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At least 73 records · Page 4Linked to original sources
PubMed2001

Influence of film additives on stabilizing drug release rates from pellets coated with acrylic polymers.

The objective of this study was to investigate the influence of talc and triethyl citrate (TEC) on stabilizing the drug release rates following curing and storage at elevated temperature of pellets coated with an aqueous acrylic polymeric dispersion. Core pellets containing anhydrous theophylline (20%), microcrystalline cellulose, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The aqueous dispersions were prepared by adding up to 30% TEC as a plasticizer and talc up to 200% as an antiadherent to a mixture of Eudragit RS 30D/RL 30D (95:5). The theophylline pellets were coated in a fluidized-bed coating unit and then cured at elevated temperatures. Theophylline pellets were successfully coated with the Eudragit dispersions that contained up to 200% talc, based on the dry polymer weight, and the coating efficiency was greater than 93%. Our results demonstrated that the polymer, which was plasticized by TEC, was able to function as a film-forming agent for dispersions containing high levels of talc. No sticking of the coated pellets was observed during the coating process or during the curing or equilibrating phase, even with high levels of TEC in the film. The dissolution rate of theophylline from the coated pellets was delayed when the film coating dispersion contained high levels of talc. Additionally, the stability of the drug release profiles from the coated pellets after storage was significantly improved. Furthermore, a modified dissolution testing used to simulate mechanical stresses that may be encountered in vivo showed the film coated pellets would have sufficient strength. The results of this study demonstrated that high levels of film additives in the acrylic dispersion contributed to the stabilization of the drug release rates as well as the reproducibility of the coating process.

Acrylic Resins↗
PubMed2007

Decreased protein kinase C (PKC) in platelets of pediatric bipolar patients: effect of treatment with mood stabilizing drugs.

Pediatric bipolar disorder (PBD) is a major public health concern, however, its neurobiology is poorly understood. We, therefore, studied the role of protein kinase C (PKC) in the pathophysiology of bipolar illness. We determined PKC activity and immunolabeling of various PKC isozymes (i.e., PKC alpha, PKC betaI, PKC betaII, and PKC delta) in the cytosol and membrane fractions of platelets obtained from PBD patients and normal control subjects. PKC activity and PKC isozymes were also determined after 8 weeks of pharmacotherapy of PBD patients (n=16) with mood stabilizers. PKC activity and the protein expression of PKC betaI and betaII, but not PKC alpha or PKC delta, were significantly decreased in both membrane as well as cytosol fractions of platelets obtained from medication-free PBD patients compared with normal control subjects. Eight weeks of pharmacotherapy resulted in significantly increased PKC activity but no significant changes in any of the PKC isozymes in PBD patients. These results indicate that decreases of specific PKC isozymes and decreased PKC activity may be associated with the pathophysiology of PBD and that pharmacotherapy with mood stabilizing drugs results in an increase and normalization of PKC activity along with improvement in clinical symptoms.

Adolescent↗
PubMed1994

The structural basis of camptothecin interactions with human serum albumin: impact on drug stability.

The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camptothecins with HSA in phosphate-buffered saline (pH 7.4) at 37 degrees C. The alpha-hydroxy delta-lactone ring moiety of camptothecin (C), 10-hydroxycamptothecin (HC), 10,11-(methylenedioxy)camptothecin (MC) and 9-chloro-10,11-(methylenedioxy)camptothecin (CMC) was in each case observed to hydrolyze more rapidly and completely in the presence of HSA than in the protein's absence. Binding isotherms constructed by the method of fluorescence lifetime titration showed that HSA bound preferentially the carboxylate forms of C, HC, MC, and CMC over their lactone forms, thereby providing an explanation for the shift to the right in the lactone-carboxylate equilibrium observed for each compound upon HSA addition. In marked contrast, three analogues (SN-38, CPT-11, and topotecan) all displayed enhanced stabilities in the presence of HSA. While the lifetimes of CPT-11, topotecan, and the carboxylate forms of both drugs were insensitive to the addition of HSA, the lifetimes of both SN-38 and its carboxylate form did titrate upon HSA addition. Analysis of binding isotherms constructed for the albumin interactions of SN-38 and its carboxylate form demonstrated a higher overall association constant for the lactone form [640 (M amino acid (aa) residues)-1] relative to the carboxylate form [150 (M aa)-1]. Our studies indicate that specific modifications at the 7- and 9-positions of the quinoline nucleus, such as those contained in CPT-11, topotecan, and SN-38, enhance drug stability in the presence of HSA. In the case of SN-38, the enhanced stability was shown to be due to preferential associations between the drug's lactone form and the blood protein.

Camptothecin↗
PubMed1992

Bacteriology, drug stability and exchange of percutaneous delivery systems and antibacterial filters in long-term intrathecal infusion of opioid drugs and bupivacaine in "refractory" pain.

OBJECTIVE: To provide a basis for recommendations on the exchange of containers (syringes and cassettes) and antibacterial filters, and for choice of administration device in patients with "refractory" pain treated with long-term percutaneous intrathecal (IT) infusions of opioid (morphine or buprenorphine) and bupivacaine mixtures. DESIGN: Prospective, cohort, nonrandomized control trial-case series, with consecutive sample, no standard criterion, and cost-benefit analysis. SETTING: Tertiary care center, institutional practice as well as hospitalized and ambulatory care. PATIENTS: Eighty-nine (51 women and 38 men); 81 with malignant pain and 8 with benign "refractory" pain. INTERVENTIONS: (a) The chemical stability of the drugs in the containers during 30 days. (b) The results of bacteriologic culture of the residual volumes of the analgesic mixtures from used and reused (1-16 times) syringes (n = 135) and cassettes (n = 258), and of 5 ml of sterile isotonic saline filtered through the used Millipore filters (n = 149). The bacteriologic samples from the 89 patients were taken after 1-40 (median = 7), 1-86 (median = 20), and 5-78 (median = 31) days of IT treatment, respectively. MAIN OUTCOME MEASURES: Chemical stability: buprenorphine and bupivacaine concentrations-liquid chromatography; morphine concentrations--gas chromatography. Bacteriologic cultures: standard laboratory procedures. The hypothesis (repeated use of the infusion systems and their exchange once a month does not significantly affect drug concentrations or increase the infection risk) was elaborated before data collection began. RESULTS: The bupivacaine-opioid mixtures were found to be chemically stable within 3-10% of the original doses up to 30 days. Seventeen cultures (from five syringes, six cassettes, and six filters) in 13 patients (having no signs of meningeal infection) were found to be colonized with Staphylococcus aureus (n = 4), coagulase negative staphylococci (n = 7), viridans streptococci (n = 3), Neisseria sp (n = 4), Corynebacterium sp (n = 4), Enterobacter sp (n = 2), Klebsiella sp (n = 3), gram-negative bacilli (n = 1), and yeasts (n = 2). The place of IT treatment, its duration, and patient-related infection risk factors (age; malignancy; diabetes; presence of a colostomy, pyelostomy, or indwelling urinary catheter; and the presence and location of infection foci) were not related to the results of the cultures. However, 9 of the 17 positive cultures came from patients with skin ulcers, a notable incidence. The positive cultures had no connection with the cultured item, its in-use duration, the number of times of reuse, the analgesic drugs used, their concentrations or the presence of preservatives (sodium metabisulfite and sodium edetate), or the antiseptic agent (70% ethanol or 0.5% chlorhexidine gluconate) used during bacteriologic sampling. The bacterial growth was sparse in 14 and massive in 3 of the 17 positive cultures. One item (filter) from one patient with meningitis was sterile. CONCLUSIONS: In our population, exchange of the infusion systems when they are empty (within 1 month) and of the antibacterial filters once a month does not appear to affect the concentrations of, or increase the infection risk from, the opioid-bupivacaine mixtures. The risk of bacterial contamination/colonization of the syringes from syringe drivers does not seem to be higher than that of cassettes from external portable pumps.

Adolescent↗
PubMed1996

Drug stability and compatibility in oncology care.

Infusional chemotherapy has been increasingly used based upon the fact that most drugs have a relatively short half-life following bolus exposure, and increasing the available drug concentration over time may maximize the antitumor effect. As a practical matter, the application of infusional chemotherapy especially in an ambulatory setting, absolutely requires that the individual antineoplastic agents be stable in solution at room temperature (or at body temperature for implanted pump systems) and that the drugs in the infusion (including antiemetics) be compatible. The capacity to mix antineoplastic agents and antiemetics (also colony-stimulating factors) in a single solution facilitates infusional combination chemotherapy. Technologic advances are on the horizon which will provide the capability of administration of multiple drugs through a single access site to allow one to utilize a single delivery source obviating the need for admixtures of drugs. However, in the interim, admixtures represent the optimal method for the delivery of multi-agent chemotherapy in the setting in which continuous infusional drug delivery for 24 hours or more is employed. The goal of continuous infusion cancer chemotherapy is to ensure delivery of an unaltered cytotoxic drug, avoiding situations that could affect the stability of the infusion admixture. With cancer chemotherapy infusion therapy being administered through oncology clinics without the benefits of a pharmacist, the nurse plays a pivotal role in the preparation of the infusion, supervision of the patient, and when applicable in providing counseling on the proper storage, handling of the cytotoxic drugs, and disposal of contaminated infusion materials. Thus, by optimizing the integrity of the chemotherapeutic infusion, the patient achieves maximum benefits of cancer chemotherapy and the level of success anticipated with oncology care. The nurse may also be involved with clinical studies involving the preparation of other combinations of infusional chemotherapy including antiemetics and colony-stimulating factors, requiring integrity of the infusion to incompatibility and instability. In order to avoid failure of the infusion through improper preparation or reconstitution of the infusion or improper storage conditions and the resulting unnecessary waste and disposal expenses, the nurse needs to be fully aware of the factors affecting the stability and compatibility of the infusion and to interact with other health professionals and the literature for the critical information related to maintaining the integrity of the cancer chemotherapy infusion. "Good intentions without good communication equals potential disaster."

Ambulatory Care↗
PubMed1981

Inhibition of sarcolemma ATPases by some membrane-stabilizing drugs.

Rat sarcolemma preparations were incubated with some membranes stabilizers to study their effects on the (Na+,K+)- and Ca2+-ATPase activity. The drugs inhibited the enzymes with the same order of potency as in the earlier observed muscle contractures: chlorpromazine greater than dibucaine greater than propranolol greater than tetracaine greater than procaine (range 0.1-3.6 mM) (Røed & Brodal 1979). The contracture inducing effect of the stabilizers is suggested to be caused by a membrane depolarization due to the (Na+,K+)-ATPase inhibition. Ouabain inhibited the (Na+,K+)-ATPase activity in purified plasma membrane, but did not inherit the sarcolemma located ATPases or induce any contracture.

Animals↗