较差异无统计学意义(P>0.05).2组均无肢动情况.A组麻醉效果优于B组,差异有统计学意义(P<0.05),A组术者满意度明显高于B组,差异有统计学意义(P<0.05).2组患者舒适度差异无统计学意义(P>0.05).结论 布托啡诺经鼻腔给药用于无痛肠镜检查效果优于静脉注射.     

西米替丁结肠靶向生物粘附释药胶囊的制备

目的：研制西米替丁结肠靶向生物粘附释药胶囊。方法：处方药湿法制粒，干燥后装胶囊，采用紫外分光光度法测定含量。结果：含量测定方法回收率为98.56%，RSD为1.64%。结论：方法准确，可有效地控制该制剂的质量。     

Implementing therapeutic interchange of intravenous famotidine for cimetidine and ranitidine

The steps taken to implement a therapeutic interchange program for i.v. histamine H2-receptor antagonists and to determine the potential cost savings are described. A literature review conducted by pharmacists at a 273-bed nonteaching community hospital showed that i.v. famotidine was as safe and effective as i.v. cimetidine or ranitidine and that it was feasible to add famotidine to total parenteral nutrition (TPN) solutions. Because of famotidine's cost advantage, it was proposed that i.v. famotidine be used in place of specific dosage regimens of i.v. ranitidine or cimetidine and in TPN solutions ordered for patients receiving concurrent H2-antagonist therapy. The approval of the hospital attorney and hospital gastroenterologists was secured, and a formal proposal was submitted. The pharmacy department distributed a memorandum describing the advantages of famotidine, conducted inservice education sessions, and sought the compliance of physicians by placing reminders on order forms and patient charts and by contacting physicians directly. The program was implemented in May 1989. During the first three months, only one physician insisted that patients receive i.v. ranitidine rather than famotidine. It was projected that the interchange of i.v. famotidine for cimetidine or ranitidine would result in a total savings of $37,565 during the first year due to reductions in the cost of drugs, supplies, and nursing labor. The acceptance of a therapeutic interchange program for H2 antagonists was excellent, and the projected savings are substantial.     

Drug delivery systems 5A. Oral drug delivery

The two main advantages of controlled drug delivery systems are: maintenance of therapeutically optimum drug concentrations in the plasma through zero-order release without significant fluctuations; and elimination of the need for frequent single dose administrations. The oral and other therapeutic systems in human use have validated the concept that controlled continuous drug release can minimize the daily dose of a drug required to maintain the required therapeutic effect, while minimizing unwanted pharmacological effects. By minimizing patient intervention, a design feature of therapeutic systems, compliance is automatically enhanced. Oral drug delivery systems, in particular, have required innovation in materials science to provide materials biocompatible during prolonged contact with body tissues, bioengineering to develop drug delivery modules, and clinical pharmacology for elucidation of drug action under conditions of continuous controlled drug administration. Recent work in advanced oral delivery has been primarily focused on liposome technology and the concept that substances that are normally destroyed by the stomach can be protected long enough before they could be absorbed downstream. For cost and patient convenience, oral delivery certainly would be an attractive method. The nature of biologic substances, however, with their unique technical problems, will probably limit greatly those that can be delivered orally. Besides, where delivery rate control is critical, oral delivery, even when possible, would probably be insufficiently precise. Oral delivery would also limit the substance to bloodstream delivery to the disease site. Even so, oral controlled drug delivery systems will likely find primary usefulness in specific carefully controlled therapies and prophylactic situations with due regard for drug interactions. This system represents a potentially very significant therapeutic modality. These delivery systems will find usefulness primarily in certain well-defined and well-controllable areas with due regard for individual patient variations. The purpose of the present article is to review oral controlled-release drug delivery systems, with particular emphasis on the practical aspects of testing and fabricating these systems and the underlying mechanisms by which control over drug release rate is accomplished.     

Cost comparison of two systems for intermittent intravenous administration of small-volume injections

Pharmacy department costs for preparing and administering intermittent i.v. drug doses using a piggyback bottle system and a syringe pump system were predicted and compared. Centralized i.v. admixture service personnel time for preparation of small-volume injections in piggyback bottles was recorded for 14 days. After a four-week orientation of personnel to the syringe pump system, personnel time for preparation of doses in this system was recorded for 14 days. Material costs were itemized for each system and annual costs were predicted. Costs were calculated on the basis of the previous year's purchasing data, assuming that 80% of intermittent i.v. drug doses could be given by the syringe pump system. Syringe pump system costs were calculated for administration of one to eight drug doses through each secondary infusion set; 5-mL and 10-mL syringes were used. Preparation time was slightly longer for the syringe pump system than for the piggyback bottle system; the annualized personnel cost difference was $0.012 per dose. Based on one dose per secondary infusion set, material costs were higher for the syringe pump system. Based on administration of four doses through each secondary infusion set, overall costs were lower for the syringe pump system. Lower material acquisition costs for the syringe pump system could result in pharmacy department cost savings if at least four intermittent i.v. drug doses were administered through each secondary administration set.