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Sample records for oxycodone controlled release

  1. Oxycodone controlled release in cancer pain management.

    PubMed

    Biancofiore, Giuseppe

    2006-09-01

    Oral opioids are the treatment of choice for chronic cancer pain. Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines from the World Health Organization (WHO). This recommendation by the WHO was derived from availability, familiarity to clinicians, established effectiveness, simplicity of administration, and relative inexpensive cost. It was not based on proven therapeutic superiority over other options. Patients who experience inadequate pain relief or intolerable side effects with one opioid may often be successfully treated with another agent or with the same agent administered by a different route. Opioid rotation, or switching to an alternative opioid, helps some patients achieve better pain control with fewer associated adverse effects. Oxycodone is a mu-opioid receptor specific ligand, with clear agonist properties. It is an active potent opioid, which is in part a kappa-receptor agonist. Like morphine and other pure agonists, there is no known ceiling to the analgesic effects of oxycodone. The active metabolites of oxycodone (eg, oxymorphone) could be important in oxycodone-mediated analgesia. The main pharmacokinetic difference between oxycodone and morphine is in oral bioavailability. The bioavailability of oxycodone is >60% and the bioavailability of morphine is 20%. Controlled-release oxycodone is absorbed in a bi-exponential fashion. There is a rapid phase with a mean half-life of 37 min, accounting for 38% of the dose, and a slow phase with a half-life of 6.2 h, which accounts for the residual 62%. Oxycodone elimination is impaired by renal failure because there are both an increased volume of distribution and reduced clearance. A lot of studies prove that the efficacy of controlled-release oxycodone in cancer-pain control is at least the same as morphine, immediate-release oxycodone and hydromorphone. Its toxicity profile seems better than that of morphine. There are actually several

  2. Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy.

    PubMed

    Davis, Mellar P; Varga, James; Dickerson, Duke; Walsh, Declan; LeGrand, Susan B; Lagman, Ruth

    2003-02-01

    Oxycodone has become one of the most popular opioids in the United States. It is superior to morphine in oral absorption and bioavailability, and similar in terms of protein binding and lipophilicity. Gender more than age influences oxycodone elimination. Unlike morphine, oxycodone is metabolized by the cytochrome isoenzyme CYP2D6, which is severely impaired by liver dysfunction. Controlled-release (CR) oxycodone has become one of the most frequently utilized sustained-release opioids in the United States. Both its analgesic benefits and its side effects are similar to those of CR morphine. CR oxycodone is similar to morphine and other opioids in its abuse potential. Deaths attributable to oxycodone are usually associated with polysubstance abuse in which oxycodone is combined with psychostimulants, other opioids, benzodiazepines or alcohol. Oxycodone's kappa receptor binding has little role in abuse or addiction. The cost of CR oxycodone is prohibitive for most American hospices.

  3. Effects of Aprepitant on the Pharmacokinetics of Controlled-Release Oral Oxycodone in Cancer Patients

    PubMed Central

    Fujiwara, Yutaka; Toyoda, Masanori; Chayahara, Naoko; Kiyota, Naomi; Shimada, Takanobu; Imamura, Yoshinori; Mukohara, Toru; Minami, Hironobu

    2014-01-01

    Purpose Oxycodone is a µ-opioid receptor agonist widely used in the treatment of cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a minor proportion undergoes 3-O-demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release (CR) oxycodone. Method This study design was an open-label, single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours. Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning). The steady-state trough concentrations (Css) were measured from day 1 to day 3. Results Aprepitant increased the area under the plasma concentration-time curve (AUC0–8) of oxycodone by 25% (p<0.001) and of oxymorphone by 34% (p<0.001), as well as decreased the AUC0–8 of noroxycodone by 14% (p<0.001). Moreover, aprepitant increased Css of oxycodone by 57% (p = 0.001) and of oxymorphone by 36% (p<0.001) and decreased Css of noroxycodone by 24% (p = 0.02) at day 3 compared to day 1. Conclusions The clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose. Trial Registration UMIN.ac.jp UMIN000003580. PMID:25121773

  4. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    PubMed Central

    Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

    2015-01-01

    The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. PMID:25678774

  5. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets.

    PubMed

    Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

    2015-01-01

    The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone.

  6. Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients.

    PubMed

    Stambaugh, J E; Reder, R F; Stambaugh, M D; Stambaugh, H; Davis, M

    2001-05-01

    Thirty patients with cancer pain completed a double-blind crossover study comparing controlled-release (CR) and immediate-release (IR) oxycodone. In open-label titration (2 to 21 days), these patients were stabilized on IR oxycodone qid. They were then randomized to double-blind treatment with CR oxycodone q12h or IR oxycodone qid for 3 to 7 days followed by crossover at the same daily dose. Mean (+/- SD) pain intensity (0 = none to 10 = severe) decreased from a baseline of 6.0 +/- 2.2 to 2.7 +/- 1.1 after titration with IR oxycodone dosed qid. Pain intensity remained stable throughout double-blind treatment: 2.7 +/- 1.9 with CR oxycodone and 2.8 +/- 1.9 with IR oxycodone. Acceptability of therapy and pain scores correlated with plasma oxycodone concentrations for each interval and were similar for both medications (IR and CR oxycodone). Adverse events were similar for both formulations. Following repeat dosing under double-blind conditions, oral CR oxycodone administered q12h provided analgesia comparable to IR oxycodone given qid.

  7. Trends in Controlled-Release Oxycodone (Oxycontin[R]) Prescribing among Medicaid Recipients in Kentucky, 1998-2002. Research Note

    ERIC Educational Resources Information Center

    Havens, Jennifer R.; Talbert, Jeffrey C.; Walker, Robert; Leedham, Cynthia; Leukefeld, Carl G.

    2006-01-01

    Context: Prescription opioid abuse has emerged as a public health problem, particularly in rural America. Purpose: To examine temporal and geographic trends in rates of controlled-release oxycodone (OxyContin) prescribing for Kentucky Medicaid recipients. Methods: A cross-sectional analysis was completed in which the state was divided into 3…

  8. Intranasal administration of crushed ALO-02 (extended-release oxycodone with sequestered naltrexone): A randomized, controlled abuse-potential study in nondependent recreational opioid users.

    PubMed

    Setnik, Beatrice; Bramson, Candace; Bass, Almasa; Levy-Cooperman, Naama; Malhotra, Bimal; Matschke, Kyle; Sommerville, Kenneth W; Wolfram, Gernot; Geoffroy, Pierre

    2015-12-01

    ALO-02 is an abuse-deterrent formulation consisting of capsules filled with pellets of extended-release oxycodone surrounding sequestered naltrexone. This randomized, double-blind, placebo-/active-controlled, 4-way crossover study examined the abuse potential of crushed ALO-02 administered intranasally to healthy, nondependent, recreational opioid users. Following drug discrimination and naloxone challenge, eligible participants (n = 32) entered a 4-way crossover treatment phase: crushed single dose of 1 of 2 placebos, ALO-02 30 mg/3.6 mg (oxycodone/naltrexone) or oxycodone immediate-release (IR) 30 mg. Primary end points were Drug Liking and High, measured on visual analog scales (VAS) summarized as maximum effect (Emax ) and effect occurring over 2 hours postdose (AUE0-2  h ). Crushed ALO-02 resulted in significantly lower scores versus oxycodone IR on Drug Liking (Emax , 60.5 vs 92.8; AUE0-2  h , 105.4 vs 160.0, respectively) and High (Emax , 25.2 vs 86.9; AUE0-2  h , 27.1 vs 136.4, respectively; n = 28; P < .0001). Adverse events occurred most frequently with oxycodone IR, followed by ALO-02, then placebo, and were considered mild and consistent with opioid therapy. Crushed ALO-02 administered intranasally to nondependent recreational opioid users resulted in significantly lower scores on Drug Liking/High VAS and other positive subjective measures versus crushed oxycodone IR, suggesting less abuse potential. Demonstration of actual abuse deterrence in the real world requires further research.

  9. Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

    PubMed Central

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-01-01

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

  10. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    PubMed

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-03-15

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  11. Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users.

    PubMed

    Harris, Stephen C; Perrino, Peter J; Smith, Ira; Shram, Megan J; Colucci, Salvatore V; Bartlett, Cynthia; Sellers, Edward M

    2014-04-01

    The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmax and increased Tmax versus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1-2 hours) versus OC and Oxy API (0.5-1 hour). ODL, TDA, High VAS, and SDV Emax values were significantly lower (P ≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug-liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post-marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real-world patterns of ORF misuse, abuse, and diversion.

  12. Pain therapy with oxycodone/naloxone prolonged-release combination: case report.

    PubMed

    Błaszczyk, Feliks; Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent - morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin(®) (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control.

  13. Relapsing thrombotic microangiopathy and intravenous sustained-release oxycodone

    PubMed Central

    Nataatmadja, Melissa; Divi, Dakshinamurthy

    2016-01-01

    Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case of TMA secondary to intravenous use of sustained-release oxycodone, and the first case to demonstrate relapsing disease due to persistent intravenous opioid use. In cases such as these, TMA is suspected to be due to a polyethylene oxide (PEO) coating found on these drugs, and the disease is likely due to a directly toxic effect of PEO to endothelial cells. We hypothesize that there are unidentified genetic predispositions causing some persons to be susceptible to developing this disease. PMID:27478601

  14. Pain therapy with oxycodone/naloxone prolonged-release combination: case report

    PubMed Central

    Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent – morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin® (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

  15. Morphine or oxycodone in cancer pain?

    PubMed

    Heiskanen, T E; Ruismäki, P M; Seppälä, T A; Kalso, E A

    2000-01-01

    Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.

  16. Profile of extended-release oxycodone/acetaminophen for acute pain

    PubMed Central

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations. PMID:26527898

  17. Oral Human Abuse Potential of Oxycodone DETERx® (Xtampza® ER)

    PubMed Central

    Kopecky, Ernest A.; Levy‐Cooperman, Naama; O'Connor, Melinda; M. Sellers, Edward

    2016-01-01

    Abstract Oxycodone DETERx® (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended‐release, microsphere‐in‐capsule, abuse‐deterrent formulation designed to retain its extended‐release properties after tampering (eg, chewing/crushing). This randomized, double‐blind, placebo‐controlled, triple‐dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate‐release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high‐fat, high‐calorie meal and fasted), chewed oxycodone DETERx (high‐fat, high‐calorie meal and fasted), crushed immediate‐release oxycodone (fasted), and placebo (high‐fat, high‐calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty‐eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate‐release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate‐release oxycodone. Study treatments were well tolerated; no subjects experienced

  18. The effect of single-dose tramadol on oxycodone clearance.

    PubMed

    Curry, Steven C; Watts, David J; Katz, Kenneth D; Bikin, Dale; Bukaveckas, Bonny L

    2007-11-01

    We have noticed increased prescribing of tramadol by emergency physicians for breakthrough pain in patients chronically taking oxycodone. Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism. A randomized controlled trial in 10 human volunteers was performed to determine if single-dose tramadol therapy would impair oxycodone clearance. Subjects were randomized whether to enter the control or experimental arm of the study first, with each subject serving as his or her own control. In the control arm, each subject received 10 mg immediate-release oxycodone orally and had serial plasma oxycodone and oxymorphone concentrations measured over 8 h. The experimental arm was identical except that 100 mg tramadol was ingested 1.5 h before oxycodone. Clearance divided by fraction absorbed (CL/f) was calculated using the dose and the area under the 8-h time-plasma oxycodone concentration curve. Peak plasma oxycodone concentrations (C(max)) and time until peak oxycodone concentrations (T(max)) were secondary outcome parameters. Group size was chosen to produce a power of 0.8 to detect a 20% difference in CL/f between study arms. Values for CL/f, C(max), and T(max) were compared between study arms using two-tailed, paired t-tests. No statistically significant difference between groups was demonstrated for any parameter. We failed to demonstrate that single doses of tramadol impaired oxycodone clearance.

  19. [Cost-effective analysis of rotation from sustained-release morphine tablet to transdermal fentanyl of matrix type or sustained-release oxycodone tablet].

    PubMed

    Ise, Yuya; Wako, Tetsuya; Miura, Yoshihiko; Katayama, Shirou; Shimizu, Hisanori

    2009-12-01

    The present study was undertaken to determine the pharmacoeconomics of switching from sustained-release morphine tablet to matrix type (MT) of transdermal fontanel or sustained-release Oxycodone tablet. Cost-effective analysis was performed using a simulation model along with decision analysis. The analysis was done from the payer's perspective. The cost-effective ratio/patient of transdermal MT fontanel (22, 539 yen)was lower than that of sustained -release Oxycodone tablet (23, 630 yen), although a sensitivity analysis could not indicate that this result was reliable. These results suggest the possibility that transdermal MT fontanel was much less expensive than a sustained-release Oxycodone tablet.

  20. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    PubMed

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

  1. Developments in managing severe chronic pain: role of oxycodone-naloxone extended release.

    PubMed

    Fanelli, Guido; Fanelli, Andrea

    2015-01-01

    Chronic pain is a highly disabling condition, which can significantly reduce patients' quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC) occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC.

  2. Efficacy and tolerability of oxycodone versus fentanyl for intravenous patient-controlled analgesia after gastrointestinal laparotomy

    PubMed Central

    Ding, Zhen; Wang, Kaiguo; Wang, Baosheng; Zhou, Naibao; Li, Hao; Yan, Bo

    2016-01-01

    Abstract Background: It has been suggested that oxycodone is effective in relieving acute postoperative pain. The aim of this study was to investigate the efficacy and tolerability of oxycodone (O) versus fentanyl (F), and the adequate potency ratio of oxycodone and fentanyl in patients with intravenous patient-controlled analgesia after gastric laparotomy. Methods: In this double-blinded, randomized, controlled study, 60 patients undergoing elective gastric laparotomy were allocated to receive either oxycodone or fentanyl for postoperative intravenous patient-controlled analgesia (potency ratio 60:1). The patients received ketorolac 60 mg before the end of anesthesia and then continued with patient-controlled analgesia for 48 hours postsurgery. Pain severity, side effects and respiration rate were recorded 30 minutes, 3, 6, 12, 24, and 48 hours after the surgery. Cumulative opioid requirements and patient satisfaction were also measured. Results: The median consumption more than 48 hours after operation of oxycodone was 50 mg (range: 40.0–62.4 mg) and fentanyl was 0.8 mg (range: 0.6–1.1 mg), and the percentage of patients requiring rescue medication was not statistically significant. Numeric rating scores at rest and upon movement were significantly lower in group O than in F (P < 0.05). Whereas the incidences of adverse events were similar between the groups (33.3% vs 27.6%, P = 0.64), a significant higher sedation scores were found in patients given fentanyl at 30 minutes after the surgery (P = 0.04). Conclusion: Oxycodone was comparable to fentanyl in the relief of postoperative pain following gastric laparotomy. Oxycodone not only provides better postoperative pain relief and less sedation, but also there was a tendency toward more side effects with oxycodone. PMID:27684835

  3. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    PubMed

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18-55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant.

  4. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

    PubMed Central

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18–55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. PMID:26316698

  5. [Case of acute exacerbation of neuropathic cancer pain rapidly relieved by simultaneous oral intake of immediate release oxycodone and pregabalin].

    PubMed

    Baba, Mika; Gomwo, Ikuo

    2012-10-01

    Cancer pain consists of continuous pain lasting almost all day and transient exacerbation of pain called breakthrough pain. Breakthrough pain is classified as somatic pain and visceral pain, neuropathic pain according to the character of pain. Although the immediate release opioid is used as the first treatment of choice to breakthrough pain, the effect is not enough when it shows the character of neuropathic pain. Pregabalin has become the first medicine for the treatment of neuropathic pain, and it sometimes reveals prompt analgesic effect based on its pharmacological profile. It has also been reported that pregabalin used with oxycodine reveals analgesic effect with smaller dosage than pregabalin alone. We experienced a young patient with lung cancer suffering from sudden exacerbation of symptomatic sciatica, whose pain was markedly reduced within 30 minutes by taking immediate release oxycodone 5 mg and pregabalin 75 mg simultaneously. Conclusions : Pregabalin with immediate release oxycodone simultaneously may be able to improve acute exacerbation of neuropathic cancer pain rapidly.

  6. Oxycodone with an opioid receptor antagonist: A review.

    PubMed

    Davis, Mellar P; Goforth, Harold W

    2016-01-01

    The rationale for putting opioid antagonists with an agonist is to improve pain control, to reduce side effects, and/or to reduce abuse. The combination of prolonged release (PR) oxycodone and naloxone reduces constipation as demonstrated in multiple studies and has been designated a tamper-resistant opioid by the Food and Drug Administration. Bioequivalence of the combination product compared with PR oxycodone has not been established. Several of the pivotal studies provided suboptimal laxative support in the control arm of the randomized trials. Two noninferiority trials have demonstrated equivalent analgesia between PR oxycodone and the combination product at doses of less than 120 mg of oxycodone per day. There appears to be an analgesic ceiling above 80-120 mg of oxycodone per day. Safety monitoring during randomized trials was not been well described in published manuscripts. Benefits appear to be better for those with chronic noncancer pain compared with individuals with cancer when constipation was the primary outcome.

  7. Oxycodone. Pharmacological profile and clinical data in chronic pain management.

    PubMed

    Coluzzi, F; Mattia, C

    2005-01-01

    Opioids are widely used as effective analgesic therapy for cancer pain. Despite years of controversy, their use has been also accepted in chronic non-cancer pain. Oxycodone alone and in combination has been used for over 80 years in the treatment of a variety of pain syndromes. As single agent, the controlled release (CR) oxycodone's market in the USA grew from 10% in 1996 to 53% in 2000 and it has become a leading opioid in the United States. Recent data showed that the fixed-combination oxycodone/acetaminophen (5 mg/325 mg) is the most often prescribed opioid across all the different chronic pain diagnoses. Compared with morphine, oxycodone has a higher oral bioavailability and is about twice as potent. Pharmacokinetic-pharmacodynamic data support oxycodone as a pharmacologically active opiod that does not require conversion to oxymoprhone for pharmacological activity. Seven studies addressed the safety and efficacy of oxycodone for the treatment of non-cancer pain (low back pain, osteoarthritis pain, and painful diabetic neuropathy). Both immediate release (IR) and CR oxycodone are equally effective and safe. Along these trials, mean daily dosage of oxycodone was approximately 40 mg, with a low incidence of intolerable typical opiate side effects. In cancer pain, oxycodone can be considered a valid alternative to oral morphine to be used for opioid rotation. No difference in analgesic efficacy between CR oxycodone and CR morphine was found. Controlled-release preparations, with a long duration of action, are attractive because they offer the advantage of longer dosing intervals and sustained analgesic effect.

  8. Oxycodone versus fentanyl for intravenous patient-controlled analgesia after laparoscopic supracervical hysterectomy

    PubMed Central

    Kim, Nan Seol; Lee, Jeong Seok; Park, Su Yeon; Ryu, Aeli; Chun, Hea Rim; Chung, Ho Soon; Kang, Kyou Sik; Chung, Jin Hun; Jung, Kyung Taek; Mun, Seong Taek

    2017-01-01

    Abstract Background: Oxycodone, a semisynthetic thebaine derivative opioid, is widely used for the relief of moderate to severe pain. The aim of this study was to compare the efficacy and side effects of oxycodone and fentanyl in the management of postoperative pain by intravenous patient-controlled analgesia (IV-PCA) in patients who underwent laparoscopic supracervical hysterectomy (LSH). Methods: The 127 patients were randomized to postoperative pain treatment with either oxycodone (n = 64, group O) or fentanyl group (n = 63, group F). Patients received 7.5 mg oxycodone or 100 μg fentanyl with 30-mg ketorolac at the end of anesthesia followed by IV-PCA (potency ratio 75:1) for 48 hours postoperatively. A blinded observer assessed postoperative pain based on the numerical rating scale (NRS), infused PCA dose, patient satisfaction, sedation level, and side effects. Results: Accumulated IV-PCA consumption in group O was less (63.5 ± 23.9 mL) than in group F (85.3 ± 2.41 mL) during the first 48 hours postoperatively (P = 0.012). The NRS score of group O was significantly lower than that of group F at 4 and 8 hours postoperatively (P < .001); however, the incidence of postoperative nausea and vomiting (PONV), dizziness, and drowsiness was significantly higher in group O than in group F. Patient satisfaction was lower in group O than in group F during the 48 hours after surgery (P < 0.001). Conclusions: Oxycodone IV-PCA (potency ratio 1:75) provided superior analgesia to fentanyl IV-PCA after LSH; however, the higher incidence of side effects, including PONV, dizziness, and drowsiness, suggests that the doses used in this study were not equipotent. PMID:28272250

  9. Oxycodone: a pharmacological and clinical review.

    PubMed

    Ordóñez Gallego, A; González Barón, M; Espinosa Arranz, E

    2007-05-01

    Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma halflife is 3-5 h (half that of morphine) and stable plasma levels are reached within 24 h (2-7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone--which is also a very potent analgesic--and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3-4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin) is marketed as 10-, 20-, 40- or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm) is also available in capsules and oral solution. Side effects are those common to opioids

  10. Comparison of epidural oxycodone and epidural morphine for post-caesarean section analgesia: A randomised controlled trial

    PubMed Central

    Sng, Ban Leong; Kwok, Sarah Carol; Mathur, Deepak; Ithnin, Farida; Newton-Dunn, Clare; Assam, Pryseley Nkouibert; Sultana, Rehena; Sia, Alex Tiong Heng

    2016-01-01

    Background and Aims: Epidural morphine after caesarean section may cause moderate to severe pruritus in women. Epidural oxycodone has been shown in non-obstetric trials to reduce pruritus when compared to morphine. We hypothesised that epidural oxycodone may reduce pruritus after caesarean section. Methods: A randomised controlled trial was conducted in pregnant women at term who underwent caesarean section with combined spinal-epidural technique initiated with intrathecal fentanyl 15 μg. Women received either epidural morphine 3 mg or epidural oxycodone 3 mg via the epidural catheter after delivery. The primary outcome was the incidence of pruritus at 24 h after caesarean section. The secondary outcomes were the pruritus scores, treatment for post-operative nausea and vomiting (PONV), pain scores and maternal satisfaction. Results: One hundred women were randomised (group oxycodone O = 50, morphine M = 50). There was no difference between Group O and M in the incidence of pruritus (n [%] 28 [56%] vs. 31 [62%], P = 0.68) and the worst pruritus scores (mean [standard deviation] 2.6 (2.8) vs. 3.3 [3.1], P = 0.23), respectively. Both groups had similar pain scores at rest (2.7 [2.3] vs. 2.0 [2.7], P = 0.16) and sitting up (5.0 [2.3] vs. 4.6 [2.4], P = 0.38) at 24 h. Pruritus scores were lower at 4–8, 8–12 and 12–24 h with oxycodone, but pain scores were higher. Both groups had a similar need for treatment of PONV and maternal satisfaction with analgesia. Conclusion: There was no difference in the incidence of pruritus at 24 h between epidural oxycodone and morphine. However, pruritus scores were lower with oxycodone between 4 and 24 h after surgery with higher pain scores in the same period. PMID:27053782

  11. A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery

    PubMed Central

    Hwang, Boo-Young; Kwon, Jae-Young; Lee, Do-Won; Kim, Eunsoo; Kim, Tae-Kyun; Kim, Hae-Kyu

    2015-01-01

    Objectives: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. Methods: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. Results: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46). Conclusion: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required. PMID:26283884

  12. Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome.

    PubMed

    Frampton, James E

    2015-06-01

    An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted.

  13. The Potential Role of an Extended-Release, Abuse-Deterrent Oxycodone/Acetaminophen Fixed-Dose Combination Product for the Treatment of Acute Pain.

    PubMed

    Pergolizzi, Joseph V; Taylor, Robert; Raffa, Robert B

    2015-06-01

    Acute pain, prevalent as part of postoperative and traumatic pain, is often sub-optimally or inadequately treated. Fixed-dose combination analgesic products that combine a reduced amount of opioid with a nonopioid analgesic such as acetaminophen (paracetamol) in a single tablet offer potential pharmacodynamic and/or pharmacokinetic benefits, and may also result in an opioid-sparing effect. A new analgesic product (XARTEMIS™ XR, Mallinckrodt Brand Pharmaceuticals, Dublin, Ireland) combines oxycodone (7.5 mg) with acetaminophen (325 mg) in an immediate-release/extended-release (ER) formulation that is indicated for the treatment of acute pain. The ER formulation of this product provides stable serum drug concentrations that in this case lasts 12 h. Oxycodone/acetaminophen is a drug combination that offers safe and effective pain relief in a variety of acute pain syndromes such as postoperative pain. The combination formulation allows a smaller amount of oxycodone per tablet and the biphasic-layered matrix of the pill for ER may present obstacles to potential abusers. No opioid is totally abuse resistant, but the lower opioid content and tamper-resistant formulation of this product might discourage abuse. Clinicians must still be mindful of the acetaminophen part of this product in the patient's overall daily intake (in light of acetaminophen hepatotoxicity). The new product appears to provide an important new choice in the armamentarium against acute pain.

  14. The Adverse Events of Oxycodone in Cancer-Related Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Ma, Hu; Liu, Yuan; Huang, Lang; Zeng, Xian-Tao; Jin, Su-Han; Yue, Guo-Jun; Tian, Xu; Zhou, Jian-Guo

    2016-04-01

    The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed. We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69-1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72-1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70-1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38-1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81-1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58-1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44-1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07-1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25-0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power. The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted.

  15. Self administration of oxycodone by adolescent and adult mice affects striatal neurotransmitter receptor gene expression.

    PubMed

    Mayer-Blackwell, B; Schlussman, S D; Butelman, E R; Ho, A; Ott, J; Kreek, M J; Zhang, Y

    2014-01-31

    Illicit use of prescription opioid analgesics (e.g., oxycodone) in adolescence is a pressing public health issue. Our goal was to determine whether oxycodone self administration differentially affects striatal neurotransmitter receptor gene expression in the dorsal striatum of adolescent compared to adult C57BL/6J mice. Groups of adolescent mice (4 weeks old, n=12) and of adult mice (11 weeks old, n=11) underwent surgery during which a catheter was implanted into their jugular veins. After recovering from surgery, mice self administered oxycodone (0.25 mg/kg/infusion) 2 h/day for 14 consecutive days or served as yoked saline controls. Mice were sacrificed within 1h after the last self-administration session and the dorsal striatum was isolated for mRNA analysis. Gene expression was analyzed with real time PCR using a commercially available neurotransmitter receptor PCR array containing 84 genes. We found that adolescent mice self administered less oxycodone than adult mice over the 14 days. Monoamine oxidase A (Maoa) and neuropeptide Y receptor 5 mRNA levels were lower in adolescent mice than in adult mice without oxycodone exposure. Oxycodone self administration increased Maoa mRNA levels compared to controls in both age groups. There was a positive correlation of the amount of oxycodone self administered in the last session or across 14 sessions with Maoa mRNA levels. Gastrin-releasing peptide receptor mRNA showed a significant Drug × Age interaction, with point-wise significance. More genes in the dorsal striatum of adolescents (19) changed in response to oxycodone self administration compared to controls than in adult (4) mice. Overall, this study demonstrates that repeated oxycodone self administration alters neurotransmitter receptors gene expression in the dorsal striatum of adolescent and adult mice.

  16. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... HUMAN SERVICES Food and Drug Administration Single-Ingredient, Immediate-Release Drug Products... AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug... such products in interstate commerce. The document was published with an incorrect Web link....

  17. Comparison of oxycodone and sufentanil for patient-controlled intravenous analgesia after laparoscopic radical gastrectomy: A randomized double-blind clinical trial

    PubMed Central

    Wang, Na; Zhou, Honglan; Song, Xuesong; Wang, Jinguo

    2016-01-01

    Background: Sufentanil is widely used for patient-controlled intravenous analgesia (PCIA). Oxycodone has a powerful analgesic effect and mild side effects. We conducted this study to compare the efficacy of oxycodone and sufentanil for PCIA on postoperative pain after laparoscopic radical gastrectomy. Methodology: A total of fifty patients scheduled for laparoscopic radical gastrectomy were equally randomized to receive postoperative pain treatment with either oxycodone (Group O) or sufentanil (Group S) for 48 h postoperatively. PCIA was set on demand mode without loading dose or background infusion. Postoperative cumulative sufentanil or oxycodone consumption, pain intensity, sedation status, and side effects were assessed. Results: No significant differences were detected in visual analog scale score at rest and during coughing in the two groups at various time points after operation. Group S was associated with more doses delivered by PCIA than Group O. The overall satisfaction degree was higher in Group O. The incidences of side effects were comparable between the two groups. Conclusion: Oxycodone is a valuable alternative for PCIA in patients undergoing laparoscopic radical gastrectomy. PMID:27746551

  18. A Comparison of Oxycodone and Alfentanil in Intravenous Patient-Controlled Analgesia with a Time-Scheduled Decremental Infusion after Laparoscopic Cholecystectomy.

    PubMed

    Kwon, Young Suk; Jang, Ji Su; Lee, Na Rea; Kim, Seong Su; Kim, Young Ki; Hwang, Byeong Mun; Kang, Seong Sik; Son, Hee Jeong; Lim, So Young

    2016-01-01

    Background. Oxycodone, a semisynthetic opioid, has been widely used for acute and chronic pain. Objectives. The aim of this study was to compare the analgesic and adverse effects of oxycodone and alfentanil on postoperative pain after laparoscopic cholecystectomy. Methods. This was a prospective, randomized, double-blind study. A total of 82 patients undergoing laparoscopic cholecystectomy were randomly assigned to receive either oxycodone or alfentanil using intravenous patient-controlled analgesia (PCA). PCA was administered as a time-scheduled decremental continuous infusion based on lean body mass for 48 hours postoperatively. Patients were assessed for pain with a visual analogue scale (VAS), the cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Results. There were no significant differences (p < 0.05) between the two groups in VAS score, cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Conclusions. Our data showed that the analgesic and adverse effects of oxycodone and alfentanil were similar. Therefore, oxycodone may be a good alternative to alfentanil for pain management using intravenous PCA after laparoscopic cholecystectomy when used at a conversion ratio of 10 : 1. This trial is registered with KCT0001962.

  19. A Comparison of Oxycodone and Alfentanil in Intravenous Patient-Controlled Analgesia with a Time-Scheduled Decremental Infusion after Laparoscopic Cholecystectomy

    PubMed Central

    Jang, Ji Su; Kim, Seong Su; Kim, Young Ki; Hwang, Byeong Mun; Kang, Seong Sik; Son, Hee Jeong

    2016-01-01

    Background. Oxycodone, a semisynthetic opioid, has been widely used for acute and chronic pain. Objectives. The aim of this study was to compare the analgesic and adverse effects of oxycodone and alfentanil on postoperative pain after laparoscopic cholecystectomy. Methods. This was a prospective, randomized, double-blind study. A total of 82 patients undergoing laparoscopic cholecystectomy were randomly assigned to receive either oxycodone or alfentanil using intravenous patient-controlled analgesia (PCA). PCA was administered as a time-scheduled decremental continuous infusion based on lean body mass for 48 hours postoperatively. Patients were assessed for pain with a visual analogue scale (VAS), the cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Results. There were no significant differences (p < 0.05) between the two groups in VAS score, cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Conclusions. Our data showed that the analgesic and adverse effects of oxycodone and alfentanil were similar. Therefore, oxycodone may be a good alternative to alfentanil for pain management using intravenous PCA after laparoscopic cholecystectomy when used at a conversion ratio of 10 : 1. This trial is registered with KCT0001962. PMID:27725791

  20. A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

    PubMed Central

    Kopecky, Ernest A.; Smith, Michael D.; Fleming, Alison B.

    2016-01-01

    Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal (IN) or an intact oral (PO) preparation—with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID:26814256

  1. Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation†

    PubMed Central

    Sessler, Nelson E; Downing, Jerod M; Kale, Hrishikesh; Chilcoat, Howard D; Baumgartner, Todd F; Coplan, Paul M

    2014-01-01

    Purpose Abuse of opioid analgesics for their psychoactive effects is associated with a large number of fatalities. The effect of making opioid tablets harder to crush/dissolve on opioid-related fatalities has not been assessed. The objective of this study was to assess the impact of introducing extended-release oxycodone (ERO [OxyContin®]) tablets containing physicochemical barriers to crushing/dissolving (reformulated ERO) on deaths reported to the manufacturer. Methods All spontaneous adverse event reports of death in the US reported to the manufacturer between 3Q2009 and 3Q2013 involving ERO were used. The mean numbers of deaths/quarter in the 3 years after reformulated ERO introduction were compared with the year before. Changes in the slope of trends in deaths were assessed using spline regression. Comparison groups consisted of non-fatal reports involving ERO and fatality reports involving ER morphine. Results Reports of death decreased 82% (95% CI: −89, −73) from the year before to the third year after (131 to 23 deaths per year) reformulation; overdose death reports decreased 87% (95% CI: −93, −78) and overdose deaths with mention of abuse-related behavior decreased 86% (95% CI:−92, −75). In contrast, non-fatal ERO reports did not decrease post-reformulation, and reported ER morphine fatalities remained unchanged. The ratio of ERO fatalities to all oxycodone fatalities decreased from 21% to 8% in the year pre-reformulation to the second year post-reformulation. Conclusions These findings, when considered in the context of previously published studies using other surveillance systems, suggest that the abuse-deterrent characteristics of reformulated ERO have decreased the fatalities associated with its misuse/abuse. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24916486

  2. Hydrocodone/oxycodone overdose

    MedlinePlus

    ... Hydrocodone and oxycodone belong to a class of narcotic medicines called opiates. These medicines are man-made ... medicines may also be combined with the non-narcotic medicine, acetaminophen (Tylenol). Symptoms When you take the ...

  3. The place of oxycodone/naloxone in chronic pain management

    PubMed Central

    2013-01-01

    Opioid analgesics are usually effective in the management of severe chronic pain. However, symptoms of opioid-induced bowel dysfunction (OIBD) are common during opioid therapy. Opioid-induced bowel dysfunction is often unsuccessfully managed due to limited effectiveness and numerous adverse effects of traditional laxatives. Newer treatment possibilities directed at the pathomechanism of OIBD comprise combined prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone) tablets. Oxycodone/naloxone provides effective analgesia with limited impact on bowel function as oxycodone displays high oral bioavailability and naloxone act as local antagonist on opioid receptors in the gastrointestinal tract due to nearly complete inactivation in the liver. Oxycodone/naloxone is administered to opioid-naive patients with severe pain and those unsuccessfully treated with weak opioids. Oxycodone/naloxone may be also administered to patients treated with strong opioids who experience intense symptoms of OIBD. Studies conducted to date indicate that oxycodone/naloxone is an important drug in chronic pain management, prevention and treatment of OIBD. PMID:23788978

  4. Controlled-release microchips.

    PubMed

    Sharma, Sadhana; Nijdam, A Jasper; Sinha, Piyush M; Walczak, Robbie J; Liu, Xuewu; Cheng, Mark M-C; Ferrari, Mauro

    2006-05-01

    Efficient drug delivery remains an important challenge in medicine: continuous release of therapeutic agents over extended time periods in accordance with a predetermined temporal profile; local delivery at a constant rate to the tumour microenvironment to overcome much of the systemic toxicity and to improve antitumour efficacy; improved ease of administration, and increasing patient compliance required are some of the unmet needs of the present drug delivery technology. Microfabrication technology has enabled the development of novel controlled-release microchips with capabilities not present in the current treatment modalities. In this review, the current status and future prospects of different types of controlled-release microchips are summarised and analysed with reference to microneedle-based microchips, as well as providing an in-depth focus on microreservoir-based and nanoporous microchips.

  5. Behavioral flexibility and response selection are impaired after limited exposure to oxycodone

    PubMed Central

    Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on rats in two complementary learning and memory tasks that engage distinct learning strategies and neural circuits. Rats were trained first in either a spatial or a body-turn discrimination on a radial maze. After initial training, rats were given oxycodone or vehicle injections in their home cages for 5 d. Reversal learning was tested 36 h after the final drug exposure. We hypothesized that if oxycodone impaired behavioral flexibility, then drug-exposed rats should learn reversals more slowly than controls. Oxycodone exposure impaired spatial reversal learning when reward contingencies changed rapidly, but not when they changed slowly. During rapid reversals, oxycodone-exposed rats required more trials to reach criterion, made more perseverative errors, and were more likely to make errors after correct responses than controls. Oxycodone impaired body-turn reversal learning in similar patterns. Limited exposure to oxycodone reduced behavioral flexibility when rats were tested in a drug-free state, suggesting that impaired decision-making is an enduring consequence of oxycodone exposure. PMID:25403457

  6. Behavioral flexibility and response selection are impaired after limited exposure to oxycodone.

    PubMed

    Seip-Cammack, Katharine M; Shapiro, Matthew L

    2014-12-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on rats in two complementary learning and memory tasks that engage distinct learning strategies and neural circuits. Rats were trained first in either a spatial or a body-turn discrimination on a radial maze. After initial training, rats were given oxycodone or vehicle injections in their home cages for 5 d. Reversal learning was tested 36 h after the final drug exposure. We hypothesized that if oxycodone impaired behavioral flexibility, then drug-exposed rats should learn reversals more slowly than controls. Oxycodone exposure impaired spatial reversal learning when reward contingencies changed rapidly, but not when they changed slowly. During rapid reversals, oxycodone-exposed rats required more trials to reach criterion, made more perseverative errors, and were more likely to make errors after correct responses than controls. Oxycodone impaired body-turn reversal learning in similar patterns. Limited exposure to oxycodone reduced behavioral flexibility when rats were tested in a drug-free state, suggesting that impaired decision-making is an enduring consequence of oxycodone exposure.

  7. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    PubMed Central

    Devarakonda, Krishna; Morton, Terri; Margulis, Rachel; Giuliani, Michael; Barrett, Thomas

    2014-01-01

    Background XARTEMIS™ XR (formerly MNK-795) is a combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (ER OC/APAP). The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK) of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets) versus fasted conditions on the PK of ER OC/APAP was performed. Methods This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48) were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC]) from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion The findings from this study suggest that ER OC/APAP can be administered with or without food. PMID:25170252

  8. Controlled Release Applications of Organometals.

    ERIC Educational Resources Information Center

    Thayer, John S.

    1981-01-01

    Reviews two classes of controlled release organometals: (1) distributional, to distribute bioactive materials to control a certain target organism; and (2) protective, to protect surface or interior of some structure from attach by organisms. Specific examples are given including a discussion of controlled release for schistosomiasis. (SK)

  9. The Adverse Events of Oxycodone in Cancer-Related Pain

    PubMed Central

    Ma, Hu; Liu, Yuan; Huang, Lang; Zeng, Xian-Tao; Jin, Su-Han; Yue, Guo-Jun; Tian, Xu; Zhou, Jian-Guo

    2016-01-01

    Abstract The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed. We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69–1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72–1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70–1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38–1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81–1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58–1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44–1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07–1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25–0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power. The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted. PMID:27082588

  10. Postoperative oxycodone toxicity in a patient with chronic pain and end-stage renal disease.

    PubMed

    Tran, Bryant W; Kohan, Lynn R; Vorenkamp, Kevin E

    2015-02-15

    We present this case to review the metabolism of oxycodone and the effects of end-stage renal disease on the elimination of oxycodone and its metabolites. A 42-year-old female with end-stage renal disease who was dependent on hemodialysis presented for left hamstring posterior capsule release. She had been receiving methadone for 2 years for chronic leg pain. On postoperative day 1, the patient's medication was changed from IV hydromorphone to oral oxycodone to treat breakthrough pain. By the next day, the patient was unarousable with notable respiratory depression. She did not fully recover after urgent hemodialysis but did have full recovery after receiving an IV naloxone infusion for 22 hours. Further study of the safety of oxycodone in hemodialysis patients is warranted.

  11. Optogenetic control of ATP release

    NASA Astrophysics Data System (ADS)

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

    2013-03-01

    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  12. Birth control - slow release methods

    MedlinePlus

    Contraception - slow-release hormonal methods; Progestin implants; Progestin injections; Skin patch; Vaginal ring ... implants while breastfeeding. Progestin implants work better than birth control pills to prevent pregnancy. Very few women who ...

  13. Opioid rotation in patients initiated on oxycodone or morphine: a register study

    PubMed Central

    Ericson, Lisa; Ambring, Anneli; Björholt, Ingela; Dahm, Peter

    2013-01-01

    Purpose Strong opioids are recommended for the treatment of moderate to severe pain. However, some patients do not achieve a successful treatment outcome due to intolerable adverse events and/or inadequate analgesia, thus may benefit from switching to another opioid, a procedure known as “opioid rotation.” The type of opioid at treatment initiation may influence the risk of opioid rotation and the objective of this study was to assess such rotation after treatment initiation with two alternative treatments, controlled-release (CR) oxycodone versus CR morphine in patients suffering from non-cancer pain. Method The study reported here was a real-life study based on Swedish register data: the Prescribed Drug, National Patient, and Cause of Death registers. The captured data cover the entire Swedish population treated in specialist care. A statistical analysis plan was agreed and signed before data were accessed. Results Data from 50,223 cases were included in the analyses. The risk of rotation was 19% higher in patients initiating treatment with morphine compared with oxycodone (hazard ratio 1.19; 95% confidence interval 1.11–1.27; P < 0.001), after adjusting for such baseline variables that were both significantly correlated with the outcome variable (time to rotation) and significantly different between the groups; age at index date, osteoarthritis and number of pain-related drugs. Conclusion Patients with non-cancer pain who initiated treatment with CR morphine had a higher risk of opioid rotation than patients initiated with CR oxycodone. PMID:23717049

  14. Controlled Release from Recombinant Polymers

    PubMed Central

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

  15. Controlled release from recombinant polymers.

    PubMed

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-09-28

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

  16. Evaluation of the usefulness of an oxycodone immunoassay in combination with a traditional opiate immunoassay for the screening of opiates in urine.

    PubMed

    Gingras, Marie; Laberge, Marie-Hélène; Lefebvre, Michel

    2010-03-01

    Oxycodone is a semisynthetic opioid analgesic largely prescribed for post-operative and chronic pain management. The introduction of a slow release formulation of oxycodone has led to its frequent abuse and to an increase in emergency cases related to oxycodone overdose. Until recently, oxycodone testing has been confined to gas chromatography-mass spectrometry (GC-MS) analysis because the widely used automated opiate immunoassays poorly react to this compound. We investigated the utility of a new oxycodone immunoassay as a screening procedure to eliminate inappropriate GC-MS testing of negative urine specimens. We analyzed 96 urine specimens using GC-MS and two immunoassays, CEDIA((R)) opiates and DRI((R)) oxycodone assays from Microgenics, on a Hitachi 917 analyzer. The GC-MS allowed us to detect codeine, hydrocodone, hydromorphone, morphine, oxycodone, and oxymorphone following enzymatic hydrolysis and derivation by acetylation. The combination of the two immunoassays gave the best performance (98% sensitivity and specificity) when considering a positive result from GC-MS for any of the opiates. Considering positive GC-MS results for oxycodone or oxymorphone only, the oxycodone immunoassay resulted in two false-positives and one false-negative (50 ng/mL cutoff). Using these immunoassays for screening before GC-MS analysis provides a reduced opiate GC-MS workload without compromising quality.

  17. Controlled release liquid dosage formulation

    DOEpatents

    Benton, Ben F.; Gardner, David L.

    1989-01-01

    A liquid dual coated dosage formulation sustained release pharmaceutic having substantial shelf life prior to ingestion is disclosed. A dual coating is applied over controlled release cores to form dosage forms and the coatings comprise fats melting at less than approximately 101.degree. F. overcoated with cellulose acetate phthalate or zein. The dual coated dosage forms are dispersed in a sugar based acidic liquid carrier such as high fructose corn syrup and display a shelf life of up to approximately at least 45 days while still retaining their release profiles following ingestion. Cellulose acetate phthalate coated dosage form cores can in addition be dispersed in aqueous liquids of pH <5.

  18. Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model

    PubMed Central

    Takasu, Keiko; Ogawa, Koichi; Nakamura, Atsushi; Kanbara, Tomoe; Ono, Hiroko; Tomii, Takako; Morioka, Yasuhide; Hasegawa, Minoru; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku

    2015-01-01

    Background and Purpose We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain. Experimental Approach We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model. Key Results The supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein-gated inwardly rectifying potassium1 (Kir3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input–output relationship curve of evoked IPSCs, the increased paired-pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of presynaptic GABA release by oxycodone, but not morphine was enhanced and dependent on Kir3.1 channels. Conclusion and Implications Our results demonstrate that Kir3.1 channels are important for supraspinal antinociception and presynaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via Kir3.1 channel activation. PMID:25521524

  19. CYP2D6 Genotype Dependent Oxycodone Metabolism in Postoperative Patients

    PubMed Central

    Stamer, Ulrike M.; Zhang, Lan; Book, Malte; Lehmann, Lutz E.; Stuber, Frank; Musshoff, Frank

    2013-01-01

    Background The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. Methods Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. Results Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12th hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes. Conclusions In this postoperative setting, the number of

  20. Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications.

    PubMed

    Söderberg Löfdal, Karin C; Andersson, Marine L; Gustafsson, Lars L

    2013-05-01

    In recent years the use of the opioid oxycodone has increased markedly and replacing morphine as the first-line choice of opioid in several countries. There are formulations for oral immediate, oral extended release and intravenous use. The bioavailability is higher than for morphine and less variable. Oxycodone is primarily metabolized in the liver by the cytochrome P450 (CYP) enzymes with CYP3A as the major metabolic pathway and CYP2D6 as the minor metabolic pathway to noroxycodone, oxymorphone and noroxymorphone. Oxycodone exerts its analgesic effect via the µ-opioid receptor. The metabolism of CYP2D6 substrates varies to a large degree between individuals as a result of allele functionality. Poor metabolizers (PM) have two non-functional alleles, extensive metabolizers (EM) are homozygous with two functional alleles or heterozygous with one functional allele and ultrarapid metabolizers (UM) have more than two functional alleles. There are pronounced interethnic differences in the allele distribution. On the basis of studies performed thus far, oxycodone concentrations in comparison with EM are similar in PM and reduced in UM. The pharmacokinetics in UM are insufficiently investigated. Simultaneous inhibition of both CYP3A and CYP2D6 results in increased oxycodone concentrations and such a combination should be avoided. A similar effect is to be expected with use of a CYP3A inhibitor in CYP2D6 PM. Concomitant use of enzyme inducers such as rifampicin, St John's wort and carbamazepine should be avoided because of the risk of subtherapeutic concentrations of oxycodone. When the dosage of morphine may result in unpredictable bioavailability, like in patients with severe hepatic cirrhosis, oxycodone might be beneficial because it has higher and less variability in bioavailability between patients than morphine.

  1. OXYCODONE COMBINATIONS FOR PAIN RELIEF

    PubMed Central

    Raffa, R.B.; Pergolizzi, J.V.; Segarnick, D.J.; Tallarida, R.J.

    2014-01-01

    SUMMARY No single analgesic drug provides the perfect therapeutic/adverse effect profile for every pain condition. In addition to convenience and possibly improved compliance, a combination of analgesic drugs offers the potential, requiring verification, of providing greater pain relief and/or reduced adverse effects than the constituent drugs when used individually. We review here analgesic combinations containing oxycodone. We found surprisingly little preclinical information about the analgesic or adverse effect profiles of the combinations (with acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, morphine, gabapentin or pregabalin). Clinical experience and studies suggest that the combinations are safe and effective and may offer certain advantages. As with all combinations, the profile of adverse effects must also be determined in order to provide the clinician with the overall benefit/risk assessment. PMID:20571607

  2. The genetic influences on oxycodone response characteristics in human experimental pain.

    PubMed

    Olesen, Anne E; Sato, Hiroe; Nielsen, Lecia M; Staahl, Camilla; Droney, Joanne; Gretton, Sophy; Branford, Ruth; Drewes, Asbjørn M; Arendt-Nielsen, Lars; Riley, Julia; Ross, Joy

    2015-08-01

    Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.

  3. Intranasal oxycodone self-administration in non-dependent opioid abusers.

    PubMed

    Middleton, Lisa S; Lofwall, Michelle R; Nuzzo, Paul A; Siegel, Anthony J; Walsh, Sharon L

    2012-08-01

    Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n = 8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double-blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was tested in a separate 3-day block of sessions. The first day of each block was a sample session in which the test dose was given. Two randomized progressive ratio sessions were conducted on the next 2 days: (1) subjects could work for the test dose over 7 trials (1/7th of total dose/trial), and (2) subjects could work for either a portion of the dose (1/7th) or money ($3) over 7 trials. Physiological and subjective measures were collected before and after drug administration for all sessions. Subjects never worked to self-administer placebo regardless of whether money was available. In both self-administration sessions, oxycodone self-administration was dose-dependent. Subjects worked less for drug (28 mg oxycodone) when money was available but only modestly so. Oxycodone dose-dependently increased VAS ratings of positive drug effects (e.g., "like") during sample sessions (p < .05). These reports were positively correlated with self-administration behavior (e.g., "like," r = .65). These data suggest that both procedures are sensitive for detecting the reinforcing properties of intranasal oxycodone and may be used to further explore the characteristics of opioid compounds and potential pharmacotherapies for treatment.

  4. Modelling and simulations of controlled release fertilizer

    NASA Astrophysics Data System (ADS)

    Irfan, Sayed Ameenuddin; Razali, Radzuan; Shaari, Ku Zilati Ku; Mansor, Nurlidia

    2016-11-01

    The recent advancement in controlled release fertilizer has provided an alternative solution to the conventional urea, controlled release fertilizer has a good plant nutrient uptake they are environment friendly. To have an optimum plant intake of nutrients from controlled release fertilizer it is very essential to understand the release characteristics. A mathematical model is developed to predict the release characteristics from polymer coated granule. Numerical simulations are performed by varying the parameters radius of granule, soil water content and soil porosity to study their effect on fertilizer release. Understanding these parameters helps in the better design and improve the efficiency of controlled release fertilizer.

  5. Oxycodone

    MedlinePlus

    ... treat people who are tolerant (used to the effects of the medication) to opioid medications because they ... may decrease your dose if you experience side effects. Talk to your doctor about how you are ...

  6. Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice.

    PubMed

    Zhang, Y; Brownstein, A J; Buonora, M; Niikura, K; Ho, A; Correa da Rosa, J; Kreek, M J; Ott, J

    2015-01-29

    Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. Hippocampus was isolated for mRNA analysis from mice that had self administered oxycodone (0.25 mg/kg/infusion) 2h/day for 14 consecutive days or from yoked saline controls. Gene expression was analyzed with real-time polymerase chain reaction (PCR) using a commercially available "synaptic plasticity" PCR array containing 84 genes. We found that adolescent and adult control mice significantly differed in the expression of several genes in the absence of oxycodone exposure, including those coding for mitogen-activated protein kinase, calcium/calmodulin-dependent protein kinase II gamma subunit, glutamate receptor, ionotropic AMPA2 and metabotropic 5. Chronic oxycodone self administration increased proviral integration site 1 (Pim1) and thymoma viral proto-oncogene 1 mRNA levels compared to controls in both age groups. Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age × Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus

  7. Distribution of Oxycodone in Postmortem Fluids and Tissues

    DTIC Science & Technology

    2010-06-01

    Distribution of Oxycodone in Postmortem Fluids and Tissues Sabra R. Botch Robert D. Johnson Arvind K. Chaturvedi Russell J. Lewis Civil Aerospace...Title and Subtitle 5. Report Date June 2010 6. Performing Organization Code Distribution of Oxycodone in Postmortem Fluids and Tissues 7...16. Abstract Introduction: Oxycodone is a heavily used and abused analgesic agent. Its pharmacological effects, including euphoria, respiratory

  8. Subjective, Psychomotor, and Physiological Effects of Pregabalin Alone and in Combination With Oxycodone in Healthy Volunteers

    PubMed Central

    Zacny, James P.; Paice, Judith A.; Coalson, Dennis W.

    2011-01-01

    Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substance Act. The subjective effects of this drug have not been well-characterized, and the extent to which it alters the subjective effects of opioids has not been studied to the best of our knowledge. Using a double-blind, randomized, crossover design, 16 healthy volunteers were administered (in separate sessions) capsules containing placebo, 75 mg pregabalin, 150 mg pregabalin, 10 mg oxycodone, and 75 mg pregabalin combined with 10 mg oxycodone. Subjective, psychomotor, and physiological measures were assessed during each of the five sessions. Pregabalin produced dose-related increases in some subjective effects and decreased respiration rate, but did not impact on psychomotor performance. Abuse liability-related subjective effects such as drug liking and desire to take the drug again were not increased by either pregabalin dose. Oxycodone produced increases in several subjective effects, including ratings of drug liking. When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers. PMID:22085697

  9. Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers.

    PubMed

    Zacny, James P; Paice, Judith A; Coalson, Dennis W

    2012-01-01

    Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substances Act. The subjective effects of this drug have not been well-characterized, and the extent to which it alters the subjective effects of opioids has not been studied to the best of our knowledge. Using a double-blind, randomized, crossover design, 16 healthy volunteers were administered (in separate sessions) capsules containing placebo, 75 mg pregabalin, 150 mg pregabalin, 10 mg oxycodone, and 75 mg pregabalin combined with 10 mg oxycodone. Subjective, psychomotor, and physiological measures were assessed during each of the five sessions. Pregabalin produced dose-related increases in some subjective effects and decreased respiration rate, but did not impact on psychomotor performance. Abuse liability-related subjective effects such as drug liking and desire to take the drug again were not increased by either pregabalin dose. Oxycodone produced increases in several subjective effects, including ratings of drug liking. When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers.

  10. Intravenous oxycodone for pain relief in the first stage of labour--maternal pharmacokinetics and neonatal exposure.

    PubMed

    Kokki, Merja; Franco, Maria Gonzalez; Raatikainen, Kaisa; Välitalo, Pyry; Sankilampi, Ulla; Heinonen, Seppo; Neuvonen, Pertti J; Kokki, Hannu

    2012-09-01

    Physiological changes during pregnancy may change pharmacokinetics of compounds. Oxycodone is an increasingly used opioid agonist in acute pain management but its pharmacokinetics in labouring women has not been established. We studied the maternal pharmacokinetics and neonatal exposure of intravenous oxycodone for pain relief in the first stage of labour. The study was prospective, open-labelled and with a control group. After informed consent, 15 nulliparous parturients and newborns, and newborns in a control group were studied. In the study group, oxycodone boluses of 1 mg i.v., up to a cumulative dose of 5 mg, was administered when labour pain score was 5/10 or higher. As the control group, 30 other newborns after uncomplicated deliveries with no systemic opioids were assessed for the neonatal outcome. In the study group, maternal pharmacokinetics of oxycodone was measured from plasma concentrations during labour, and neonatal exposure was assessed from umbilical plasma samples using population pharmacokinetic methods. Maternal plasma oxycodone concentration decreased with a median half-life of 2.6 hr (range, 1.8-2.8). Oxycodone concentrations in the umbilical plasma 2.7 μg/l (0.3-14.5) were similar as in maternal plasma 2.4 (0.1-14.8) μg/l at the time of birth. No severe or unexpected adverse effects were noted. To conclude, firstly, maternal elimination half-life of i.v. oxycodone was significantly shorter than that reported in non-pregnant women, and secondly, maternal plasma oxycodone at the birth correlated well with neonatal umbilical concentrations and may, thus, be used as an estimate of neonatal exposure.

  11. Inhibition of cytochrome P450 3A by clarithromycin uniformly affects the pharmacokinetics and pharmacodynamics of oxycodone in young and elderly volunteers.

    PubMed

    Liukas, Antti; Hagelberg, Nora M; Kuusniemi, Kristiina; Neuvonen, Pertti J; Olkkola, Klaus T

    2011-06-01

    The aim of this study was to investigate the effect of the cytochrome P450 3A4 inhibitor clarithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone in young and elderly subjects. Ten young and 10 elderly healthy subjects participated in this placebo-controlled, randomized, 2-phase crossover study. Subjects took clarithromycin 500 mg or placebo twice daily for 5 days. On day 4, subjects ingested an oral dose of 10 mg oxycodone. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 hours, and pharmacological response for 12 hours. Clarithromycin decreased the apparent clearance of oxycodone by 53% in young and 48% in elderly subjects (P < 0.001) and prolonged its elimination half-life. The mean area under the plasma concentration-time curve (AUC0-∞) of oxycodone was increased by 2.0-fold (range, 1.3-fold to 2.7-fold) (P < 0.001) in young and 2.3-fold (range, 1.1-fold to 3.8-fold) (P < 0.001) in elderly subjects. The formation of noroxycodone was decreased by 74% in young and 71% in elderly subjects (P < 0.001). The ratio of AUC0-∞ of oxycodone during the clarithromycin phase compared with the one with placebo did not differ between the age groups. Clarithromycin did not alter the pharmacological response to oxycodone. Clarithromycin increased the exposure to oral oxycodone, but the magnitude of this effect was not age related. Although the pharmacological response to oxycodone was not significantly influenced by clarithromycin, dose reductions may be necessary in the most sensitive patients to avoid adverse effects when oxycodone is used concomitantly with clarithromycin.

  12. Optimal dose of intravenous oxycodone for attenuating hemodynamic changes after endotracheal intubation in healthy patients

    PubMed Central

    Park, Yong-Hee; Lee, Seung-Hyuk; Lee, Oh Haeng; Kang, Hyun; Shin, Hwa-Yong; Baek, Chong-Wha; Jung, Yong Hun; Woo, Young Cheol

    2017-01-01

    Abstract Background: Intravenous oxycodone has been used as an adjunct to anesthetic agents. This study aimed to assess the optimal dose of intravenous oxycodone for the attenuation of the hemodynamic responses to laryngoscopy and endotracheal intubation. Methods: A prospective, randomized, double-blind study was conducted. Ninety-five patients were randomly divided into 5 groups based on the oxycodone dose: 0, 0.05, 0.1, 0.15, 0.2 mg/kg. After administering the assigned dose of intravenous oxycodone, anesthesia was induced with thiopental. Heart rate (HR) and blood pressure (BP) were measured at baseline, before intubation, and 1, 2, and 3 minutes after intubation. The percentage increase of BP was calculated as (highest BP after intubation − baseline BP)/baseline BP × 100 (%). The percentage increase of HR was calculated in same formula as above. Hypertension was defined as a 15% increase of systolic BP from baseline, and probit analysis was conducted. Results: Hemodynamic data from 86 patients were analyzed. The percentage increase of mean arterial pressure after intubation in groups 0.05, 0.1, 0.15, and 0.2 was significantly different from that in the control (P < 0.001). For HR, the percentage increase was lower than control group when oxycodone was same or more than 0.1 mg/kg (P < 0.05). Using probit analysis, the 95% effective dose (ED95) for preventing hypertension was 0.159 mg/kg (95% confidence interval [CI], 0.122–0.243). In addition, ED50 was 0.020 mg/kg (95% CI, −0.037 to 0.049). However, oxycodone was not effective for maintaining the HR in our study dosage. There were no significant differences in the incidence of hypotension during induction between groups. Conclusions: Using 0.1 mg/kg of intravenous oxycodone is sufficient to attenuate the increase of BP and HR during induction period in healthy patients. The ED95, which was 0.159 mg/kg, can be useful to adjust the dosage of IV oxycodone for maintain stable BP

  13. Opioid withdrawal presenting only nausea during tapering of oxycodone after celiac plexus block: a case report.

    PubMed

    Sakamoto, Akiyuki; Takayama, Hiroto; Mamiya, Keiko; Koizumi, Tomonobu

    2016-01-01

    Celiac plexus block (CPB) is an effective treatment for patients suffering pain. CPB may allow for a reduction in opioid dosage, and may alleviate some of the unwanted side effects of these drugs. However, there is a substantial risk of withdrawal symptoms after reduction of opioid dose. We describe a case of pancreatic cancer developing opioid withdrawal after CPB, who presented only nausea. A 70-year-old man was referred to our hospital due to severe pancreatic cancer pain. He was administered oxycodone (oxycontin®) at 240 mg per day, and presented nausea and anorexia as side effects. CPB was performed due to insufficient pain relief. His pain disappeared on the same day as treatment. Oxycodone was reduced to 160 mg/day, and further reduced two days later to 80 mg/day. However, he complained of more severe nausea and loss of appetite even after tapering of oxycodone. Physical examination, blood chemistry examination, and brain computed tomography (CT) showed no abnormalities. Administration of fast-release oxycodone (Oxinome®) at a dose of 10 mg immediately improved his nausea. There have been no previous reports of nausea as the sole symptom of opioid withdrawal. The present case indicates that unless opioid side effects improve after dosage reduction, the possibility that they may be withdrawal symptoms should also be considered.

  14. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  15. Synapsins Differentially Control Dopamine and Serotonin Release

    PubMed Central

    Kile, Brian M.; Guillot, Thomas S.; Venton, B. Jill; Wetsel, William C.; Augustine, George J.; Wightman, R. Mark

    2010-01-01

    Synapsins are a family of synaptic vesicle proteins that are important for neurotransmitter release. Here we have used triple knockout (TKO) mice lacking all three synapsin genes to determine the roles of synapsins in the release of two monoamine neurotransmitters, dopamine and serotonin. Serotonin release evoked by electrical stimulation was identical in substantia nigra pars reticulata slices prepared from TKO and wild-type mice. In contrast, release of dopamine in response to electrical stimulation was approximately doubled in striatum of TKO mice, both in vivo and in striatal slices, in comparison to wild-type controls. This was due to loss of synapsin III, because deletion of synapsin III alone was sufficient to increase dopamine release. Deletion of synapsins also increased the sensitivity of dopamine release to extracellular calcium ions. Although cocaine did not affect the release of serotonin from nigral tissue, this drug did enhance dopamine release. Cocaine-induced facilitation of dopamine release was a function of external calcium, an effect that was reduced in TKO mice. We conclude that synapsins play different roles in the control of release of dopamine and serotonin, with release of dopamine being negatively regulated by synapsins, specifically synapsin III, while serotonin release appears to be relatively independent of synapsins. These results provide further support for the concept that synapsin function in presynaptic terminals varies according to the neurotransmitter being released. PMID:20660258

  16. Comparison of relative oxycodone consumption in surgical pleth index-guided analgesia versus conventional analgesia during sevoflurane anesthesia

    PubMed Central

    Won, Young Ju; Lim, Byung Gun; Lee, So Hyun; Park, Sangwoo; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon

    2016-01-01

    Abstract Background: The surgical pleth index (SPI) is proposed for titration of analgesic drugs during general anesthesia. Several reports have investigated the effect of SPI on the consumption of opioids including remifentanil, fentanyl, and sufentanil during anesthesia, but there are no reports about oxycodone. We aimed to investigate intravenous oxycodone consumption between SPI-guided analgesia and conventional analgesia practices during sevoflurane anesthesia in patients undergoing thyroidectomy. Methods: Forty-five patients undergoing elective thyroidectomy were randomly assigned to an SPI group (SPI-guided analgesia group, n = 23) or a control group (conventional analgesia group, n = 22). Anesthesia was maintained with sevoflurane to achieve bispectral index values between 40 and 60. In the SPI group, oxycodone 1 mg was administered intravenously at SPI values over 50; in the control group, oxycodone 1 mg was administered intravenously at the occurrence of tachycardia or hypertension event. Intraoperative oxycodone consumption and extubation time were recorded. The number of hemodynamic and somatic movement events was recorded, as were postoperative pain and recovery scores. Results: Patients’ characteristics were comparable between the groups. Intraoperative oxycodone consumption in the SPI group was significantly lower than the control group (3.5 ± 2.4 vs 5.1 ± 2.4 mg; P = 0.012). Extubation time was significantly shorter in the SPI group (10.6 ± 3.5 vs 13.4 ± 4.6 min; P = 0.026). Hemodynamic and somatic movement events during anesthesia were comparable between the groups, as were numeric rating scales for pain and modified Aldrete scores at postanesthesia care unit. Conclusions: SPI-guided analgesia reduces intravenous oxycodone consumption and extubation time compared with conventional analgesia based on clinical parameters during sevoflurane anesthesia in patients undergoing thyroidectomy. PMID:27583920

  17. An update on oxycodone: lessons for death investigators in Australia.

    PubMed

    Pilgrim, Jennifer L; Yafistham, Sabrina Putrianita; Gaya, Sanjeev; Saar, Eva; Drummer, Olaf H

    2015-03-01

    Oxycodone is one of the most abused prescription drugs. Iatrogenic factors that lead to oxycodone-related death, such as mis-prescribing, present an opportunity for death prevention if identified early. This study investigated deaths involving oxycodone in Australia to explore potentially inappropriate prescribing and the coroner's investigation. The National Coronial Information System identified cases from 2001 to 2011 where oxycodone was detected by toxicological analysis. There were 806 oxycodone-related deaths, with a significant increase in the 11-year period, from 21 deaths in 2001, up almost sevenfold in 2011 (139 deaths). Most deaths were caused by combined drug toxicity (63.4%) or oxycodone toxicity alone (11.8%). Most individuals were male (59.1%), aged 35-44 years (26.7%), who died unintentionally (56.4%), with mental illness (52.1%) and/or a history of acute or chronic pain (46.2%). 312 cases (39%) described a legitimate prescription for oxycodone, of which most involved non-cancer related chronic pain. About three quarters of the indications were deemed appropriate. There were at least 43 different indications treated with oxycodone that were inappropriate. The majority of oxycodone-related cases involved minor to no description of the drugs involved (n = 600; 74.4%). A moderate description of oxycodone involvement was given in 162 cases (20.1%), while only 44 cases (5.5%) involved a thorough examination and recommendations from the coroners on oxycodone and other drugs involved in death. This study emphasized the need for medical practitioners to exercise caution when prescribing oxycodone and for coroners to provide more consistent and detailed information regarding drug use, in order to identify and implement preventive strategies.

  18. Decreased responsiveness to oxycodone: A case of a pharmacokinetic drug interaction?

    PubMed

    Pon, Doreen; Hwang, Joon; Lo, Teresa; Zyl, Carin Van

    2015-01-01

    Concurrent administration of oxycodone and phenytoin may cause, through induction of CYP3A4 enzymes, decreased analgesic effects of oxycodone. However, no descriptions of this interaction exist. A patient who was on oxycodone for chronic back pain was admitted to the hospital. Five days after initiating fosphenytoin, the patient experienced a dramatic escalation in his pain and lack of response to oxycodone breakthrough doses. Changing oxycodone to hydromorphone resulted in significantly improved analgesia. Concurrent use of fosphenytoin and oxycodone may increase the conversion of oxycodone to inactive metabolites, resulting in decreased analgesia. This may be avoided using hydromorphone, morphine, or oxymorphone.

  19. Controlling protein release using biodegradable microparticles

    NASA Astrophysics Data System (ADS)

    Kline, Benjamin Patrick

    Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

  20. Controlled drug release from bifunctionalized mesoporous silica

    SciTech Connect

    Xu Wujun; Gao Qiang; Xu Yao Wu Dong; Sun Yuhan; Shen Wanling; Deng Feng

    2008-10-15

    Serial of trimethylsilyl-carboxyl bifunctionalized SBA-15 (TMS/COOH/SBA-15) have been studied as carriers for controlled release of drug famotidine (Famo). To load Famo with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized by one-pot synthesis under the assistance of KCl. The mesostructure of carboxyl functionalized SBA-15 (COOH/SBA-15) could still be kept even though the content of carboxyl groups was up to 57.2%. Increasing carboxyl content could effectively enhance the loading capacity of Famo. Compared with pure SBA-15, into which Famo could be hardly adsorbed, the largest drug loading capacity of COOH/SBA-15 could achieve 396.9 mg/g. The release of Famo from mesoporous silica was studied in simulated intestine fluid (SIF, pH=7.4). For COOH/SBA-15, the release rate of Famo decreased with narrowing pore size. After grafting TMS groups on the surface of COOH/SBA-15 with hexamethyldisilazane, the release of Famo was greatly delayed with the increasing content of TMS groups. - Graphical abstract: Trimethylsilyl-carboxyl bifunctionalized SBA-15 has been studied as carrier for controlled release of drug famotidine. To load drug with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized. After grafting trimethylsilyl groups on the surface of carboxyl functionalized SBA-15, the release of Famo was greatly delayed with the increasing content of TMS groups.

  1. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

    PubMed

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2013-09-01

    This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

  2. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts

    PubMed Central

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2014-01-01

    This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  3. Oxycodone/paracetamol: a low-dose synergic combination useful in different types of pain.

    PubMed

    Gatti, Antonio; Sabato, Elisabetta; Di Paolo, Anna Rita; Mammucari, Massimo; Sabato, Alessandro Fabrizio

    2010-01-01

    The combination of two analgesic agents offers several advantages in the treatment of chronic pain. Paracetamol (acetaminophen) has central analgesic activity without a nonsteroidal anti-inflammatory drug (NSAID)-like or opioid-like effect. Oxycodone is a semisynthetic opioid agonist. The oral fixed-dose combination of oxycodone and paracetamol immediate-release formulation has a synergistic mechanism of action that is useful for moderate-to-severe pain and for nonresponders to NSAIDs or paracetamol alone. This fixed-dose combination offers several advantages: lower individual drug doses can be used because of their synergistic mechanisms of action, its opioid-sparing effect and it has a good efficacy and tolerability profile. Efficacy and safety of this fixed-dose combination were assessed in a wide range of clinical settings: in patients with osteoarthritis or chronic musculoskeletal pain, including when complicated by a neuropathic component; for chronic pain in elderly patients; cancer-related pain; postoperative pain; and for neuropathic pain, in the latter case usually given in combination with an NSAID or other drugs. The large variety of indications for which this fixed-dose combination may be useful can be attributed to the pharmacological synergy between oxycodone and paracetamol and because lower individual drug dosages can be used, suggesting that this should be a first-line agent for the treatment of chronic moderate-to-severe pain.

  4. Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers

    PubMed Central

    Lichtor, Stephanie A.

    2008-01-01

    Rationale Nonmedical use and abuse of prescription opioids is a significant problem in the USA. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids. Objectives The aim of this study is to directly compare the psychopharmacological profile of two oral opioids within the same subject. Methods A randomized, placebo-controlled, crossover study was done in which 20 non-drug-abusing volunteers ingested 10 and 20 mg of oxycodone, 30 and 60 mg of morphine, and placebo in separate sessions. Drug doses were equated on an objective measure of opiate effects: miosis. Subjective, psychomotor, reinforcing, and physiological effects of the opioids were assessed. Results In general, the two opioids at equimiotic doses produced similar prototypic opiate-like effects and psychomotor impairment of similar magnitude. However, several effects were found only with 20 mg oxycodone. Both drugs produced abuse liability-related subjective effects but also dysphoric effects, particularly with 60 mg morphine. Neither drug at either dose functioned as a reinforcer, as measured by the Multiple Choice Procedure. Relative potency ratios indicated an average oxycodone:morphine ratio of 1:3. Conclusions The psychopharmacological profile of oxycodone and morphine at equimiotic doses had many similarities; however, differences were found in producing abuse liability-related and dysphoric effects. In the medical community, it is commonly accepted that oral oxycodone is 1.5 to 2 times as potent as oral morphine in producing analgesia; using this ratio, although patients may experience similar degrees of pain relief, those receiving oxycodone may be experiencing stronger and potentially different psychopharmacological effects. PMID:17899018

  5. Uniform biodegradable microparticle systems for controlled release

    PubMed Central

    Xia, Yujie; Pack, Daniel W.

    2014-01-01

    Drug delivery methods can impact efficacy as much as the nature of the drug itself. Microparticles made of biodegradable polymers such as poly(D,L-lactide-co-glycolide) and poly(lactic acid) (PLA) have been studied extensively for controlled release of diverse drugs. By using a modified solvent extraction/evaporation method called precision particle fabrication (PPF), uniform microparticles such as single-wall microspheres, double-wall microspheres and liquid-core microcapsules have been fabricated with precise control of their geometric structures. By producing particles of uniform size, which has crucial impact on drug release behaviors, PPF-fabricated microparticles provide unique insights about drug release mechanism. Using small-molecule and macromolecule model drugs, our group demonstrated that physicochemical properties of the polymers and drugs and structural properties of the matrix can greatly impact drug distribution within microparticles, particle erosion and drug release rates. By careful selection of particle size and shell thickness, uniform microparticles can achieve “zero-order”, pulsatile or tandem release of drugs. PMID:12106984

  6. Preventing and controlling accidental gas releases

    NASA Astrophysics Data System (ADS)

    Moskowitz, P. D.; Fthenakis, V. M.; Kalb, P. D.

    1988-07-01

    Toxic, flammable, and explosive gases may be used in photovoltaic cell research laboratories and in commercial manufacturing facilities. Accidental release of these materials can present hazards to life and property. Accidents can arise from a variety of mechanical and human related failures. These can occur from the time materials are received at the loading dock of the facility to the time treated gases are discharged to the atmosphere through a stack. Each type of initiating event may require a different control approach. These may range from the training and certification of plant workers charged with the handling of gas cylinder hookups to installation of emergency pollution control systems. Since engineering options for controlling released materials are limited, emphasis should be placed on administrative and engineering approaches for preventing such accidents. These are likely to be the most effective approaches for protecting life and property.

  7. EPICS application source/release control

    SciTech Connect

    Zieman, B.; Anderson, J.; Kraimer, M

    1995-12-31

    This manual describes a set of Application Source/Release Control tools (appSR) that can be used to develop software for EPICS based control systems. The Application Source/Release Control System (appSR) has been unbundled from base EPICS and is now available as an EPICS extension. Due to this unbundling, two new directories must be added to a user`s path (see section ``Environment`` on page 3 for more information) and a new command getapp must be issued after the getrel command to get a specific version of appSR (see section ``Creating The Initial Application System Area`` on page 7 for more information). It is now required that GNU make version 3.71 or later be used for makes instead of SUN make. Users should now type gmake instead of make.

  8. Evaluation of ongoing oxycodone abuse among methadone-maintained patients.

    PubMed

    Dunn, Kelly E; Sigmon, Stacey C; McGee, Mark R; Heil, Sarah H; Higgins, Stephen T

    2008-12-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges.

  9. Controlled release fertilizer workshop, 1991: Proceedings

    SciTech Connect

    Scheib, R.M.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority`s National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC`s Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across` the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  10. Controlled release fertilizer workshop, 1991: Proceedings

    SciTech Connect

    Scheib, R.M.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority's National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC's Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across' the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  11. RAPID DOPAMINE TRANSMISSION WITHIN THE NUCLEUS ACCUMBENS DRAMATICALLY DIFFERS FOLLOWING MORPHINE AND OXYCODONE DELIVERY

    PubMed Central

    Mabrouk, Omar S.; Lovic, Vedran; Singer, Bryan F.; Kennedy, Robert T.; Aragona, Brandon J.

    2014-01-01

    While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug naïve rats using fast-scan cyclic voltammetry and rapid (1 min) microdialysis coupled with mass spectrometry. In addition to measuring rapid dopamine transmission, microdialysis HPLC-MS measures changes in GABA, glutamate, monoamines, monoamine metabolites, and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug-evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid-induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior. PMID:25208732

  12. Injectable controlled release depots for large molecules

    PubMed Central

    Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

    2014-01-01

    Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

  13. Injectable controlled release depots for large molecules.

    PubMed

    Schwendeman, Steven P; Shah, Ronak B; Bailey, Brittany A; Schwendeman, Anna S

    2014-09-28

    Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few "real world" biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LARproducts, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.

  14. Controlled Release Formulations of Auxinic Herbicides

    NASA Astrophysics Data System (ADS)

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

    2013-04-01

    Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

  15. Control of bisphosphonate release using hydroxyapatite granules.

    PubMed

    Seshima, Hisashi; Yoshinari, Masao; Takemoto, Shinji; Hattori, Masayuki; Kawada, Eiji; Inoue, Takashi; Oda, Yutaka

    2006-08-01

    The efficacy of hydroxyapatite (HAp) as a carrier was investigated to establish a method of local administration of bisphosphonates (Bps), which has currently been administered systemically. HAp granules (300-500 microm in size) with different physicochemical features were prepared by altering the sintering temperature. To ascertain the physicochemical properties of the HAp granules, their crystallinity was assessed using X-ray diffraction, the surface morphology was examined under scanning electron microscopy, and the specific surface area and calcium dissolution were evaluated. Different Bps-HAp composites were subsequently prepared and the concentration of Bps released from these composites was measured. The influence of Bps-HAp composites on the rate of osteoclast survival was also evaluated. The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. These findings indicated that Bps-HAp composites could be locally administered as a drug delivery system to areas with bone resorption.

  16. Temperature-Controlled Clamping and Releasing Mechanism

    NASA Technical Reports Server (NTRS)

    Rosing, David; Ford, Virginia

    2005-01-01

    A report describes the development of a mechanism that automatically clamps upon warming and releases upon cooling between temperature limits of approx. =180 K and approx. =293 K. The mechanism satisfied a need specific to a program that involved repeated excursions of a spectrometer between a room-temperature atmospheric environment and a cryogenic vacuum testing environment. The mechanism was also to be utilized in the intended application of the spectrometer, in which the spectrometer would be clamped for protection during launch of a spacecraft and released in the cold of outer space to allow it to assume its nominal configuration for scientific observations. The mechanism is passive in the sense that its operation does not depend on a control system and does not require any power other than that incidental to heating and cooling. The clamping and releasing action is effected by bolt-preloaded stacks of shape-memory-alloy (SMA) cylinders. In designing this mechanism, as in designing other, similar SMA mechanisms, it was necessary to account for the complex interplay among thermal expansion, elastic and inelastic deformation under load, and SMA thermomechanical properties.

  17. 28 CFR 541.50 - Release from a control unit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit. (a) Only the Executive Panel may release an inmate from a control unit. The following factors...

  18. A rapid technique for prediction of nutrient release from controlled release fertilizers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrient release from soluble granular fertilizers can be modified by polymer coating to extend the total duration nutrient release up to 3 to 9 months and rate of release to match the nutrient requirement of the plant during the growing period. Hence these products are termed as “Controlled Release...

  19. [A study of 31 terminally ill cancer patients who received pure oxycodone injections at home].

    PubMed

    Sasaki, Tsubasa; Kawagoe, Izumi

    2014-11-01

    Since the launch of pure oxycodone injections in May 2012, it has been possible to use oxycodone without opioid rotation. Although an extremely important step showing progress, very few studies regarding the use of pure oxycodone injections have been performed. In this study, we evaluated the safety and efficacy of pure oxycodone injections in 31 terminally ill cancer patients receiving home care. The difficulty in oral oxycodone intake was the main reason for changing to pure oxycodone injections. The mean administered period of subcutaneous pure oxycodone was 5.6 ± 6.7 days. One out of 5 patients receiving pure oxycodone injections complained of worsening sleepiness. However, other symptoms improved. In addition, in cases wherein pure oxycodone injection was the initiating opioid, 1 out of 6 patients showed no improvement of respiratory discomfort, while other symptoms improved. It was difficult to evaluate more patients because of the short period for administration. Although 5 patients experienced skin problems, they were successfully managed by changing the injection site. Of these 5 patients, 2 patients had sensitive skin, with a previous history of alcohol rash. In conclusion, our study suggests that pure oxycodone injections are beneficial over oral oxycodone treatment for terminally ill cancer patients. However, further evaluation of skin problems associated with pure oxycodone injections is required by performing larger studies.

  20. A Responsive Battery with Controlled Energy Release.

    PubMed

    Wang, Xiaopeng; Gao, Jian; Cheng, Zhihua; Chen, Nan; Qu, Liangti

    2016-11-14

    A new type of responsive battery with the fascinating feature of pressure perceptibility has been developed, which can spontaneously, timely and reliably control the power outputs (e.g., current and voltage) in response to pressure changes. The device design is based on the structure of the Zn-air battery, in which graphene-coated sponge serves as pressure-sensitive air cathode that endows the whole system with the capability of self-controlled energy release. The responsive batteries exhibit superior battery performance with high open-circuit voltage (1.3 V), and competitive areal capacity of 1.25 mAh cm(-2) . This work presents an important move towards next-generation intelligent energy storage devices with energy management function.

  1. A fatal drug interaction between oxycodone and clonazepam.

    PubMed

    Burrows, David L; Hagardorn, Andrea N; Harlan, Gretel C; Wallen, Ellen D B; Ferslew, Kenneth E

    2003-05-01

    A case is presented of a fatal drug interaction caused by ingestion of oxycodone (Oxycontin) and clonazepam (Klonapin). Oxycodone is an opium alkaloid used in long-term pain management therapy. Clonazepam is a benzodiazepine used for the treatment of seizures and panic disorders. The Drug Abuse Warning Network (DAWN) has reported an increase of 108% in the last two years of emergency department episodes related to Oxycontin. Six billion prescriptions were written for Oxycontin in the year 2000, an 18-fold increase from four years previous (1). Oxycontin has recently gained enormous notoriety at the local and national levels; however, there are very few previously documented cases of lethal drug interactions between oxycodone and clonazepam. Synergistic effects between these two drugs are postulated to arise from different agonistic mechanisms producing similar physiological changes. It is also theorized that clonazepam may inhibit the metabolism of oxycodone. A 38-year-old white female was found dead in Jefferson County, Tennessee in March of 2001. The deceased had physical evidence of previous drug abuse and positive serological findings of hepatitis B and C. Prescription pill bottles filled under the name of the deceased, as well as another name, were found with the body. Serum, urine and gastric contents from the deceased were screened for numerous drugs and metabolites using a combination of thin layer chromatography and immunoassay techniques (EMIT and FPIA). Analysis of biological specimens from the deceased revealed the presence of: benzodiazepines, opiates (oxycodone), and trazodone metabolites in the serum; cannabinoids, benzodiazepines, opiates (oxycodone), trazodone, trazodone metabolites, nicotine, and nicotine metabolite in the urine; and benzodiazepines, opiates (oxycodone), nicotine, and nicotine metabolite in the gastric contents. Quantitative analyses for clonazepam was performed by high performance liquid chromatography (HPLC) and revealed a

  2. A Rapid Test for Prediction of Nutrient Release from Controlled Release Fertilizers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutrient release from soluble granular fertilizers can be modified by polymer coating. The coating technology can be fine-tuned to change the duration (3 to 9 months) and rate of nutrient release, hence these products are termed as controlled release fertilizers (CRF). There is a need to develop a r...

  3. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects.

    PubMed

    Pöyhiä, R; Seppälä, T; Olkkola, K T; Kalso, E

    1992-06-01

    1. The pharmacokinetics and metabolism of oxycodone were studied in nine healthy young volunteers in a cross-over study. Each subject received oxycodone chloride once intramuscularly (0.14 mg kg-1) and twice orally (0.28 mg kg-1) at intervals of 2 weeks. A double-blind randomized pretreatment with amitriptyline (10-50 mg a day) or placebo was given prior to oral oxycodone. 2. The concentrations of oxycodone, noroxycodone and oxymorphone in plasma and the 24 h urine recoveries of their conjugated and unconjugated forms were measured by gas chromatography. 3. No differences were found between treatments in mean Cmax and AUC values of oxycodone which varied from 34 to 38 ng ml-1 and from 208 to 245 ng ml-1 h, respectively. The median tmax of oxycodone was 1 h in all groups. The bioavailability of oral relative to i.m. oxycodone was 60%. The mean renal clearance of oxycodone was 0.07-0.08 l min-1. The kinetics of oxycodone were unaffected by amitriptyline. 4. The mean ratio of the AUC(0.24 h) values of unconjugated noroxycodone to oxycodone was 0.45 after i.m. oxycodone and 0.6-0.8 after oral oxycodone. Plasma oxymorphone concentrations were below the limit of the assay. Eight to 14% of the dose of oxycodone was excreted in the urine as unconjugated and conjugated oxycodone over 24 h. Oxymorphone was excreted mainly as a conjugate whereas noroxycodone was recovered mostly in an unconjugated form.

  4. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats

    PubMed Central

    Pravetoni, M; Raleigh, MD; Le Naour, M; Tucker, AM; Harmon, TM; Jones, JM; Birnbaum, AK; Portoghese, PS; Pentel, PR

    2012-01-01

    Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)4 linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components. PMID:22583811

  5. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats.

    PubMed

    Pravetoni, M; Raleigh, M D; Le Naour, M; Tucker, A M; Harmon, T M; Jones, J M; Birnbaum, A K; Portoghese, P S; Pentel, P R

    2012-06-29

    Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)(4) linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components.

  6. Can an immunoassay become a standard technique in detecting oxycodone and its metabolites?

    PubMed

    Abadie, Jude M; Allison, Kim H; Black, David A; Garbin, James; Saxon, Andrew J; Bankson, Daniel D

    2005-01-01

    Opiate toxicology testing is routinely performed in the hospital setting to identify abusers and/or to determine those patients who are not taking prescribed opiate analgesics such as oxycodone. Commercially available assays for opiate detection in urine have decreased sensitivity for oxycodone, which contributes to a high false-negative rate. Functioning as a beta site, our Veterans Affairs hospital evaluated a new enzyme immunoassay, DRI Oxycodone Assay, for its use in the qualitative and semiquantitative detection of oxycodone in urine. We hypothesize that an immunoassay for oxycodone with superior sensitivity and specificity, when compared to the traditional opiate assays, would reduce the need for more expensive and time-consuming confirmatory testing. We used the new liquid homogenous enzyme immunoassay to determine oxycodone results in a total of 148 urine samples from 4 different sample groups. Gas chromatography-mass spectroscopy was subsequently used to confirm the presence or absence of oxycodone (or its primary metabolite, noroxycodone). We also evaluated within-run, between-run, and linearity studies and conducted a crossover study to establish a cutoff value for oxycodone. In our patient population, we used the new DRI immunoassay to evaluate 17,069 urine samples to estimate oxycodone misuse profiles (patients not taking prescribed oxycodone or taking oxycodone without a prescription) during a 4-month period. The sensitivity and specificity of the new oxycodone immunoassay were 97.7% and 100%, respectively, at the cutoff concentration of 300 ng/mL. The assay linearity was 1,250 ng/mL, and the sensitivity was 10 ng/mL. Within-run precision and between-run coefficient of variation were 2.3% and 1.8%, respectively. None of the 15 compounds that we evaluated for interference had crossover significant enough to produce a positive oxycodone result when using 300 ng/mL as the cutoff value. None of the 17,069 oxycodone immunoassays was followed with a request

  7. 28 CFR 541.50 - Release from a control unit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... general population of the institution which has a control unit. ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control...

  8. Fentanyl tolerance in the treatment of cancer pain: a case of successful opioid switching from fentanyl to oxycodone at a reduced equivalent dose.

    PubMed

    Sutou, Ichiro; Nakatani, Toshihiko; Hashimoto, Tatsuya; Saito, Yoji

    2015-06-01

    Opioids are not generally deemed to have an analgesic ceiling effect on cancer pain. However, there have been occasional reports of tolerance to opioid development induced by multiple doses of fentanyl. The authors report a case of suspected tolerance to the analgesic effect of opioid, in which an increasing dose of fentanyl failed to relieve the patient's cancer pain symptoms, but opioid switching to oxycodone injections enabled a dose reduction to below the equivalent dose conversion ratio. The patient was a 60-year-old man diagnosed with pancreatic body carcinoma with multiple metastases. The base dose consisted of 12 mg/day of transdermal fentanyl patches (equivalent to 3.6 mg/day, 150 μg/h fentanyl injection), and rescue therapy consisted of 10 mg immediate-release oxycodone powders. Despite the total daily dose of fentanyl reaching 5.6 mg (equivalent to 560 mg oral morphine), the analgesic effect was inadequate; thus, an urgent adjustment was necessary. Due to the moderate dose of fentanyl, the switch to oxycodone injection was done incrementally at a daily dose equivalent to 25% of the fentanyl injection. The total dose of oxycodone was replaced approximately 53.5% of the dose of fentanyl prior to opioid switching.

  9. Factors controlling gastric-glucagon release.

    PubMed Central

    Lefèbvre, P J; Luyckx, A S

    1977-01-01

    A system consisting of an isolated dog stomach perfused with whole blood has been designed to study gastric glucagon secretion. Under basal conditions, gastric glucagon release was 0.0-3.1 ng glucagon/100g of stomach per min. Arginine, at an arterial plasma concentration averaging 10 mM, elicited a rapid glucagon release. This gastric glucagon release was almost completely abolished by somatostatin (100 ng/ml). The release of gastric glucagon was not affected by hyperglycemia alone but was reduced by about 40% when hyperglycemia was concomitant with an hyperinsulinemia within the physiological range. These observations support the concept that adequate concentrations of insulin are necessary in order for hyperglycemia to inhibit gastric glucagon secretion. Furthermore, it is suggested that the isolated perfused dog stomach might provide a unique tool permitting investigation of alpha-cell function in the absence of endogenously released insulin. PMID:845258

  10. Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release.

    PubMed

    Yin, Junfa; Cui, Yue; Yang, Gengliang; Wang, Hailin

    2010-11-07

    Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release are fabricated by the combination of template synthesis and ATRP grafting. The release of R-propranolol from the imprinted nanotubes in rats is restricted while the release of pharmacologically active S-enantiomer is greatly promoted.

  11. Tailoring nanoarchitectonics to control the release profile of payloads

    NASA Astrophysics Data System (ADS)

    Jiang, Shuai; Lv, Liping; Li, Qifeng; Wang, Junwei; Landfester, Katharina; Crespy, Daniel

    2016-06-01

    We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2-mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads.We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2-mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00917d

  12. [Nutrient release characteristics and use efficiency of slow- and controlled release fertilizers].

    PubMed

    Duan, Lu-Lu; Zhang, Min; Liu, Gang; Shang, Zhao-Cong; Yang, Yi

    2009-05-01

    Water extraction method and soil incubation method were used to study the nutrient release characteristics of four slow- and controlled release fertilizers (CRF1, CRF2, SCU, and IBDU), and pot experiment was conducted to assess the effects of the release characteristics on the nutrient requirements of canola (Brassica napus L.). The nutrient release curves of test fertilizers in water were S pattern for CRF1 and CRF2, burst pattern for SCU, and reverse L pattern for IBDU. The nutrient release characteristics of the four fertilizers in water and in soil all fitted binomial equations, suggesting that there existed some similarities in the nutrient release in the two media. The nutrient uptake and biomass of canola plants treated with CRF1 and CRF2 were significantly higher than those treated with SCU and IBDU, and CRF2 had the greatest effect. The nutrient release curves of CRF1 and CRF2 accorded more closely with the nutrient requirements of canola.

  13. Environmental Release Prevention and Control Plan

    SciTech Connect

    Mamatey, A.; Arnett, M.

    1997-10-01

    During the history of SRS, continual improvements in facilities, process, and operations, and changes in the site`s mission have reduced the amount of radioactive liquid releases. In the early years of SRS (1958 to 1965), the amount of tritium discharged to the Savannah River averaged approximately 61,000 curies a year. During the mid-1980`s (1983 to 1988), liquid releases of tritium averaged 27,000 curies a year. By 1996, liquid releases of tritium are projected to be just 3000 curies for the year. This large projected decrease is the result of the planned shut-down of all reactors and the anticipated significant decline in the amount of tritium migrating from the site seepage basins and the Solid Waste Disposal Facility.

  14. Effects of filtration on the presence of particulate and oxycodone content of injections prepared from crushed OxyContin® tablets.

    PubMed

    Patel, Pankaj; Patel, Rahul P; Brandon, Susan; McLean, Stuart; Bruno, Raimondo; de Graaff, Barbara

    2012-07-01

    It is common for injecting drug users (IDU) to prepare injections by crushing tablets which are not designed for parental administration. The injection of insoluble tablet excipients can lead to serious local and systemic medical complications. The aim of the study was to investigate the effectiveness of various types of filters in removing harmful insoluble particles from the injections prepared using crushed oxycodone tablets. Injections were prepared from a sustained-release oxycodone tablet formulation. The filtration of tablet extracts was carried out following procedures used by IDU using makeshift filter and commercially available filters. Particulate contamination and oxycodone content were analysed using light microscopy and spectrophotometer. Unfiltered extracts contained hundreds of thousands of particles of sufficient size to cause harms. Cigarette filters removed large particles but failed to remove small particles. The combination of cigarette filter and syringe filter (0.45 μm or 0.22 μm) reduced the particle count by 90 - 95%. A double membrane syringe filter (0.8/0.2 μm) removed more than 99% of the particles. Recovery of oxycodone was more than 95% with the tested syringe filters. Particulate contamination in injections prepared from crushed tablets can be effectively removed using a combination process of cigarette filter and syringe filters, or a 0.8/0.2 μm syringe filter. Compared to other filters, the 0.8/0.2 μm syringe filter did not block, the filtration was quick and easy to perform, and did not retain oxycodone. The use of a 0.8/0.2 μm syringe filter can provide an important harm reduction measure for IDU.

  15. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    PubMed

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand.

  16. Ventilatory responses of healthy subjects to intravenous combinations of morphine and oxycodone under imposed hypercapnic and hypoxaemic conditions

    PubMed Central

    Ladd, L A; Kam, P C; Williams, D B; Wright, A W E; Smith, M T; Mather, L E

    2005-01-01

    Aims Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to healthy human subjects. Methods A placebo-controlled, randomized, crossover study was performed in 12 male volunteers. Ventilatory responses to hypoxaemia and hypercapnia were determined from 1-h intravenous infusions of saline (‘placebo’), 15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their combination in the dose ratios of 1 : 2, 1 : 1, 2 : 1. Drug and metabolite concentrations in serial peripheral venous blood samples were measured by high-performance liquid chromatography–MS/MS. Results ‘Placebo’ treatment was without significant ventilatory effects. There were no systematic differences between active drug treatments on either the slopes or intercepts of the hypoxaemic and hypercapnia ventilation responses. During drug treatment, the mean minute ventilation at PetCO2 = 55 mmHg (VE55) decreased to 74% of the subjects’ before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59, 79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15, respectively. Recovery was more prolonged with increasing oxycodone doses, corresponding to its greater potency and lower clearance compared with morphine. Conclusions Although adverse ventilatory effects of these drugs were found as expected, no unexpected or disproportionate effects of any of the morphine and oxycodone treatments were found that might impede their use in combination for pain management. PMID:15842550

  17. Overview study of LNG release prevention and control systems

    SciTech Connect

    Pelto, P.J.; Baker, E.G.; Holter, G.M.; Powers, T.B.

    1982-03-01

    The liquefied natural gas (LNG) industry employs a variety of release prevention and control techniques to reduce the likelihood and the consequences of accidental LNG releases. A study of the effectiveness of these release prevention and control systems is being performed. Reference descriptions for the basic types of LNG facilities were developed. Then an overview study was performed to identify areas that merit subsequent and more detailed analyses. The specific objectives were to characterize the LNG facilities of interest and their release prevention and control systems, identify possible weak links and research needs, and provide an analytical framework for subsequent detailed analyses. The LNG facilities analyzed include a reference export terminal, marine vessel, import terminal, peakshaving facility, truck tanker, and satellite facility. A reference description for these facilities, a preliminary hazards analysis (PHA), and a list of representative release scenarios are included. The reference facility descriptions outline basic process flows, plant layouts, and safety features. The PHA identifies the important release prevention operations. Representative release scenarios provide a format for discussing potential initiating events, effects of the release prevention and control systems, information needs, and potential design changes. These scenarios range from relatively frequent but low consequence releases to unlikely but large releases and are the principal basis for the next stage of analysis.

  18. Controlled release of biologically active silver from nanosilver surfaces.

    PubMed

    Liu, Jingyu; Sonshine, David A; Shervani, Saira; Hurt, Robert H

    2010-11-23

    Major pathways in the antibacterial activity and eukaryotic toxicity of nanosilver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nanosilver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nanosilver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nanosilver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nanosilver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over 4 orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by preoxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and releasing inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through a bacterial inhibition zone assay carried out on selected formulations of controlled release nanosilver.

  19. Electrospinning nanofibers for controlled drug release

    NASA Astrophysics Data System (ADS)

    Banik, Indrani

    Electrospinning is the most widely studied technique for the synthesis of nanofibers. Electrospinning is considered as one of the technologies that can produce nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This technology has the potential for enhancing the oral delivery of poorly soluble drugs. The electrospun mats were made using Polycaprolactone/PCL, Poly(DL-lactide)/PDL 05 and Poly(DL-lactide-co-glycolide)/PLGA. The drugs incorporated in the electrospun fibers were 5-Fluorouracil and Rapamycin. The evidence of the drugs being embedded in the polymers was obtained by scanning electron microscopy (SEM), Raman and infrared spectroscopy. The release of 5-Fluorouracil and Rapamycin were followed by UV-VIS spectroscopy.

  20. Application of advanced polymeric materials for controlled release pesticides

    NASA Astrophysics Data System (ADS)

    Rahim, M.; Hakim, M. R.; Haris, H. M.

    2016-08-01

    The objective of this work was to study the capability of advanced polymeric material constituted by chitosan and natural rubber matrices for controlled release of pesticides (1-hydroxynaphthalene and 2-hydroxynaphthalene) in aqueous solution. The released amount of pesticides was measured spectrophotometrically from the absorbance spectra applying a standardized curve. The release of the pesticides was studied into refreshing and non-refreshing neutral aqueous media. Interestingly, formulation successfully indicated a consistent, controlled and prolonged release of pesticides over a period of 35 days.

  1. One hundred seventy two deaths involving the use of oxycodone in Palm Beach County.

    PubMed

    Wolf, Barbara C; Lavezzi, Wendy A; Sullivan, Linda M; Flannagan, Lisa M

    2005-01-01

    Oxycodone is a potent semi-synthetic narcotic prescribed for the management of pain. Previous investigators have reported that the abuse of oxycodone is most frequently seen in conjunction with the abuse of other drugs, although fatalities have been reported with oxycodone alone. We undertook a retrospective review of cases investigated by the Palm Beach County Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of oxycodone. A total of 172 consecutive cases were studied, including 18 in which death was attributed to oxycodone toxicity, 117 to combined drug toxicity, 23 to trauma, 9 to natural causes and 5 to another drug or drugs. The postmortem blood concentrations of oxycodone overlapped among the groups. The mean blood oxycodone concentration among the cases of oxycodone toxicity was 0.69 mg/L, combined drug toxicity 0.72 mg/L and trauma 0.62 mg/L. Concentrations were lower in cases of deaths attributed to natural causes and to another drug or drugs (mean each 0.087 mg/L). Benzodiazepines, detected in 96 cases, were the most common co-intoxicants in the cases of combined drug toxicity, followed by cocaine, which was found in 41. The most frequently encountered benzodiazepine was alprazolam. This study confirms that deaths in which oxycodone is a factor are most commonly cases of combined drug toxicity. The high incidence of alprazolam as a co-intoxicant has not been previously recognized.

  2. Quinine as a potential tracer for medication adherence: A pharmacokinetic and pharmacodynamic assessment of quinine alone and in combination with oxycodone in humans

    PubMed Central

    Babalonis, Shanna; Hampson, Aidan J.; Lofwall, Michelle R.; Nuzzo, Paul A.; Walsh, Sharon L.

    2015-01-01

    Effective strategies to monitor pharmacotherapy adherence are necessary, and sensitive biological markers are lacking. This study examined a sub-therapeutic dose of quinine as a potential adherence tracer. Primary aims included examination of the plasma and urinary pharmacokinetic profile of once-daily quinine; secondary aims assessed pharmacokinetic/pharmacodynamic interactions with oxycodone (a CYP3A and CYP2D substrate). Healthy, non-dependent opioid users (n=9) were enrolled in this within-subject, double-blind, placebo-controlled, inpatient study. Participants received the following oral doses, Day 1: oxycodone (30 mg), Days 2-4: quinine (80 mg), Day 5: quinine and oxycodone (2 hrs post-quinine). Blood and 24-hr urine samples were collected throughout the study, and pharmacodynamic outcomes were assessed during experimental sessions (Days 1, 4, 5). Quinine displayed a plasma Tmax ∼2 hrs and t1/2 ∼10 hrs. Oxycodone and noroxycodone parameters (Tmax, Cmax, t1/2) were similar with or without quinine present, although drug exposure (AUC) was slightly greater when combined with quinine. No pharmacodynamic interactions were detected and doses were safely tolerated. During washout, quinine urinary concentrations steadily declined (elimination t1/2 ∼16 hrs), with a 94% decrease observed 72 hrs post-dose. Overall, low-dose quinine appears to be a good candidate for a medication additive to monitor adherence for detection of missed medication. PMID:26032168

  3. Quinine as a potential tracer for medication adherence: A pharmacokinetic and pharmacodynamic assessment of quinine alone and in combination with oxycodone in humans.

    PubMed

    Babalonis, Shanna; Hampson, Aidan J; Lofwall, Michelle R; Nuzzo, Paul A; Walsh, Sharon L

    2015-12-01

    Effective strategies to monitor pharmacotherapy adherence are necessary, and sensitive biological markers are lacking. This study examined a subtherapeutic dose of quinine as a potential adherence tracer. Primary aims included examination of the plasma and urinary pharmacokinetic profile of once-daily quinine; secondary aims assessed pharmacokinetic/pharmacodynamic interactions with oxycodone (a CYP3A and CYP2D substrate). Healthy, nondependent opioid users (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled inpatient study. Participants received the following oral doses: day 1, oxycodone (30 mg); days 2-4, quinine (80 mg); day 5, quinine and oxycodone (2 hours postquinine). Blood and 24-hour urine samples were collected throughout the study, and pharmacodynamic outcomes were assessed during experimental sessions (days 1, 4, 5). Quinine displayed a plasma Tmax ∼2 hours and t1/2 ∼10 hours. Oxycodone and noroxycodone parameters (Tmax , Cmax , t1/2 ) were similar with or without quinine present, although drug exposure (AUC) was slightly greater when combined with quinine. No pharmacodynamic interactions were detected, and doses were safely tolerated. During washout, quinine urinary concentrations steadily declined (elimination t1/2 ∼16 hours), with a 94% decrease observed 72 hours postdose. Overall, low-dose quinine appears to be a good candidate for a medication additive to monitor adherence for detection of missed medication.

  4. Release and control of hydrogen sulfide during sludge thermal drying

    SciTech Connect

    Weng, Huanxin; Dai, Zhixin; Ji, Zhongqiang; Gao, Caixia; Liu, Chongxuan

    2015-04-15

    The release of hydrogen sulfide (H2S) during sludge drying is a major environmental problem because of its toxicity to human health. A series of experiments were performed to investigate the mechanisms and factors controlling the H2S release. Results of this study show that: 1) the biomass and activity of sulfate-reducing bacteria (SRB) in sludge were the major factors controlling the amount of H2S release, 2) the sludge drying temperature had an important effect on both the extent and the timing of H2S release from the sludge, and 3) decreasing sludge pH increased the H2S release. Based on the findings from this study, a new system that integrates sludge drying and H2S gas treatment was developed to reduce the amount of H2S released from sludge treatments.

  5. Diffuse-interface theory for structure formation and release behavior in controlled drug release systems.

    PubMed

    Saylor, David M; Kim, Chang-Soo; Patwardhan, Dinesh V; Warren, James A

    2007-11-01

    A common method of controlling drug release has been to incorporate the drug into a polymer matrix, thereby creating a diffusion barrier that slows the rate of drug release. It has been demonstrated that the internal microstructure of these drug-polymer composites can significantly impact the drug release rate. However, the effect of processing conditions during manufacture on the composite structure and the subsequent effects on release behavior are not well understood. We have developed a diffuse-interface theory for microstructure evolution that is based on interactions between drug, polymer and solvent species, all of which may be present in either crystalline or amorphous states. Because the theory can be applied to almost any specific combination of material species and over a wide range of environmental conditions, it can be used to elucidate and quantify the relationships between processing, microstructure and release response in controlled drug release systems. Calculations based on the theory have now demonstrated that, for a characteristic delivery system, variations in microstructure arising due to changes in either drug loading or processing time, i.e. evaporation rate, could have a significant impact on both the bulk release kinetics and the uniformity of release across the system. In fact, we observed that changes in process time alone can induce differences in bulk release of almost a factor of two and typical non-uniformities of +/-30% during the initial periods of release. Because these substantial variations may have deleterious clinical ramifications, it is critical that both the system microstructure and the control of that microstructure are considered to ensure the device will be both safe and effective in clinical use.

  6. Preparation, characterization and optimization of glipizide controlled release nanoparticles

    PubMed Central

    Emami, J.; Boushehri, M.S. Shetab; Varshosaz, J.

    2014-01-01

    The purpose of the present study was to develop glipizide controlled release nanoparticles using alginate and chitosan thorough ionotropic controlled gelation method. Glipizide is a frequently prescribed second generation sulfonylurea which lowers the blood glucose in type-two diabetics. Quick absorption of the drug from the gastrointestinal tract along with short half- life of elimination makes it a good candidate for controlled release formulations. Alginate-chitosan nanoparticles (ACNP) are convenient controlled delivery systems for glipizide, due to both the release limiting properties of the system, and the bioadhesive nature of the polymers. In the present study, glipizide loaded alginate-chitosan nanoparticles (GlACNP) were prepared, and the particle characteristics including particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), loading percent (LP), and mean release time (MRT), as well as the morphology of the nanoparticles, the drug-excipient compatibility, and the release kinetics along with the drug diffusion mechanism were evaluated. The results suggested that ionotropic controlled gelation method offers the possibility of preparing the nanoparticles in mild conditions in an aqueous environment, and can lead to the preparation of particles with favorable size, controlled release characteristics, and high entrapment efficiency, serving as a convenient delivery system for glipizide. The particle and release characteristics can be efficiently optimized using the Box-Behnken design. Based on the findings of the present study, it is expected that this novel formulation be a superior therapeutic alternative to the currently available glipizide delivery systems. PMID:25657802

  7. Best Practices for Controlling Lead and Copper Release

    EPA Science Inventory

    Presentation draft, covering summary of current state-of-the-art knowledge for the best treatment strategies for minimizing lead release and controlling copper release. The presentation is intended to aid with compliance with the Lead and Copper Rule, but also provide a guide to...

  8. Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

    NASA Astrophysics Data System (ADS)

    Qian, Kun; Guo, Yanzhen; He, Lin

    2012-01-01

    Imidacloprid is a neonicotinoids insecticide, which is important for the cash crops such as tomato, rape and so on. The conventional formulation does not only increase the loss of pesticide but also leads to environmental pollution. Controlled-release formulations of pesticide are highly desirable not only for attaining the most effective utilization of the pesticide, but also for reducing environmental pollution. Pesticide imidacloprid was incorporated in poly (styrene-diacetone crylamide)-based formulation to obtain controlled release properties, and the imidacloprid nanocontrolled release formulation was characterized by infrared (IR) and field emission scanning electron microscope (FESEM). Factors related to loading efficiency, swelling and release behaviors of the formulation were investigated. It showed that the loading efficiency could reach about 40% (w/w). The values for the diffusion exponent "n" were in the range of 0.31-0.58, which indicated that the release of imidacloprid was diffusion-controlled. The time taken for 50% of the active ingredient to be released into water, T50, was also calculated for the comparison of formulations in different conditions. The results showed that the formulation with higher temperature and more diacetone crylamide had lower value of T50, which means a quicker release of the active ingredient. This study highlighted some pieces of evidence that improved pesticide incorporation and slower release were linked to potential interactions between the pesticide and the polymer.

  9. PREVENTION REFERENCE MANUAL: CONTROL TECHNOLOGIES, VOL. 2. POST-RELEASE MITIGATION MEASURES FOR CONTROLLING ACCIDENTAL RELEASES OF AIR TOXICS

    EPA Science Inventory

    The volume discusses prevention and protection measures for controlling accidental releases of air toxics. The probability of accidental releases depends on the extent to which deviations (in magnitude and duration) in the process can be tolerated before a loss of chemical contai...

  10. Controlled Release of Biologically Active Silver from Nanosilver Surfaces

    PubMed Central

    Liu, Jingyu; Sonshine, David A.; Shervani, Saira; Hurt, Robert H.

    2010-01-01

    Major pathways in the antibacterial activity and eukaryotic toxicity of nano-silver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nano-silver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nano-silver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nano-silver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nano-silver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over four orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by pre-oxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and release inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through bacterial inhibition zone assay carried out on selected formulations of controlled release nano-silver. PMID:20968290

  11. A controlled biochemical release device with embedded nanofluidic channels

    NASA Astrophysics Data System (ADS)

    Yang, Haifeng; Hong, Wei; Dong, Liang

    2012-04-01

    A controlled release device is developed by embedding nanofluidic biomolecule reservoirs into a polymer network of a stimuli-responsive hydrogel. The reservoirs are made of liquid core-polymer shell nanofibers using co-electrospinning. The mechanism of controlled release is based on buckling instability of the polymer shell under combined axial and radial compression, caused by volume changes of hydrogel responding to a specific stimulus. The device decouples releasable biomolecules from a hydrogel polymer matrix, avoiding chemical interactions between biomolecules and hydrogel polymer chains, and thus, alleviating nontrivial chemical and biological engineering design of hydrogel formulations. Temperature-sensitive hydrogel is used as a model hydrogel.

  12. [Drug release system controlled by near infrared light].

    PubMed

    Niidome, Takuro

    2013-01-01

    Gold nanorods have absorption bands in the near-infrared region; in this spectral range, light penetrates deeply into tissues. The absorbed light energy is converted into heat by gold nanorods. This is the so-called photothermal effect. Gold nanorods are therefore expected to act not only as thermal converters for photothermal therapy, but also as controllers for drug-release systems responding to irradiation with near-infrared light. To achieve a controlled-release system that could be triggered by light irradiation, the gold nanorods were modified with double-stranded DNA (dsDNA). When the dsDNA-modified gold nanorods were irradiated with near-infrared light, single-stranded DNA (ssDNA) was released from the gold nanorods because of the photothermal effect. The release of ssDNA was also observed in tumors grown on mice after near-infrared light irradiation. We also proposed a different controlled-release system responding to near-infrared light. Gold nanorods were modified with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the gold nanorods were irradiated with near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. Such controlled-release systems triggered by near-infrared light irradiation will be expanded for gold nanorod drug delivery system applications.

  13. Pharmacokinetics of oxycodone after intravenous and subcutaneous administration in Japanese patients with cancer pain.

    PubMed

    Kokubun, Hideya; Yoshimoto, Tetsusuke; Hojo, Minoru; Fukumura, Kazuya; Matoba, Motohiro

    2014-12-01

    ABSTRACT In Japan, Oxycodone hydrochloride injection formulation has been approved in 2012. However, its pharmacokinetics has been poorly studied. The aim of this study is to evaluate the pharmacokinetics of oxycodone after intravenous and subcutaneous administration of oxycodone hydrochloride injection in Japanese patients with cancer pain. Noncompartmental analysis and population pharmacokinetic analysis were performed. We conducted a multicenter open-label study of oxycodone hydrochloride administered as constant infusion with the dose titrated individually according to the pain intensity in patients with cancer pain. Pharmacokinetic parameters for plasma oxycodone and its metabolites were estimated using pharmacokinetics of oxycodone was evaluated using a total of 344 plasma concentrations obtained from 89 patients. The estimated geometric mean clearance (CL) of oxycodone was 24.3 L per hour after constant intravenous infusion and 29.5 L per hour after constant subcutaneous infusion, respectively. Population pharmacokinetic analysis indicated that body surface area was the influencing factor on CL and there were no pharmacokinetic differences for CL between intravenous and subcutaneous infusion. These results provide important information for the clinical use of oxycodone injection.

  14. Modifying sorbents in controlled release formulations to prevent herbicides pollution.

    PubMed

    Flores Céspedes, F; Villafranca Sánchez, M; Pérez García, S; Fernández Pérez, M

    2007-10-01

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism. Sorption capacity of the sorbents for chloridazon and metribuzin, ranging from 0.53mgkg(-1) for the metribuzin sorption on bentonite to 2.03x10(5)mgkg(-1) for the sorption of chloridazon on the activated carbon, was the most important factor modulating the herbicide release.

  15. Toxicology and characteristics of fatal oxycodone toxicity cases in New South Wales, Australia 1999-2008.

    PubMed

    Darke, Shane; Duflou, Johan; Torok, Michelle

    2011-05-01

    All cases of fatal oxycodone toxicity presenting to the New South Wales Department of Forensic Medicine over the period January 1, 1999, to December 31, 2008, were retrieved. A total of 70 cases were identified. The mean age was 48.9 years, 58.6% were men, 21.4% were suicides, and in 30% oxycodone had not been prescribed to the decedent. Injecting drug users constituted 27.1% of cases, and oxycodone tablets were injected immediately prior to death by 21.4%. The mean blood oxycodone concentration was 0.40 mg/L (range 0.06-53.00 mg/L). In all cases, psychoactive substances other than oxycodone were also detected, most frequently hypnosedatives (68.6%), other opioids (54.3%), antidepressants (41.4%), and alcohol (32.9%). Preexisting systemic disease was common: cardiovascular (64.2%), pulmonary (49.3%), hepatic (66.7%), and renal (43.9%).

  16. Modeling controlled nutrient release from polymer coated fertilizers: diffusion release from single granules.

    PubMed

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A comprehensive model describing the complex and "non-Fickian" (mathematically nonlinear) nature of the release from single granules of membrane coated, controlled release fertilizers (CRFs) is proposed consisting of three stages: i. a lag period during which water penetrates the coating of the granule dissolving part of the solid fertilizer in it ii. a period of linear release during which water penetration into and release out occur concomitantly while the total volume of the granules remains practically constant; and iii. a period of "decaying release", starting as the concentration inside the granule starts to decrease. A mathematical model was developed based on vapor and nutrient diffusion equations. The model predicts the release stages in terms of measurable geometrical and chemophysical parameters such as the following: the product of granule radius and coating thickness, water and solute permeability, saturation concentration of the fertilizer, and its density. The model successfully predicts the complex and "sigmoidal" pattern of release that is essential for matching plant temporal demand to ensure high agronomic and environmental effectiveness. It also lends itself to more complex statistical formulations which account for the large variability within large populations of coated CRFs and can serve for further improving CRF production and performance.

  17. Controlled release of tocopherols from polymer blend films

    NASA Astrophysics Data System (ADS)

    Obinata, Noe

    Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies

  18. Controlled release of curcumin from poly(HEMA-MAPA) membrane.

    PubMed

    Caka, Müşerref; Türkcan, Ceren; Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

    2017-05-01

    In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

  19. Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats.

    PubMed

    Leri, Francesco; Burns, Lindsay H

    2005-10-01

    Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and alleviate opioid tolerance and dependence. Our present studies in male Sprague-Dawley rats assessed the abuse potential of oxycodone+ultra-low-dose naltrexone (NTX) versus oxycodone alone. The lowest NTX dose (1 pg/kg/infusion), but not slightly higher doses (10 and 100 pg/kg/infusion), enhanced oxycodone (0.1 mg/kg/infusion) intravenous self-administration, suggesting a reduced rewarding potency per infusion. During tests of reinstatement performed in extinction conditions, co-self-administration of any of these three NTX doses significantly reduced drug-seeking precipitated by priming injections of oxycodone (0.25 mg/kg, s.c.), a drug-conditioned cue, or foot-shock stress. During self-administration on a progressive-ratio schedule, animals self-administering oxycodone (0.1 mg/kg/infusion)+NTX (1 pg/kg/infusion) reached a "break-point" sooner and showed a trend toward less responding compared to rats self-administering oxycodone alone (0.1 mg/kg/infusion). In the final experiment, the addition of ultra-low-dose NTX (10 pg/kg, s.c.) enhanced the acute stimulatory effect of oxycodone (1 mg/kg, s.c.), as well as locomotor sensitization produced by repeated oxycodone administration (7 x 1 mg/kg, s.c.). In summary, this work shows that ultra-low-dose NTX co-treatment augments the locomotor effects of oxycodone as it enhances opioid analgesia, but reduces oxycodone's rewarding potency and subsequent vulnerability to relapse.

  20. Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

    PubMed

    Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

    2016-10-15

    Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid.

  1. Prenatal Oxycodone Exposure Alters CNS Endothelin Receptor Expression in Neonatal Rats.

    PubMed

    Devarapalli, M; Leonard, M; Briyal, S; Stefanov, G; Puppala, B L; Schweig, L; Gulati, A

    2016-05-01

    Prenatal opioid exposure such as oxycodone is linked to significant adverse effects on the developing brain. Endothelin (ET) and its receptors are involved in normal development of the central nervous system. Opioid tolerance and withdrawal are mediated through ET receptors. It is possible that adverse effect of oxycodone on the developing brain is mediated through ET receptors. We evaluated brain ETA and ETB receptor expression during postnatal development in rats with prenatal oxycodone exposure. Timed pregnant Sprague-Dawley rats received either oxycodone or placebo throughout gestation. After birth, male rat pups were sacrificed on postnatal day (PND) 1, 7, 14 or 28. Brain ETA and ETB receptor expression was determined by Western blot analysis. Oxycodone pups compared to placebo demonstrated congenital malformations of the face, mouth, and vertebrae at the time of birth [4/69 (5.7%) vs. 0/60 (0%); respectively] and intrauterine growth retardation [10/69 (15%) vs. 2/60 (3.3%); respectively]. On PND 28, oxycodone pups compared to placebo had lower body and kidney weight. ETA receptor expression in the oxycodone group was significantly higher compared to placebo on PND 1 (p=0.035), but was similar on PND 7, 14, or 28. ETB receptor expression decreased in oxycodone compared to placebo on PND 1 and 7 (p=0.001); and increased on PND 28 (p=0.002), but was similar on PND 14. Oxycodone-exposed rat pups had lower birth weight and postnatal weight gain and greater congenital malformations. ETB receptor expression is altered in the brain of oxycodone-treated rat pups indicating a possible delay in CNS development.

  2. HIV risk behavior in opioid dependent adults seeking detoxification treatment: an exploratory comparison of heroin and oxycodone users.

    PubMed

    Meade, Christina S; McDonald, Leah J; Weiss, Roger D

    2009-01-01

    Heroin users are at high risk for HIV infection, but little is known about HIV risk in oxycodone users. This study examined HIV risk behaviors in heroin (n = 27) and oxycodone (n = 23) users seeking inpatient detoxification at a private psychiatric hospital. Drug use histories were similar, except oxycodone users used marijuana more frequently. Injection drug risk occurred exclusively among heroin users. The rates of sexual activity (66%), unprotected intercourse (69%), sex while intoxicated (74%), and sex with strangers (24%) were similar, but more oxycodone users had multiple partners (39% vs. 6%, p < .05). HIV prevention efforts should target both heroin and oxycodone users.

  3. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    NASA Astrophysics Data System (ADS)

    Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

    2009-04-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  4. Controlled Release in Transdermal Pressure Sensitive Adhesives using Organosilicate Nanocomposites

    PubMed Central

    Shaikh, Sohel; Birdi, Anil; Qutubuddin, Syed; Lakatosh, Eric; Baskaran, Harihara

    2010-01-01

    Polydimethyl siloxane (PDMS) based pressure sensitive adhesives (PSA) incorporating organo-clays at different loadings were fabricated via solution casting. Partially exfoliated nanocomposites were obtained for the hydroxyl terminated PDMS in ethyl acetate solvent as determined by X-ray diffraction (XRD) and atomic force microscopy (AFM). Drug release studies showed that the initial burst release was substantially reduced and the drug release could be controlled by the addition of organo-clay. Shear strength and shear adhesion failure temperature (SAFT) measurements indicated substantial improvement in adhesive properties of the PSA nanocomposite adhesives. Shear strength showed more than 200 % improvement at the lower clay loadings and the SAFT increased by about 21% due to the reinforcement provided by the nano-dispersed clay platelets. It was found that by optimizing the level of the organosilicate additive to the polymer matrix, superior control over drug release kinetics and simultaneous improvements in adhesive properties could be attained for a transdermal PSA formulation. PMID:17786555

  5. [Controlled release hydromorphone for visceral, somatic and neuropathic pain].

    PubMed

    Alon, E; Cachin, C

    2010-03-03

    The aim of this multicentre, longitudinal investigation was to document the efficacy and tolerability profiles of controlled release hydromorphone in patients with heavy visceral, somatic or neuropathic pain under practical conditions. To this end, a prospective observational study was conducted in 57 centres in Switzerland, on a total of 196 patients. After an average of 43 days of treatment with controlled release hydromorphone, the intensity of momentary pain dropped by 46.5% and that of maximum pain dropped by 41.3%, with the efficacy of the treatment being most pronounced with visceral and somatic pain. At the same time, the prevalence of sleep disorders as a result of pain decreased from initially 86.7% to 21.0%. Controlled release hydromorphone was excellently tolerated in this group of elderly (average age 70.6 years), multimorbid pain patients receiving various medical treatments (average of 2.4 drugs in addition to pain medication), even in the voluntary long-term extension study of up to 96 days. No medical interactions were reported. Six and thirteen weeks after introducing the treatment, 89.8% and 85.2%, respectively, were still taking controlled release hydromorphone. Controlled release hydromorphone is a recommendable option for practical treatment of heavy and extremely heavy pain of various genesis.

  6. Formulation of controlled release gellan gum macro beads of amoxicillin.

    PubMed

    Babu, R Jayachandra; Sathigari, Sateesh; Kumar, M Thilek; Pandit, J K

    2010-01-01

    Gellan gum has been reported to have wide pharmaceutical applications such as tablet binder, disintegrant, gelling agent and as a controlled release polymer. Multiparticulate delivery systems spread out more uniformly in the gastrointestinal tract and reduce the local irritation. The purpose of this study is to explore possible applicability of gellan macro beads as an oral controlled release system of a sparingly soluble drug, amoxicillin. Gellan gum beads were prepared by ionotropic gelation with calcium ions. The effect of drug loading, stirring time, polymer concentration, electrolyte (CaCl2) concentration, curing time etc. influencing the preparation of the gellan gum macro beads and the drug release from gellan gum beads were investigated in this study. Optimal preparation conditions allowed very high incorporation efficiency for amoxicillin (91%) The release kinetics of amoxicillin from gellan beads followed the diffusion model for an inert porous matrix in the order: 0.1 N HCl > phosphate buffer > distilled water. Change in curing time did not significantly affect the release rate constant, but drug concentration, polymer concentration and electrolyte concentration significantly affect the release rate of amoxicillin from the beads. The gellan macro beads may be suitable for gastro retentive controlled delivery of amoxicillin.

  7. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations.

    PubMed

    Zhou, Deliang; Law, Devalina; Reynolds, Judie; Davis, Lynn; Smith, Clifford; Torres, Jose L; Dave, Viraj; Gopinathan, Nishanth; Hernandez, Daniel T; Springman, Mary Kay; Zhou, Casey Chun

    2014-06-01

    The purpose of this study is to identify critical physicochemical properties of hydroxypxropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance.

  8. Sol-gel encapsulation for controlled drug release and biosensing

    NASA Astrophysics Data System (ADS)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  9. Wetting mechanisms of gel-based controlled-release fertilizers.

    PubMed

    Shavit, U; Reiss, M; Shaviv, A

    2003-02-14

    The release mechanism of gel-based controlled release fertilizers (CRFs) involves water penetration into dry mixtures of fertilizers and gel forming polymers. Water penetration provides an upper limit to the whole release process. Where wetting prediction is often based on models that describe the flow of the liquid phase, vapor motion may become significant when a sharp wetting front exists. In this study we examine the role of vapor and fluid flows in the wetting process of CRFs consisting of urea or KNO(3) mixed with polyacrylamide (PAM). Vapor adsorption isotherms were obtained for typical fertilizer-PAM mixtures. Wetting and release experiments were conducted by dividing the CRFs into regions alternately filled with a pure fertilizer and mixtures of PAM and fertilizer. The experiments were designed in such a way that when the wetting front reaches a mixtures interface, its motion depends on the gradient imposed by the difference in osmotic potential (OP). The coupled equations of vapor and liquid flow in initially dry conditions were solved numerically to demonstrate the conceptual understanding gained by the experiments. The results show that wetting front motion is affected by transport and adsorption of vapor. It was also shown that the release rate is different when wetting is governed by vapor flow or by liquid flow. The release pattern from a multi-regions device was consistent with the wetting pattern, demonstrating the possibility to tailor the release according to periods of peak demand.

  10. Application of cellulose acetate for controlled release of thymol.

    PubMed

    Milovanovic, Stoja; Markovic, Darka; Aksentijevic, Ksenija; Stojanovic, Dusica B; Ivanovic, Jasna; Zizovic, Irena

    2016-08-20

    Cellulose acetate (CA) was investigated as a carrier towards development of material with controlled release of thymol as a natural substance with strong antibacterial properties using high pressure techniques. Effect of thymol content on CA was confirmed by SEM, FTIR and DSC methods. Kinetic of thymol release from CA was tested using simulated gastric and intestinal fluids (hydrochloric acid and phosphate buffer saline). Results were correlated with Korsmeyer-Peppas and Weibull model. Depending on the thymol content and chemical nature of the release medium, the time of thymol release varied from one to three days indicating CA as a promising carrier of thymol with potential uses from medicine to agriculture. The impregnated CA showed antibacterial activity against 23 tested bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) which is particularly important bearing in mind that this strain causes fatal infections in humans and animals.

  11. Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

    PubMed Central

    Ho, Vincent; Stewart, Maxwell; Boyd, Peter

    2008-01-01

    Introduction Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. Case presentation A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. Conclusion We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity. PMID:18452597

  12. Method and apparatus for controlling accidental releases of tritium

    DOEpatents

    Galloway, Terry R. [Berkeley, CA

    1980-04-01

    An improvement in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release.

  13. Method and apparatus for controlling accidental releases of tritium

    DOEpatents

    Galloway, T.R.

    1980-04-01

    An improvement is described in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release. 1 fig.

  14. Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses

    PubMed Central

    White, Charles J.; DiPasquale, Stephen A.; Byrne, Mark E.

    2016-01-01

    Purpose The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. Methods Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. Results By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. Conclusions The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops. PMID:26945177

  15. Press-coating of immediate release powders onto coated controlled release tablets with adhesives.

    PubMed

    Waterman, Kenneth C; Fergione, Michael B

    2003-05-20

    A novel adhesive coating was developed that allows even small quantities of immediate-release (IR) powders to be press-coated onto controlled-release (CR), coated dosage forms without damaging the CR coating. The process was exemplified using a pseudoephedrine osmotic tablet (asymmetric membrane technology, AMT) where a powder weighing less than 25% of the core was pressed onto the osmotic tablet providing a final combination tablet with low friability. The dosage form with the adhesive plus the press-coated powder showed comparable sustained drug release rates to the untreated dosage form after an initial 2-h lag. The adhesive layer consisted of an approximately 100- microm coating of Eudragit RL, polyethylene glycol (PEG) and triethyl citrate (TEC) at a ratio of 5:3:1.2. This coating provides a practical balance between handleability before press-coating and good adhesion.

  16. Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery? A Randomized Controlled Trial

    PubMed Central

    Qazi, Saddiq Mohammad; Sindby, Eske Jesper; Nørgaard, Martin Agge

    2015-01-01

    Introduction: Postoperative pain-management with non-steroid anti-inflammatory drugs has been controversial, due to related side-effects. We investigated whether there was a significant difference between an oxycodone-based pain-management regimen versus a slow-release ibuprofen based regimen, in a short term post-cardiac surgery setting. Particular attention was given to the rate of myocardial infarction, sternal healing, gastro-intestinal complications, renal failure and all-cause mortality. Methods: This was a single-centre, open label parallel design randomised controlled study. Patients, who were undergoing cardiac surgery for the first time, were randomly allocated either to a regimen of slow-release oxycodone (10 mg twice daily) or slow-release ibuprofen (800 mg twice daily) combined with lansoprazole. Data relating to blood-tests, angiographies, surgical details and administered medicine were obtained from patient records. The follow-up period was 1 to 37 months (median 25 months). Results: One hundred eighty-two patients were included in the trial and available for intention to treat analysis. There were no significant difference between the groups (P>0.05) in the rates of sternal healing, postoperative myocardial infarction or gastrointestinal bleeding. The preoperative levels of creatinine were found to increase by 100% in nine patients (9.6%) in the ibuprofen group, resulting in an acute renal injury (in accordance with the RIFLE-criteria). Eight of these patients returned to normal renal function within 14 days. The levels of creatinine in patients in the oxycodone group were not found to increase to the same magnitude. Conclusion: The results of this study suggest that patients treated postoperatively, following cardiac surgery, are at no greater risk of harm if short term slow release ibuprofen combined with lansoprazole treatment is used when compared to an oxycodone based regimen. Renal function should, however, be closely monitored and in the

  17. Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation.

    PubMed

    Webster, Lynn R

    2007-08-01

    Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. To evaluate the safety and efficacy of the oxycodone/naltrexone combination, three clinical studies have been conducted, one in healthy volunteers and the other two in patients with chronic pain. The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.

  18. Controlled release tablet formulation containing natural Δ(9)-tetrahydrocannabinol.

    PubMed

    Punyamurthula, Nagendra S; Hingorani, Tushar; Adelli, Goutham; Gul, Waseem; ElSohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit

    2016-01-01

    Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of Δ(9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress®), dicalcium phosphate anhydrous (Emcompress®) and microcrystalline cellulose (Avicel® 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic® F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol® and Compritol® in the compression blend. Addition of Pluronic® F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25 °C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management.

  19. Controlled release of alendronate from nitrogen-doped mesoporous carbon

    SciTech Connect

    Saha, Dipendu; Spurri, Amanda; Chen, Jihua; Hensley, Dale K.

    2016-04-13

    With this study, we have synthesized a nitrogen doped mesoporous carbon with the BET surface area of 1066 m2/g, total pore volume 0.6 cm3/g and nitrogen content of 0.5%. Total alendronate adsorption in this carbon was ~5%. The release experiments were designed in four different media with sequential pH values of 1.2, 4.5, 6.8 and 7.4 for 3, 1, 3 and 5 h, respectively and at 37 °C to imitate the physiological conditions of stomach, duodenum, small intestine and colon, respectively. Release of the drug demonstrated a controlled fashion; only 20% of the drug was released in the media with pH = 1.2, whereas 64% of the drug was released in pH = 7.4. This is in contrary to pure alendronate that was completely dissolved within 30 min in the first release media (pH = 1.2) only. The relatively larger uptake of alendronate in this carbon and its sustained fashion of release can be attributed to the hydrogen bonding between the drug and the nitrogen functionalities on carbon surface. Based on this result, it can be inferred that this formulation may lower the side effects of oral delivery of alendronate.

  20. Controlled release of alendronate from nitrogen-doped mesoporous carbon

    DOE PAGES

    Saha, Dipendu; Spurri, Amanda; Chen, Jihua; ...

    2016-04-13

    With this study, we have synthesized a nitrogen doped mesoporous carbon with the BET surface area of 1066 m2/g, total pore volume 0.6 cm3/g and nitrogen content of 0.5%. Total alendronate adsorption in this carbon was ~5%. The release experiments were designed in four different media with sequential pH values of 1.2, 4.5, 6.8 and 7.4 for 3, 1, 3 and 5 h, respectively and at 37 °C to imitate the physiological conditions of stomach, duodenum, small intestine and colon, respectively. Release of the drug demonstrated a controlled fashion; only 20% of the drug was released in the media withmore » pH = 1.2, whereas 64% of the drug was released in pH = 7.4. This is in contrary to pure alendronate that was completely dissolved within 30 min in the first release media (pH = 1.2) only. The relatively larger uptake of alendronate in this carbon and its sustained fashion of release can be attributed to the hydrogen bonding between the drug and the nitrogen functionalities on carbon surface. Based on this result, it can be inferred that this formulation may lower the side effects of oral delivery of alendronate.« less

  1. Controlled antiseptic release by alginate polymer films and beads.

    PubMed

    Liakos, Ioannis; Rizzello, Loris; Bayer, Ilker S; Pompa, Pier Paolo; Cingolani, Roberto; Athanassiou, Athanassia

    2013-01-30

    Biodegradable polymeric materials based on blending aqueous dispersions of natural polymer sodium alginate (NaAlg) and povidone iodine (PVPI) complex, which allow controlled antiseptic release, are presented. The developed materials are either free standing NaAlg films or Ca(2+)-cross-linked alginate beads, which properly combined with PVPI demonstrate antibacterial and antifungal activity, suitable for therapeutic applications, such as wound dressing. Glycerol was used as the plasticizing agent. Film morphology was studied by optical and atomic force microscopy. It was found that PVPI complex forms well dispersed circular micro-domains within the NaAlg matrix. The beads were fabricated by drop-wise immersion of NaAlg/PVPI/glycerol solutions into aqueous calcium chloride solutions to form calcium alginate beads encapsulating PVPI solution (CaAlg/PVPI). Controlled release of PVPI was possible when the composite films and beads were brought into direct contact with water or with moist media. Bactericidal and fungicidal properties of the materials were tested against Escherichia coli bacteria and Candida albicans fungi. The results indicated very efficient antibacterial and antifungal activity within 48 h. Controlled release of PVPI into open wounds is highly desired in clinical applications to avoid toxic doses of iodine absorption by the wound. A wide variety of applications are envisioned such as external and internal wound dressings with controlled antiseptic release, hygienic and protective packaging films for medical devices, and polymer beads as water disinfectants.

  2. CONTROLLED RELEASE, BLIND TEST OF DNAPL REMEDIATION BY ETHANOL FLUSHING

    EPA Science Inventory

    A dense nonaqueous phase liquid (DNAPL) source zone was established within a sheet-pile
    isolated cell through a controlled release of perchloroethylene (PCE) to evaluate DNAPL
    remediation by in-situ cosolvent flushing. Ethanol was used as the cosolvent, and the main remedia...

  3. Biopolymers in controlled release devices for agricultural applications.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of biopolymers such as starch for agricultural applications including controlled release devices is growing due the environmental benefits. Recently, concerns have grown about the worldwide spread of parasitic mites (Varroa destructor) that infect colonies of honey bees (Apis mellifera L.). ...

  4. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    ERIC Educational Resources Information Center

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  5. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  6. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  7. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  8. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  9. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  10. Multifunctional conducting fibres with electrically controlled release of ciprofloxacin.

    PubMed

    Esrafilzadeh, Dorna; Razal, Joselito M; Moulton, Simon E; Stewart, Elise M; Wallace, Gordon G

    2013-08-10

    We hereby present a new method of producing coaxial conducting polymer fibres loaded with an antibiotic drug that can then be subsequently released (or sustained) in response to electrical stimulation. The method involves wet-spinning of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) fibre, which served as the inner core to the electropolymerised outer shell layer of polypyrrole (Ppy). Ciprofloxacin hydrochloride (Cipro) was selected as the model drug and as the dopant in the Ppy synthesis. The release of Cipro in phosphate buffered saline (PBS) from the fibres was controlled by switching the redox state of Ppy.Cipro layer. Released Cipro under passive and stimulated conditions were tested against Gram positive (Streptococcus pyogenes) and Gram negative (Escherichia coli) bacteria. Significant inhibition of bacterial growth was observed against both strains tested. These results confirm that Cipro retains antibacterial properties during fibre fabrication and electrochemically controlled release. In vitro cytotoxicity testing utilising the neural B35 cell line confirmed the cytocompatibility of the drug loaded conducting fibres. Electrical conductivity, cytocompatibility and tuning release profile from this flexible fibre can lead to promising bionic applications such as neuroprosthetics and localised drug delivery.

  11. Controlled release of ethylene via polymeric films for food packaging

    NASA Astrophysics Data System (ADS)

    Pisano, Roberto; Bazzano, Marco; Capozzi, Luigi Carlo; Ferri, Ada; Sangermano, Marco

    2015-12-01

    In modern fruit supply chain a common method to trigger ripening is to keep fruits inside special chambers and initiate the ripening process through administration of ethylene. Ethylene is usually administered through cylinders with inadequate control of its final concentration in the chamber. The aim of this study is the development of a new technology to accurately regulate ethylene concentration in the atmosphere where fruits are preserved: a polymeric film, containing an inclusion complex of α-cyclodextrin with ethylene, was developed. The complex was prepared by molecular encapsulation which allows the entrapment of ethylene into the cavity of α-cyclodextrin. After encapsulation, ethylene can be gradually released from the inclusion complex and its release rate can be regulated by temperature and humidity. The inclusion complex was dispersed into a thin polymeric film produced by UV-curing. This method was used because is solvent-free and involves low operating temperature; both conditions are necessary to prevent rapid release of ethylene from the film. The polymeric films were characterized with respect to thermal behaviour, crystalline structure and kinetics of ethylene release, showing that can effectively control the release of ethylene within confined volume.

  12. Microparticle dispensers for the controlled release of insect pheromones.

    PubMed

    Stipanovic, Arthur J; Hennessy, Patrick J; Webster, Francis X; Takahashi, Yae

    2004-04-21

    The potential utility of micrometer-sized particles as controlled-release devices for the volatilization of insect pheromones for mating disruption applications is evaluated in this study for two pheromone/model compound systems (codlemone/1-dodecanol and disparlure/1,2-epoxyoctadecane). To expedite the measurement of release rates from these particle devices, two techniques based on thermogravimetric analysis (TGA) have been exploited: isothermal TGA (I-TGA) at elevated temperatures (40-80 degrees C) with N(2) convection and volatilization temperature (VT) by dynamic TGA. A correlation between these two methods has been established. Samples that exhibit a higher VT provide a lower release rate from a particle substrate. Using these techniques, it has been demonstrated that chemical interactions between adsorbed liquids and particle surfaces may play a small role in defining release characteristics under conditions of low surface area, whereas parameters associated with total surface area and micropore structure appear to be much more significant in retarding evaporation for uncoated particles containing an adsorbed liquid. Additional regulation of release rates was achieved by coating the particle systems with water-soluble or water-dispersible polymers. By careful selection of particle porosity and coating composition, it is envisioned that the evaporation rate of pheromones can be tailored to specific insect control applications.

  13. Polymer-xerogel composites for controlled release wound dressings.

    PubMed

    Costache, Marius C; Qu, Haibo; Ducheyne, Paul; Devore, David I

    2010-08-01

    Many polymers and composites have been used to prepare active wound dressings. These materials have typically exhibited potentially toxic burst release of the drugs within the first few hours followed by a much slower, potentially ineffective drug release rate thereafter. Many of these materials also degraded to produce inflammatory and cytotoxic products. To overcome these limitations, composite active wound dressings were prepared here from two fully biodegradable and tissue compatible components, silicon oxide sol-gel (xerogel) microparticles that were embedded in tyrosine-poly(ethylene glycol)-derived poly(ether carbonate) copolymer matrices. Sustained, controlled release of drugs from these composites was demonstrated in vitro using bupivacaine and mepivacaine, two water-soluble local anesthetics commonly used in clinical applications. By systematically varying independent compositional parameters of the composites, including the hydrophilic:hydrophobic balance of the tyrosine-derived monomers and poly(ethylene glycol) in the copolymers and the porosity, weight ratio and drug content of the xerogels, drug release kinetics approaching zero-order were obtained. Composites with xerogel mass fractions up to 75% and drug payloads as high as 13% by weight in the final material were fabricated without compromising the physical integrity or the controlled release kinetics. The copolymer-xerogel composites thus provided a unique solution for the sustained delivery of therapeutic agents from tissue compatible wound dressings.

  14. Use of polysulfone in controlled-release NPK fertilizer formulations.

    PubMed

    Tomaszewska, Maria; Jarosiewicz, Anna

    2002-07-31

    Encapsulation of fertilizers in polymeric coatings is a method used to reduce fertilizer losses and to minimize environmental pollution. Polysulfone was used for a coating preparation for soluble NPK granular fertilizer in controlled-release fertilizer formulations. The coatings were formed by the phase inversion technique (wet method). The influence of the polymer concentration in the film-forming solution on the physical properties of the coatings was examined. The coating structure controls the diffusion of the elements from the interior of the fertilizer granule. It was experimentally confirmed that the use of polysulfone as a coating for a soluble fertilizer decreases the release rate of components. Moreover, the release rate of nutrients from coated granules decreases with the decrease of the coating porosity. In the case of coating with 38.5% porosity, prepared from 13.5% polymer solution after 5 h of test, 100% of NH(4)(+) was released, whereas only 19.0% of NH(4)(+) was released after 5 h for the coating with 11% porosity. In addition, coating of fertilizers leads to improvement of handling properties, and the crushing strength of all coated fertilizers was an average 40% higher than that for uncoated NPK fertilizer.

  15. Controlled release of molecular components of dendrimer/bioactive complexes

    DOEpatents

    Segalman, Daniel J.; Wallace, J. Shield

    1998-01-01

    A method for releasing molecules (guest molecules) from the matrix formed by the structure of another molecule (host molecule) in a controllable manner has been invented. This method has many applications in science and industry. In addition, applications based on such molecular systems may revolutionize significant areas of medicine, in particular the treatment of cancer and of viral infection. Similar effects can also be obtained by controlled fragmentation of a source molecule, where the molecular fragments form the active principle.

  16. Controlled release of molecular components of dendrimer/bioactive complexes

    DOEpatents

    Segalman, D.J.; Wallace, J.S.

    1998-08-18

    A method for releasing molecules (guest molecules) from the matrix formed by the structure of another molecule (host molecule) in a controllable manner has been invented. This method has many applications in science and industry. In addition, applications based on such molecular systems may revolutionize significant areas of medicine, in particular the treatment of cancer and of viral infection. Similar effects can also be obtained by controlled fragmentation of a source molecule, where the molecular fragments form the active principle. 13 figs.

  17. Polyelectrolyte complexes stabilize and controllably release vascular endothelial growth factor.

    PubMed

    Huang, Min; Vitharana, Samadhi N; Peek, Laura J; Coop, Tina; Berkland, Cory

    2007-05-01

    Angiogenesis has long been a desired therapeutic approach to improve clinical outcomes of conditions typified by ischemia. Vascular endothelial growth factor (VEGF) has demonstrated the ability to generate new blood vessels in vivo, but trials using intravenous delivery have not yet produced clinical success. Localized, sustained delivery of VEGF has been proven necessary to generate blood vessels as demonstrated by implantable, controlled release devices. Ultimately, nanoparticles delivered by intravenous injection may be designed to accumulate in target tissues and sustain the local VEGF concentration; however, injectable nanosuspensions that control the release of stabilized VEGF must first be developed. In this study, we utilize the heparin binding domain of VEGF to bind the polyanion dextran sulfate, resulting in an enhanced thermal stability of VEGF. Coacervation of the VEGF-bound dextran sulfate with selected polycations (chitosan, polyethylenimine, or poly-L-lysine) produced nanoparticles approximately 250 nm in diameter with high VEGF encapsulation efficiency (50-85%). Release of VEGF from these formulations persisted for >10 days and maintained high VEGF activity as determined by ELISA and a mitogenic bioassay. Chitosan-dextran sulfate complexes were preferred because of their biodegradability, desirable particle size ( approximately 250 nm), entrapment efficiency ( approximately 85%), controlled release (near linear for 10 days), and mitogenic activity.

  18. Controlled-release systems for the insect growth regulator pyriproxyfen.

    PubMed

    Schwartz, Liliana; Wolf, David; Markus, Arie; Wybraniec, Sławomir; Wiesman, Zeev

    2003-09-24

    A simple technique was developed for the production of controlled-release systems (CRSs) for pyriproxyfen, an insect growth regulator active against the larvae of Culex pipiens, the most common species of mosquito found in developed countries. The CRSs consisted of a spongy core material encapsulated in a coating of a polyurethane or polyurea hydrogel, into which the active ingredient had been incorporated. The coating also included a surfactant to improve the low solubility in water of pyriproxyfen. The light core material enabled the CRS to float on the water surface, where the mosquitoe larvae are found. The type and amount of the polymeric coating and the amount of surfactant influenced the release profiles into water of the active ingredient. The release profiles of the CRSs were adjusted to the life cycle of the C. pipiens mosquito in order to obtain their optimal activity on the eighth day, which corresponds to the time of larval maturity.

  19. Intelligent type controlled release systems by radiation techniques

    NASA Astrophysics Data System (ADS)

    Kaetsu, Isao; Uchida, Kumao; Shindo, Hironori; Gomi, Seiji; Sutani, Kouichi

    1999-06-01

    Intelligent controlled release systems have been designed and constructed. The systems have a sensor-actuator gate consisting of polyelectrolyte hydrogel layer with immobilized enzymes inside fine holes of polyethylene terephthalate (PET) film and silicon wafer as base materials. Excimer-laser or ion-beam irradiation was used for the etching of holes in PET film and photo-lithography was used for the etching of silicon wafer. U.V. and γ-ray irradiations were used for the polymerization and immobilization of electrolyte layers in the holes. Various kinds of signal responsive release systems such as pH responsive, substrate responsive, Ca 2+ responsive, photo-responsive and electric field responsive systems have been developed using those techniques. Some integrated systems have been designed and constructed by combination of unit systems in series and in parallel and proved the selective signal transfer and the successive signal responsive release functions.

  20. Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release.

    PubMed

    Rao, Lang; Meng, Qian-Fang; Huang, Qinqin; Liu, Pei; Bu, Lin-Lin; Kondamareddy, Kiran Kumar; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

    2016-06-01

    Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane-coated nanocarriers for controlled drug delivery is demonstrated.

  1. Optogenetic Control of Serotonin and Dopamine Release in Drosophila Larvae

    PubMed Central

    2014-01-01

    Optogenetic control of neurotransmitter release is an elegant method to investigate neurobiological mechanisms with millisecond precision and cell type-specific resolution. Channelrhodopsin-2 (ChR2) can be expressed in specific neurons, and blue light used to activate those neurons. Previously, in Drosophila, neurotransmitter release and uptake have been studied after continuous optical illumination. In this study, we investigated the effects of pulsed optical stimulation trains on serotonin or dopamine release in larval ventral nerve cords. In larvae with ChR2 expressed in serotonergic neurons, low-frequency stimulations produced a distinct, steady-state response while high-frequency patterns were peak shaped. Evoked serotonin release increased with increasing stimulation frequency and then plateaued. The steady-state response and the frequency dependence disappeared after administering the uptake inhibitor fluoxetine, indicating that uptake plays a significant role in regulating the extracellular serotonin concentration. Pulsed stimulations were also used to evoke dopamine release in flies expressing ChR2 in dopaminergic neurons and similar frequency dependence was observed. Release due to pulsed optical stimulations was modeled to determine the uptake kinetics. For serotonin, Vmax was 0.54 ± 0.07 μM/s and Km was 0.61 ± 0.04 μM; and for dopamine, Vmax was 0.12 ± 0.03 μM/s and Km was 0.45 ± 0.13 μM. The amount of serotonin released per stimulation pulse was 4.4 ± 1.0 nM, and the amount of dopamine was 1.6 ± 0.3 nM. Thus, pulsed optical stimulations can be used to mimic neuronal firing patterns and will allow Drosophila to be used as a model system for studying mechanisms underlying neurotransmission. PMID:24849718

  2. Cellulose, chitosan, and keratin composite materials. Controlled drug release.

    PubMed

    Tran, Chieu D; Mututuvari, Tamutsiwa M

    2015-02-03

    A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm(+)Cl(-)]), an ionic liquid, was used as the sole solvent, and because the [BMIm(+)Cl(-)] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds.

  3. Sustainable practices for fertilizer use through controlled release techniques

    NASA Astrophysics Data System (ADS)

    Faez, Roselena; Messa, Lucas; Froes, José; Souza, Claudinei

    2015-04-01

    Controlled release fertilizers are efficient tools that increase the sustainability of agricultural practices. However, the biodegradability of the matrices and the determination of the release into soil still require some investigation. This work describes the preparation of potassium-containing microspheres based on chitosan- montmorillonite clay as fertilizer double coated. The release profile in water (ion conductivity measurement) and soil (ion movement performed with time-domain reflectometry (TDR) technique) were evaluated. The potassium-containing microspheres were placed in a 7.5-L container filled with soil (Typic dystrophic LVd). The container was prepared with a water drainage system consisting of a thin layer of gravel at the bottom, which was followed by a geotextile fabric to prevent the loss of soil. The container was filled with soil (9 kg) in layers of 0.05 m to simulate the original bulk density of 1.30 g.cm-3. Each container received 4 g of microspheres placed at a single spot. They were placed at a depth of 10 cm. The fertilizer release was monitored using three electromagnetic probes for TDR that consisted of three continuous metal rods of 20 cm, which were in contact with the material and can be used to estimate the moisture and electrical conductivity. One probe was installed at the center of the container, which meant the rod was in contact with the microspheres in the soil. The other two probes were installed 5 cm from the central probe, and they were only in contact with the soil. Therefore, the purpose of these probes was to monitor the lateral displacement of the fertilizer from the microspheres in the soil. The release in water is fast than in soil, since the total amount of fertilizer in water was delivery during only one week and in soil during 60 days the fertilizer still continue drifting. The composite based on chitosan biopolymer as controlled release material is an efficient method to monitor the fertilizer consumption.

  4. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    NASA Astrophysics Data System (ADS)

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T.; Khashab, Niveen M.; Kosel, Jurgen

    2016-06-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  5. Thermally controlled protein release from gelatin dextran hydrogels

    NASA Astrophysics Data System (ADS)

    Aso, Y.; Yoshioka, S.; Nakai, Y.; Kojima, S.

    1999-06-01

    Biodegradable hydrogels in which drug release was controlled by sol-gel transition were prepared. Gelatin was used as a component because it exhibits sol-gel transition in response to temperature changes. Glycidyl methacrylated (GMA) dextran was crosslinked by low dose γ-irradiation in the presence of gelatin and the model drugs, β-galactosidase ( β-GA), bovine serum albumin (BSA) or 5-fluorouracil (5-FU). The enzyme activity of β-GA remained greater than 95% after irradiation. Temperature-responsive release of β-GA and BSA resulted from the sol-gel transition of gelatin. Sol-gel transition was confirmed by the temperature dependence of the spin-spin relaxation time of the gel polymer protons. The protein release rate was affected by both the degree of GMA substitution and the gelatin concentration. Desired release rate could be achieved by adjusting these factors. The release rate of 5-FU was not affected by the sol-gel transition of gelatin.

  6. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    PubMed Central

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T.; Khashab, Niveen M.; Kosel, Jurgen

    2016-01-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads. PMID:27335342

  7. pH-controlled drug release for dental applications

    NASA Astrophysics Data System (ADS)

    Wironen, John Francis

    A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

  8. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine.

    PubMed

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions.

  9. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine

    PubMed Central

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions. PMID:26839847

  10. A new biodegradable polythiourethane as controlled release matrix polymer.

    PubMed

    Campiñez, M D; Ferris, C; de Paz, M V; Aguilar-de-Leyva, A; Galbis, J; Caraballo, I

    2015-03-01

    The main aim of this paper is the synthesis and characterization of a new linear functional biodegradable polythiourethane-d,l-1,4-dithiothreitol-hexamethylene diisocyanate [PTU(DTT-HMDI)]. The SeDeM diagram has been obtained to investigate its suitability to be processed through a direct compression process. Furthermore, the ability of this polymer to act as controlled release matrix forming excipient has been studied. Four batches of matrices containing 10-40% of polymer and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using the paddle method and the polymer percolation threshold has been estimated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index (IGC=4.59) for the polymer are very close to the values considered as adequate for direct compression even with no addition of flow agents. Furthermore, the results of the drug release studies show a high ability of the polymer to control the drug release. The excipient percolation threshold has been estimated between 20% and 30% w/w of polymer.

  11. Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

    PubMed Central

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil. PMID:24696655

  12. Controlled release of agrochemicals intercalated into montmorillonite interlayer space.

    PubMed

    Wanyika, Harrison

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil.

  13. Controlled release for local delivery of drugs: barriers and models.

    PubMed

    Weiser, Jennifer R; Saltzman, W Mark

    2014-09-28

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors - such as diffusion, convection, and elimination - that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin.

  14. Differential activation of the μ-opioid receptor by oxycodone and morphine in pain-related brain regions in a bone cancer pain model

    PubMed Central

    Nakamura, Atsushi; Hasegawa, Minoru; Minami, Kazuhisa; Kanbara, Tomoe; Tomii, Takako; Nishiyori, Atsushi; Narita, Minoru; Suzuki, Tsutomu; Kato, Akira

    2013-01-01

    Background and Purpose Bone cancer pain is chronic and often difficult to control with opioids. However, recent studies have shown that several opioids have distinct analgesic profiles in chronic pain. Experimental Approach To clarify the mechanisms underlying these distinct analgesic profiles, functional changes in the μ-opioid receptor were examined using a mouse femur bone cancer (FBC) model. Key Results In the FBC model, the Bmax of [3H]-DAMGO binding was reduced by 15–45% in the periaqueductal grey matter (PAG), region ventral to the PAG (vPAG), mediodorsal thalamus (mTH), ventral thalamus and spinal cord. Oxycodone (10−8–10−5 M) and morphine (10−8–10−5 M) activated [35S]-GTPγS binding, but the activation was significantly attenuated in the PAG, vPAG, mTH and spinal cord in the FBC model. Interestingly, the attenuation of oxycodone-induced [35S]-GTPγS binding was quite limited (9–26%) in comparison with that of morphine (46–65%) in the PAG, vPAG and mTH, but not in the spinal cord. Furthermore, i.c.v. oxycodone at doses of 0.02–1.0 μg per mouse clearly inhibited pain-related behaviours, such as guarding, limb-use abnormalities and allodynia-like behaviour in the FBC model mice, while i.c.v. morphine (0.05–2.0 μg per mouse) had only partial or little analgesic effect on limb-use abnormalities and allodynia-like behaviour. Conclusion and Implications These results show that μ-opioid receptor functions are attenuated in several pain-related regions in bone cancer in an agonist-dependent manner, and suggest that modification of the μ-opioid receptor is responsible for the distinct analgesic effect of oxycodone and morphine. PMID:22889192

  15. Controlled release of carbofuran from an alginate-bentonite formulation: water release kinetics and soil mobility.

    PubMed

    Fernández-Pérez, M; Villafranca-Sánchez, M; González-Pradas, E; Martinez-López, F; Flores-Céspedes, F

    2000-03-01

    The insecticide-nematicide carbofuran was incorporated in alginate-based granules to obtain controlled-release (CR) properties. The basic formulation [sodium alginate (1.61%)-carbofuran (0. 59%)-water] was modified by addition of sorbents. The effect on carbofuran release rate, caused by the incorporation of natural and acid-treated bentonite (0.5 and 1.0 M H(2)SO(4)) in alginate formulation, was studied by immersion of the granules in water under shaking. The time taken for 50% of the active ingredient to be released into water, t(50), was longer for those formulations containing natural bentonite (6.1 h) or acid-treated bentonite (9.0 and 11.7 h for 0.5 and 1.0 M H(2)SO(4) treatments, respectively) than for the preparation without bentonite (4.7 h). It appears from the results that the release of carbofuran from the various formulations is controlled by a diffusion mechanism according to the n values obtained, which were close to 0.5 in all cases. The mobility of carbofuran from alginate-based CR formulations was investigated by using soil columns packed with a clay soil (53% clay and 0.08% organic matter). Two alginate-based CR formulations containing natural bentonite or acid-treated bentonite (0.5 M H(2)SO(4)) were compared to technical grade carbofuran. The use of alginate-based CR formulations resulted in a reduction of the leached amount of carbofuran compared with the total amount of pesticide leached using the technical product (50 and 75% for CR granules containing natural and acid-treated bentonite, respectively). Alginate-bentonite CR formulations might be efficient systems for reducing carbofuran leaching in clay soils, which would reduce the risk of groundwater pollution.

  16. Stability indicating HPLC method for the estimation of oxycodone and lidocaine in rectal gel.

    PubMed

    Gebauer, M G; McClure, A F; Vlahakis, T L

    2001-07-31

    An HPLC method for the quantification of oxycodone and lidocaine in a gel matrix is described. The mobile phase consisted of methanol--water--acetic acid (35:15:1 v/v/v) and was delivered at 1.5 ml/min through a 4.6 x 250 mm Zorbax SB-C8 column. Oxycodone was detected at 285 nm and lidocaine at 264 nm. Linear calibration curves were obtained for oxycodone in the range of 0.05--1.5% (w/w) and for lidocaine in the range of 0.1--5.0% (w/w). Oxycodone and lidocaine were treated with hydrogen peroxide and the oxidation products were readily separated on the column. The method was applied to assess the stability of a gel containing oxycodone hydrochloride (0.3% w/w) and lidocaine (1.5% w/w). The gel was stored under refrigeration in ready-to-use syringes and under these conditions oxycodone and lidocaine were stable for at least 1 year. The gel is useful in the management of tenesmus in rectal cancer.

  17. Controlled Release System for Localized and Sustained Drug Delivery Applications

    NASA Astrophysics Data System (ADS)

    Rodriguez, Lidia Betsabe

    Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is

  18. Controlled exosome release from the retinal pigment epithelium in situ.

    PubMed

    Locke, Christina J; Congrove, Nicole R; Dismuke, W Michael; Bowen, Trent J; Stamer, W Daniel; McKay, Brian S

    2014-12-01

    Retinal Pigment Epithelial cells (RPE) express both GPR143 and myocilin, which interact in a signal transduction-dependent manner. In heterologous systems, activation of GPR143 with ligand causes transient recruitment of myocilin to internalized receptors, which appears to be the entry point of myocilin to the endocytic pathway. In some but not all cells, myocilin also traffics through the multivesicular body (MVB) and is released on the surface of exosomes in a signal transduction-dependent fashion. Little is known regarding the role of exosomes in RPE, but they likely serve as a mode of communication between the RPE and the outer retina. In this study, we used posterior poles with retina removed from fresh human donor eyes as a model to test the relationship between GPR143, myocilin, and exosomes in an endogenous system. We isolated exosomes released by RPE using differential centrifugation of media conditioned by the RPE for 25 min, and then characterized the exosomes using nanoparticle tracking to determine the number and size of the exosomes. Next, we tested whether ligand stimulation of GPR143 using l-DOPA altered RPE exosome release. Finally, we investigated whether myocilin was present on the exosomes released by RPE and whether l-DOPA stimulation of GPR143 caused recruitment of myocilin to the endocytic pathway, as we have previously observed using cultured cells. Activation of GPR143 halted RPE exosome release, while simultaneously recruiting myocilin to the endocytic compartment. Together, our results indicate that GPR143 and myocilin function in a signal transduction system that can control exosome release from RPE.

  19. Dendrimeric micelles for controlled drug release and targeted delivery

    PubMed Central

    Ambade, Ashootosh V.; Savariar, Elamprakash N.; Thayumanavan, S.

    2008-01-01

    This review highlights the developments in dendrimer-based micelles for drug delivery. Dendrimers, the perfectly branched monodisperse macromolecules, have certain structural advantages that make them attractive candidates as drug carriers for controlled release or targeted delivery. As polymeric micelle-based approaches precede the work in dendrimers, these are also discussed briefly. The review concludes with a perspective on possible applications of biaryl-based dendrimeric micelles that exhibit environment-dependent conformations, in drug delivery. PMID:16053329

  20. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

    PubMed Central

    Vijayakumar, Vediappan; Subramanian, Kaliappagounder

    2013-01-01

    Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

  1. Efficacy and gastrointestinal tolerability of oral oxycodone/naloxone combination for chronic pain in outpatients with cancer: an observational study.

    PubMed

    Cuomo, Arturo; Russo, Gennaro; Esposito, Gennaro; Forte, Cira Antonietta; Connola, Marianna; Marcassa, Claudio

    2014-12-01

    Combination opioid agonist/antagonist therapy has been shown to preserve bowel function in patients with chronic cancer pain. This retrospective study evaluated the efficacy and tolerability of prolonged-released fixed-dose oxycodone-naloxone (PR OXN) in consecutive outpatients with chronic cancer pain. Of 206 patients prescribed PR OXN (mean age 61.3 ± 12.9 years; 52.9% female), 31.5% were opioid naïve. PR OXN was associated with a significant decrease in pain score measured on a visual analogue scale over 28 days (P < .0001), without adverse effects on bowel function, nor change in laxative use. PR OXN efficacy and tolerability were similar in opioid-naïve and -experienced patients, and among age-stratified subgroups. No severe side effects occurred. In a real-life outpatient setting, PR OXN provided analgesia without bowel dysfunction in patients with chronic cancer pain.

  2. Corrected QT interval prolongation after an overdose of escitalopram, morphine, oxycodone, zopiclone and benzodiazepines.

    PubMed

    Baranchuk, Adrian; Simpson, Christopher S; Methot, Michelle; Gibson, Kara; Strum, David

    2008-07-01

    Escitalopram is the recently marketed S-enantiomer of the widely used antidepressant citalopram. Data from intentional overexposure to this medication are limited. Twelve-lead electrocardiogram (ECG) effects from racemic citalopram have been described; however, the present report is the first, to the best of the authors' knowledge, that describes all the reported abnormalities in a single patient receiving escitalopram. A 52-year-old man with a history of depression treated with escitalopram 10 mg/day, extended-release morphine 30 mg/day and zopiclone 15 mg/day was found unconscious at his home. He was known to have attempted suicide three weeks previously. Partially emptied bottles of escitalopram, morphine, oxycodone, zopiclone, lorazepam and diazepam were found close to the patient. He was transferred to the emergency department, where airway management and other supportive care were initiated. The patient was transferred to the intensive care unit. The initial 12-lead ECG demonstrated junctional rhythm at 48 beats/min, a wide complex escape (145 ms) with right bundle branch morphology and a prolonged corrected QT interval at 650 ms. Cardiac monitoring was undertaken. No ventricular arrhythmias or torsade de pointes were detected. No specific treatment for shortening the QT was implemented. Another 12-lead ECG performed 48 h later demonstrated sinus tachycardia with a normal corrected QT, normal PR interval and normal QRS duration. The effects of the overdose of escitalopram on the ECG and its interactions with other drugs are reviewed.

  3. Understanding controlled drug release from mesoporous silicates: theory and experiment.

    PubMed

    Ukmar, T; Maver, U; Planinšek, O; Kaučič, V; Gaberšček, M; Godec, A

    2011-11-07

    Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes.

  4. Osmotic, controlled-release methylphenidate for the treatment of ADHD.

    PubMed

    Coghill, David; Seth, Sarah

    2006-10-01

    Methylphenidate (MPH) is the most commonly used and best-studied stimulant medication for attention-deficit hyperactivity disorder. However, its short duration of action usually results in a requirement to administer multiple daily doses in order to achieve optimal clinical benefit. Although a wax-matrix-based SR formulation of MPH has been available since the 1990s, it was not well accepted into clinical practice. The variable absorption profile and lack of an immediate-release component results in a slower onset of action compared with immediate-release MPH. Hence, there was a need to develop alternative longer-lasting preparations of MPH that were as efficacious as IR MPH, but which also addressed the problems inherent in multiple daily dosing. An osmotic, controlled-release (OROS) formulation of MPH HCl has been developed over the past 10 years for once-daily administration. OROS MPH has been widely accepted by clinicians and is now the most widely prescribed MPH product in North America. Clinical trials have shown OROS MPH to have a continued action over a 12-h period, to be superior to placebo and to be as effective as immediate-release MPH dosed three times daily, in reducing symptoms of attention-deficit hyperactivity disorder, with similar incidence of side effects. There have been a smaller number of trials comparing OROS MPH with non-stimulant treatments, such as atomoxetine.

  5. Nanovalve-Controlled Cargo Release Activated by Plasmonic Heating

    PubMed Central

    Croissant, Jonas; Zink, Jeffrey I.

    2012-01-01

    The synthesis and operation of a light-operated nanovalve that controls the pore openings of mesoporous silica nanoparticles containing gold cores nanoparticles is described. The nanoparticles, consisting of 20 nm gold cores inside ~150 nm mesoporous silica spheres, were synthesized using a unique one-pot method. The nanovalves are comprised of cucurbit[6]uril rings encircling stalks that are attached to the ~2 nm pore openings. Plasmonic heating of the gold core raises the local temperature and decreases the ring-stalk binding constant, thereby unblocking the pore and releasing the cargo molecules that were preloaded inside. Bulk heating of the suspended particles to 60 °C is required to release the cargo, but no bulk temperature change was observed in the plasmonic heating release experiment. High intensity irradiation caused thermal damage to the silica particles, but low intensity illumination caused a sufficient local temperature increase to operate the valves without damaging the nanoparticles containers. These light-stimulated, thermally activated mechanized nanoparticles demonstrate a new system with potential utility for on-command drug release. PMID:22540671

  6. Multimonth controlled small molecule release from biodegradable thin films

    PubMed Central

    Hsu, Bryan B.; Park, Myoung-Hwan; Hagerman, Samantha R.; Hammond, Paula T.

    2014-01-01

    Long-term, localized delivery of small molecules from a biodegradable thin film is challenging owing to their low molecular weight and poor charge density. Accomplishing highly extended controlled release can facilitate high therapeutic levels in specific regions of the body while significantly reducing the toxicity to vital organs typically caused by systemic administration and decreasing the need for medical intervention because of its long-lasting release. Also important is the ability to achieve high drug loadings in thin film coatings to allow incorporation of significant drug amounts on implant surfaces. Here we report a sustained release formulation for small molecules based on a soluble charged polymer–drug conjugate that is immobilized into nanoscale, conformal, layer-by-layer assembled films applicable to a variety of substrate surfaces. We measured a highly predictable sustained drug release from a polymer thin film coating of 0.5–2.7 μm that continued for more than 14 mo with physiologically relevant drug concentrations, providing an important drug delivery advance. We demonstrated this effect with a potent small molecule nonsteroidal anti-inflammatory drug, diclofenac, because this drug can be used to address chronic pain, osteoarthritis, and a range of other critical medical issues. PMID:25092310

  7. Development of controlled drug release systems based on thiolated polymers.

    PubMed

    Bernkop-Schnürch, A; Scholler, S; Biebel, R G

    2000-05-03

    The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

  8. Controlled release of ibuprofen by meso-macroporous silica

    NASA Astrophysics Data System (ADS)

    Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J. M.; González, C.

    2014-02-01

    Structured meso-macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EO19PO39EO19) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption-desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso-macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system.

  9. Optical control of insulin release using a photoswitchable sulfonylurea

    PubMed Central

    Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C.; Frank, James A.; Marchetti, Piero; Bugliani, Marco; Shapiro, A. M. James; Trapp, Stefan; Rutter, Guy A.; Hodson, David J.; Trauner, Dirk

    2014-01-01

    Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM. PMID:25311795

  10. Optical control of insulin release using a photoswitchable sulfonylurea.

    PubMed

    Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C; Frank, James A; Marchetti, Piero; Bugliani, Marco; Shapiro, A M James; Trapp, Stefan; Rutter, Guy A; Hodson, David J; Trauner, Dirk

    2014-10-14

    Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM.

  11. Graphene as a photothermal switch for controlled drug release

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Tatini, Francesca; Cavigli, Lucia; Ottaviano, Stefania; Ghini, Giacomo; Pini, Roberto

    2014-06-01

    Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor-made pharmacological treatments of chronic diseases, including cancer, anaemia and diabetes.Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor

  12. Controlled release of ibuprofen by meso–macroporous silica

    SciTech Connect

    Santamaría, E. Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-02-15

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5

  13. INVITED PAPER: Control of sudden releases in channel flow

    NASA Astrophysics Data System (ADS)

    Katopodes, Nikolaos D.

    2009-12-01

    We present a method for the detection and real-time control of chemical releases in channel flow. Sensor arrays capable of detecting a broad menu of chemical agents are required at strategic locations of the channel. The sensors detect the instantaneous, spatially distributed concentration of the chemical agent and transmit the associated information to a predictive control model. The model provides optimal operation scenarios for computer controlled bleed valves mounted on the channel walls and connected to a common manifold. Control and elimination of the chemical cloud are achieved by optimal blowing and suction of ambient fluid. Gradient information is obtained by use of adjoint equations, so optimization of the control actions is achieved with the highest possible efficiency. The control is optimized over a finite prediction horizon and instructions are sent to the valve manifold. Next, the sensor arrays detect all changes effected by the control and report them to the control model, which advances the process over the next control horizon. Non-reflective boundary conditions for the adjoint equations are derived by a characteristic analysis, which minimizes spurious information in the computation of sensitivities.

  14. Controlled release of plasmid DNA from hyaluronan nanoparticles.

    PubMed

    Mahor, Sunil; Collin, Estelle; Dash, Biraja C; Pandit, Abhay

    2011-07-01

    Encapsulation of plasmid DNA (pDNA) in nanoparticulate gene delivery systems offers the possibility of control in dosing, enhanced pDNA uptake, increased resistance to nuclease degradation and sustained release of functionally active pDNA over time. Extracellular matrix based biomaterial i.e. hyaluronan (HA) was used to encapsulate pDNA (pCMV-GLuc, Gaussia Luciferase reporter plasmid DNA having CMV promoter) in submicron size particulate system. Nano size range (~400-600 nm) pDNA loaded hyaluronan nanoparticles were formulated by ionic gelation followed by the cross-linking method with high encapsulation efficiency (~75-85%). The particle preparation process was further optimized for molecular weight, cross-linking method, cross-linking time and plasmid/polymer ratio. The entrapped plasmid maintained its structural and functional integrity as revealed by agarose gel electrophoresis. The pDNA was released from the hyaluronan nanoparticles in a controlled manner over a period of one month. In vitro transfection by one-week released pDNA from nanoparticles with transfecting agent branched polyethyleneimine (bPEI) resulted in significantly higher expression levels than those in pDNA alone which demonstrated the functional bioactivity of released pDNA. For cellular localization studies, the hyaluronan nanoparticles encapsulated with FITC-dextran were incubated with adipose derived stem cells (ADSCs) and localization in the cellular environment were investigated. The results of this study illustrate that hyaluronan nanoparticles were rapidly internalized by the cells through nonspecific endocytosis and remained intact in the cytosol for up to 24 h.

  15. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer

    PubMed Central

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-01-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse “L” curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was “S” curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies. PMID:26348791

  16. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer.

    PubMed

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-09-08

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse "L" curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was "S" curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies.

  17. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer

    NASA Astrophysics Data System (ADS)

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-09-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse “L” curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was “S” curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies.

  18. A microfluidic chip for controlled release of drugs from microcapsules

    PubMed Central

    Cheng, Wen-Chuan; He, Yuan; Chang, An-Yi; Que, Long

    2013-01-01

    A new microfluidic device with liquid-droplet merging and droplet storage functions for the controlled release of drugs from microcapsules is reported. A switching channel is designed and integrated within the microfluidic device, facilitating the generation and capturing of uniform droplets by the storage chambers. The drug model is the MnCO3 microparticle, which is encapsulated by a microcapsule and fabricated using a simple layer-by-layer nanoassembly process. The merging function is used for dynamically adding the control solution into the droplets, which contain drugs within the microcapsules (DWμCs) and water. The storage chambers are used for collecting DWμCs-laden droplets so that the controlled-drug release in specific droplets can be monitored for an extended period of time, which has been experimentally implemented successfully. This technology could offer a promising technical platform for the long-term observation and studies of drug effects on specific cells in a controlled manner, which is especially useful for single cell analysis. PMID:24396536

  19. Voltage-Responsive Controlled Release Film with Cargo Release Self-Monitoring Property Based on Hydrophobicity Switching.

    PubMed

    Jiao, Xiangyu; Li, Yanan; Li, Fengyu; Sun, Ruijuan; Wang, Wenqian; Wen, Yongqiang; Song, Yanlin; Zhang, Xueji

    2017-03-16

    Herein, voltage-responsive controlled release film was constructed by grafting ferrocene on the mesoporous inverse opal photonic crystal (mIOPC). The film achieved free-blockage controlled release and realized the monitoring of cargo release without external indicator. Free-blockage was attributed to the voltage switchable nanovalves which undergo hydrophobic-to-hydrophilic transition when applying voltage. Monitoring of cargo release was attributed to the optical property of mIOPC, the bandgap of mIOPC had a red shift when the solution invaded in. The film was hydrophobic enough to stop solution intrusion. Once the voltage was applied, the film became hydrophilic, leading to invasion of the solution. As a result, the cargos were released and the bandgap of mIOPC was red-shifted. Therefore, in this paper both a free-blockage controlled release film and a release sensing system was prepared. The study provides new insights into highly effective controlled release and release sensing without indicator.

  20. Sex differences in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone in the Sprague-Dawley rat.

    PubMed

    Chan, Samuel; Edwards, Stephen R; Wyse, Bruce D; Smith, Maree T

    2008-03-01

    1. The pharmacokinetics and oxidative metabolism of oxycodone were investigated following intravenous and oral administration in male and female Sprague-Dawley (SD) rats. 2. High-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS) was used to quantify plasma concentrations of oxycodone and its oxidative metabolites noroxycodone and oxymorphone following administration of single bolus intravenous (5 mg/kg) and oral (10 mg/kg) doses of oxycodone. 3. The mean (+/-SEM) clearance of intravenous oxycodone was significantly higher in male than female SD rats (4.9 +/- 0.3 vs 3.1 +/- 0.3 L/h per kg, respectively; P < 0.01). Mean areas under the plasma concentration versus time curves (AUC) for oxycodone were significantly higher in female than male SD rats following intravenous (approximately 1.6-fold; P < 0.01) and oral (approximately sevenfold; P < 0.005) administration. 4. The oral bioavailability of oxycodone was low (at 1.2 and 5.0%, respectively) in male and female SD rats, a finding consistent with high first-pass metabolism. Noroxycodone : oxycodone AUC ratios were significantly higher in male than female SD rats after intravenous (approximately 2.4-fold; P < 0.005) and oral (approximately 12-fold; P < 0.005) administration. 5. Circulating oxymorphone concentrations remained very low following both routes of administration. Noroxycodone : oxymorphone AUC ratios were greater in male than female SD rats after intravenous (approximately 13- and fivefold, respectively) and oral (approximately 90- and sixfold, respectively) administration. 6. Sex differences were apparent in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone. Systemic exposure to oxycodone was greater in female compared with male SD rats, whereas systemic exposure to metabolically derived noroxycodone was higher in male than female SD rats. 7. Oral administration of oxycodone to the SD rat is a poor model of the human for

  1. A mathematical model for pulsatile release: controlled release of rhodamine B from UV-crosslinked thermoresponsive thin films.

    PubMed

    Yang, Rongbing; Vo T N, Tuoi; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Meere, Martin G; Rochev, Yury

    2012-05-10

    A controlled drug delivery system fabricated from a thermoresponsive polymer was designed to obtain a pulsatile release profile which was triggered by altering the temperature of the dissolution medium. Two stages of release behaviour were found: fast release for a swollen state and slow (yet significant and non-negligible) release for a collapsed state. Six cycles of pulsatile release between 4 °C and 40 °C were obtained. The dosage of drug (rhodamine B) released in these cycles could be controlled to deliver approximately equal doses by altering the release time in the swollen state. However, for the first cycle, the swollen release rate was found to be large, and the release time could not be made short enough to prevent a larger dose than desired being delivered. A model was developed based on Fick's law which describes pulsatile release mathematically for the first time, and diffusion coefficients at different temperatures (including temperatures corresponding to both the fully swollen and collapsed states) were estimated by fitting the experimental data with the theoretical release profile given by this model. The effect of temperature on the diffusion coefficient was studied and it was found that in the range of the lower critical solution temperature (LCST), the diffusion coefficient increased with decreasing temperature. The model predicts that the effective lifetime of the system lies in the approximate range of 1-42 h (95% of drug released), depending on how long the system was kept at low temperature (below the LCST). Therefore this system can be used to obtain a controllable pulsatile release profile for small molecule drugs thereby enabling optimum therapeutic effects.

  2. Photosensitive cross-linked block copolymers with controllable release.

    PubMed

    Yu, Lili; Lv, Cong; Wu, LiZhu; Tung, ChenHo; Lv, WanLiang; Li, ZhongJin; Tang, XinJing

    2011-01-01

    We intend to form photosensitive block copolymer micelles for controllable release of encapsulated substances. Here, we designed and synthesized a new photocleavable cross-linker (2-nitrophenyl ethylene glycol dimethacrylate) for methyl methacrylate (MMA) atom transfer radical polymerization. Four different ratios (0:1, 1:26, 1:16, 1:8.8) of the photocleavable cross-linker to MMA monomer were used and four block copolymers (P0, P1, P2, P3) were synthesized with PEO-Br as the macroinitiator. Gel permeation chromatography and (1) H NMR studies showed that linear polymer molecules could be cross-linked by the photocleavable linker. The fluorescence studies of the encapsulated Nile Red (NR) showed that there were lower critical micelle concentrations for the polymer P1, P2 and P3 than polymer P0. And dynamic light scattering and SEM confirmed the formation of polymer micelles. Photolysis experiments demonstrated that NR encapsulated in the polymer micelles could be released upon UV irradiation (365 nm, 11 mW cm(-2)) due to the breakage of the photocleavable linker and the generation of more hydrophilic acid moieties, which destabilized polymer micelles. Our study shows a new strategy for the possibility of photocontrollable drug release for hydrophobic drugs.

  3. Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone.

    PubMed

    Beaver, W T; Wallenstein, S L; Rogers, A; Houde, R W

    1978-10-01

    The relative analgesic potency of oral and intramuscular codeine was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral codeine was 6/10 as potent as the intramuscular form. This is a high oral/parenteral analgesic relative potency ratio compared with morphine, metopon and oxymorphone and correlates well with the results of recent studies which have determined the oral vs. intramuscular bioavailability of codeine in man. Oral and intramuscular oxycodone were also compared in a similar patient group. Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.

  4. Tunable controlled release of molecular species from Halloysite nanotubes

    NASA Astrophysics Data System (ADS)

    Elumalai, Divya Narayan

    Encouraged by potential applications in rust coatings, self-healing composites, selective delivery of drugs, and catalysis, the transport of molecular species through Halloysite nanotubes (HNTs), specifically the storage and controlled release of these molecules, has attracted strong interest in recent years. HNTs are a naturally occurring biocompatible nanomaterial that are abundantly and readily available. They are alumosilicate based tubular clay nanotubes with an inner lumen of 15 nm and a length of 600-900 nm. The size of the inner lumen of HNTs may be adjusted by etching. The lumen can be loaded with functional agents like antioxidants, anticorrosion agents, flame-retardant agents, drugs, or proteins, allowing for a sustained release of these agents for hours. The release times can be further tuned for days and months by the addition of tube end-stoppers. In this work a three-dimensional, time-quantified Monte Carlo model that efficiently describes diffusion through and from nanotubes is implemented. Controlled delivery from Halloysite Nanotubes (HNT) is modeled based on interactions between the HNT's inner wall and the nanoparticles (NP) and among NPs themselves. The model was validated using experimental data published in the literature. The validated model is then used to study the effect of multiple parameters like HNT diameter and length, particle charge, ambient temperature and the creation of smart caps at the tube ends on the release of encapsulated NPs. The results show that release profiles depend on the size distribution of the HNT batch used for the experiment, as delivery is sensitive to HNT lumen and length. The effect of the addition of end-caps to the HNTs, on the rate of release of encapsulated NPs is also studied here. The results show that the release profiles are significantly affected by the addition of end caps to the HNTs and is sensitive to the end-cap pore lumen. A very good agreement with the experiment is observed when a weight

  5. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    NASA Astrophysics Data System (ADS)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  6. Mathematical modeling of triamcinolone acetonide drug release from the I-vation intravitreal implant (a controlled release platform).

    PubMed

    Barnett, Peter J

    2009-01-01

    In-vitro drug release of triamcinolone acetonide from the I-vation implant can be controlled and tuned by varying its formulation ingredients. These release characteristics can be modeled using a parabolic partial differential equation to describe one dimensional Fickian drug diffusion in a durable polymer matrix.

  7. Gelatin methacrylate microspheres for controlled growth factor release.

    PubMed

    Nguyen, Anh H; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C

    2015-02-01

    Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles (MPs) formulated with a wide range of different cross-linking densities (15-90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor than conventional GA cross-linked MPs, despite the GA MPs having an order of magnitude greater gelatin content. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 and basic fibroblast growth factor and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery.

  8. Gelatin Methacrylate Microspheres for Growth Factor Controlled Release

    PubMed Central

    Nguyen, Anh H.; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C.

    2014-01-01

    Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles formulated with a wide range of different cross-linking densities (15–90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor over conventional GA cross-linked MPs, despite an order of magnitude greater gelatin content of GA MPs. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery. PMID:25463489

  9. Controlled iodine release from polyurethane sponges for water decontamination.

    PubMed

    Aviv, Oren; Laout, Natalia; Ratner, Stanislav; Harik, Oshrat; Kunduru, Konda Reddy; Domb, Abraham J

    2013-12-28

    Iodinated polyurethane (IPU) sponges were prepared by immersing sponges in aqueous/organic solutions of iodine or exposing sponges to iodine vapors. Iodine was readily adsorbed into the polymers up to 100% (w/w). The adsorption of iodine on the surface was characterized by XPS and SEM analyses. The iodine loaded IPU sponges were coated with ethylene vinyl acetate (EVA), in order to release iodine in a controlled rate for water decontamination combined with active carbon cartridge, which adsorbs the iodine residues after the microbial inactivation. The EVA coated IPU were incorporated in a water purifier and tested for iodine release to water and for microbial inactivation efficiency according to WQA certification program against P231/EPA for 250l, using 25l a day with flow rate of 6-8min/1l. The antimicrobial activity was also studied against Escherichia coli and MS2 phage. Bacterial results exceeded the minimal requirement for bacterial removal of 6log reduction throughout the entire lifespan. At any testing point, no bacteria was detected in the outlet achieving more than 7.1 to more than 8log reduction as calculated upon the inlet concentration. Virus surrogate, MS2, reduction results varied from 4.11log reduction under tap water, and 5.11log reduction under basic water (pH9) to 1.32 for acidic water (pH5). Controlled and stable iodine release was observed with the EVA coated IPU sponges and was effective in deactivating the bacteria and virus present in the contaminated water and thus, these iodinated PU systems could be used in water purification to provide safe drinking water. These sponges may find applications as disinfectants in medicine.

  10. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    PubMed

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  11. Physical and chemical control of released microorganisms at field sites

    SciTech Connect

    Donegan, K.; Seidler, R.; Matyac, C.

    1991-01-01

    An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. The decontamination treatments of burning and biocide application, alone and in combination with tilling, were evaluated for their ability to reduce populations of bacteria released on the phylloplane. Field plots of bush beans sprayed with the bacterium Erwinia herbicola, received the following treatments: (1) control, (2) control + till, (3) burn, (4) burn + till, (5) Kocide (cupric hydroxide), (6) Kocide + till, (7) Agri-strep (streptomycin sulfate), and (8) Agri-strept + till. Leaves and soil from the plots were sampled -1, 1, 5, 8, 12, 15, 19, and 27 days after application of the decontamination treatments. Burning produced a significant and persistent reduction in the number of bacteria whereas tilling, alone or in combination with the biocide treatments, stimulated a significant and persistent reduction in the number of bacteria, whereas tilling, alone or in combination with the biocide treatments, stimulated a significant increase in bacterial populations that persisted for several weeks.

  12. Evaluation of a soil incubation method to characterize nitrogen release patterns of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry B; Obreza, Thomas A; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release patterns of slow-release fertilizers (SRF) and controlled-release fertilizers (CRF) during the last few decades. These technologies have been developed mainly by manufacturers, and are product-specific, based on the regulation and analysis of each SRF and CRF product. Despite previous efforts to characterize SRF and CRF materials, no standardized, validated method exists to assess their nutrient release patterns. However, the increased production and distribution of these materials in specialty and nonspecialty markets requires an appropriate method to verify product claims and material performance. A soil incubation column leaching procedure was evaluated to determine its suitability as a standard method to estimate nitrogen (N) release patterns of SRFs and CRFs during 180 days. The influence of three soil/sand ratios, three incubation temperatures, and four soils on method behavior was assessed using five SRFs and three CRFs. In general, the highest soil/sand ratio increased the N release rate of all materials, but this effect was more marked for the SRFs. Temperature had the greatest influence on N release rates. For CRFs, the initial N release rates and the percentage N released/day increased as temperature increased. For SRFs, raising the temperature from 25 to 35 degreesC increased initial N release rate and the total cumulative N released, and almost doubled the percentage released/day. The percentage N released/day from all products generally increased as the texture of the soil changed from sandy to loamy (lowa>California>Pennsylvania>Florida). The soil incubation technique was demonstrated to be robust and reliable for characterizing N release patterns from SRFs and CRFs. The method was reproducible, and variations in soil/sand ratio, temperature, and soil had little effect on the results.

  13. Modeling controlled nutrient release from a population of polymer coated fertilizers: statistically based model for diffusion release.

    PubMed

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A statistically based model for describing the release from a population of polymer coated controlled release fertilizer (CRF) granules by the diffusion mechanism was constructed. The model is based on a mathematical-mechanistic description of the release from a single granule of a coated CRF accounting for its complex and nonlinear nature. The large variation within populations of coated CRFs poses the need for a statistically based approach to integrate over the release from the individual granules within a given population for which the distribution and range of granule radii and coating thickness are known. The model was constructed and verified using experimentally determined parameters and release curves of polymer-coated CRFs. A sensitivity analysis indicated the importance of water permeability in controlling the lag period and that of solute permeability in governing the rate of linear release and the total duration of the release. Increasing the mean values of normally distributed granule radii or coating thickness, increases the lag period and the period of linear release. The variation of radii and coating thickness, within realistic ranges, affects the release only when the standard deviation is very large or when water permeability is reduced without affecting solute permeability. The model provides an effective tool for designing and improving agronomic and environmental effectiveness of polymer-coated CRFs.

  14. Controlling Hazardous Releases while Protecting Passengers in Civil Infrastructure Systems

    NASA Astrophysics Data System (ADS)

    Rimer, Sara P.; Katopodes, Nikolaos D.

    2015-11-01

    The threat of accidental or deliberate toxic chemicals released into public spaces is a significant concern to public safety, and the real-time detection and mitigation of such hazardous contaminants has the potential to minimize harm and save lives. Furthermore, the safe evacuation of occupants during such a catastrophe is of utmost importance. This research develops a comprehensive means to address such scenarios, through both the sensing and control of contaminants, and the modeling of and potential communication to occupants as they evacuate. A computational fluid dynamics model is developed of a simplified public space characterized by a long conduit (e.g. airport terminal) with unidirectional ambient flow that is capable of detecting and mitigating the hazardous contaminant (via boundary ports) over several time horizons using model predictive control optimization. Additionally, a physical prototype is built to test the real-time feasibility of this computational flow control model. The prototype is a blower wind-tunnel with an elongated test section with the capability of sensing (via digital camera) an injected `contaminant' (propylene glycol smoke), and then mitigating that contaminant using actuators (compressed air operated vacuum nozzles) which are operated by a set of pressure regulators and a programmable controller. Finally, an agent-based model is developed to simulate ``agents'' (i.e. building occupants) as they evacuate a public space, and is coupled with the computational flow control model such that agents must interact with a dynamic, threatening environment. NSF-CMMI #0856438.

  15. The Disposition of Oxycodone and Metabolite in Human Hair.

    PubMed

    Reisfield, Gary M; Jones, Joseph T

    2015-01-01

    The disposition of oxycodone (OC) and metabolites in hair remains poorly characterized. We present a case involving a pharmacist in an impaired professionals' monitoring program in whom hair testing yielded OC on two occasions. On both occasions, his hair was negative for the oxymorphone (OM) metabolite at the cutoff concentration of 100 pg/mg. He claimed that, absent the detection of metabolite, the OC necessarily represented external contamination. This prompted a review of the laboratory's OC-positive hair results for the quarter April-June 2014. Overall, 466 specimens contained OC, with a mean (median) concentration of 2,375 (1,060) pg/mg. Of these OC-positive specimens, only 47 (10%) contained detectable OM. When OC was present at or below the mean (median) concentration, only 2.2% (1.3%) of specimens were OM-positive. In the setting of OC administration, the detection of OM in hair is unlikely at a cutoff concentration of 100 pg/mg. More consistent demonstration of OC metabolite(s) in hair will require the validation of methods to detect OM at lower concentrations and/or methods to detect noroxycodone.

  16. Controlled Release Pulmonary Administration of Curcumin Using Swellable Biocompatible Microparticles

    PubMed Central

    El-Sherbiny, Ibrahim M.; Smyth, Hugh D. C.

    2012-01-01

    This study involves a promising approach to achieve sustained pulmonary drug delivery. Dry powder particulate carriers were engineered to allow simultaneous aerosol lung delivery, evasion of macrophage uptake, and sustained drug release through a controlled polymeric architecture. Chitosan grafted with PEG was synthesized and characterized (FTIR, EA, DSC and 2D-XRD). Then, a series of respirable amphiphilic hydrogel microparticles were developed via spray drying of curcumin-loaded PLGA nanoparticles with chitosan-grafted-PEG or chitosan. The nano and microparticles were fully characterized using an array of physicochemical analytical methods including particle size, surface morphology, dynamic swelling, density, moisture content and biodegradation rates. The PLGA nanoparticles and the hydrogel microspheres encapsulating the curcumin-loaded PLGA nanoparticles showed average size of (221-243 nm) and (3.1-3.9 μm), respectively. The developed carriers attained high swelling within a few minutes, showed low moisture content as dry powders (0.9-1.8%), desirable biodegradation rates, high drug loading (up to 97%), and good sustained release. An aerosolization study was conducted using a next generation impactor and promising aerosolization characteristics were shown. In vitro macrophage uptake studies, cytotoxicity and in-vitro TNF-α assays were performed for the investigated particles. These assays revealed promising bio-interactions for the respirable/swellable nano-micro particles developed in this study as potential carriers for sustained pulmonary drug delivery. PMID:22136259

  17. Unconventional mechanisms control cyclic respiratory gas release in flying Drosophila.

    PubMed

    Lehmann, Fritz-Olaf; Heymann, Nicole

    2005-10-01

    The high power output of flight muscles places special demands on the respiratory gas exchange system in insects. In small insects, respiration relies on diffusion, and for elevated locomotor performance such as flight, instantaneous gas exchange rates typically co-vary with the animal's metabolic activity. By contrast, under certain conditions, instantaneous release rate of carbon dioxide from the fruit fly Drosophila flying in a virtual-reality flight arena may oscillate distinctly at low frequency (0.37+/-0.055 Hz), even though flight muscle mechanical power output requires constant metabolic activity. Cross-correlation analysis suggests that this uncoupling between respiratory and metabolic rate is not driven by conventional types of convective flow reinforcement such as abdominal pumping, but might result from two unusual mechanisms for tracheal breathing. Simplified analytical modeling of diffusive tracheal gas exchange suggests that cyclic release patterns in the insect occur as a consequence of the stochastically synchronized control of spiracle opening area by the four large thoracic spiracles. Alternatively, in-flight motion analysis of the abdomen and proboscis using infra-red video imaging suggests utilization of the proboscis extension reflex (PER) for tracheal convection. Although the respiratory benefit of synchronized spiracle opening activity in the fruit fly is unclear, proboscis-induced tracheal convection might potentially help to balance the local oxygen supply between different body compartments of the flying animal.

  18. A framework to investigate drug release variability arising from hypromellose viscosity specifications in controlled release matrix tablets.

    PubMed

    Mitchell, Shawn A; Balwinski, Karen M

    2008-06-01

    Substitution level, particle size, and molecular weight are key properties of hypromellose (HPMC) known to be important to its performance in pharmaceutical-controlled release applications. The hypromellose monographs indirectly specify acceptable ranges for the molecular weight of HPMC products, expressed as the apparent viscosity of a 2% aqueous solution. The purpose of this study was to provide a framework to systematically investigate the amount of drug release variability that might be expected for typical controlled release formulations over the monograph viscosity ranges for hypromellose. An approach to estimate the expected drug release variability was developed based on scaling laws in the literature. New experimental data were generated with pentoxifylline, theophylline, and hydrochlorothiazide as model drugs to explore the applicability of this approach to a range of formulations. This methodology predicted that drug release variability over the United States Pharmacopeia (USP) viscosity ranges would be greatest for the lower viscosity grades of hypromellose, such as E50 and K100 LV. Drug release variability due to hypromellose viscosity variations is expected to be larger for formulations having substantial contributions from erosional drug release, and smaller for formulations with a predominantly diffusional drug release mechanism. These predictions need to be validated experimentally.

  19. Induction of xenobiotic receptors, transporters, and drug metabolizing enzymes by oxycodone.

    PubMed

    Hassan, Hazem E; Myers, Alan L; Lee, Insong J; Mason, Clifford W; Wang, Duan; Sinz, Michael W; Wang, Hongbing; Eddington, Natalie D

    2013-05-01

    Perturbations of the expression of transporters and drug-metabolizing enzymes (DMEs) by opioids can be the locus of deleterious drug-drug interactions (DDIs). Many transporters and DMEs are regulated by xenobiotic receptors [XRs; e.g., pregnane X receptor (PXR), constitutive androstane receptor (CAR), and Aryl hydrocarbon receptor (AhR)]; however, there is a paucity of information regarding the influence of opioids on XRs. The objective of this study was to determine the influence of oxycodone administration (15 mg/kg intraperitoneally twice daily for 8 days) on liver expression of XRs, transporters, and DMEs in rats. Microarray, quantitative real-time polymerase chain reaction and immunoblotting analyses were used to identify significantly regulated genes. Three XRs (e.g., PXR, CAR, and AhR), 27 transporters (e.g., ABCB1 and SLC22A8), and 19 DMEs (e.g., CYP2B2 and CYP3A1) were regulated (P < 0.05) with fold changes ranging from -46.3 to 17.1. Using MetaCore (computational platform), we identified a unique gene-network of transporters and DMEs assembled around PXR, CAR, and AhR. Therefore, a series of transactivation/translocation assays were conducted to determine whether the observed changes of transporters/DMEs are mediated by direct activation of PXR, CAR, or AhR by oxycodone or its major metabolites (noroxycodone and oxymorphone). Neither oxycodone nor its metabolites activated PXR, CAR, or AhR. Taken together, these findings identify a signature hepatic gene-network associated with repeated oxycodone administration in rats and demonstrate that oxycodone alters the expression of many transporters and DMEs (without direct activation of PXR, CAR, and AhR), which could lead to undesirable DDIs after coadministration of substrates of these transporters/DMEs with oxycodone.

  20. Randomised Phase II Trial (NCT00637975) Evaluating Activity and Toxicity of Two Different Escalating Strategies for Pregabalin and Oxycodone Combination Therapy for Neuropathic Pain in Cancer Patients

    PubMed Central

    Garassino, Marina Chiara; Piva, Sheila; La Verde, Nicla; Spagnoletti, Ilaria; Iorno, Vittorio; Carbone, Claudia; Febbraro, Antonio; Bianchi, Anna; Bramati, Annalisa; Moretti, Anna; Ganzinelli, Monica; Marabese, Mirko; Gentili, Marta; Torri, Valter; Farina, Gabriella

    2013-01-01

    Purpose Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy. Methods Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%. Results More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%. Conclusions Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control. Trial Registration ClinicalTrials.gov NCT00637975 PMID:23577077

  1. Impact of release rates on the effectiveness of augmentative biological control agents.

    PubMed

    Crowder, David W

    2007-01-01

    To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoids or predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism.

  2. Impact of Release Rates on the Effectiveness of Augmentative Biological Control Agents

    PubMed Central

    Crowder, David W.

    2007-01-01

    To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoidsor predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID:20307240

  3. Radio controlled release apparatus for animal data acquisition devices

    DOEpatents

    Stamps, James Frederick

    2000-01-01

    A novel apparatus for reliably and selectively releasing a data acquisition package from an animal for recovery. The data package comprises two parts: 1) an animal data acquisition device and 2) a co-located release apparatus. One embodiment, which is useful for land animals, the release apparatus includes two major components: 1) an electronics package, comprising a receiver; a decoder comparator, having at plurality of individually selectable codes; and an actuator circuit and 2) a release device, which can be a mechanical device, which acts to release the data package from the animal. To release a data package from a particular animal, a radio transmitter sends a coded signal which is decoded to determine if the code is valid for that animal data package. Having received a valid code, the release device is activated to release the data package from the animal for subsequent recovery. A second embodiment includes floatation means and is useful for releasing animal data acquisition devices attached to sea animals. This embodiment further provides for releasing a data package underwater by employing an acoustic signal.

  4. Development of controlled release spheroids using natural polysaccharide as release modifier.

    PubMed

    Kulkarni, Giriraj T; Gowthamarajan, K; Dhobe, Rohan R; Yohanan, Fenni; Suresh, B

    2005-01-01

    A polysaccharide hydrogel was isolated from the seeds of Tamarindus indica (tamarind) and was used as release modifier for the preparation of diclofenac sodium spheroids, using extrusion-spheronization technique. The process was studied for the effect of variables to arrive at spheroids with satisfactory particle shape, size and size-distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density, and flow properties. The in vitro release studies exhibited a zero-order release kinetics that was confirmed by Higuchi's and Peppas' models. A credible correlation was obtained among swelling index, viscosity, surface roughness of the polysaccharide, and in vitro dissolution profile of the spheroids. In the comparative bioavailability study, we found that the developed spheroids were able to sustain the drug release over 8 hr and could improve the extent of absorption and bioavailability of the drug.

  5. Controlling protein release from scaffolds using polymer blends and composites.

    PubMed

    Ginty, Patrick J; Barry, John J A; White, Lisa J; Howdle, Steve M; Shakesheff, Kevin M

    2008-01-01

    We report the development of three protein loaded polymer blend and composite materials that modify the release kinetics of the protein from poly(dl-lactic acid) (P(dl)LA) scaffolds. P(dl)LA has been combined with either poly(ethylene glycol) (PEG), poly(caprolactone) (PCL) microparticles or calcium alginate fibres using supercritical CO(2) (scCO(2)) processing to form single and dual protein release scaffolds. P(dl)LA was blended with the hydrophilic polymer PEG using scCO(2) to increase the water uptake of the resultant scaffold and modify the release kinetics of an encapsulated protein. This was demonstrated by the more rapid release of the protein when compared to the release rate from P(dl)LA only scaffolds. For the P(dl)LA/alginate scaffolds, the protein loaded alginate fibres were processed into porous protein loaded P(dl)LA scaffolds using scCO(2) to produce dual release kinetics from the scaffolds. Protein release from the hydrophilic alginate fibres was more rapid in the initial stages, complementing the slower release from the slower degrading P(dl)LA scaffolds. In contrast, when protein loaded PCL particles were loaded into P(dl)LA scaffolds, the rate of protein release was retarded from the slow degrading PCL phase.

  6. Behavioral Flexibility and Response Selection Are Impaired after Limited Exposure to Oxycodone

    ERIC Educational Resources Information Center

    Seip-Cammack, Katharine M.; Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on…

  7. Discriminative stimulus, reinforcing, physical dependence, and antinociceptive effects of oxycodone in mice, rats, and rhesus monkeys.

    PubMed

    Beardsley, Patrick M; Aceto, Mario D; Cook, Charles D; Bowman, Edward R; Newman, Jennifer L; Harris, Louis S

    2004-08-01

    Despite oxycodone's (4,5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one) history of clinical use and the attention it has received as a drug of abuse, few reports have documented its pharmacology's relevance to its abuse or its mechanism of action. The purposes of the present study were to further characterize the analgesic effects of oxycodone, its mechanism of action, and its effects in terms of its relevance to its abuse liability. The results indicate that oxycodone had potent antinociceptive effects in the mouse paraphenylquinone writhing, hot-plate, and tail-flick assays, in which it appeared to be acting as a mu-opioid receptor agonist. It generalized to the heroin discriminative stimulus and served as a positive reinforcer in rats and completely suppressed withdrawal signs in morphine-dependent rhesus monkeys. These results suggest that the analgesic and abuse liability effects of oxycodone are likely mediated through mu-opioid receptors and provide the first laboratory report of its discriminative stimulus, reinforcing, and morphine cross-dependency effects.

  8. Method of achieving the controlled release of thermonuclear energy

    DOEpatents

    Brueckner, Keith A.

    1986-01-01

    A method of achieving the controlled release of thermonuclear energy by illuminating a minute, solid density, hollow shell of a mixture of material such as deuterium and tritium with a high intensity, uniformly converging laser wave to effect an extremely rapid build-up of energy in inwardly traveling shock waves to implode the shell creating thermonuclear conditions causing a reaction of deuterons and tritons and a resultant high energy thermonuclear burn. Utilizing the resulting energy as a thermal source and to breed tritium or plutonium. The invention also contemplates a laser source wherein the flux level is increased with time to reduce the initial shock heating of fuel and provide maximum compression after implosion; and, in addition, computations and an equation are provided to enable the selection of a design having a high degree of stability and a dependable fusion performance by establishing a proper relationship between the laser energy input and the size and character of the selected material for the fusion capsule.

  9. Controlled release of NSAIDs bound to polyacrylic carrier systems.

    PubMed

    Parejo, C; Gallardo, A; San Román, J

    1998-12-01

    The synthesis, characterization and properties of new acrylic "polymeric drugs" derived from the NSAIDs agents ibuprofen and ketoprofen are described. The swelling behavior in hydrated medium and the controlled release from hydrophilic copolymers of the NSAIDs derivatives and 2-hydroxyethylmethacrylate, HEMA, are discussed, considering the hydrolytical reactivity of the acrylamide or acrylic ester functional groups, the aromatic or aliphatic structure of the spacer side groups, and the hydrophilic character of the copolymer systems. The results obtained demonstrated that the swelling degree of copolymers depends on the average composition of copolymers, decreasing with the increase of the average fraction of the corresponding acrylic derivative of ibuprofen or ketoprofen in the copolymer system. In addition, polymers which support the NSAIDs active component through aromatic amide links, are more sensitive to hydrolytical processes than those of alkyl ester functions. The results obtained demonstrate that these supports could be applied for direct administration, transdermal, systemic or intra-articular injection, as well as in the form of films on wounds.

  10. Novel anhydrous emulsions: formulation as controlled release vehicles.

    PubMed

    Suitthimeathegorn, Orawan; Jaitely, Vikas; Florence, Alexander T

    2005-07-25

    Novel anhydrous emulsions, which may offer some advantages as depot or reservoir vehicles for lipophilic drugs in controlled delivery systems, were formulated using castor oil as the disperse phase and dimethicone or cyclopentasiloxane as the continuous phase. Among the emulsifiers studied only silicone surfactants (cyclomethicone/dimethicone copolyols) which were miscible in silicone oil stabilized the emulsions. Cyclomethicone/PEG/PPG-18/18 Dimethicone and Cyclopentasiloxane/PEG/PPG-18/18 Dimethicone were more effective in lowering the interfacial tension between castor oil and both dimethicone and cyclopentasiloxane. Emulsions formulated using either of these two surfactants were found to be stable against phase separation and exhibited least globule growth over 168 h. The average particle size was found to be 2-6 microm in these systems formed by probe sonication. Slow release patterns of 3H-dehydroepiandrosterone (DHEA) and 3H-dexamethasone solubilized in the disperse castor oil phase into an aqueous dialyzing medium were observed over 48 h.

  11. Controlled release: a cultural analysis of collegiate polydrug use.

    PubMed

    Quintero, Gilbert

    2009-03-01

    Social science research on polydrug use among young adult college students is scant, adopts definitions of this practice that are often devoid of sociocultural context, and emphasizes a very narrow range of use patterns. This article, based on ethnographic interviews from a study of collegiate prescription drug misuse, expands this focus by offering a cultural analysis of polydrug use. Two specific types of collegiate polydrug use, simultaneous interaction and sequential management, are examined within a cultural framework that relates these practices to the expression of two complementary values--control and release. The college experience provides young people with a culturally sanctioned "time-out" period that affords freedom from many of the roles, responsibilities, and other constraints that come to structure later adult life. At the same time, college students are expected to meet academic and social demands that require organization, initiative, and direction. Specific types of polydrug use provide young adults with a means to navigate these competing prescriptions that are characteristic of contemporary college life.

  12. Effect of soil moisture on the release of alachlor from alginate-based controlled-release formulations.

    PubMed

    Nasser, Ahmed; Mingelgrin, Uri; Gerstl, Zev

    2008-02-27

    The release of alachlor from controlled-release formulations (CRFs) based on alginate-montmorillonite matrices into aqueous polyethylene glycol (PEG) solutions of different concentrations and into a soil at different moisture contents was studied. In distilled water and in PEG-containing solutions displaying -0.1 MPa potential and up, the beads imbibe water and swell. The ensuing increase in weight is about 5%, and the increase in the bead's diameter is about 10%. At water potentials of -0.5 MPa and lower, loss of weight and shrinkage of the beads were observed. The changes in weight and diameter of the alginate-clay beads incubated in a Hamra loamy sand soil at 26.5% moisture content (w/w; -0.18 MPa) were similar to those observed in PEG solutions of >-0.5 MPa moisture potential. The weight and diameter losses observed in the drier soils (12.0 and 7.1% water content; -0.49 and -1.11 MPa) were similar to those in the more concentrated PEG solutions. A decrease in the rate of release of the active ingredient from the beads into soil was observed as the water potential decreased (drier soils). The release of the active ingredient from the investigated CRFs displayed a linear relationship to the square root of time, suggesting a diffusion-controlled-release rate. Data extracted from this relationship enabled the formulation of a mathematical model that correlates rate of release to water content.

  13. Understanding and Controlling iron Release in Distribution Systems

    EPA Science Inventory

    Generation of red-water resulting from the release of iron from drinking water distribution system materials is a major consumer complaint of drinking water systems. The objective of this presentation is to provide a fundamental basis for iron release from drinking water distrib...

  14. Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights.

    PubMed

    Hines, Daniel J; Kaplan, David L

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial used in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in the formulation of drug release devices. Mathematical modeling is a useful tool for identifying, characterizing, and predicting mechanisms of controlled release. The advantages and limitations of poly(lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled-release technology that utilize PLGA. Mathematical modeling applied toward controlled-release rates from PLGA-based devices also will be discussed to provide a complete picture of a state-of-the-art understanding of the control that can be achieved with this polymeric system, as well as the limitations.

  15. [Rate of controlled-release urea pervasion through membrane determined by ultraviolet spectrophotometry].

    PubMed

    Zuo, Xiu-jin; Wang, Zhen-xin; Dai, Xiao-min; Zhou, Yi; Ma, Xiao-jun

    2006-06-01

    Application of controlled-release nitrogenous fertilizers can improve the efficiency of fertilizers and reduce the environmental pollution. Controlled-release urea (coated urea) is one of the controlled-release nitrogenous fertilizers developed quickly in the recent years. The rate of controlled-release urea pervasion through membrane is the most important index of the capacity of controlled release. There is a maximum absorption at lambda=426 nm with complex in acidic solution, using p-dimethylaminozenzaldehyde as color reagent, and the absorbance exhibits a linear reponses to the urea concentration over the range of 7.5-210 microg x mL(-1). The method for determining the rate of controlled-release urea pervasion through membrane was realized through determining the content of urea in the liquor, the recovery efficiency of the method is 96.1%-103.9%.

  16. Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

    PubMed Central

    Hines, Daniel J.; Kaplan, David L.

    2013-01-01

    Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

  17. Preparation and characterization of metoprolol controlled-release solid dispersions.

    PubMed

    Varshosaz, Jaleh; Faghihian, Hossein; Rastgoo, Kobra

    2006-01-01

    In recent years, great attention has been paid to using solid dispersions to make sustained-release drugs. The objective of this study is to produce sustained-release systems of metoprolol tartrate using solid dispersion techniques and to evaluate their physicochemical characteristics. The solid dispersions were produced by melting and solvent methods, containing 7%, 15%, or 25% of the drug and different ratios of Eudragit RLPO and RSPO in ratios of 0:10, 3:7, 5:5, 7:3, and 10:0. Drug release profiles were determined by USP XXIII rotating paddle method in phosphate buffer solution (pH 6.8). XRD, DSC, IR, and microscopic observations were performed to evaluate the physical characteristics of solid dispersions. Results showed that the drug release from dispersions was at a slower rate than pure drug and physical mixtures. Moreover, the formulations containing greater ratios of Eudragit RSPO showed slower release rates and smaller DE8% but larger mean dissolution time than those containing greater ratios of Eudragit RLPO. Dispersions with particle size of less than 100 microm containing 7% of metoprolol and Eudragit RL:RS 5:5 (solvent method) and those with the ratio of 3:7 (melting method) had similar release pattern to Lopressor sustained-release tablets by zero-order and Higuchi kinetics, respectively.

  18. Controlled-release NPK fertilizer encapsulated by polymeric membranes.

    PubMed

    Jarosiewicz, Anna; Tomaszewska, Maria

    2003-01-15

    The commercial granular fertilizer NPK6-20-30 was coated using polysulfone (PSF), polyacrylonitrile (PAN), and cellulose acetate (CA). The coatings were formed from the polymer solutions by the phase inversion technique. Measurements of the thickness and porosity of the prepared coatings and a microphotographic observation of the coatings were performed. The physical properties of the coatings influence the release rate of macronutrients which are present in the core of the coated fertilizer. In the case of PAN coating with 60.45% porosity, prepared from a 16% polymer solution, 100% of NH(4)(+) and P(2)O(5) was released after 4 h of test and 99.7% of K(+) after 5 h of test, whereas in the case of coating with 48.8% porosity, 31.8% of NH(4)(+), 16.7% of P(2)O(5), and 11.6% of K(+) was released after 5 h. In all experiments, different selectivities of the coatings in terms of the release of components were observed. The release of potassium through the coatings made of PSF and PAN was the slowest. The same tendency was observed for the release of nitrogen through a coating of CA. The release of fertilizer active components was the slowest in the case of PSF. The lowest porosity coating was prepared from the 18% PSF solution.

  19. Materials for pharmaceutical dosage forms: molecular pharmaceutics and controlled release drug delivery aspects.

    PubMed

    Mansour, Heidi M; Sohn, Minji; Al-Ghananeem, Abeer; Deluca, Patrick P

    2010-09-15

    Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

  20. Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

    PubMed Central

    Mansour, Heidi M.; Sohn, MinJi; Al-Ghananeem, Abeer; DeLuca, Patrick P.

    2010-01-01

    Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. PMID:20957095

  1. Use of natural and biobased materials for controlled-release of urea in water: Environmental applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Urea pearls were encapsulated in cloisite-based matrices using different natural materials (lignin, beeswax and latex) to control the release of urea over time. It was found that all cloisite-based fertilizer tablets showed better release profiles than neat urea tablets. The best release profile was...

  2. Quantifying Winter Discharge of Controlled Release Fertilizers to Determine Environmental Impact and Plant Uptake

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is widely believed in the nursery industry that controlled release fertilizers (CRF) release nutrients only when temperatures are greater than ˜4ºC (40ºF). Research recently conducted in Southern California reported CRF continue to release nitrate and phosphorus throughout the winter months. We...

  3. 46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise, an...— (1) Institute a quality control procedure to ensure that all production release mechanisms are... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control,...

  4. 46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., tests, quality control, and conformance of release mechanisms. (a) Unless the Commandant directs.... The manufacturer must— (1) Institute a quality control procedure to ensure that all production release... 46 Shipping 6 2012-10-01 2012-10-01 false Production inspections, tests, quality control,...

  5. Presynaptic control of dopamine release by BETA-phenylethylamine

    SciTech Connect

    Zharikova, A.D.; Godukhin, O.V.

    1985-04-01

    The authors study the effect of extracellular ions (Ca/sup 2 +/, Na/sup 2 +/) on the beta-phenylethylamine (beta-PEA) releasing effect, dependence of this effect on the membrane potential of dopaminergic endings, and the participation of dopamine presynaptic autoreceptors in the realization of the effects of beta-PEA on dopamine (DA) release. Experi ments were carried out on noninbred male albino rats. By means of a microsyringe, (/sup 3/H)-DA hydrochloride was injected. The significance of the difference in levels of (/sup 3/H)-DA release during analogous periods of perfusion in the groups of animals compared was estimated by Student's test. These experiments in vivo thus demonstrated the ability of beta-PEA to regulate DA release in different directions depending on the functional state of the dopaminergic neuron.

  6. Magnetic-Responsive Release Controlled by Hot Spot Effect.

    PubMed

    Guisasola, Eduardo; Baeza, Alejandro; Talelli, Marina; Arcos, Daniel; Moros, María; de la Fuente, Jesús M; Vallet-Regí, María

    2015-11-24

    Magnetically triggered drug delivery nanodevices have attracted great attention in nanomedicine, as they can feature as smart carriers releasing their payload at clinician's will. The key principle of these devices is based on the properties of magnetic cores to generate thermal energy in the presence of an alternating magnetic field. Then, the temperature increase triggers the drug release. Despite this potential, the rapid heat dissipation in living tissues is a serious hindrance for their clinical application. It is hypothesized that magnetic cores could act as hot spots, this is, produce enough heat to trigger the release without the necessity to increase the global temperature. Herein, a nanocarrier has been designed to respond when the temperature reaches 43 °C. This material has been able to release its payload under an alternating magnetic field without the need of increasing the global temperature of the environment, proving the efficacy of the hot spot mechanism in magnetic-responsive drug delivery devices.

  7. Heparinized nanohydroxyapatite/collagen granules for controlled release of vancomycin.

    PubMed

    Coelho, Catarina C; Sousa, Susana R; Monteiro, Fernando J

    2015-10-01

    The purpose of this study was to develop a bone substitute material capable of preventing or treating osteomyelitis through a sustainable release of vancomycin and simultaneously inducing bone regeneration. Porous heparinized nanohydroxyapatite (nanoHA)/collagen granules were characterized using scanning electron microscopy, micro-computed tomography and attenuated total reflectance Fourier transform infrared spectroscopy. After vancomycin adsorption onto the granules, its releasing profile was studied by UV molecular absorption spectroscopy. The heparinized granules presented a more sustainable release over time, in comparison with nonheparinized nanoHA and nanoHA/collagen granules. Vancomycin was released for 360 h and proved to be bioactive until 216 h. Staphylococcus aureus adhesion was higher on granules containing collagen, guiding the bacteria to the material with antibiotic, improving their eradication. Moreover, cytotoxicity of the released vancomycin was assessed using osteoblast cultures, and after 14 days of culture in the presence of vancomycin, cells were able to remain viable, increasing their metabolic activity and colonizing the granules, as observed by scanning electron microscopy and confocal laser scanning microscopy. These findings suggest that heparinized nanoHA/collagen granules are a promising material to improve the treatment of osteomyelitis, as they are capable of releasing vancomycin, eliminating the bacteria, and presented morphological and chemical characteristics to induce bone regeneration.

  8. Control of oxygen release from peroxides using polymers.

    PubMed

    Steg, Hilde; Buizer, Arina T; Woudstra, Willem; Veldhuizen, Albert G; Bulstra, Sjoerd K; Grijpma, Dirk W; Kuijer, Roel

    2015-07-01

    An important limitation in cell therapy for the regeneration of tissue is the initial lack of oxygen. After implantation of large 3D cell-seeded structures, cells die rather than contribute to tissue regenerating. Here we've tested oxygen-releasing materials to improve cell survival and growth after implantation. Calcium peroxide (CaO2) in a polymer matrix was used as source of oxygen. Two polymers were tested in order to slow down and extend the period of oxygen release, poly(D,L-lactic acid) and poly(lactic-co-glycolic acid). Compared to CaO2 particles, both releasing systems showed an initially higher and shorter oxygen release. Human mesenchymal stromal cells cultured on casted films of these oxygen-releasing composites required catalase to proliferate, indicating the production of cytotoxic hydrogen peroxide as intermediate. Poly(D,L-lactic acid) and poly(lactic-co-glycolic acid) are less suited for slowly oxygen-releasing materials. Catalase was able to reduce the cytotoxic effect of H2O2.

  9. Controlled release of sulfasalazine release from "smart" pectin gel microspheres under physiological simulated fluids.

    PubMed

    Costas, Luciana; Pera, Licia M; López, Azucena Gómez; Mechetti, Magdalena; Castro, Guillermo R

    2012-07-01

    Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used mainly for the treatment of an inflammatory bowel and other diseases. Two pectins with different methylation degrees were blended to synthesized gel microspheres by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was found to be around of 99% in all formulations tested. However, different SLZ release profiles related to the methylation degrees of pectin were observed. Mixture of low methylated (LM) and high methylated (HM) pectins in the presence of calcium(II) displayed the best microsphere morphologies among the formulations tested determined by optical and electronic microscopies. The percentage of drug release using a mixture of LM and HM pectins after 255 min in simulated gastric fluid (pH = 1.2), simulated intestinal fluid (pH = 6.8), and phosphate buffer (pH = 7.4) were 15.0%, 47.0%, and 52.2%, respectively.

  10. Oxycodone induces overexpression of P-glycoprotein (ABCB1) and affects paclitaxel's tissue distribution in Sprague Dawley rats.

    PubMed

    Hassan, Hazem E; Myers, Alan L; Lee, Insong J; Coop, Andrew; Eddington, Natalie D

    2007-09-01

    Previous studies suggest that P-glycoprotein (P-gp) modulates the PK/PD of many compounds including opioid agonists and chemotherapeutic agents. The objective of this study was to assess the P-gp affinity status of oxycodone, the P-gp expression, and the paclitaxel's tissue distribution in oxycodone-treated rats. P-gp ATPase assay, Caco-2 transepithelial permeability studies, and mdr1a/b (-/-) mice were used to assess the P-gp affinity status of oxycodone. P-gp expression was determined by Western blot analysis while [(14)C] paclitaxel's distributions in the liver, kidney, brain, and plasma tissues were determined by liquid scintillation counter. Oxycodone stimulated the P-gp ATPase activity in a concentration-dependant manner. The Caco-2 secretory transport of oxycodone was reduced from 3.64 x 10(-5) to 1.96 x 10(-5) cm/s (p < 0.05) upon preincubation with the P-gp inhibitor, verapamil. The brain levels of oxycodone in mdr1a/b (+/+) were not detectable (<15 ng/mL) while in mdr1a/b (-/-) the average levels were 115 +/- 39 ng/mL. The P-gp protein levels were increased by 1.3-4.0 folds while paclitaxel's tissue distributions were decreased by 38-90% (p < 0.05) in oxycodone-treated rats. These findings display that oxycodone is a P-gp substrate, induces overexpression of P-gp, and affects paclitaxel's tissue distribution in a manner that may influence its chemotherapeutic activity.

  11. Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

    PubMed

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Roberts, Clive J

    2014-01-30

    Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer.

  12. Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

    PubMed

    Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

    2016-01-01

    In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design.

  13. Controlled protein release from monodisperse biodegradable double-wall microspheres of controllable shell thickness

    PubMed Central

    Xia, Yujie; Ribeiro, Pedro F.; Pack, Daniel W.

    2013-01-01

    Biodegradable polymer microparticles are promising delivery depots for protein therapeutics due to their relatively simple fabrication and facile administration. Double-wall microspheres (DWMS) comprising a core and shell made of two distinct polymers may provide enhanced control of the drug release profiles. Using precision particle fabrication (PPF) technology, monodisperse DWMS were fabricated with model protein bovine serum albumin (BSA)-loaded poly(lactide-co-glycolide) (PLG) core and drug-free poly(d,l-lactic acid) (PDLL) shell of uniform thickness. Monolithic single-wall microspheres were also fabricated to mimic the BSA-loaded PLG core. Using ethyl acetate and dichloromethane as shell- and core-phase solvents, respectively, BSA was encapsulated selectively in the core region within DWMS with higher loading and encapsulation efficiency compared to using dichloromethane as core and shell solvents. BSA in vitro release rates were retarded by the presence of the drug-free PDLL shell. Moreover, increasing PDLL shell thickness resulted in decreasing BSA release rate. With a 14-µm thick PDLL shell, an extended period of constant-rate release was achieved. PMID:23954731

  14. Correlation between the administration of morphine or oxycodone and the development of infections in patients with cancer pain.

    PubMed

    Suzuki, Miharu; Sakurada, Tomoya; Gotoh, Kazumi; Watanabe, Satoshi; Satoh, Nobunori

    2013-11-01

    Morphine and oxycodone are widely used in the therapy for cancer pain. Although some previous studies have reported that morphine induces immunosuppression and oxycodone does not, whether this is true for human infections is unclear. We performed a retrospective study on the correlation between the administration of morphine or oxycodone and the development of infections in patients with cancer pain. This study was undertaken in 841 inpatients receiving only 1 opioid continuously for more than 10 days. Development of infections was based on (1) antibiotic administration and (2) diagnosis of infections, positive microbial culture test, or increase in white blood cells or C-reactive protein. Liver, kidney, and hematological cancer, antineoplastic drugs, radiotherapy, steroid, immunosuppressive agents, granulocyte colony-stimulating factor, and thyroid inhibitors were defined as the exclusion criteria in consideration of influence on immune system or metabolism and excretion of morphine and oxycodone. A total of 60 morphine and 74 oxycodone cases were included, which resulted in 18 and 10 infection cases. Significantly more patients treated with morphine developed infections than those patients treated with oxycodone (odds ratio = 3.60, 95% confidence interval = 1.40-9.26). No significant differences were seen in the other variables analyzed. Although perhaps some confounding variables were included because this was an observational rather than randomized study, these results suggested that morphine's immunosuppressive effect may contribute to the development of infections in patients with cancer pain.

  15. Mathematical modeling of a flat-membrane-controlled release device

    SciTech Connect

    Ramraj, R.; Farrell, S.; Loney, N.W.

    1999-08-01

    The closed form solution to a mathematical model of a flat membrane device successfully predicts the release profile of benzoic acid. Physically, the device consists of a given concentration of benzoic acid in octanol (reservoir) bounded by a microporous flat film (Cellgard 2400) with water-filled pores. The prediction shows excellent agreement with the experimentally derived release profile (maximum difference < 10%). Predicted results are obtained from the use of the steady state plus the first term of the transient solution (infinite series) and with the use of the first nonzero eigenvalue.

  16. Involvement of α₂-adrenoceptors, imidazoline, and endothelin-A receptors in the effect of agmatine on morphine and oxycodone-induced hypothermia in mice.

    PubMed

    Bhalla, Shaifali; Andurkar, Shridhar V; Gulati, Anil

    2013-10-01

    Potentiation of opioid analgesia by endothelin-A (ET(A)) receptor antagonist, BMS182874, and imidazoline receptor/α₂-adrenoceptor agonists such as clonidine and agmatine are well known. It is also known that agmatine blocks morphine hyperthermia in rats. However, the effect of agmatine on morphine or oxycodone hypothermia in mice is unknown. The present study was carried out to study the role of α₂-adrenoceptors, imidazoline, and ET(A) receptors in morphine and oxycodone hypothermia in mice. Body temperature was determined over 6 h in male Swiss Webster mice treated with morphine, oxycodone, agmatine, and combination of agmatine with morphine or oxycodone. Yohimbine, idazoxan, and BMS182874 were used to determine involvement of α₂-adrenoceptors, imidazoline, and ET(A) receptors, respectively. Morphine and oxycodone produced significant hypothermia that was not affected by α₂-adrenoceptor antagonist yohimbine, imidazoline receptor/α₂ adrenoceptor antagonist idazoxan, or ET(A) receptor antagonist, BMS182874. Agmatine did not produce hypothermia; however, it blocked oxycodone but not morphine-induced hypothermia. Agmatine-induced blockade of oxycodone hypothermia was inhibited by idazoxan and yohimbine. The blockade by idazoxan was more pronounced compared with yohimbine. Combined administration of BMS182874 and agmatine did not produce changes in body temperature in mice. However, when BMS182874 was administered along with agmatine and oxycodone, it blocked agmatine-induced reversal of oxycodone hypothermia. This is the first report demonstrating that agmatine does not affect morphine hypothermia in mice, but reverses oxycodone hypothermia. Imidazoline receptors and α₂-adrenoceptors are involved in agmatine-induced reversal of oxycodone hypothermia. Our findings also suggest that ET(A) receptors may be involved in blockade of oxycodone hypothermia by agmatine.

  17. The effects of control release fertilizer (CRF) on palm growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nutri-Pak is a slow release fertilizer in a micro-pore polyethylene packet where moisture enters the packet through micro-pores located on both sides of the packet. Water dissolves the fertilizer and it slowly seeps through the same micro-pores as a vapor into the soil gradually providing nutrients ...

  18. Pluronic/gelatin composites for controlled release of actives.

    PubMed

    Tatini, Duccio; Tempesti, Paolo; Ridi, Francesca; Fratini, Emiliano; Bonini, Massimo; Baglioni, Piero

    2015-11-01

    This paper describes the preparation and the release properties of composite materials based on Pluronic F127 and gelatin hydrogels, which could be of interest in the field of enteral nutrition or drug administration. The composites were prepared by exploiting the opposite responsivity to temperature of a 20% w/w Pluronic F127 aqueous solution (critical gelation temperature around 23 °C) and gelatin (gel-sol temperature transition around 30 °C). Pluronic domains dispersed within a gelatin matrix were obtained by injecting cold Pluronic F127 solutions inside hot gelatin solutions, while homogenizing either with a magnetic stirrer or a high-energy mechanical disperser. Calorimetry indicates that the composites retain the individual gelling properties of Pluronic and gelatin. Different releasing properties were obtained as a function of the preparation protocol, the temperature and the pH. The release profiles have been studied by a Weibull analysis that clearly points out the dominating role of gelatin at 25 °C. At 37 °C the release accounts for a combined effect from both Pluronic F127 and gelatin, showing a more sustained profile with respect to gelatin hydrogels. This behavior, together with the ability of Pluronic F127 to upload both hydrophilic and hydrophobic drugs and flavors, makes these innovative composite materials very good candidates as FDA-approved carriers for enteral administration.

  19. Cellulose acetate electrospun fiber mats for controlled release of silymarin.

    PubMed

    Phiriyawirut, Manisara; Phaechamud, Thawatchai

    2012-01-01

    In this research, the silymarin-loaded electrospun cellulose acetate (CA) fibers were prepared which containing silymarin in various amounts (i.e., 2.5-20 wt.% based on the weight of CA powder). Incorporation of silymarin in the neat CA solution did not affect the morphology of the resulting fibers, as both the neat and the silymarin-loaded CA fibers were smooth. The average diameters of silymarin-loaded CA fiber ranged between 550-900 nm. No presence of the silymarin aggregates of any kind was observed on the surfaces of these fibers, suggesting that the silymarin was encapsulated well within the fibers. These results were confirmed by lowering the glass transition temperature and the melting temperature of the silymarin-loaded electrospun CA fibers which is determined by DSC technique. The release characteristic of silymarin from the silymarin-loaded CA fiber mats was investigated by the total immersion in the solution of 1/1 phosphate buffer/methanol medium pH 7.4 at 37 degrees C. The silymarin release from the silymarin-loaded electrospun CA fiber mat is monotonously increased to reach the maximum value at 480 min. The maximum amount of silymarin released from these materials increases with the increasing of initial silymarin loading in the spinning CA solutions. Since no aggregation of silymarin was found on the surface of the silymarin-loaded fibers, the release of the silymarin from fiber mats was mainly by the diffusion.

  20. 46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and... SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING..., tests, quality control, and conformance of release mechanisms. (a) Unless the Commandant...

  1. Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

    PubMed

    Maejima, T; Kubo, M; Osawa, T; Nakajima, K; Kobayashi, M

    1998-03-01

    The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

  2. Use of a novel modified TSI for the evaluation of controlled-release aerosol formulations. I.

    PubMed

    McConville, J T; Patel, N; Ditchburn, N; Tobyn, M J; Staniforth, J N; Woodcock, P

    2000-11-01

    When considering the development of potential controlled-release pulmonary drug delivery systems, there is at present no standard method available for the assessment of in vitro drug release profiles necessary to understand how the drug might release following deposition in the lungs. For this purpose, the twin-stage impinger (TSI), apparatus A of the BP, has been redesigned and tested. This modified TSI was found capable of discriminating between drug release rates from conventional and different dry powder formulations consisting of model controlled-release excipients, providing information related to (a) drug diffusion properties of controlled-release dry powder blends with different excipient components and (b) the effect of varying drug concentration within a given formulation.

  3. Formation, release and control of dioxins in cement kilns.

    PubMed

    Karstensen, Kåre Helge

    2008-01-01

    Co-processing of hazardous wastes in cement kilns have for decades been thought to cause increased emissions of PCDD/PCDFs--a perception that has been evaluated in this study. Hundreds of PCDD/PCDF measurements conducted by the cement industry and others in the last few years, on emissions and solid materials, as well as recent test burns with hazardous wastes in developing countries do not support this perception. Newer data has been compared with older literature data and shows in particular that many emission factors have to be reconsidered. Early emission factors for cement kilns co-processing hazardous waste, which are still used in inventories, are shown to be too high compared with actual measurements. Less than 10 years ago it was believed that the cement industry was the main contributor of PCDD/PCDFs to air; data collected in this study indicates however that the industry contributes with less than 1% of total emissions to air. The Stockholm Convention on POPs presently ratified by 144 parties, classifies cement kilns co-processing hazardous waste as a source category having the potential for comparatively high formation and release of PCDD/PCDFs. This classification is based on early investigations from the 1980s and 1990s where kilns co-processing hazardous waste had higher emissions compared to those that did not burn hazardous waste. However, the testing of these kilns was often done under worst case scenario conditions known to favour PCDD/PCDF formation. More than 2000 PCDD/PCDF cement kiln measurements have been evaluated in this study, representing most production technologies and waste feeding scenarios. They generally indicate that most modern cement kilns co-processing waste today can meet an emission level of 0.1ngI-TEQ/m(3), when well managed and operated. In these cases, proper and responsible use of waste including organic hazardous waste to replace parts of the fossil fuel does not seem to increase formation of PCDD/PCDFs. Modern preheater

  4. Dynamic Control of Neurotransmitter Release by Presynaptic Potential

    PubMed Central

    Zbili, Mickael; Rama, Sylvain; Debanne, Dominique

    2016-01-01

    Action potentials (APs) in the mammalian brain are thought to represent the smallest unit of information transmitted by neurons to their postsynaptic targets. According to this view, neuronal signaling is all-or-none or digital. Increasing evidence suggests, however, that subthreshold changes in presynaptic membrane potential before triggering the spike also determines spike-evoked release of neurotransmitter. We discuss here how analog changes in presynaptic voltage may regulate spike-evoked release of neurotransmitter through the modulation of biophysical state of voltage-gated potassium, calcium and sodium channels in the presynaptic compartment. The contribution of this regulation has been greatly underestimated and we discuss the impact for information processing in neuronal circuits. PMID:27994539

  5. Controlled drug release on amine functionalized spherical MCM-41

    NASA Astrophysics Data System (ADS)

    Szegedi, Agnes; Popova, Margarita; Goshev, Ivan; Klébert, Szilvia; Mihály, Judit

    2012-10-01

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N2 physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41.

  6. A thermosensitive chitosan-based hydrogel for controlled release of insulin

    NASA Astrophysics Data System (ADS)

    Gao, Ting-Ting; Kong, Ming; Cheng, Xiao-Jie; Xia, Gui-Xue; Gao, Yuan-Yuan; Chen, Xi-Guang; Cha, Dong Su; Park, Hyun Jin

    2014-06-01

    Present study aims at synthesizing a thermosensitive hydrogel for controlled release of insulin. According to a modified method, hydroxybutyl chitosan (HBC) hydrogel possessed thermal sensitivity is prepared which can form hydrogel at over 25°C. The HBC hydrogel is non-cytotoxic to mice fibroblasts cells (L929). Insulin is 100% entrapped in the hydrogel, 38% of which is released in vitro from the concentration of 5% hydrogel after 48 h, whereas by enzymolysis with lysozyme, 80% of the total insulin is released after 48 h. This study suggests that HBC hydrogel could be utilized for controlled release of insulin in a non-invasive manner.

  7. Controlled Release of Antigens for One Dose Immunization

    DTIC Science & Technology

    1983-01-01

    microencapsulation of antigen coated alum or by microencapsulating clusters of smaller (᝺ microns) microcapsules . Microcapsules under 10 microns in... microencapsulation were studied to determine what criteria must be satisfied to provide a protective immune response to hepatitis B surface antigen... microencapsulated in poly (DL-lactide-co- glycolide) in a form that was too large to be phagocytized and had an antigen release profile similar to that achieved with

  8. Cellulose acetate butyrate microparticles for controlled release of carbamazepine.

    PubMed

    Arnaud, P; Boué, C; Chaumeil, J C

    1996-01-01

    Cellulose acetate butyrate microparticles loaded in carbamazepine were prepared by a solvent evaporation technique. A decrease of the amount of organic solvent (from 80 to 40 ml of methylene chloride) increased the microparticle average diameter (73-111 and 207 microns) and decreased the carbamazepine release rate (T50% increased from 3.3 to 16.8 and 166.4 min). The microparticle area under the curve at 120 min was similar to that obtained with Tegretol LP 200 tablets.

  9. Electrospun biodegradable nanofiber nonwovens for controlled release of proteins.

    PubMed

    Maretschek, Sascha; Greiner, Andreas; Kissel, Thomas

    2008-04-21

    Electrospinning of emulsions composed of an organic poly(l-lactide) solution and an aqueous protein solution yielded protein containing nanofiber nonwovens (NNs) having a mean fiber diameter of approximately 350 nm. Cytochrome C was chosen as a hydrophilic model protein for encapsulation. SEM imaging and gas adsorption measurements were carried out to determine morphology and surface characteristics of the different nanofiber nonwovens. Transmission electron microscopy was used to clarify the localization of the protein within the NN. PLLA NNs exhibited a highly hydrophobic surface which led to a slow wetting. It was shown that the protein release was dependent on the surface tension of the release medium. Electrospinning of emulsions consisting of an organic solution of PLLA and an aqueous solution of hydrophilic polymers yielded fibers composed of a polymer blend. The resulting NNs exhibited a less hydrophobic surface, which gave us the opportunity to tailor the release profile via this technology. Furthermore it was investigated how the addition of different amounts of hydrophilic polymer to the aqueous phase influenced the morphology of the resulting NNs.

  10. Controlled drug release on amine functionalized spherical MCM-41

    SciTech Connect

    Szegedi, Agnes; Popova, Margarita; Goshev, Ivan; Klebert, Szilvia; Mihaly, Judit

    2012-10-15

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N{sub 2} physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41. - Graphical abstract: Determination of surface amino groups by ninhidrin method. Highlights: Black-Right-Pointing-Pointer Spherical MCM-41 modified by different amounts of APTES was studied. Black-Right-Pointing-Pointer Ibuprofen (IBU) adsorption and release characteristics was tested. Black-Right-Pointing-Pointer The ninhydrin reaction was used for the quantitative determination of amino groups. Black-Right-Pointing-Pointer Stoichiometric amount of APTES is enough for totally covering the surface with amino groups. Black-Right-Pointing-Pointer Good correlation was found between the amino content and IBU adsorption capacity.

  11. Long-term Controlled Drug Release from bi-component Electrospun Fibers

    NASA Astrophysics Data System (ADS)

    Xu, Shanshan; Zhang, Zixin; Xia, Qinghua; Han, Charles

    Multi-drug delivery systems with timed programmed release are hard to be produced due to the complex drug release kinetics which mainly refers to the diffusion of drug molecules from the fiber and the degradation of the carrier. This study focused on the whole life-time story of the long-term drug releasing fibrous systems. Electrospun membrane utilizing FDA approved polymers and broad-spectrum antibiotics showed specific drug release profiles which could be divided into three stages based on the profile slope. With throughout morphology observation, cumulative release amount and releasing duration, releasing kinetics and critical factors were fully discussed during three stages. Through changing the second component, approximately linear drug release profile and a drug release duration about 13 days was prepared, which is perfect for preventing post-operative infection. The addition of this semi-crystalline polymer in turn influenced the fiber swelling and created drug diffusion channels. In conclusion, through adjusting and optimization of the blending component, initial burst release, delayed release for certain duration, and especially the sustained release profile could all be controlled, as well as specific anti-bacterial behavior could be obtained.

  12. Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

    PubMed

    Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

    2013-11-01

    The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non

  13. Controlled release of folic acid through liquid-crystalline folate nanoparticles.

    PubMed

    Misra, Rahul; Katyal, Henna; Mohanty, Sanat

    2014-11-01

    The present study explores folate nanoparticles as nano-carriers for controlled drug delivery. Cross-linked nanoparticles of liquid crystalline folates are composed of ordered stacks. This paper shows that the folate nanoparticles can be made with less than 5% loss in folate ions. In addition, this study shows that folate nanoparticles can disintegrate in a controlled fashion resulting in controlled release of the folate ions. Release can be controlled by the size of nanoparticles, the extent of cross-linking and the choice of cross-linking cation. The effect of different factors like agitation, pH, and temperature on folate release was also studied. Studies were also carried out to show the effect of release medium and role of ions in the release medium on disruption of folate assembly.

  14. Preparation and characterization of controlled release matrices based on novel seaweed interpolyelectrolyte complexes.

    PubMed

    Prado, Héctor J; Matulewicz, María C; Bonelli, Pablo R; Cukierman, Ana L

    2012-06-15

    Novel interpolyelectrolyte complexes (IPECs) between naturally sulfated polysaccharides of the seaweed Polysiphonia nigrescens (PN) and cationized agaroses (CAG) and Eudragit E (EE) were prepared using an organic solvent free process, characterized, and explored for controlled drug release. Tablets containing model drug ibuprofen and IPECs were prepared by direct compression. Drug release in acid medium was low owing to the low solubility of ibuprofen in that condition and to the matrix action. Zero order drug release was determined in the buffer stage (pH=6.8), with Fickian diffusion predominating over relaxation during the initial phases. Relaxation appears to increase along the release process and even overcomes diffusion for some systems. Drug release profiles could be controlled by varying the content of IPECs in the tablets. Also, the change in molecular weight and the degree of substitution of the components allowed altering the release profiles.

  15. Controlled antibody release from gelatin for on-chip sample preparation.

    PubMed

    Zhang, Xichen; Wasserberg, Dorothee; Breukers, Christian; Terstappen, Leon W M M; Beck, Markus

    2016-05-10

    A practical way to realize on-chip sample preparation for point-of-care diagnostics is to store the required reagents on a microfluidic device and release them in a controlled manner upon contact with the sample. For the development of such diagnostic devices, a fundamental understanding of the release kinetics of reagents from suitable materials in microfluidic chips is therefore essential. Here, we study the release kinetics of fluorophore-conjugated antibodies from (sub-) μm thick gelatin layers and several ways to control the release time. The observed antibody release is well-described by a diffusion model. Release times ranging from ∼20 s to ∼650 s were determined for layers with thicknesses (in the dry state) between 0.25 μm and 1.5 μm, corresponding to a diffusivity of 0.65 μm(2) s(-1) (in the swollen state) for our standard layer preparation conditions. By modifying the preparation conditions, we can influence the properties of gelatin to realize faster or slower release. Faster drying at increased temperatures leads to shorter release times, whereas slower drying at increased humidity yields slower release. As expected in a diffusive process, the release time increases with the size of the antibody. Moreover, the ionic strength of the release medium has a significant impact on the release kinetics. Applying these findings to cell counting chambers with on-chip sample preparation, we can tune the release to control the antibody distribution after inflow of blood in order to achieve homogeneous cell staining.

  16. 76 FR 73679 - Manufacturer of Controlled Substances; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... controlled substances: Drug Schedule Codeine-N-oxide (9053) I Dihydromorphine (9145) I Morphine-N-oxide (9307... Oxycodone (9143) II Hydromorphone (9150) II Hydrocodone (9193) II Morphine (9300) II Oripavine (9330)...

  17. 77 FR 7603 - Manufacturer of Controlled Substances; Notice of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ... controlled substances: Drug Schedule Codeine-N-oxide (9053) I Dihydromorphine (9145) I Morphine-N-oxide (9307... Dihydrocodeine (9120) II Oxycodone (9143) II Hydromorphone (9150) II Hydrocodone (9193) II Morphine (9300)...

  18. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats.

    PubMed

    Wiebelhaus, Jason M; Walentiny, D Matthew; Beardsley, Patrick M

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone's abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects.

  19. Controlled Release of Salicylic Acid from Biodegradable Cross-Linked Polyesters.

    PubMed

    Dasgupta, Queeny; Chatterjee, Kaushik; Madras, Giridhar

    2015-09-08

    The purpose of this work was to develop a family of cross-linked poly(xylitol adipate salicylate)s with a wide range of tunable release properties for delivering pharmacologically active salicylic acid. The synthesis parameters and release conditions were varied to modulate polyester properties and to understand the mechanism of release. Varying release rates were obtained upon longer curing (35% in the noncured polymer to 10% in the cured polymer in 7 days). Differential salicylic acid loading led to the synthesis of polymers with variable cross-linking and the release could be tuned (100% release for the lowest loading to 30% in the highest loading). Controlled release was monitored by changing various factors, and the release profiles were dependent on the stoichiometric composition, pH, curing time, and presence of enzyme. The polymer released a combination of salicylic acid and disalicylic acid, and the released products were found to be nontoxic. Minimal hemolysis and platelet activation indicated good blood compatibility. These polymers qualify as "bioactive" and "resorbable" and can, therefore, find applications as immunomodulatory resorbable biomaterials with tunable release properties.

  20. Preparation and investigation of controlled-release glipizide novel oral device with three-dimensional printing.

    PubMed

    Li, Qijun; Wen, Haoyang; Jia, Danyang; Guan, Xiaoying; Pan, Hao; Yang, Yue; Yu, Shihui; Zhu, Zhihong; Xiang, Rongwu; Pan, Weisan

    2017-04-01

    The purpose of this study was to explore the feasibility of combining fused deposition modeling (FDM) 3D printing technology with hot melt extrusion (HME) to fabricate a novel controlled-release drug delivery device. Glipizide used in the treatment of diabetes was selected as model drug, and was successfully loaded into commercial polyvinyl alcohol(PVA) filaments by HME method. The drug-loaded filaments were printed through a dual-nozzle 3D printer, and finally formed a double-chamber device composed by a tablet embedded within a larger tablet (DuoTablet), each chamber contains different contents of glipizide. The drug-loaded 3D printed device was evaluated for drug release under in-vitro dissolution condition, and we found the release profile fit Korsmeyer-Peppas release kinetics. With the double-chamber design, it is feasible to design either controlled drug release or delayed drug release behavior by reasonably arranging the concentration distribution of the drug in the device. The characteristics of the external layer performed main influence on the release profile of the internal compartment such as lag-time or rate of release. The results of this study suggest the potential of 3D printing to fabricate controlled-release drug delivery system containing multiple drug concentration distributions via hot melt extrusion method and specialized design configurations.

  1. Controlled release of insulin from folic acid-insulin complex nanoparticles.

    PubMed

    Gupta, Rajat; Mohanty, Sanat

    2017-03-03

    Associative interactions between folic acid and proteins are well known. This work leverages these interactions to engineer folic acid nanoparticles for controlled release of insulin during diabetes therapy. The insulin-loaded folic acid nanoformulation is synthesized during this study to achieve better insulin loading and encapsulation than previous strategies. The maximum insulin loading in the FA particles was kept at 6mg with less than 10% insulin loss during the synthesis process which is significantly better compare to previous strategies. The folic acid nanoparticles of 50-150nm size are further characterized in the present study. The release behaviour of insulin from the nanoparticles has been studied to quantify released insulin and folic acid with time using high performance liquid chromatography. Insulin release results suggest that more than 90% of the insulin is encapsulated and released within 24h from folic acid nanoparticles. The analysis of folic acid release along with insulin release indicates that the particles are formed by folic acid-insulin complexation at the molecular level. The release of insulin from nanoparticles is controllable with the change in the crosslinking salt concentration as well as the amount of folic acid loaded during particle synthesis. These results prove that folic acid nanocarriers are capable to control the release of therapeutic proteins.

  2. Application of Electrostatic Extrusion – Flavour Encapsulation and Controlled Release

    PubMed Central

    Manojlovic, Verica; Rajic, Nevenka; Djonlagic, Jasna; Obradovic, Bojana; Nedovic, Viktor; Bugarski, Branko

    2008-01-01

    The subject of this study was the development of flavour alginate formulations aimed for thermally processed foods. Ethyl vanilline was used as the model flavour compound. Electrostatic extrusion was applied for the encapsulation of ethyl vanilline in alginate gel microbeads. The obtained microbeads with approx. 10 % w/w of ethyl vanilline encapsulated in about 2 % w/w alginate were uniformly sized spheres of about 450 μm. Chemical characterization by H-NMR spectroscopy revealed that the alginate used in this study had a high content (67 %) of guluronic residues and was rich in GG diad blocks (FGG = 55%) and thus presented a high-quality immobilisation matrix. The thermal behaviour of alginate beads encapsulating ethyl vanilline was investigated by thermogravimetric (TG) and differential scanning calorimetry measurements (TG-DSC) under heating conditions which mimicked usual food processing to provide information about thermal decomposition of alginate matrix and kinetics of aroma release. Two well resolved weight losses were observed. The first one was in the 50-150 °C temperature range with the maximum at approx. 112 °C, corresponding to the dehydration of the polymer network. The second loss in the 220-325 °C temperature range, with a maximum at ∼ 247 °C corresponded to the release of vanilline. The obtained results indicate that up to 230 °C most of the vanilline remained intacta, while prolonged heating at elevated temperatures led to the entire loss of the aroma compound. PMID:27879775

  3. Controlled growth factor release from synthetic extracellular matrices

    NASA Astrophysics Data System (ADS)

    Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

    2000-12-01

    Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

  4. Coordinated coupling control of tethered space robot using releasing characteristics of space tether

    NASA Astrophysics Data System (ADS)

    Huang, Panfeng; Zhang, Fan; Xu, Xiudong; Meng, Zhongjie; Liu, Zhengxiong; Hu, Yongxin

    2016-04-01

    Tethered space robot (TSR) is a new concept of space robot, which is released from the platform satellite, and retrieved via connected tether after space debris capture. In this paper, we propose a new coordinate control scheme for optimal trajectory and attitude tracking, and use releasing motor torque to instead the tension force, since it is difficult to track in practical. Firstly, the 6-DOF dynamics model of TSR is derived, in which the dynamics of tether releasing system is taken into account. Then, we propose and design the coordinated coupled controller, which is composed of a 6-DOF sliding mode controller and a PD controller tether's releasing. Thrust is treated as control input of the 6-DOF sliding mode controller to control the in-plane and out-of-plane angle of the tether and attitude angles of the TSR. The torque of releasing motor is used as input of PD controller, which controls the length rate of space tether. After the verification of the control scheme, finally, the simulation experiment is presented in order to validate the effectiveness of this control method. The results show that TSR can track the optimal approaching trajectory accurately. Simultaneously, the attitude angles can be changed to the desired attitude angles in control period, and the terminal accuracy is ±0.3°.

  5. Recent advances in chitosan films for controlled release of drugs.

    PubMed

    Mengatto, Luciano N; Helbling, Ignacio M; Luna, Julio A

    2012-08-01

    Chitosan is a versatile carrier for biologically active agent from a small molecule such as an antibiotic to macromolecules such as proteins and nucleic acids. In addition, drug delivery devices based on chitosan can be available in a variety of morphologies including films, fibers, nanoparticles and microspheres. Otherwise the inherent advantages of this polymer such as biocompatibility, tissue adhesions and hydrophilic nature, chitosan can be modified to accomplish a specific purpose, for example improves release kinetics. In this review, recent patents of chitosan-based film systems for drug delivery are presented and discussed. This review include matrix type systems, membrane coated systems and film forming solution. For each one of these systems, several examples of manufacture processes, bioactive agents to be delivered and specifics applications are considered. This work highlights the use of chitosan in the film technology for drug delivery, presenting examples of chitosan used in an unmodified state and examples of modifications of the polymer backbone.

  6. Controls on Fe(II)-Activated Trace Element Release from Goethite and Hematite

    SciTech Connect

    Frierdich, Andrew J.; Catalano, Jeffrey G.

    2012-03-26

    Electron transfer and atom exchange (ETAE) between aqueous Fe(II) and Fe(III) oxides induces surface growth and dissolution that affects trace element fate and transport. We have recently demonstrated Ni(II) cycling through goethite and hematite (adsorbed Ni incorporates into the mineral structure and preincorporated Ni releases to solution) during Fe(II)-Fe(III) ETAE. However, the chemical parameters affecting net trace element release remain unknown. Here, we examine the chemical controls on Ni(II) and Zn(II) release from Ni- and Zn-substituted goethite and hematite during reaction with Fe(II). Release follows a rate law consistent with surface reaction limited mineral dissolution and suggests that release occurs near sites of Fe(III) reductive dissolution during Fe(II)-Fe(III) ETAE. Metal substituent type affects reactivity; Zn release is more pronounced from hematite than goethite, whereas the opposite trend occurs for Ni. Buildup of Ni or Zn in solution inhibits further release but this resumes upon fluid exchange, suggesting that sustained release is possible under flow conditions. Mineral and aqueous Fe(II) concentrations as well as pH strongly affect sorbed Fe(II) concentrations, which directly control the reaction rates and final metal concentrations. Our results demonstrate that structurally incorporated trace elements are mobilized from iron oxides into fluids without abiotic or microbial net iron reduction. Such release may affect micronutrient availability, contaminant transport, and the distribution of redox-inactive trace elements in natural and engineered systems.

  7. Munc13 controls the location and efficiency of dense-core vesicle release in neurons.

    PubMed

    van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K; de Jong, Arthur; de Wit, Heidi; Verhage, Matthijs; Toonen, Ruud F

    2012-12-10

    Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2-null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically.

  8. Munc13 controls the location and efficiency of dense-core vesicle release in neurons

    PubMed Central

    van de Bospoort, Rhea; Farina, Margherita; Schmitz, Sabine K.; de Jong, Arthur; de Wit, Heidi

    2012-01-01

    Neuronal dense-core vesicles (DCVs) contain diverse cargo crucial for brain development and function, but the mechanisms that control their release are largely unknown. We quantified activity-dependent DCV release in hippocampal neurons at single vesicle resolution. DCVs fused preferentially at synaptic terminals. DCVs also fused at extrasynaptic sites but only after prolonged stimulation. In munc13-1/2–null mutant neurons, synaptic DCV release was reduced but not abolished, and synaptic preference was lost. The remaining fusion required prolonged stimulation, similar to extrasynaptic fusion in wild-type neurons. Conversely, Munc13-1 overexpression (M13OE) promoted extrasynaptic DCV release, also without prolonged stimulation. Thus, Munc13-1/2 facilitate DCV fusion but, unlike for synaptic vesicles, are not essential for DCV release, and M13OE is sufficient to produce efficient DCV release extrasynaptically. PMID:23229896

  9. Reduced Antinociception of Opioids in Rats and Mice by Vaccination with Immunogens Containing Oxycodone and Hydrocodone Haptens

    PubMed Central

    Pravetoni, Marco; Le Naour, Morgan; Tucker, Ashli M.; Harmon, Theresa M.; Hawley, Tara M.; Portoghese, Philip S.; Pentel, Paul R.

    2013-01-01

    Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (6OXY(Gly)4OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (6OXY(Gly)4–KLH) for the treatment of oxycodone abuse. In this study, oxycodone-based and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 6OXY(Gly)4–KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both oxycodone and hydrocodone. An analogous C6-linked hydrocodone vaccine blocked hydrocodone effects but less so than 6OXY(Gly)4–KLH. C8-Linked hydrocodone immunogens had only limited efficacy. Amide conjugation showed higher haptenation ratios and greater efficacy than thioether conjugation to maleimide activated KLH (mKLH). The 6OXY(Gly)4–KLH vaccine may be used for treatment of prescription opioid abuse. PMID:23249238

  10. Topical application of a novel oxycodone gel formulation (tocopheryl phosphate mixture) in a rat model of peripheral inflammatory pain produces localized pain relief without significant systemic exposure.

    PubMed

    Smith, Maree T; Wyse, Bruce D; Edwards, Stephen R; El-Tamimy, Mahmoud; Gaetano, Giacinto; Gavin, Paul

    2015-07-01

    This study was designed to assess the analgesic efficacy and systemic exposure of oxycodone administered topically in a novel tocopheryl phosphate mixture (TPM) gel formulation, to the inflamed hindpaws in a rat model of inflammatory pain. Unilateral hindpaw inflammation was induced in male Sprague-Dawley rats by intraplantar (i.pl.) injection of Freund's complete adjuvant (FCA). Mechanical hyperalgesia and hindpaw inflammation were assessed by measuring paw pressure thresholds and hindpaw volume, respectively, just prior to i.pl. FCA and again 5-6 days later. The analgesic effects of oxycodone administered topically (1 mg in TPM gel) or by i.pl. injection (50 μg), were assessed. Systemic oxycodone exposure was assessed over an 8-h postdosing interval following topical application. Skin permeation of oxycodone from the gel formulation was assessed in vitro using Franz diffusion cells. Oxycodone administered topically or by i.pl. injection produced significant (p < 0.05) analgesia in the inflamed hindpaws. Systemic oxycodone exposure was insignificant after topical dosing. The in vitro cumulative skin permeation of oxycodone was linearly related to the amount applied. Topical TPM/oxycodone gel formulations have the potential to alleviate moderate to severe inflammatory pain conditions with minimal systemic exposure, thereby avoiding central nervous system (CNS)-mediated adverse effects associated with oral administration of opioid analgesics.

  11. Controlled release of cyclosporine A self-nanoemulsifying systems from osmotic pump tablets: near zero-order release and pharmacokinetics in dogs.

    PubMed

    Zhang, Xi; Yi, Yueneng; Qi, Jianping; Lu, Yi; Tian, Zhiqiang; Xie, Yunchang; Yuan, Hailong; Wu, Wei

    2013-08-16

    It is very important to enhance the absorption simultaneously while designing controlled release delivery systems for poorly water-soluble and poorly permeable drugs (BCS IV). In this study, controlled release of cyclosporine (CyA) was achieved by the osmotic release strategy taking advantage of the absorption-enhancing capacity of self-nanoemulsifying drug delivery systems (SNEDDSs). The liquid SNEDDS consisting of Labrafil M 1944CS, Transcutol P and Cremophor EL was absorbed by the osmotic tablet core excipients (sucrose, lactose monohydrate, polyethylene oxide, and partly pregelatinized starch) and then transformed into osmotic tablets. Near zero-order release could be achieved for CyA-loaded nanoemulsions reconstituted from the SNEDDS. In general, the influencing factor study indicated that the release rate increased with increase of inner osmotic pressure, ratio of osmotic agent to suspending agent, content of pore-forming agent, and size of release orifice, whereas the thickness of the membrane impeded the release of CyA nanoemulsion. Pharmacokinetic study showed steady blood CyA profiles with prolonged Tmax and MRT, and significantly reduced Cmax for self-nanoemulsifying osmotic pump tablet (SNEOPT) in comparison with highly fluctuating profiles of the core tablet and Sandimmune Neoral(®). However, similar oral bioavailability was observed for either controlled release or non-controlled release formulations. It was concluded that simultaneous controlling on CyA release and absorption-enhancing had been achieved by a combination of osmotic tablet and SNEDDS.

  12. 77 FR 40069 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... adverse effects include respiratory depression, decreased blood pressure, coma, respiratory arrest, and... for respiratory depression, respiratory arrest, and death. FDA also found that the DOSAGE...

  13. Controlled release of lidocaine hydrochloride from the surfactant-doped hybrid xerogels.

    PubMed

    Wu, Zhijian; Joo, Hyeonwoo; Lee, Tai Gyu; Lee, Kangtaek

    2005-06-02

    We investigate the controlled release of lidocaine hydrochloride from the doped silica-based xerogels. In the xerogel preparation, tetraethoxysilane (TEOS), methyltriethoxysilane (MTES), and propyltriethoxysilane (PTES) are used as precursors, and a nonionic surfactant Igepal CO 720 is used as a dopant. The experimental results suggest that the release of lidocaine hydrochloride can be easily controlled by partially substituting TEOS with the organosilanes, and/or by adding the dopant. Adding the organosilane precursors lowers the release of both the drug and the surfactant in the order of TEOS, MTES/TEOS, and PTES/TEOS xerogels. The release from the PTES/TEOS xerogels is much lower than that from the other xerogels. The release of lidocaine hydrochloride is obviously suppressed by the addition of Igepal CO 720, while the release of Igepal CO 720 is slightly promoted by the addition of the drug. The overall release process is found to be diffusion-controlled, and the release behaviors can be well explained by considering the effects of the textual properties of the xerogels and the interactions among the drug, the surfactant, and the xerogel matrices.

  14. Huperzine A-phospholipid complex-loaded biodegradable thermosensitive polymer gel for controlled drug release.

    PubMed

    Cai, Xiaoqing; Luan, Yuxia; Jiang, Yue; Song, Aixin; Shao, Wei; Li, Zhonghao; Zhao, Zhongxi

    2012-08-20

    The huperzine A-phospholipid complex loaded biodegradable thermosensitive PLGA-PEG-PLGA polymer gel was studied as injectable implant system for controlled release of huperzine-A (HA). First, HA molecules were successfully incorporated into the soybean phosphatidylcholine (SP) molecules to form the huperzine-A-soybean phosphatidylcholine complexes (HA-SPC), which was proved by FT-IR, DSC, XRD, solubility study, TEM, etc. The results indicated that hydrogen bonds and electrostatic interaction between HA and SP molecules play an important role in the formation of HA-SPC. Secondly, the HA-SPC was loaded into biodegradable PLGA-PEG-PLGA thermosensitive gel as injectable implant material to control the release of HA. The in vitro and in vivo drug release behaviors of the prepared products were studied. The in vitro release studies demonstrated that the HA-SPC-loaded gel significantly reduced the initial burst of drug release and extended the release period to about 2 weeks. The in vivo pharmacokinetics study of HA-SPC-loaded gel in rabbits showed that plasma concentration of HA (2.54-0.15ng/mL) was detected for nearly 2 weeks from delivery systems upon single subcutaneous injection. What's more, the in vitro release pattern correlated well with the in vivo pharmacokinetics profile. The present study indicates that HA-SPC loaded PLGA-PEG-PLGA thermal gel may be an attractive candidate vehicle for controlled HA release.

  15. Design Release Reliability Prediciton Test Set, Weapon Control, Aircraft, AN/ASM-184A(V).

    DTIC Science & Technology

    This report presents a design release reliability prediction for the Test Set, Weapon Control , Aircraft , AN/ASM-184A(V). The data and methods used to arrive at this prediction are included. (Author)

  16. Controlled-release fertilizer composition substantially coated with an impermeable layer

    SciTech Connect

    Ankeny, Mark

    2016-03-29

    A controlled-release fertilizer composition is provided that is substantially coated with an impermeable layer. The fertilizer composition may further include one or more hollow sections to allow for root penetration and efficient delivery of nutrients.

  17. Ketotifen controlled release from cellulose acetate propionate and cellulose acetate butyrate membranes.

    PubMed

    Sobral, Manuela C C M; Sobral, Abilio J F N; Guthrie, J T; Gil, M H

    2008-02-01

    Ketotifen was immobilised in cellulose acetate propionate (CAP) membranes and in cellulose acetate butyrate (CAB) membranes. The characteristics of each system were evaluated under a range of experimental conditions. The topography and uniformity of the membranes was assessed using scanning electron microscopy. The release characteristics associated with Ketotifen were monitored spectrophotometrically. The swelling capacity of the membranes was evaluated and attributed to the combined effects of diffusion and of complex dissociation, during swelling. The materials produced were able to provide controlled release of Ketotifen due to their controlled swelling behaviour and adequate release properties. The results showed that the release of Ketotifen from the CAB membranes is higher but the release from the CAP membranes is more uniform.

  18. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    SciTech Connect

    Matteini, P; Ratto, F; Rossi, F; Pini, R

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  19. [Research advances on controlled-release mechanisms of nutrients in coated fertilizers].

    PubMed

    Zhang, Haijun; Wu, Zhijie; Liang, Wenju; Xie, Hongtu

    2003-12-01

    Using encapsulation techniques to coat easily soluble fertilizers is an important way to improve fertilizer use efficiency while reduce environmental hazards. Based on a wide range of literature collection on coated fertilizer research, the theories, processes, and characters of nutrient controlled-release from coated fertilizer were discussed, and the factors affecting nutrient controlled-release and the mathematical simulations on it were reviewed. The main tendencies related to this research in China were also put forward.

  20. Controlled-release approaches towards the chemotherapy of tuberculosis

    PubMed Central

    Saifullah, Bullo; Hussein, Mohd Zobir B; Al Ali, Samer Hasan Hussein

    2012-01-01

    Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization’s 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18–24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs) seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages. PMID:23091386

  1. Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling

    SciTech Connect

    Yang, Rui-feng; Zhao, Guo-wei; Liang, Shu-ting; Zhang, Yuan; Sun, Li-hong; Chen, Hou-zao; Liu, De-pei

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Mitofilin deficiency caused disruption of the cristae structures in HeLa cells. Black-Right-Pointing-Pointer Mitofilin deficiency reduced cell proliferation and increased cell sensitivity to apoptotic stimuli. Black-Right-Pointing-Pointer Mitofilin deficiency accelerated the release of cytochrome c from mitochondria. Black-Right-Pointing-Pointer Mitofilin deficiency accelerated STS-induced intrinsic apoptotic pathway without interfering with the activation of Bax. -- Abstract: Mitochondria amplify caspase-dependent apoptosis by releasing proapoptotic proteins, especially cytochrome c. This process is accompanied by mitochondrial cristae remodeling. Our studies demonstrated that mitofilin, a mitochondrial inner membrane protein, acted as a cristae controller to regulate cytochrome c release during apoptosis. Knockdown of mitofilin in HeLa cells with RNAi led to fragmentation of the mitochondrial network and disorganization of the cristae. Mitofilin-deficient cells showed cytochrome c redistribution between mitochondrial cristae and the intermembrane space (IMS) upon intrinsic apoptotic stimuli. In vitro cytochrome c release experiments further confirmed that, compared with the control group, tBid treatment led to an increase in cytochrome c release from mitofilin-deficient mitochondria. Furthermore, the cells with mitofilin knockdown were more prone to apoptosis by accelerating cytochrome c release upon the intrinsic apoptotic stimuli than controls. Moreover, mitofilin deficiency did not interfere with the activation of proapoptotic member Bax upon intrinsic apoptotic stimuli. Thus, mitofilin distinctly functions in cristae remodeling and controls cytochrome c release during apoptosis.

  2. Super Strypi Navigation, Guidance & Control (NGC) v. Release 04

    SciTech Connect

    Anderson, Mark A.; Bigelow, Matthew; Gilkey, Jeff C.; Hutchinson, Lance V.; Madsen, Jared D.; Meindl, Mark A.; Outka, David E.; Schrempp, Mark T.

    2016-05-27

    The Super Strypi Navigation, Guidance & Control Software is a real-time implementation of the navigation, guidance and control algorithms designed to deliver a payload to a desired orbit for the rail launched Super Strypi launch vehicle. The software contains all flight control algorithms required from pre-launch until orbital insertion. The flight sequencer module calls the NG&C functions at the appropriate times of flight. Additional functionality includes all the low level drivers and I/O for communicating to other systems within the launch vehicle and to the ground support equipment. The software is designed such that changes to the launch location and desired orbit can be changed without recompiling the code.

  3. Controlled-release fertilizer (CRF): a green fertilizer for controlling non-point contamination in agriculture.

    PubMed

    Mao, Xiao-yun; Sun, Ke-jun; Wang, De-han; Liao, Zong-wen

    2005-01-01

    Fertilizers contribute greatly to high yields but also result in environmental non-point contamination, including the emission of greenhouse gas (N2O) and eutrophication of water bodies. How to solve this problem has become a serious challenge, especially for China as its high ecological pressure. Controlled-release fertilizer(CRF) has been developed to minimize the contamination while keeping high yield and has become a green fertilizer for agriculture. Several CRFs made with special coating technology were used for testing the fertilizer effects in yield and environment through pot experiment and field trial. The result indicated that the CRFs had higher N use efficiency, thus reducing N loss through leaching and volatilization while keeping higher yields. Comparing with imported standard CRFs, the test on CRFs showed similar fertilizer effect but with much lower cost. CRFs application is becoming a new approach for minimizing non-point contamination in agriculture.

  4. Alternative Asbestos Control Method and the Asbestos Releasability Research

    EPA Science Inventory

    Alternative Asbestos Control Method shows promise in speed, cost, and efficiency if equally protective. ORD conducted side by side test of AACM vs NESHAP on identical asbestos-containing buildings at Fort Chaffee. This abstract and presentation are based, at least in part, on pr...

  5. Mussel-inspired thermosensitive polydopamine-graft-poly(N-isopropylacrylamide) coating for controlled-release fertilizer.

    PubMed

    Ma, Zhiyuan; Jia, Xin; Hu, Jiamei; Liu, Zhiyong; Wang, Heyun; Zhou, Feng

    2013-12-18

    A thermoresponsive release multi-element compound fertilizer was first reported on the basis of a polydopamine-graft-poly(N-isopropylacrylamide) bilayer coated on a salty core by a combination of dopamine chemistry and surface-initiated atom transfer radical polymerization techniques, and the control of nutrient release in response to the environmental temperature was investigated. The successful synthesized stimuli-responsive fertilizers were confirmed by transmission electron microscopy (TEM), Fourier transforms infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and gel permeation chromatography (GPC). The release of elements from fertilizer was determined by an inductively coupled plasma (ICP) emission spectrometer. The thermosensitive fertilizers exhibit outstanding stimuli-responsive permeability to encapsulated nutrients, and the release rate of coated elements can be tailored by the ambient temperature. They can release nutrients easily at T < lower critical solution temperature (LCST) but slow at T > LCST. This strategy of grafting thermoresponsive polymer brushes on polydopamine (Pdop)-coated substrates is useful to prepare a stimuli-responsive release system, which can adjust the release rate according to different conditions, and will be effective and promising in the research and development of a stimuli-sensitive controlled-release system.

  6. Taurine and the control of basal hormone release from rat neurohypophysis.

    PubMed

    Song, Zhilin; Hatton, Glenn I

    2003-10-01

    Pituicytes of pituitary neural lobe are rich in the amino acid taurine, which they release upon hypoosmotic stimulation. As a generally inhibitory amino acid, taurine is thought to activate receptors on neural lobe nerve terminals and exert some control over hormone release. Previous work has shown the presence of glycine and GABA(A) receptors in neural lobe, both of which have affinity for taurine. Using a perifused explant system, we studied the effects of taurine activation of glycine and GABA(A) receptors on basal hormone release. Somewhat surprisingly, taurine induced increases in basal release of both vasopressin and oxytocin. Taurine-induced increases in oxytocin release were blocked by bicuculline, suggesting involvement of GABA(A) receptors. Increases in vasopressin release were not blocked by bicuculline, indicating involvement of receptors other than GABA(A). Although combined bicuculline and strychnine, an antagonist at most glycine receptors, also did not block increased vasopressin release, picrotoxin (a Cl(-) channel blocker) was effective in blocking increases in both vasopressin and oxytocin release. The other receptor(s) involved in taurine actions is postulated to be strychnine-insensitive glycine receptors. Thus, taurine in neural lobe may act via both a GABA(A) receptor and one or more types of glycine receptors to depolarize nerve terminal membranes under basal conditions. Taurine-induced partial depolarization resulting in Na(+) channel inactivation is probably responsible for its previously observed inhibition of stimulated hormone release from neural lobe.

  7. Microstructural control of modular peptide release from microporous biphasic calcium phosphate.

    PubMed

    Polak, Samantha J; Lee, Jae Sung; Murphy, William L; Tadier, Solène; Grémillard, Laurent; Lightcap, Ian V; Wagoner Johnson, Amy J

    2017-03-01

    Drug release from tissue scaffolds is commonly controlled by using coatings and carriers, as well as by varying the binding affinity of molecules being released. This paper considers modulating synthetic peptide incorporation and release through the use of interconnected microporosity in biphasic calcium phosphate (BCP) and identifies the microstructural characteristics important to the release using experiments and a model of relative diffusivity. First, the release of three modular peptides designed to include an osteocalcin-inspired binding sequence based on bone morphogenic protein-2 (BMP-2) was compared and one was selected for further study. Next, the incorporation and release of the peptide from four types of substrates were compared: non-microporous (NMP) substrates had no microporosity; microporous (MP) substrates were either 50% microporous with 5μm pores (50/5), 60% microporous with 5μm pores (60/5), or 50% microporous with 50μm pores (50/50). Results showed that MP substrates incorporated significantly more peptide than NMP ones, but that the three different microporous substrates all incorporated the same total amount of peptide. NMP had a markedly lower release rate compared to each of three of the MP samples, though the initial burst release was the highest. The initial release and the release rate for the 60/5 samples were different from the 50/50, though they were not statistically different from the 50/5. The model indicated that the pore interconnection to pore size ratio, affecting the constriction between pores, had the greatest influence on the calculated relative diffusivity. While the model was consistent with the trends observed experimentally, the quantitative experimental results suggested that to attain an appreciable difference in release characteristics, both pore size and pore fraction should be changed for this system. These results contribute to rational scaffold design by showing that microstructure, specifically microporosity

  8. Preparation and characterization of controlled-release fertilizers coated with marine polysaccharide derivatives

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Liu, Song; Qin, Yukun; Chen, Xiaolin; Xing, Rong'e.; Yu, Huahua; Li, Kecheng; Li, Pengcheng

    2016-10-01

    Encapsulation of water-soluble nitrogen fertilizers by membranes can be used to control the release of nutrients to maximize the fertilization effect and reduce environmental pollution. In this research, we formulated a new double-coated controlled-release fertilizer (CRF) by using food-grade microcrystalline wax (MW) and marine polysaccharide derivatives (calcium alginate and chitosan-glutaraldehyde copolymer). The pellets of water-soluble nitrogen fertilizer were coated with the marine polysaccharide derivatives and MW. A convenient and eco-friendly method was used to prepare the CRF. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were used to characterize the morphology and composition of the products. The nitrogen-release properties were determined in water using UV-Vis spectrophotometry. The controlled-release properties of the fertilizer were improved dramatically after coating with MW and the marine polysaccharide derivatives. The results show that the double-coated CRFs can release nitrogen in a controlled manner, have excellent controlled-release features, and meet the European Standard for CRFs.

  9. Microfluidic Synthesis of Microfibers for Magnetic-Responsive Controlled Drug Release and Cell Culture

    PubMed Central

    Lin, Yung-Sheng; Huang, Keng-Shiang; Yang, Chih-Hui; Wang, Chih-Yu; Yang, Yuh-Shyong; Hsu, Hsiang-Chen; Liao, Yu-Ju; Tsai, Chia-Wen

    2012-01-01

    This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture. PMID:22470443

  10. [Effects of slow/controlled release fertilizers on the growth and nutrient use efficiency of pepper].

    PubMed

    Tang, Shuan-Hu; Zhang, Fa-Bao; Huang, Xu; Chen, Jian-Sheng; Xu, Pei-Zhi

    2008-05-01

    Pot trails were conducted from 2003 to 2005 to study the effects of slow/controlled release fertilizers on the growth and nutrient use efficiency of pepper. The results indicated that in comparison with conventional splitting fertilization (T1), basal application of polymer-coated controlled release fertilizer (T2) enhanced the single fruit mass and vitamin C concentration, improved the root activity, and increased the fruit yield by 8.4%, but no significant effect was observed on the dissoluble sugar concentration in fruit. NH4MgPO4-coated controlled release fertilizer (T3) increased the dissoluble sugar concentration by 5.67%, but had less effect on single fruit mass and vitamin C concentration. Under the application of T3, the root system had a vigorous growth at early stages but became infirm at later stages, resulting in a lower yield. Comparing with T1, the application of 3 slow release fertilizers increased the dissoluble sugar concentration in fruit, enhanced the root activity, but had less effect on the yield. All test slow/controlled release fertilizers increased the use efficiency of N, P, and K significantly, with an exception for T2 which increased the use efficiency of N and K but decreased that of P. It was demonstrated that an appropriate application of slow/controlled release fertilizers could enhance pepper' s root activity and improve nutrient use efficiency.

  11. Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations

    PubMed Central

    Gesquiere, Ina; Darwich, Adam S; Van der Schueren, Bart; de Hoon, Jan; Lannoo, Matthias; Matthys, Christophe; Rostami, Amin; Foulon, Veerle; Augustijns, Patrick

    2015-01-01

    Aims The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB. Methods A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6–8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB. Results After administration of metoprolol immediate and controlled release, no statistically significant difference in the observed area under the curve (AUC0–24 h) was shown, although a tendency towards an increased oral exposure could be observed as the AUC0–24 h was 32.4% [95% confidence interval (CI) 1.36, 63.5] and 55.9% (95% CI 5.73, 106) higher following RYGB for the immediate and controlled-release formulation, respectively. This could be explained by surgery-related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract. The PBPK values predicted by modelling and simulation were similar to the observed data, confirming its validity. Conclusions The disposition of metoprolol from an immediate-release and a controlled-release formulation was not significantly altered after RYGB; there was a tendency to an increase, which was also predicted by PBPK modelling and simulation. PMID:25917170

  12. Controlled release of chlorhexidine digluconate using β-cyclodextrin and microfibrillated cellulose.

    PubMed

    Lavoine, Nathalie; Tabary, Nicolas; Desloges, Isabelle; Martel, Bernard; Bras, Julien

    2014-09-01

    This study aims to develop a high-performance delivery system using microfibrillated cellulose (MFC)-coated papers as a controlled release system combined with the well-known drug delivery agent, β-cyclodextrin (βCD). Chlorhexidine digluconate (CHX), an antibacterial molecule, was mixed with a suspension of MFC or a βCD solution or mixed with both the substances, before coating onto a cellulosic substrate. The intermittent diffusion of CHX (i.e., diffusion interrupted by the renewal of the release medium periodically) was conducted in an aqueous medium, and the release mechanism of CHX was elucidated by field emission gun-scanning electron microscopy, SEM, NMR, and Fourier transform infrared analyses. According to the literature, both βCD and MFC are efficient controlled delivery systems. This study indicated that βCD releases CHX more gradually and over a longer period of time compared to MFC, which is mainly due to the ability of βCD to form an inclusion complex with CHX. Furthermore from the release study, a complementary action when the two compounds were combined was deduced. MFC mainly affected the burst effect, while βCD primarily controlled the amount of CHX released over time. In this paper, two different types of controlled release systems are proposed and compared. Depending on the final application, the use of βCD alone would release low amounts of active molecules over time (slow delivery), whereas the combination of β-cyclodextrin and MFC would be more suitable for the release of higher amounts of active molecules over time (rapid delivery).

  13. Do Diuretics have Antinociceptive Actions: Studies of Spironolactone, Eplerenone, Furosemide and Chlorothiazide, Individually and with Oxycodone and Morphine.

    PubMed

    Jokinen, Viljami; Lilius, Tuomas; Laitila, Jouko; Niemi, Mikko; Kambur, Oleg; Kalso, Eija; Rauhala, Pekka

    2017-01-01

    Spironolactone, eplerenone, chlorothiazide and furosemide are diuretics that have been suggested to have antinociceptive properties, for example via mineralocorticoid receptor antagonism. In co-administration, diuretics might enhance the antinociceptive effect of opioids via pharmacodynamic and pharmacokinetic mechanisms. Effects of spironolactone (100 mg/kg, i.p.), eplerenone (100 mg/kg, i.p.), chlorothiazide (50 mg/kg, i.p.) and furosemide (100 mg/kg, i.p.) were studied on acute oxycodone (0.75 mg/kg, s.c.)- and morphine (3 mg/kg, s.c.)-induced antinociception using tail-flick and hot plate tests in male Sprague Dawley rats. The diuretics were administered 30 min. before the opioids, and behavioural tests were performed 30 and 90 min. after the opioids. Concentrations of oxycodone, morphine and their major metabolites in plasma and brain were quantified by mass spectrometry. In the hot plate test at 30 and 90 min., spironolactone significantly enhanced the antinociceptive effect (% of maximum possible effect) of oxycodone from 10% to 78% and from 0% to 50%, respectively, and that of morphine from 12% to 73% and from 4% to 83%, respectively. The brain oxycodone and morphine concentrations were significantly increased at 30 min. (oxycodone, 46%) and at 90 min. (morphine, 190%). We did not detect any independent antinociceptive effects with the diuretics. Eplerenone and chlorothiazide did not enhance the antinociceptive effect of either opioid. The results suggest that spironolactone enhances the antinociceptive effect of both oxycodone and morphine by increasing their concentrations in the central nervous system.

  14. Effects of Acute and Repeated Administration of Oxycodone and Naloxone-Precipitated Withdrawal on Intracranial Self-Stimulation in Rats

    PubMed Central

    Wiebelhaus, Jason M.; Walentiny, D. Matthew

    2016-01-01

    Incidence of prescription opioid abuse and overdose, often led by oxycodone, continues to increase, producing twice as many overdose deaths as heroin. Surprisingly, preclinical reports relevant to oxycodone’s abuse-related effects are relatively sparse considering its history and patient usage. The goal of this study was to characterize dose- and time-dependent effects of acute and repeated oxycodone administration in a frequency-rate intracranial self-stimulation (ICSS) procedure, an assay often predictive of drug-related reinforcing effects, in male Sprague-Dawley rats. We hypothesized that oxycodone would produce a biphasic profile of rate-increasing and rate-decreasing effects maintained by ICSS similar to μ-opioid receptor agonists. Oxycodone (0.03, 0.3, 1, and 3 mg/kg, s.c.) produced dose- and time-dependent alterations on ICSS, with the predicted biphasic profile of rate-increasing effects at lower stimulation frequencies followed by rate-decreasing effects at higher frequencies. Peak effects were observed between 30 and 60 minutes, which were reversed by naloxone pretreatment (30 minutes). Tolerance to rate-decreasing effects was observed over a 5-day period when rats were treated with 1 mg/kg oxycodone twice a day. Subsequently, the dosing regimen was increased to 3 mg/kg twice a day over 10 days, although further marked tolerance did not develop. When then challenged with 10 mg/kg naloxone, a significant suppression below baseline levels of ICSS-maintained responding occurred indicative of dependence that recovered to baseline within 5 hours. The results of this study provide the first report of acute and chronic effects of oxycodone on responding maintained by ICSS presentation and the use of ICSS-maintained responding to characterize its tolerance and dependence effects. PMID:26491062

  15. Controlled-Release Personal Use Arthropod Repellent Formulation

    DTIC Science & Technology

    1985-09-25

    deodorant , or other cosmetic enhancers, and rinsed with 70% ethanol. For each subject control site, (5 cm in diameter), anG two test sites, 6 x 16.7 cm...Camouflage 0-1 c) Polyurethane Rifle Stocks 51 Metals S-1 a) Aluminum General Equipeent 6) Natural Products -- I a) Leather Boots 7) Textiles T-1 a...The area was slightly tacky to touch and a definite loss of gloss was noted. * e. metals Aluminum was not visibly affected by all three solutions. f

  16. Controlled release of an anti-cancer drug from DNA structured nano-films

    NASA Astrophysics Data System (ADS)

    Cho, Younghyun; Lee, Jong Bum; Hong, Jinkee

    2014-02-01

    We demonstrate the generation of systemically releasable anti-cancer drugs from multilayer nanofilms. Nanofilms designed to drug release profiles in programmable fashion are promising new and alternative way for drug delivery. For the nanofilm structure, we synthesized various unique 3-dimensional anti cancer drug incorporated DNA origami structures (hairpin, Y, and X shaped) and assembled with peptide via layer-by-layer (LbL) deposition method. The key to the successful application of these nanofilms requires a novel approach of the influence of DNA architecture for the drug release from functional nano-sized surface. Herein, we have taken first steps in building and controlling the drug incorporated DNA origami based multilayered nanostructure. Our finding highlights the novel and unique drug release character of LbL systems in serum condition taken full advantages of DNA origami structure. This multilayer thin film dramatically affects not only the release profiles but also the structure stability in protein rich serum condition.

  17. Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

    PubMed

    Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

    2008-08-07

    The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

  18. Controlled release properties of zein-fatty acid blend films for multiple bioactive compounds.

    PubMed

    Arcan, Iskender; Yemenicioğlu, Ahmet

    2014-08-13

    To develop edible films having controlled release properties for multiple bioactive compounds, hydrophobicity and morphology of zein films were modified by blending zein with oleic (C18:1)Δ⁹, linoleic (C18:2)Δ(9,12), or lauric (C₁₂) acids in the presence of lecithin. The blend zein films showed 2-8.5- and 1.6-2.9-fold lower initial release rates for the model active compounds, lysozyme (LYS) and (+)-catechin (CAT), than the zein control films, respectively. The change of fatty acid chain length affected both CAT and LYS release rates while the change of fatty acid double bond number affected only the CAT release rate. The film morphologies suggested that the blend films owe their controlled release properties mainly to the microspheres formed within their matrix and encapsulation of active compounds. The blend films showed antilisterial activity and antioxidant activity up to 81 μmol Trolox/cm². The controlled release of multiple bioactive compounds from a single film showed the possibility of combining application of active and bioactive packaging technologies and improving not only safety and quality but also health benefits of packed food.

  19. Thermally Responsive Hydrogel Blends: A General Drug Carrier Model for Controlled Drug Release.

    PubMed

    Ma, Chongbo; Shi, Ye; Pena, Danilo A; Peng, Lele; Yu, Guihua

    2015-06-15

    Thermally responsive hydrogels have drawn significant research attention recently because of their simple use as drug carrier at human body temperature. Here we design a hybrid hydrogel that incorporates a hydrophilic polymer, polyethyleneimine (PEI), into the thermally responsive hydrogel poly(N-isopropylacrylamide) (PNIPAm), as a general drug carrier model for controlled drug release. In this work, on one hand, PEI modifies the structure and the size of the pores in the PNIPAm hydrogel. On the other hand, PEI plays an important role in tuning the water content in the hydrogel and controls the water release rate of the hydrogel below the lower critical solution temperature (LCST), resulting in a tunable release rate of the drugs at human body temperature (37 °C). Different release rates are shown as different amounts of PEI are incorporated. PEI controls the release rate, dependent on the charge characteristics of the drugs. The hydrogel blends described in this work extend the concept of a general drug carrier for loading both positively and negatively charged drugs, as well as the controlled release effect.

  20. E-Control: First Public Release of Remote Control Software for VLBI Telescopes

    NASA Technical Reports Server (NTRS)

    Neidhardt, Alexander; Ettl, Martin; Rottmann, Helge; Ploetz, Christian; Muehlbauer, Matthias; Hase, Hayo; Alef, Walter; Sobarzo, Sergio; Herrera, Cristian; Himwich, Ed

    2010-01-01

    Automating and remotely controlling observations are important for future operations in a Global Geodetic Observing System (GGOS). At the Geodetic Observatory Wettzell, in cooperation with the Max-Planck-Institute for Radio Astronomy in Bonn, a software extension to the existing NASA Field System has been developed for remote control. It uses the principle of a remotely accessible, autonomous process cell as a server extension for the Field System. The communication is realized for low transfer rates using Remote Procedure Calls (RPC). It uses generative programming with the interface software generator idl2rpc.pl developed at Wettzell. The user interacts with this system over a modern graphical user interface created with wxWidgets. For security reasons the communication is automatically tunneled through a Secure Shell (SSH) session to the telescope. There are already successful test observations with the telescopes at O Higgins, Concepcion, and Wettzell. At Wettzell the software is already used routinely for weekend observations. Therefore the first public release of the software is now available, which will also be useful for other telescopes.

  1. 77 FR 16264 - Manufacturer of Controlled Substances, Notice of Registration; Noramco Inc. (GA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-20

    ... controlled substances: Drug Schedule Codeine-N-oxide (9053) I Dihydromorphine (9145) I Morphine-N-oxide (9307... Oxycodone (9143) II Hydromorphone (9150) II Hydrocodone (9193) II Morphine (9300) II Oripavine (9330)...

  2. Controlled release of an osteogenic peptide from injectable biodegradable polymeric composites.

    PubMed

    Hedberg, Elizabeth L; Tang, Andrew; Crowther, Roger S; Carney, Darrell H; Mikos, Antonios G

    2002-12-05

    Poly(D,L-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) blend microparticles loaded with the osteogenic peptide TP508 were added to a mixture of poly(propylene fumarate) (PPF), poly(propylene fumarate)-diacrylate (PPF-DA), and sodium chloride (NaCl) for the fabrication of PPF composite scaffolds that could allow for tissue ingrowth as well as for the controlled release of TP508 when implanted in an orthopedic defect site. In this study, PPF composites were fabricated and the in vitro release kinetics of TP508 were determined. TP508 loading within the PLGA/PEG microparticles, PEG content within the PLGA/PEG microparticles, the microparticle content of the PPF composite polymer component, and the leachable porogen initial mass percent of the PPF composites were varied according to a fractional factorial design and the effect of each variable on the release kinetics was determined for up to 28 days. Each composite formulation released TP508 with a unique release profile. The initial release (release through day 1) of the PLGA/PEG microparticles was reduced upon inclusion in the PPF composite formulations. Day 1 normalized cumulative mass release from PPF composites ranged from 0.14+/-0.01 to 0.41+/-0.01, whereas the release from PLGA/PEG microparticles ranged from 0.31+/-0.02 to 0.58+/-0.01. After 28 days, PPF composites released 53+/-4% to 86+/-2% of the entrapped peptide resulting in cumulative mass releases ranging from 0.14+/-0.01 microg TP508/mm(3) scaffold to 2.46+/-0.05 microg TP508/mm(3) scaffold. The results presented here demonstrate that PPF composites can be used for the controlled release of TP508 and that alterations in the composite's composition can lead to modulation of the TP508 release kinetics. These composites can be used to explore the effects varied release kinetics and dosages on the formation of bone in vivo.

  3. Preparation of acetylsalicylic acid-acylated chitosan as a novel polymeric drug for drug controlled release.

    PubMed

    Liu, Changkun; Wu, Yiguang; Zhao, Liyan; Huang, Xinzheng

    2015-01-01

    The acetylsalicylic acid-acylated chitosan (ASACTS) with high degree of substitution (DS) was successfully synthesized, and characterized with FTIR, (1)H NMR and elemental analysis methods. The optimum synthesis conditions were obtained which gave the highest DS (about 60%) for ASACTS. Its drug release experiments were carried out in simulated gastric and intestine fluids. The results show that the drugs in the form of acetylsalicylic acid (ASA) and salicylic acid (SA) were released in a controlled manner from ASACTS only in simulated gastric fluid. The release profile can be best fitted with logistic and Weibull model. The research results reveal that ASACTS can be a potential polymeric drug for the controlled release of ASA and SA in the targeted gastric environment.

  4. Synthesis and characterization of a HAp-based biomarker with controlled drug release for breast cancer.

    PubMed

    González, Maykel; Merino, Ulises; Vargas, Susana; Quintanilla, Francisco; Rodríguez, Rogelio

    2016-04-01

    A biocompatible hybrid porous polymer-ceramic material was synthesized to be used as a biomarker in the treatment of breast cancer. This device was equipped with the capacity to release medicaments locally in a controlled manner. The biomaterial was Hydroxyapatite(HAp)-based and had a controlled pore size and pore volume fraction. It was implemented externally using a sharp end and a pair of barbed rings placed opposite each other to prevent relative movement once implanted. The biomarker was impregnated with cis-diamine dichloride platinum (II) [Cl2-Pt-(NH3)2]; the rate of release was obtained using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and release occurred over the course of three months. Different release profiles were obtained as a function of the pore volume fraction. The biomaterial was characterized using scanning electron microscopy (SEM) and Raman spectroscopy.

  5. Control of drug release from capsules using high frequency energy transmission systems.

    PubMed

    Gröning, R; Bensmann, H; Müller, R S

    2008-11-19

    In the present investigations new drug delivery systems have been developed, which are controlled by a computer and a high frequency energy transmission system. The capsules consist of a drug reservoir, a high frequency receiver, a gas generating section and a piston to pump a drug solution or drug suspension out of the reservoir. Mechanical energy is generated inside the capsule through electrolysis, if a 27 MHz high frequency field is in resonance with the receiver inside the capsule. Two different miniaturised oscillatory circuits were constructed, which act as the receivers in the capsules. Tramadol was used in release experiments as a model drug. Delayed and pulsed release profiles were obtained. A computer-controlled system was constructed, in which the programmed release profiles are compared with the actual release of the drug.

  6. Intercalation and controlled release properties of vitamin C intercalated layered double hydroxide

    NASA Astrophysics Data System (ADS)

    Gao, Xiaorui; Lei, Lixu; O'Hare, Dermot; Xie, Juan; Gao, Pengran; Chang, Tao

    2013-07-01

    Two drug-inorganic composites involving vitamin C (VC) intercalated in Mg-Al and Mg-Fe layered double hydroxides (LDHs) have been synthesized by the calcination-rehydration (reconstruction) method. Powder X-ray diffraction (XRD), Fourier transform infrared (FTIR), and UV-vis absorption spectroscopy indicate a successful intercalation of VC into the interlayer galleries of the LDH host. Studies of VC release from the LDHs in deionised water and in aqueous CO32- solutions imply that Mg3Al-VC LDH is a better controlled release system than Mg3Fe-VC LDH. Analysis of the release profiles using a number of kinetic models suggests a solution-dependent release mechanism, and a diffusion-controlled deintercalation mechanism in deionised water, but an ion exchange process in CO32- solution.

  7. Development and Evaluation of Oral Controlled Release Chlorpheniramine-Ion Exchange Resinate Suspension

    PubMed Central

    Kadam, A. U.; Sakarkar, D. M.; Kawtikwar, P. S.

    2008-01-01

    An oral controlled release suspension of chlorpheniramine maleate was prepared using ion-exchange resin technology. A strong cation exchange resin Indion 244 was utilized for the sorption of the drug and the drug resinates was evaluated for various physical and chemical parameters. The drug-resinate complex was microencapsulated with a polymer Eudragit RS 100 to further retard the release characteristics. Both the drug-resinate complex and microencapsulated drug resinate were suspended in a palatable aqueous suspension base and were evaluated for controlled release characteristic. Stability study indicated that elevated temperature did not alter the sustained release nature of the dosage form indicating that polymer membrane surrounding the core material remained intact throughout the storage period. PMID:20046790

  8. Enhanced controlled release of loratadine from the ethylene-vinyl acetate matrix containing plasticizer.

    PubMed

    Cho, Cheong-Weon; Kim, Seong-Jin; Yang, Kyu-Ho; Song, Jae-Haeng; Jeong, Hyun-Jon; Shin, Sang-Chul

    2008-09-01

    An ethylene-vinyl acetate (EVA) matrix containing plasticizer was prepared as a potential controlled release system for loratadine. The EVA matrix containing loratadine was prepared as the transdermal device using casting methods. The solubility of loratadine according to the volume fraction of PEG 400 was determined. The effects of the drug concentration, temperature, and plasticizers on the release of the drug were determined at 37 degrees C using 40% PEG 400 solution as the receptor medium using the modified Keshary-Chien cell. Some types of plasticizers. such as citrates and phthalates, were used to prepare the pores and increase the flexibility of the EVA matrix. The solubility test according to the PEG 400 volume fraction revealed the highest solubility in the 40% PEG 400 solution. The rate of drug released from the EVA matrix increased with increasing temperature and drug loading. There was a linear relationship between the release rate and the square root of the loading dose. The activation energy for drug release from the EVA matrix with a loading dose of 1%, 2%, 3%, 4%, and 5% was estimated to be 6.83, 6.80, 6.77, 6.71, and 6.65 kcal/mol, respectively Among the plasticizers used, diethyl phthalate showed the highest level of loratadine release. In conclusion, an EVA matrix containing plasticizer could be used to enhance the controlled release of loratadine.

  9. Coordination and control of posture and ball release in basketball free-throw shooting.

    PubMed

    Verhoeven, F Martijn; Newell, Karl M

    2016-10-01

    The objective of this study was to investigate the coordination of a whole-body task (basketball free-throw) in which success in performance outcome can be achieved through a manifold of combinations of postural and movement trajectory configurations. Participants were healthy men (19-24years) with a range of skill levels that were tested for the accuracy of 50 basketball free-throws with both their dominant and non-dominant hand. The trial-to-trial variance in release parameters as well as postural stability of the shooter and synchronization of postural movement and ball release were strong predictors of performance, with non-elite shooters having a higher mean and variability of center-of-mass (COM) speed at the time of ball release. The synchronization between the time of peak COM and the time of ball release increased as a function of skill level and hand dominance, with the better performers releasing the ball more closely to the time of COM peak height. These findings reveal how, in addition to successfully controlling the trial-to-trial variability along the solution manifold of release parameters, the relative importance of the coordination of postural control and ball release properties on shooting success changes as a function of skill level.

  10. A Cryptographic Framework for the Controlled Release Of Certified Data

    NASA Astrophysics Data System (ADS)

    Bangerter, Endre; Camenisch, Jan; Lysyanskaya, Anna

    The problem of privacy protection is to control the dissemination of personal data. There exist various privacy principles that describe at a conceptual level what measures have to be taken to protect privacy. Examples of these principles are an individual's right to access and to request correction of data about oneself and the requirement for an individual to consent to the disclosure of her personal data. Another principle is that of data minimization: It states that an individual should only disclose the minimal necessary data for a given purpose. Determining these data is often a difficult task, and one usually needs to balance an individual's privacy interests and the legitimate interest of other parties in the individual's data. An example of this trade-off is an individual's wish to be anonymous conflicting with her requirements imposed by law enforcement to be able to identify and get hold of criminals. Such trade-offs impose limits on privacy that cannot be overcome by any technology.

  11. Single wall carbon nanohorn as a drug carrier for controlled release

    NASA Astrophysics Data System (ADS)

    Xu, Jianxun; Yudasaka, Masako; Kouraba, Sachio; Sekido, Mitsuru; Yamamoto, Yuhei; Iijima, Sumio

    2008-08-01

    A single wall carbon nanohorn (SWNH) is a new kind of single-graphene tubules with a diameter of 2-5 nm and a length 40-50 nm. In this work, we used oxidized SWNH (SWNHox) to incorporate vancomycin hydrochloride (VCM) for its controlled release by taking advantage of the interactions between VCM and SWNHox. Phospholipid-poly(ethylene glycol) was used to modify the hydrophobic surface of SWNHox to improve its dispersion in aqueous systems. In the release study using this complex, a stable release of VCM was achieved for an extended period.

  12. 46 CFR 160.133-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and... SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise,...

  13. 46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 6 2014-10-01 2014-10-01 false Production inspections, tests, quality control, and... SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise,...

  14. 46 CFR 160.170-15 - Production inspections, tests, quality control, and conformance of release mechanisms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 6 2013-10-01 2013-10-01 false Production inspections, tests, quality control, and... SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING..., quality control, and conformance of release mechanisms. (a) Unless the Commandant directs otherwise,...

  15. Experimental Physics and Industrial Control System (EPICS): Application source/release control for EPICS R3.11.6

    SciTech Connect

    Zieman, B.; Kraimer, M.

    1994-03-25

    This manual describes a set of tools that can be used to develop software for EPICS based control systems. It provides the following features: Multiple applications; the entire system is composed of an arbitrary number of applications: Source/Release Control; all files created or modified by the applications developers can be put under sccs (a UNIX Source/Release control utility): Multiple Developers; it allows a number of applications developers to work separately during the development phase but combine their applications for system testing and for a production system; Makefiles: makefiles are provided to automatically rebuild various application components. For C and state notation programs, Imagefiles are provided.

  16. Modified tamarind kernel polysaccharide: a novel matrix for control release of aspirin.

    PubMed

    Ghosh, Sandipta; Pal, Sagar

    2013-07-01

    pH dependent hydrogels of modified tamarind kernel polysaccharide (TKP) were synthesized by grafting with polyacrylamide chains on TKP backbone in presence of microwave irradiation and initiator. The present study is carried out to design oral controlled drug delivery systems for aspirin using synthesized hydrogels as carrier in form of tablets. TKP-g-PAM based hydrogels show significant enhancement for control release of aspirin. Release behavior of aspirin has been evaluated using USP type I apparatus in 900 mL of buffer solutions (pH 1.2, 6.8, 7.4), maintained at 37°C at 100 rpm. It is observed that with increase in percentage of grafting (% G), swelling of matrices increases whereas erosion and rate of drug release decrease. The effect of % G onto t50 value (time taken for release of 50% drug) has also been discussed. The release characteristics from the matrices under study show non-Fickian diffusion mechanism, suggesting the controlled release of aspirin.

  17. Controlled release by novel lysostaphin-loaded hydroxyapatite/chitosan composites.

    PubMed

    Wang, Jin-Cheng; Xue, Bai; Ge, Kui-Kui; Wang, Yi-Han; Li, Guo-Dong; Huang, Qing-Shan

    2014-09-01

    Lysostaphin is highly effective on eliminating methicillin resistant Staphylococcus aureus (MRSA). In order to achieve controlled release of lysostaphin, a biocompatible drug carrier is needed. Hydroxyapatite/chitosan (HA/CS) composites were chosen to carry lysostaphin and sample composites with different weight ratios of HA to CS, including 80/20, 70/30, 60/40, and 40/60, were prepared. Multiple analyses were performed to determine the structural and physicochemical properties of the composites, including scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. We immersed HA/CS composites loaded with 1 wt% lysostaphin to test in vitro release activity and cultured MC3T3-E1 cells to carry out biocompatibility test. The result of the release behavior of the composites revealed that the controlled release of lysostaphin from 60/40 HA/CS composites was the highest release rate of (87.4 ± 2.8)%, which lasted for 120 hours. In biocompatibility testing, MC3T3-E1 cells were able to proliferate on the surface of these composites, and the extract liquid from the composites could increase the growth of the cells. These results demonstrate the controlled release of lysostaphin from HA/CS composites and their biocompatibility, suggesting the potential application of these composites to bone injury and infection applications.

  18. Improving the controlled release of water-insoluble emodin from amino-functionalized mesoporous silica

    NASA Astrophysics Data System (ADS)

    Xu, Yunqiang; Wang, Chunfeng; Zhou, Guowei; Wu, Yue; Chen, Jing

    2012-06-01

    Several types of amino-functionalized mesoporous silica, including F5-SBA-15, F10-SBA-15, and F15-SBA-15 were prepared through co-condensation of tetraethoxysilane (TEOS) and (3-aminopropyl)triethoxysilane (APTES) in varying molar ratios (5 mol%, 10 mol%, and 15 mol%) via a hydrothermal process. The materials obtained were characterized by means of small-angle X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption, Fourier transformed infrared spectra, and X-ray photoelectron spectroscopy. Increasing APTES molar ratios decreased the degree of orderliness of the functionalized mesoporous silica. Pure and amino-functionalized SBA-15 samples were employed as supports for the controlled release of water-insoluble drug emodin. Loading experiments showed that drug loading capacities mainly depended on the surface areas and pore diameters of the carriers. Controlled release profiles of emodin-loaded samples were studied in phosphate buffered saline (PBS, pH 7.4), and results indicated that the emodin release rate could be controlled by surface amino-functionalized carriers. Emodin loaded on functionalized mesoporous supports exhibited a lower release rate than that of loaded on pure SBA-15, emodin loaded on F10-SBA-15 showed the smallest release amount (71.74 wt%) after stirring in PBS for 60 h. Findings suggest that functionalized mesoporous SBA-15 is a promising carrier for achieving prolonged release time periods.

  19. Chitosan-polycarbophil complexes in swellable matrix systems for controlled drug release.

    PubMed

    Lu, Z; Chen, W; Hamman, J H

    2007-10-01

    A prerequisite for progress in the design of novel drug delivery systems is the development of excipients that are capable of fulfilling multifunctional roles such as controlling the release of the drug according to the therapeutic needs. Although several polymers have been utilised in the development of specialised drug delivery systems, their scope in dosage form design can be enlarged through combining different polymers. When a polymer is cross-linked or complexed with an oppositely charged polyelectrolyte, a three-dimensional network is formed in which the drug can be incorporated to control its release. The swelling properties and release kinetics of two model drugs with different water solubilities (i.e. diltiazem and ibuprofen) from monolithic matrix tablets consisting of an interpolyelectrolyte complex between chitosan and polycarbophil are reported. Matrix tablets consisting of this polymeric complex without drug or excipients exhibited extremely high swelling properties that are completely reversible upon drying. The drug release from matrix systems with different formulations depended on the concentration of the chitosan-polycarbophil interpolyelectrolyte complex and approached zero order release kinetics for both model drugs. The chitosan-polycarbophil interpolyelectrolyte complex has demonstrated a high potential as an excipient for the production of swellable matrix systems with controlled drug release properties.

  20. In vitro characterization of a controlled-release ocular insert for delivery of brimonidine tartrate.

    PubMed

    Mealy, J E; Fedorchak, M V; Little, S R

    2014-01-01

    Glaucoma is the second leading cause of blindness in the US. Brimonidine tartrate (BT) is a modern anti-glaucoma agent that is currently administered as frequently as a thrice-daily topical eye drop medication. Accordingly, compliance with BT regimens is low, limiting overall effectiveness. One attempt that has previously proved effective in addressing non-adherence is the formation of ocular inserts, such as the Ocusert(®), whose diffusion-based control released an older drug (pilocarpine) for a week-long period. Modern controlled drug-release technology provides an avenue for extending the release of practically any drug (including new drugs such as BT) for as long as 1 month from a singular insert. Currently, no controlled-release formulations for BT exist. This work outlines the development and characterization of a BT-releasing ocular insert designed from poly(lactic co-glycolic) acid/polyethylene glycol (PEG). It was found that a formulation containing 15% PEG can be created that produces a linear BT-release profile corresponding to BT eye drop delivery estimates. Additionally, these inserts were shown, through the use of atomic force microscopy and scanning electron microscopy, to have smooth surfaces and physical properties suitable for ophthalmic use.

  1. Construction of a controlled-release delivery system for pesticides using biodegradable PLA-based microcapsules.

    PubMed

    Liu, Baoxia; Wang, Yan; Yang, Fei; Wang, Xing; Shen, Hong; Cui, Haixin; Wu, Decheng

    2016-08-01

    Conventional pesticides usually need to be used in more than recommended dosages due to their loss and degradation, which results in a large waste of resources and serious environmental pollution. Encapsulation of pesticides in biodegradable carriers is a feasible approach to develop environment-friendly and efficient controlled-release delivery system. In this work, we fabricated three kinds of polylactic acid (PLA) carriers including microspheres, microcapsules, and porous microcapsules for controlled delivery of Lambda-Cyhalothrin (LC) via premix membrane emulsification (PME). The microcapsule delivery system had better water dispersion than the other two systems. Various microcapsules with a high LC contents as much as 40% and tunable sizes from 0.68 to 4.6μm were constructed by manipulating the process parameters. Compared with LC technical and commercial microcapsule formulation, the microcapsule systems showed a significantly sustained release of LC for a longer period. The LC release triggered by LC diffusion and matrix degradation could be optimally regulated by tuning LC contents and particle sizes of the microcapsules. This multi-regulated release capability is of great significance to achieve the precisely controlled release of pesticides. A preliminary bioassay against plutella xylostella revealed that 0.68μm LC-loaded microcapsules with good UV and thermal stability exhibited an activity similar to a commercial microcapsule formulation. These results demonstrated such an aqueous microcapsule delivery system had a great potential to be further explored for developing an effective and environmentally friendly pesticide-release formulation.

  2. Controlled release behaviour and antibacterial effects of antibiotic-loaded titania nanotubes.

    PubMed

    Feng, Wenchao; Geng, Zhen; Li, Zhaoyang; Cui, Zhenduo; Zhu, Shengli; Liang, Yanqin; Liu, Yunde; Wang, Renfeng; Yang, Xianjin

    2016-05-01

    Bacterial infections have been identified as the main cause of orthopaedic implant failure. Owing to their high antibiotic delivery efficiency, titania nanotubes loaded with antibiotics constitute one of the most promising strategies for suppressing bacterial infections. However, it is difficult to control the drug-release behaviour of such nanotubes. Although sealing the nanotubes with a polymer solution provides sustained release effects to a certain extent, it inevitably influences their initial antibacterial activity. This study reports on the controlled release of gentamicin sulphate (GS) from titania nanotube surfaces whereby their initial antibacterial activity remains unaffected. Titania nanotubes were fabricated via electrochemical anodization and loaded with GS through physical adsorption. Experimental results showed that this loading method is feasible and efficient. The GS-loaded titania nanotubes were further covered by a thin film comprising a mixture of GS and chitosan (GSCH). The release kinetics confirmed that the drug release could be controlled by this thin film. Moreover, such a film was shown to not only inhibit initial bacterial adherence owing to its strong antibacterial properties but also enhance cell viability. Thus, GS-loaded titania nanotubes coated with GSCH have considerable potential as biomaterials for preventing initial release and peri-implant infection in the field of orthopaedics.

  3. Tapentadol Prolonged Release for Chronic Pain: A Review of Clinical Trials and 5 Years of Routine Clinical Practice Data.

    PubMed

    Baron, Ralf; Eberhart, Leopold; Kern, Kai-Uwe; Regner, Stefan; Rolke, Roman; Simanski, Christian; Tölle, Thomas

    2016-09-09

    Tapentadol prolonged release (PR) for the treatment of moderate to severe chronic pain combines 2 modes of action. These are μ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule that allow higher analgesic potency through modulation of different pharmacological targets within the pain transmitting systems. At the same time, this can also serve as a clue for modulation of different pain-generating mechanisms according to nociceptive, neuropathic, or mixed pain conditions. Tapentadol PR has now been on the market for 5 years, with over 4.6 million people treated worldwide. A panel of pain specialists convened in Germany to review the clinical program and to discuss the role of tapentadol PR in the management of chronic pain. The clinical study program demonstrated effective and generally well-tolerated treatment for up to 2 years in a broad range of chronic pain conditions, including those with neuropathic pain components. This was confirmed in routine clinical practice observations. Head-to-head studies with World Health Organization (WHO) III opioids such as oxycodone controlled release and oxycodone/naloxone PR showed at least comparable pain relief in the treatment of moderate-to-severe musculoskeletal pain. Rotation from poorly tolerated WHO III opioids to tapentadol PR provided effective pain relief and better symptom control for musculoskeletal pain compared to previous medication. Functionality, health status and quality of life also improved under tapentadol PR treatment. The gastrointestinal tolerability profile was more favorable compared to other tested WHO III opioids. Tapentadol PR has a good safety profile and no evidence of acquired tolerance from the long-term data so far collected. Overall, tapentadol PR represents an effective and generally well-tolerated alternative to "classical" opioidergic drugs.

  4. Controlled release of isoproturon, imidacloprid, and cyromazine from alginate-bentonite-activated carbon formulations.

    PubMed

    Garrido-Herrera, F J; Gonzalez-Pradas, E; Fernandez-Pérez, M

    2006-12-27

    Different alginate-based systems of isoproturon, imidacloprid, and cyromazine have been investigated in order to obtain controlled release (CR) properties. The basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was modified using different amounts of bentonite and activated carbon. The higher values of encapsulation efficiency corresponded to those formulations prepared with higher percentages of activated carbon, showing higher encapsulation efficiency values for isoproturon and imidacloprid than for cyromazine, which has a higher water solubility. The kinetic experiments of imidacloprid/isoproturon release in water have shown us that the release rate is higher in imidacloprid systems than in those prepared with isoproturon. Moreover, it can be deduced that the use of bentonite and/or activated carbon sorbents reduces the release rate of the isoproturon and imidacloprid in comparison with the technical product and with alginate formulation without modifying agents. The highest decrease in release rate corresponds to the formulations prepared with the highest percentage of activated carbon. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T50, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the pesticide release data, the release of isoproturon and imidacloprid from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents and the permeability of the formulations were the most important factors modulating pesticide release. Finally, a linear correlation of the T50 values and the content of activated carbon in formulations were obtained.

  5. Controllable biodegradability, drug release behavior and hemocompatibility of PTX-eluting magnesium stents.

    PubMed

    Lu, Ping; Fan, Hainan; Liu, Yin; Cao, Lu; Wu, Xiangfeng; Xu, Xinhua

    2011-03-01

    Cardiovascular magnesium-based stents have been already applied in patients. However, their high corrosion rate hinders their clinical application. In this study, we adopt a new approach in the design of a Mg-based stent to improve the biodegradation rate and the drug release rate. By fabricating a micro-arc oxidation/poly-l-lactic acid (MAO/PLLA) composite coating on the magnesium alloy AZ81 substrate, the corrosion resistance decreased and the biodegradation rate became controllable. The drug release coating was composed of one Poly(dl-lactide-co-glycolide)/paclitaxel (PLGA/PTX) layer and one pure PLGA blank layer without paclitaxel, and this coating also functions to provide controlled biodegradation rate of the stent. The drug release rate was controlled by controlling the ratio of the LA:GA of the PLGA without PTX. The scanning electron microscopy (SEM) images were used to demonstrate the morphology of the samples before and after this modification. The blood compatibility of the samples was demonstrated by the platelet adhesion test. The drug release was determined by ultraviolet-visible (UV-visible) spectrophotometer. The result showed that the PLLA effectively sealed the micro-cracks and micro-holes on the surface of the MAO coating to give controllable biodegradation of the AZ81. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases that would come from the uncontrolled oxidation/corrosion of AZ81. The samples modified had better hemocompatibility than 316L stainless steel.

  6. PCL-forsterite nanocomposite fibrous membranes for controlled release of dexamethasone.

    PubMed

    Kharaziha, Mahshid; Fathi, Mohammad Hossein; Edris, Hossein; Nourbakhsh, Nosrat; Talebi, Ardeshir; Salmanizadeh, Sharareh

    2015-01-01

    The well-known treatment of the alveolar bone defects is guided tissue regeneration (GTR). Engineered membranes combined with osteo-differentiation factors have been offered a promising strategy for GTR application. Recently, poly(ε-caprolactone) (PCL)-forsterite (PCL-F) nanocomposite fibrous membranes have been developed. However, PCL-F membranes could not promote bone tissue regeneration. The aim of this research is to encapsulate an osteogenic factor [dexamethasone (DEX)] in PCL-F membranes and evaluate the effects of forsterite nanopowder (particle size = 25-45 nm) and fiber organization on DEX delivery for GTR application. The hypothesis is that the release kinetic and profile of DEX could be controlled through variation of forsterite content (0, 5 and 10 wt%) and fiber arrangement (aligned and random). Results demonstrated while DEX release was sustained over a period of 4 weeks, its kinetic was governed by the membrane architecture and composition. For example, aligned PCL-F nanocomposite fibrous membrane consisting of 10 %(w/v) forsterite nanopowder exhibited the least initial burst release (13 % release in the first 12 h) and allowed sustained release of DEX. Additionally, forsterite nanopowder inclusion changed the kinetic of DEX release from Fickian diffusion to an anomalous transport. The bioactivity of released DEX was estimated using culturing the stem cells from human exfoliated deciduous teeth (SHED) on the membranes. Results demonstrated that proliferation and osteogenic differentiation of SHED could be governed by DEX release process. While DEX release from the membranes decreased SHED proliferation, stimulated the matrix mineralization. Our finding indicated that aligned PCL-F/DEX membrane could be used as a carrier for the sustained release of drugs relevant for GTR trophy.

  7. Preparation and Physicochemical Evaluation of Controlled-release Carbon Source Tablet for Groundwater in situ Denitrification

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Kang, J. H.; Yeum, Y.; Han, K. J.; Kim, D. W.; Park, C. W.

    2015-12-01

    Nitric nitrogen could be the one of typical pollution source such asNO3-through domestic sewage, livestock and agricultural wastewater. Resident microflorain aquifer has known to remove the nitric nitrogen spontaneously following the denitration process with the carbon source (CS) as reactant. However, it could be reacted very slowly with the rack of CS and there have been some studies for controlled addition of CS (Ref #1-3). The aim of this study was to prepare the controlled-release carbon source (CR-CS) tablet and to evaluate in vitro release profile for groundwater in situ denitrification. CR-CS tablet could be manufactured by direct compression method using hydraulic laboratory press (Caver® 3850) with 8 mm rounded concave punch/ die.Seven kinds of CR-CS tablet were prepared to determine the nature of the additives and their ratio such as sodium silicate, dicalcium phosphate, bentonite and sand#8.For each formulation, the LOD% and flowability of pre-mixed powders and the hardness of compressed tablets were analyzed. In vitro release study was performed to confirm the dissolution profiles following the USP Apparatus 2 method with Distilled water of 900mL, 20 °C. As a result, for each lubricated powders, they were compared in terms of ability to give an acceptable dry pre-mixed powder for tableting process. The hardness of the compressed tablets is acceptable whatever the formulations tested. After in vitro release study, it could confirm that the different formulations of CR-CS tablet have a various release rate patterns, which could release 100% at 3 hrs, 6 hrs and 12 hrs. The in vitro dissolution profiles were in good correlation of Higuchi release kinetic model. In conclusion, this study could be used as a background for development and evaluation of the controlled-release carbon source (CR-CS) tablet for the purification of groundwater following the in situ denitrification.

  8. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP).

    PubMed

    Allison, David B; Gadde, Kishore M; Garvey, William Timothy; Peterson, Craig A; Schwiers, Michael L; Najarian, Thomas; Tam, Peter Y; Troupin, Barbara; Day, Wesley W

    2012-02-01

    A 56-week randomized controlled trial was conducted to evaluate safety and efficacy of a controlled-release combination of phentermine and topiramate (PHEN/TPM CR) for weight loss (WL) and metabolic improvements. Men and women with class II and III obesity (BMI ≥ 35 kg/m(2)) were randomized to placebo, PHEN/TPM CR 3.75/23 mg, or PHEN/TPM CR 15/92 mg, added to a reduced-energy diet. Primary end points were percent WL and proportions of patients achieving 5% WL. Secondary end points included waist circumference (WC), systolic and diastolic blood pressure (BP), fasting glucose, and lipid measures. In the primary analysis (randomized patients with at least one postbaseline weight measurement who took at least one dose of assigned drug or placebo), patients in the placebo, 3.75/23, and 15/92 groups lost 1.6%, 5.1%, and 10.9% of baseline body weight (BW), respectively, at 56 weeks (P < 0.0001). In categorical analysis, 17.3% of placebo patients, 44.9% of 3.75/23 patients, and 66.7% of 15/92 patients, lost at least 5% of baseline BW at 56 weeks (P < 0.0001). The 15/92 group had significantly greater changes relative to placebo for WC, systolic and diastolic BP, fasting glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The most common adverse events were paresthesia, dry mouth, constipation, dysgeusia, and insomnia. Dropout rate from the study was 47.1% for placebo patients, 39.0% for 3.75/23 patients, and 33.6% of 15/92 patients. PHEN/TPM CR demonstrated dose-dependent effects on weight and metabolic variables in the direction expected to be beneficial with no evidence of serious adverse events induced by treatment.

  9. A controlled release of ibuprofen by systematically tailoring the morphology of mesoporous silica materials

    SciTech Connect

    Qu Fengyu; Zhu Guangshan; Lin Huiming; Zhang Weiwei; Sun Jinyu; Li Shougui; Qiu Shilun . E-mail: sqiu@mail.jlu.edu.cn

    2006-07-15

    A series of mesoporous silica materials with similar pore sizes, different morphologies and variable pore geometries were prepared systematically. In order to control drug release, ibuprofen was employed as a model drug and the influence of morphology and pore geometry of mesoporous silica on drug release profiles was extensively studied. The mesoporous silica and drug-loaded samples were characterized by X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. It was found that the drug-loading amount was directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drug release profiles could be controlled by tailoring the morphologies of mesoporous silica carriers. - Graphical abstract: The release of ibuprofen is controlled by tailoring the morphologies of mesoporous silica. The mesoporous silica and drug-loaded samples are characterized by powder X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. The drug-loading amount is directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drug release profiles can be controlled by tailoring the morphologies of mesoporous silica carriers.

  10. Polydopamine film coated controlled-release multielement compound fertilizer based on mussel-inspired chemistry.

    PubMed

    Jia, Xin; Ma, Zhi-yuan; Zhang, Guo-xiang; Hu, Jia-mei; Liu, Zhi-yong; Wang, He-yun; Zhou, Feng

    2013-03-27

    This work reports on a facile and reliable method to prepare a polydopamine film coated controlled-release multielement compound fertilizer (PCMCF) based on mussel-inspired chemistry for the first time. The polydopamine (Pdop) film was coated on double copper potassium pyrophosphate trihydrate, providing three essential nutrients (Cu, K, and P) by spontaneous oxidative polymerization of dopamine. The thickness of the polymer coating of the fertilizer was controlled by using the multistep deposition technique. The morphology and composition of the products were characterized by transmission electron microscopy, inductively coupled plasma emission spectrometer, a vis spectrophotometer, and a Kjeltec autoanalyzer. The controlled-release behavior of four elements, including nitrogen from Pdop, was evaluated in water and in soil (sterilized or not). The results revealed that the coated fertilizers had good slow-release properties, incubated in either water or soil. It is noted that the release rate of nutrients of PCMCF can be tailored by the thickness of the Pdop coating, and the Pdop coating can be biodegraded in soil. This coating technology will be effective and promising in the research and development of controlled-release fertilizer.

  11. Interpenetrating polymer network of locust bean gum-poly (vinyl alcohol) for controlled release drug delivery.

    PubMed

    Kaity, Santanu; Isaac, Jinu; Ghosh, Animesh

    2013-04-15

    A novel interpenetrating polymer network (IPN) microspheres of locust bean gum (LBG) and poly (vinyl alcohol) (PVA) was developed for oral controlled release of buflomedil hydrochloride (BH) by emulsion crosslinking method using glutaraldehyde as crosslinker. The effects of gum-polymer ratio, concentration of crosslinker and internal phase viscosity were evaluated thoroughly. Drug entrapment efficiency, particle size distribution, swelling property and in vitro release characteristics with kinetic modelling of microspheres were evaluated. The microspheres were characterised by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), solid state C(13) NMR, X-ray diffraction study (XRD) and differential scanning colorimetry (DSC). The microspheres showed control release property without showing any incompatibility in IPN device. Hence, IPN microspheres of LBG and PVA can be used as a potential carrier for controlled oral delivery of highly water soluble drugs like BH.

  12. Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

    NASA Astrophysics Data System (ADS)

    Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

    2016-06-01

    The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications.

  13. Application of photoremovable protecting group for controlled release of plant growth regulators by sunlight.

    PubMed

    Atta, Sanghamitra; Ikbal, Mohammed; Kumar, Ashutosh; Pradeep Singh, N D

    2012-06-04

    We report a novel technique for controlled release of plant growth regulators (PGRs) by sunlight using photoremovable protecting group (PRPG) as a delivery device. In the present work, carboxyl-containing PGRs of the auxin group [indoleacetic acid (IAA) and naphthoxyacetic acid (NOAA)] were chemically caged using PRPGs of coumarin derivatives. Photophysical studies showed that caged PGRs exhibited good fluorescence properties. Irradiation of caged PGRs by sunlight in both aqueous ethanol and soil media resulted in controlled release of PGRs. The results of the bioactivity experiments indicated that caged PGRs showed better enhancement in the root and shoot length growth of Cicer arietinum compared to PGRs after 10days of sunlight exposure. Our results indicated that use of PRPG as a delivery device for controlled release of PGRs by sunlight in soil holds great interest for field application since it can overcome the rapid loss of PGRs in environmental conditions.

  14. Chemical controls on abiotic and biotic release of geogenic arsenic from Pleistocene aquifer sediments to groundwater.

    PubMed

    Gillispie, Elizabeth C; Andujar, Erika; Polizzotto, Matthew L

    2016-08-10

    Over 150 million people in South and Southeast Asia consume unsafe drinking water from arsenic-rich Holocene aquifers. Although use of As-free water from Pleistocene aquifers is a potential mitigation strategy, such aquifers are vulnerable to geogenic As pollution, placing millions more people at potential risk. The goal of this research was to define chemical controls on abiotic and biotic release of geogenic As to groundwater. Batch incubations of sediments with natural chemical variability from a Pleistocene aquifer in Cambodia were conducted to evaluate how interactions among arsenic, manganese and iron oxides, and dissolved and sedimentary organic carbon influenced As mobilization from sediments. The addition of labile dissolved organic carbon produced the highest concentrations of dissolved As after >7 months, as compared to sediment samples incubated with sodium azide or without added carbon, and the extent of As release was positively correlated with the percent of initial extractable Mn released from the sediments. The mode of As release was impacted by the source of DOC supplied to the sediments, with biological processes responsible for 81% to 85% of the total As release following incubations with lactate and acetate but only up to 43% to 61% of the total As release following incubations with humic and fulvic acids. Overall, cycling of key redox-active elements and organic-carbon reactivity govern the potential for geogenic As release to groundwater, and results here may be used to formulate better predictions of the arsenic pollution potential of aquifers in South and Southeast Asia.

  15. Controlled Release of Ciprofloxacin from Core-Shell Nanofibers with Monolithic or Blended Core.

    PubMed

    Zupančič, Špela; Sinha-Ray, Sumit; Sinha-Ray, Suman; Kristl, Julijana; Yarin, Alexander L

    2016-04-04

    Sustained controlled drug release is one of the prominent contributions for more successful treatment outcomes in the case of several diseases. However, the incorporation of hydrophilic drugs into nanofibers, a promising novel delivery system, and achieving a long-term sustained release still pose a challenging task. In this work we demonstrated a robust method of avoiding burst release of drugs and achieving a sustained drug release from 2 to 4 weeks using core-shell nanofibers with poly(methyl methacrylate) (PMMA) shell and monolithic poly(vinyl alcohol) (PVA) core or a novel type of core-shell nanofibers with blended (PVA and PMMA) core loaded with ciprofloxacin hydrochloride (CIP). It is also shown that, for core-shell nanofibers with monolithic core, drug release can be manipulated by varying flow rate of the core PVA solution, whereas for core-shell nanofibers with blended core, drug release can be manipulated by varying the ratios between PMMA and PVA in the core. During coaxial electrospinning, when the solvent from the core evaporates in concert with the solvent from the shell, the interconnected pores spanning the core and the shell are formed. The release process is found to be desorption-limited and agrees with the two-stage desorption model. Ciprofloxacin-loaded nanofiber mats developed in the present work could be potentially used as local drug delivery systems for treatment of several medical conditions, including periodontal disease and skin, bone, and joint infections.

  16. Environmental Influences on the Release of Ophiosphaerella agrostis Ascospores Under Controlled and Field Conditions.

    PubMed

    Kaminski, John E; Dernoeden, Peter H; O'Neill, Nichole R

    2005-11-01

    ABSTRACT Ophiosphaerella agrostis, the causal agent of dead spot of creeping bentgrass (Agrostis stolonifera), can produce prodigious numbers of pseudothecia and ascospores throughout the summer. The environmental conditions and seasonal timings associated with O. agrostis ascospore release are unknown. The objectives of this research were to (i) determine the influence of light and relative humidity on ascospore release in a controlled environment, (ii) document the seasonal and daily discharge patterns of ascospores in the field, and (iii) elucidate environmental conditions that promote ascospore release under field conditions. In a growth chamber, a sharp decrease (100 to approximately 50%; 25 degrees C) in relative humidity resulted in a rapid (1- to 3-h) discharge of ascospores, regardless of whether pseudothecia were incubated in constant light or dark. In the field, daily ascospore release increased between 1900 and 2300 h and again between 0700 and 1000 h local time. The release of ascospores occurred primarily during the early morning hours when relative humidity was decreasing and the canopy began to dry, or during evening hours when relative humidity was low and dew began to form. Few ascospores were released between 1100 and 1800 h when the bentgrass canopy was dry. The release of ascospores also was triggered by precipitation. Of the ascospores collected during precipitation events, 87% occurred within 10 h of the beginning of each event.

  17. Controlled release of ketorolac through nanocomposite films of hydrogel and LDH nanoparticles

    NASA Astrophysics Data System (ADS)

    Xu, Zhi Ping; Gu, Zi; Cheng, Xiaoxi; Rasoul, Firas; Whittaker, Andrew K.; Lu, Gao Qing Max

    2011-03-01

    A novel nanocomposite film for sustained release of anionic ophthalmic drugs through a double-control process has been examined in this study. The film, made as a drug-loaded contact lens, consists principally of a polymer hydrogel of 2-hydroxyethyl methacrylate (HEMA), in whose matrix MgAl-layered double hydroxide (MgAl-LDH) nanoparticles intercalated with the anionic drug are well dispersed. Such nanocomposite films (hydrogel-LDH-drug) contained 0.6-0.8 mg of MgAl-LDH and 0.08-0.09 mg of the ophthalmic drug (ketorolac) in 1.0 g of hydrogel. MgAl-drug-LDH nanoparticles were prepared with the hydrodynamic particle size of 40-200 nm. TEM images show that these nanoparticles are evenly dispersed in the hydrogel matrix. In vitro release tests of hydrogel-LDH-drug in pH 7.4 PBS solution at 32 °C indicate a sustained release profile of the loaded drug for 1 week. The drug release undergoes a rapid initial burst and then a monotonically decreasing rate up to 168 h. The initial burst release is determined by the film thickness and the polymerization conditions, but the following release rate is very similar, with the effective diffusion coefficient being nearly constant (3.0 × 10-12 m2/s). The drug release from the films is mechanistically attributed to anionic exchange and the subsequent diffusion in the hydrogel matrix.

  18. Controlled release behaviors of chitosan/α, β-glycerophosphate thermo-sensitive hydrogels

    NASA Astrophysics Data System (ADS)

    Liu, Wei-Fang; Kang, Chuan-Zhen; Kong, Ming; Li, Yang; Su, Jing; Yi, An; Cheng, Xiao-Jie; Chen, Xi-Guang

    2012-09-01

    Chitosan/α, β-glycerophosphate (CS/α, β-GP) thermo-sensitive hydrogels presented flowable solution state at low temperature and semisolid hydrogel when the ambient temperature increased. In this research, different concentrations of metronidazole encapsulated, CS and α, β-GP, as well as different acid solvents, were chosen to evaluate their influences on the drug release behaviors from CS/α, β-GP hydrogels. It was found that there was a sustaining release during the first 3 h followed by a plateau. SEM images showed that drugs were located both on the surface and in the interior of hydrogels. The optimal preparation conditions of this hydrogel for drug release were as follows: 1.8% (w/v) CS in HAc solvent, 5.6% (w/v) α, β-GP and 5 g/L metronidazole encapsulation. Cytotoxicity evaluation found no toxic effect. In order to control the release rate, 2.5 g/L chitosan microspheres with spherical shape and smooth surface were incorporated, and it was found that the initial release process was alleviated, while drug concentration had no obvious effect on the release rate. It could be concluded that the metronidzole release behaviors could be optimized according to practical applications.

  19. Controlled-Release Carbamazepine Matrix Granules and Tablets Comprising Lipophilic and Hydrophilic Components

    PubMed Central

    Barakat, Nahla S.; Elbagory, Ibrahim M.; Almurshedi, Alanood S.

    2009-01-01

    The objective of this study was to investigate the effect of lipophilic (Compritol® 888 ATO) and hydrophilic components (combination of HPMC and Avicel) on the release of carbamazepine from granules and corresponding tablet. Wet granulation followed by compression was employed for preparation of granules and tablets. The matrix swelling behavior was investigated. The dissolution profiles of each formulation were compared to those of Tegretol® CR tablets and the mean dissolution time (MDT), dissolution efficiency (DE%), and similarity factor (f2 factor) were calculated. It was found that increase in the concentration of HPMC results in reduction in the release rate from granules and achievement of zero-order is difficult from the granules. The amount of HPMC plays a dominant role for the drug release. The release mechanism of CBZ from matrix tablet formulations follows non-Fickian diffusion shifting to Case II by the increase of HPMC content, indicating significant contribution of erosion. Increasing in drug loading resulted in acceleration of the drug release and in anomalous controlled-release mechanism due to delayed hydration of the tablets. These results suggest that wet granulation followed by compression could be a suitable method to formulate sustained release CBZ tablets. PMID:19555310

  20. Use of bentonite and activated carbon in controlled release formulations of carbofuran.

    PubMed

    Fernández-Pérez, M; Villafranca-Sánchez, M; Flores-Céspedes, F; Garrido-Herrera, F J; Pérez-García, S

    2005-08-24

    Controlled release systems (CRS), unlike the conventional formulations, facilitate a gradual and controlled discharge of the pesticides, reducing the losses by evaporation and leaching and minimizing pesticide pollution. In this study, carbofuran-an insecticide-nematicide identified as a groundwater pollutant-was incorporated in alginate-based granules to obtain controlled release properties. The effect on carbofuran release rate caused by the incorporation of bentonite, activated carbon, and different mixtures of both sorbents in alginate basic formulation was studied by immersion of the granules in water. The water uptake, sorption capacity of the sorbent, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated by the comparison of the preparations. T(50) values were higher for those formulations containing bentonite and/or activated carbon (T(50) values range from 14.76 h for the alginate formulation containing only bentonite as the sorbent to 29.5 weeks for the alginate formulation containing only activated carbon as the sorbent) than for the preparation without these sorbents (11.72 h). On the basis of a parameter of an empirical equation used to fit the insecticide-nematicide release data, it appears that the release of carbofuran from the various formulations into water is controlled by a diffusion mechanism. The sorption capacity of the sorbents for carbofuran was the most important factor modulating carbofuran release. In addition, it was observed that there is a linear correlation of the T(50) values and the content of activated carbon in dry granules.

  1. Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

    PubMed

    Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

    2016-06-01

    Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment.

  2. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    SciTech Connect

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-06-16

    In spite of the massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Here we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases, and we use molecular simulations to demonstrate it. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Finally, our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.

  3. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    NASA Astrophysics Data System (ADS)

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-06-01

    Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.

  4. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    DOE PAGES

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-06-16

    In spite of the massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Here we show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases, and we usemore » molecular simulations to demonstrate it. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Finally, our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release.« less

  5. Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.

    PubMed

    Zhang, Yulong; Dong, Rui; Park, Yujin; Bohner, Marc; Zhang, Xinli; Ting, Kang; Soo, Chia; Wu, Benjamin M

    2016-09-10

    NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research.

  6. Design and evaluation of osmotic pump-based controlled release system of Ambroxol Hydrochloride.

    PubMed

    Cheng, Xiongkai; Sun, Min; Gao, Yan; Cao, Fengliang; Zhai, Guangxi

    2011-08-01

    The purpose of the present study was to design and evaluate an osmotic pump-based drug delivery system for controlling the release of Ambroxol Hydrochloride (Amb). Citric acid, lactose and polyethylene glycol 6000 (PEG 6000) were employed as osmotic agents. Surelease EC containing polyethylene glycol 400 (PEG 400) controlling the membrane porosity was used as semi-permeable membrane. The formulation of tablet core was optimized by orthogonal design and evaluated by weighted mark method. The influences of the amount of PEG 400 and membrane thickness on Amb release were investigated. The optimal osmotic pump tablet (OPT) was evaluated in different release media and at different stirring rates. The major release power confirmed was osmotic pressure. The release of Amb from OPT was verified at a rate of approximately zero-order, and cumulative release percentage at 12?h was 92.6%. The relative bioavailability of Amb OPT in rabbits relative to the commercial sustained capsule was 109.6%. Our results showed that Amb OPT could be a practical preparation with a good prospect.

  7. Zinc polycarboxylate dental cement for the controlled release of an active organic substance: proof of concept.

    PubMed

    Ali, Mohammad Naseem; Edwards, Mark; Nicholson, John W

    2010-04-01

    The potential of employing zinc polycarboxylate dental cement as a controlled release material has been studied. Benzalkonium chloride was used as the active ingredient, and incorporated at concentrations of 1, 2 and 3% by mass within the cement. At these levels, there was no observable effect on the speed of setting. Release was followed using an ion-selective electrode to determine changes in chloride ion concentration with time. This technique showed that the additive was released when the cured cement was placed in water, with release occurring by a diffusion mechanism for the first 3 h, but continuing beyond that for up to 1 week. Diffusion coefficients were in the range 5.62 x 10(-6) cm(2) s(-1) (for 1% concentration) to 10.90 x 10(-6) cm(2) s(-1) (for 3% concentration). Up to 3% of the total loading of benzalkonium chloride was released from the zinc polycarboxylate after a week, which is similar to that found in previous studies with glass-ionomer cement. It is concluded that zinc polycarboxylate cement is capable of acting as a useful material for the controlled release of active organic compounds.

  8. Fluoride coatings on orthodontic wire for controlled release of fluorine ion.

    PubMed

    Lee, Su-Hee; Kim, Hae-Won; Kong, Young-Min; Kim, Hyoun-Ee; Lee, Sung-Ho; Chang, Young-Il

    2005-10-01

    The purpose of this study was to develop a new method of releasing fluorine in a controlled manner for applications in the field of orthodontic Ti-based wire, namely the coating of fluorides on Ti. Thin films of two fluoride compounds, CaF(2) and MgF(2), were coated on Ti via the electron-beam evaporation method. The fluorine was released rapidly from the as-deposited MgF(2) coating within a short period(,) and then the release rate slowed down. When the MgF(2) coating was heat treated, this initial burst effect was decreased, but a significant amount of cracks were generated. On the other hand, in the case of the as-deposited CaF(2) coating, fluorine was released linearly for the entire period, without an initial burst. In the heat-treated CaF(2) coatings the trend was similarly observed. The linear fluorine release from the CaF(2) coatings, even in the as-deposited state, was attributed to the high degree of crystallinity of the coatings. A preliminary cell test showed favorable cell viability on both the fluoride coatings. Given their sustained and controlled fluorine release, these fluoride coatings, particularly CaF(2), are suggested to be potentially useful in the field of orthodontic Ti-based wire.

  9. Diffusion characteristics and controlled release of bacterial fertilizers from modified calcium alginate capsules.

    PubMed

    Liu, Chien-Hung; Wu, Jane-Yii; Chang, Jo-Shu

    2008-04-01

    An indigenous Cellulosimicrobium cellulans GS6 isolate able to solubilize insoluble phosphate complexes in soil is a potential bacterial fertilizer. Enclosure of the phosphate-solubilizing bacterium (PSB) in biodegradable capsules may protect the PSB cells inoculated into soil and, in the meantime, enable the control of cell release that confers long-term fertilizing effects. In this study, calcium alginate (CA) was used as the core matrix to encapsulate cells of C. cellulans GS6. The cell-liberating properties of the CA-based capsules were modified by blending with a variety of supplemental materials (SM), including chitin, cellulose, olive oil, and gelatin. The experimental results showed that the maximum cell-release percentage (MCR%) of the capsules decreased in the order of CA-cellulose>CA-olive oil>CA-chitin>CA-gelatin>CA. Furthermore, a mass transport model was developed to accurately describe the kinetics of cell release results for each capsule. The diffusion coefficient (D(e)) of each capsule was also determined from the model simulation. We found that the estimated D(e) values are positively correlated to the release rate with rare exceptions. Lastly, as our results underscored the crucial roles that the type of capsules plays in the rate and amount of cell release, controlled release of the bacterial fertilizer (C. cellulans GS6 cells) may be achieved via the design of capsule materials.

  10. Nanostructural control of methane release in kerogen and its implications to wellbore production decline

    PubMed Central

    Ho, Tuan Anh; Criscenti, Louise J.; Wang, Yifeng

    2016-01-01

    Despite massive success of shale gas production in the US in the last few decades there are still major concerns with the steep decline in wellbore production and the large uncertainty in a long-term projection of decline curves. A reliable projection must rely on a mechanistic understanding of methane release in shale matrix–a limiting step in shale gas extraction. Using molecular simulations, we here show that methane release in nanoporous kerogen matrix is characterized by fast release of pressurized free gas (accounting for ~30–47% recovery) followed by slow release of adsorbed gas as the gas pressure decreases. The first stage is driven by the gas pressure gradient while the second stage is controlled by gas desorption and diffusion. We further show that diffusion of all methane in nanoporous kerogen behaves differently from the bulk phase, with much smaller diffusion coefficients. The MD simulations also indicate that a significant fraction (3–35%) of methane deposited in kerogen can potentially become trapped in isolated nanopores and thus not recoverable. Our results shed a new light on mechanistic understanding gas release and production decline in unconventional reservoirs. The long-term production decline appears controlled by the second stage of gas release. PMID:27306967

  11. Controlled release from drug microparticles via solventless dry-polymer coating.

    PubMed

    Capece, Maxx; Barrows, Jason; Davé, Rajesh N

    2015-04-01

    A novel solvent-less dry-polymer coating process employing high-intensity vibrations avoiding the use of liquid plasticizers, solvents, binders, and heat treatments is utilized for the purpose of controlled release. The main hypothesis is that such process having highly controllable processing intensity and time may be effective for coating particularly fine particles, 100 μm and smaller via exploiting particle interactions between polymers and substrates in the dry state, while avoiding breakage yet achieving conformal coating. The method utilizes vibratory mixing to first layer micronized polymer onto active pharmaceutical ingredient (API) particles by virtue of van der Waals forces and to subsequently mechanically deform the polymer into a continuous film. As a practical example, ascorbic acid and ibuprofen microparticles, 50-500 μm, are coated with the polymers polyethylene wax or carnauba wax, a generally recognized as safe material, resulting in controlled release on the order of seconds to hours. As a novelty, models are utilized to describe the coating layer thickness and the controlled-release behavior of the API, which occurs because of a diffusion-based mechanism. Such modeling would allow the design and control of the coating process with application for the controlled release of microparticles, particularly those less than 100 μm, which are difficult to coat by conventional solvent coating methods.

  12. Preparation of TiO2 nanotubes/mesoporous calcium silicate composites with controllable drug release.

    PubMed

    Xie, Chunling; Li, Ping; Liu, Yan; Luo, Fei; Xiao, Xiufeng

    2016-10-01

    Nanotube structures such as TiO2 nanotube (TNT) arrays produced by self-ordering electrochemical anodization have been extensively explored for drug delivery applications. In this study, we presented a new implantable drug delivery system that combined mesoporous calcium silicate coating with nanotube structures to achieve a controllable drug release of water soluble and antiphlogistic drug loxoprofen sodium. The results showed that the TiO2 nanotubes/mesoporous calcium silicate composites were successfully fabricated by a simple template method and the deposition of mesoporous calcium silicate increased with the soaking time. Moreover, the rate of deposition of biological mesoporous calcium silicate on amorphous TNTs was better than that on anatase TNTs. Further, zinc-incorporated mesoporous calcium silicate coating, produced by adding a certain concentration of zinc nitrate into the soaking system, displayed improved chemical stability. A significant improvement in the drug release characteristics with reduced burst release and sustained release was demonstrated.

  13. Synthetic PMMA-grafted polysaccharides as hydrophilic matrix for controlled-release forms.

    PubMed

    Castellano, I; Goñi, I; Ferrero, M C; Muñoz, A; Jiménez-Castellanos, R; Gurruchaga, M

    1999-12-01

    This paper describes the rheological behavior of starch and cellulose acrylic graft copolymers synthesized with the aim of obtaining controlled-release excipients. The rheological characteristics determine the final release properties of matrix tablets. The study of the storage and loss moduli (G' and G", respectively) and the viscosity allowed us to know if the polymer behavior was that of a gel and, hence, if it could act as a barrier to drug diffusion. Since dynamic measurements showed a storage modulus higher than the loss modulus, we assessed that all the polymers were gels. Thus, knowing that all the graft copolymers had acceptable properties for compression, the release of theophylline as a model drug at different pH was studied. Polymers with higher absorption capacity, viscosity, and compactibility allowed formulations with slower release rates.

  14. [Analysis of influence factors and control methods on iron release phenomenon in drinking water distribution system].

    PubMed

    Niu, Zhang-bin; Wang, Yang; Zhang, Xiao-jian; He, Wen-Jie; Han, Hong-da; Yin, Pei-jun

    2006-02-01

    Variation rule of iron in drinking water distribution systems was studied, and it was found that the iron released from the scale to the bulk water was the primary reason for iron overstep. The main chemical composition of the scale in cast iron pipe and galvanized steel pipe was iron in a northern city in China. In the drinking water distribution systems, when the value of dissolved oxygen or chlorine residual was low, the iron release phenomenon was severe. The reason for that was the passivation layer of the corrosion scale was destroyed in reductive condition and the result was a great amount of iron in ferrous form was released. According to the research results, the control methods for iron release and 'red water' phenomenon were indicated.

  15. Controlled release of manganese into water from coated experimental fertilizers: laboratory characterization.

    PubMed

    Novillo, J; Rico, M I; Alvarez, J M

    2001-03-01

    The release of manganese into water from controlled-release formulations containing manganese EDTA or manganese lignosulfonate was studied. These fertilizers were obtained in the laboratory by adhering the source of manganese over urea pellets and by adding a coating. The materials used as adhesives and coatings were mixtures of rosins plus tricalcium phosphate. With regard to the chemical composition, these formulations conformed to national and international standards for commercial fertilizers. The rate of release of manganese was a function of both the source of manganese used and the coating thickness. Under the same conditions the release of manganese was greater for formulations with manganese EDTA than with manganese lignosulfonate. To predict the kinetic behaviors of the two series of formulations, mathematical equations were established. The manganese source plus rosin coatings improved the handling and storage characteristics of the commercial urea pellets. The study of the rosin coatings using scanning electron microscopy showed that they were compact and homogeneous.

  16. Role of nitric oxide in control of prolactin release by the adenohypophysis.

    PubMed Central

    Duvilanski, B H; Zambruno, C; Seilicovich, A; Pisera, D; Lasaga, M; Diaz, M C; Belova, N; Rettori, V; McCann, S M

    1995-01-01

    Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or

  17. Chitosan coatings to control release and target tissues for therapeutic delivery.

    PubMed

    Jennings, Jessica Amber; Wells, Carlos Montez; McGraw, Gregory S; Velasquez Pulgarin, Diego A; Whitaker, Marsalas D; Pruitt, Reginald L; Bumgardner, Joel David

    2015-07-01

    The natural biopolymer chitosan has versatile applications in therapeutic delivery. Coating drug delivery matrices or biomaterials with chitosan offers several advantages in drug delivery, including control of drug release, slowing degradation rate and improving biocompatibility. Advanced uses of chitosan in coating form include targeting drug delivery vehicles to specific tissue as well as providing a stimulus-controlled release response. The present review summarizes the current applications of chitosan coatings in the context of different biomaterial delivery technologies, as well as future directions of chitosan coatings for drug delivery technologies under development.

  18. Misrepresentation of Randomized Controlled Trials in Press Releases and News Coverage: A Cohort Study

    PubMed Central

    Yavchitz, Amélie; Boutron, Isabelle; Bafeta, Aida; Marroun, Ibrahim; Charles, Pierre; Mantz, Jean; Ravaud, Philippe

    2012-01-01

    Background Previous studies indicate that in published reports, trial results can be distorted by the use of “spin” (specific reporting strategies, intentional or unintentional, emphasizing the beneficial effect of the experimental treatment). We aimed to (1) evaluate the presence of “spin” in press releases and associated media coverage; and (2) evaluate whether findings of randomized controlled trials (RCTs) based on press releases and media coverage are misinterpreted. Methods and Findings We systematically searched for all press releases indexed in the EurekAlert! database between December 2009 and March 2010. Of the 498 press releases retrieved and screened, we included press releases for all two-arm, parallel-group RCTs (n = 70). We obtained a copy of the scientific article to which the press release related and we systematically searched for related news items using Lexis Nexis. “Spin,” defined as specific reporting strategies (intentional or unintentional) emphasizing the beneficial effect of the experimental treatment, was identified in 28 (40%) scientific article abstract conclusions and in 33 (47%) press releases. From bivariate and multivariable analysis assessing the journal type, funding source, sample size, type of treatment (drug or other), results of the primary outcomes (all nonstatistically significant versus other), author of the press release, and the presence of “spin” in the abstract conclusion, the only factor associated, with “spin” in the press release was “spin” in the article abstract conclusions (relative risk [RR] 5.6, [95% CI 2.8–11.1], p<0.001). Findings of RCTs based on press releases were overestimated for 19 (27%) reports. News items were identified for 41 RCTs; 21 (51%) were reported with “spin,” mainly the same type of “spin” as those identified in the press release and article abstract conclusion. Findings of RCTs based on the news item was overestimated for ten (24%) reports. Conclusion

  19. Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets

    PubMed Central

    Jayasree, J.; Sivaneswari, S.; Hemalatha, G.; Preethi, N.; Mounika, B.; Murthy, S. Vasudeva

    2014-01-01

    Objective: The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance. Materials and Methods: Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release. Results and Discussion: Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release. Conclusion: Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability. PMID:25426439

  20. Controlled release of cytokines using silk-biomaterials for macrophage polarization.

    PubMed

    Reeves, Andrew R D; Spiller, Kara L; Freytes, Donald O; Vunjak-Novakovic, Gordana; Kaplan, David L

    2015-12-01

    Polarization of macrophages into an inflammatory (M1) or anti-inflammatory (M2) phenotype is important for clearing pathogens and wound repair, however chronic activation of either type of macrophage has been implicated in several diseases. Methods to locally control the polarization of macrophages is of great interest for biomedical implants and tissue engineering. To that end, silk protein was used to form biopolymer films that release either IFN-γ or IL-4 to control the polarization of macrophages. Modulation of the solubility of the silk films through regulation of β-sheet (crystalline) content enabled a short-term release (4-8 h) of either cytokine, with smaller amounts released out to 24 h. Altering the solubility of the films was accomplished by varying the time that the films were exposed to water vapor. The released IFN-γ or IL-4 induced polarization of THP-1 derived macrophages into the M1 or M2 phenotypes, respectively. The silk biomaterials were able to release enough IFN-γ or IL-4 to repolarize the macrophage from M1 to M2 and vice versa, demonstrating the well-established plasticity of macrophages. High β-sheet content films that are not soluble and do not release the trapped cytokines were also able to polarize macrophages that adhered to the surface through degradation of the silk protein. Chemically conjugating IFN-γ to silk films through disulfide bonds allowed for longer-term release to 10 days. The release of covalently attached IFN-γ from the films was also able to polarize M1 macrophages in vitro. Thus, the strategy described here offers new approaches to utilizing biomaterials for directing the polarization of macrophages.

  1. Design of controlled release inert matrices of naltrexone hydrochloride based on percolation concepts.

    PubMed

    Caraballo, I; Melgoza, L M; Alvarez-Fuentes, J; Soriano, M C; Rabasco, A M

    1999-04-20

    The percolation theory is a statistical theory able to study chaotic or disordered systems that has been applied in the pharmaceutical field since 1987. Through the application of this theory, the design of controlled release inert matrices has been improved. The aim of the present paper is to estimate the percolation thresholds, the most important concept of the percolation theory, which characterise the release behaviour of controlled release inert matrices of naltrexone hydrochloride. Matrix tablets were prepared using naltrexone hydrochloride as a potent narcotic antagonist and Eudragit(R) RS-PM as matrix forming material in different ratios, keeping constant the drug and excipient particle sizes. In vitro release assays were carried out exposing only one side of the tablets to the dissolution medium. The drug percolation threshold was estimated using different methods. The method of Leuenberger and Bonny gives 31.11+/-7.95% v/v as the critical porosity, which corresponds to a percolation range from 12 to 20% (w/w) of drug content. The release profiles and the release kinetics are in agreement with this result. A change in the exponent k (from 0.29 to 0.57) has been found in this region. Using scanning electron microscopy, the percolation threshold has been observed in a higher concentration range (20-35% w/w). This fact can be attributed to the low accuracy of the visual methods, mainly due to the extrapolation from 2D to 3D systems. If a percolating cluster is observed in two dimensions, the percolation threshold of the 3D system will be already clearly exceeded. The excipient percolation threshold is estimated between 25.4 and 31.1% (v/v) based on the release profiles and the analysis of the release kinetics.

  2. Ciprofloxacin Controlled-Solid Lipid Nanoparticles: Characterization, In Vitro Release, and Antibacterial Activity Assessment

    PubMed Central

    2017-01-01

    The objective of this research was to formulate ciprofloxacin (CIP) in solid lipid nanoparticles (SLNs) in an attempt to develop a controlled drug delivery system. An ultrasonic melt-emulsification method was used for preparing CIP-loaded SLNs. Key findings included that SLNs were successfully produced with average particle sizes ranging from 165 to 320 nm and polydispersity index in the range of 0.18–0.33. High entrapment efficiency values were reported in all formulations. The atomic force scanning microscopic images showed spherical shape with the size range closer to those found by the particle size analyzer. CIP release exhibited controlled-release behavior with various lipids. Ciprofloxacin solid lipid nanoparticles formula containing stearic acid (CIPSTE) displayed the strongest burst effect and the most rapid release rate. The release data revealed a better fit to the Higuchi diffusion model. After storing the CIPSTE formula at room temperature for 120 days, no significant difference in particle size and zeta potential was found. CIP-loaded SLNs exhibited superior antibacterial activity. Incorporation of CIP into SLNs leads to controlled release and a superior antibacterial effect of CIP. PMID:28194408

  3. Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

    PubMed Central

    Pakulska, Malgosia M.; Elliott Donaghue, Irja; Obermeyer, Jaclyn M.; Tuladhar, Anup; McLaughlin, Christopher K.; Shendruk, Tyler N.; Shoichet, Molly S.

    2016-01-01

    Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules. PMID:27386554

  4. Nanoscale architectural tuning of parylene patch devices to control therapeutic release rates

    NASA Astrophysics Data System (ADS)

    Pierstorff, Erik; Lam, Robert; Ho, Dean

    2008-11-01

    The advent of therapeutic functionalized implant coatings has significantly impacted the medical device field by enabling prolonged device functionality for enhanced patient treatment. Incorporation of drug release from a stable, biocompatible surface is instrumental in decreasing systemic application of toxic therapeutics and increasing the lifespan of implants by the incorporation of antibiotics and anti-inflammatories. In this study, we have developed a parylene C-based device for controlled release of Doxorubicin, an anti-cancer chemotherapy and definitive read-out for preserved drug functionality, and further characterized the parylene deposition condition-dependent tunability of drug release. Drug release is controlled by the deposition of a layer of 20-200 nm thick parylene over the drug layer. This places a porous layer above the Doxorubicin, limiting drug elution based on drug accessibility to solvent and the solvent used. An increase in the thickness of the porous top layer prolongs the elution of active drug from the device from, in the conditions tested, the order of 10 min to the order of 2 d in water and from the order of 10 min to no elution in PBS. Thus, the controlled release of an anti-cancer therapeutic has been achieved via scalably fabricated, parylene C-encapsulated drug delivery devices.

  5. On-demand controlled release of docetaxel from a battery-less MEMS drug delivery device.

    PubMed

    Pirmoradi, Fatemeh Nazly; Jackson, John K; Burt, Helen M; Chiao, Mu

    2011-08-21

    We report the development of a magnetically controlled MEMS device capable of on-demand release of defined quantities of an antiproliferative drug, docetaxel (DTX). Controlled release of DTX with a dosage suitable for the treatment of diabetic retinopathy has been achieved for 35 days. The device consists of a drug-loaded microreservoir (Ø6 mm ×∼550 μm), sealed by an elastic magnetic PDMS (polydimethylsiloxane) membrane (Ø6 mm × 40 μm) with a laser-drilled aperture (∼100 × 100 μm(2)). By applying a magnetic field, the magnetic PDMS membrane deforms, causing the discharge of the drug solution from the device. Controlled DTX release at a rate of 171 ± 16.7 ng per actuation interval has been achieved for 35 days using a 255 mT magnetic field. The background leakage of drug solution through the aperture was negligible at 0.053 ± 0.014 ng min(-1). The biological activity of the released drug was investigated using a cytotoxicity assay (cell apoptosis) for two cell lines, HUVEC (human umbilical vein endothelial cells) and PC3 (prostate cancer) cells. Reproducible release rates have been achieved and DTX within the PDMS MEMS reservoir maintains full pharmacological efficacy for more than two months. This device is a proof-of-concept development for targeted delivery of hydrophobic drugs such as DTX and other taxane-based agents that require accurate delivery in nanomolar concentrations.

  6. Micro-/mesoporous carbons for controlled release of antipyrine and indomethacin

    SciTech Connect

    Saha, Dipendu; Moken, Tara; Chen, Jihua; Hensley, Dale K.; Delaney, Kristen; Hunt, Marcus A.; Nelson, Karl; Spurri, Amada; Benham, Lauren; Brice, Robin; Azoro, Martina

    2015-02-24

    Here, we have demonstrated the potential of meso- and microporous carbons in controlled release applications and targeted oral drug delivery. We have employed two mesoporous and two microporous carbons for the sustained release of one water-soluble drug (antipyrine) and one water-insoluble drug (indomethacin), using these as models to examine the controlled release characteristics. The micro-/mesoporous carbons were characterized as having a BET surface area of 372–2251 m2 g–1 and pore volume 0.63–1.03 cm3 g–1. The toxicity studies with E. coli bacterial cells did not reveal significant toxicity, which is in accordance with our previous studies on human cells with similar materials. Mucin adsorption tests with type III pork mucin demonstrated 20–30% mucin adsorption by the carbon samples and higher mucin adsorption could be attributed to higher surface area and more oxygen functionalities. Antipyrine and indomethacin loading was 6–78% in these micro-/mesoporous carbons. The signatures in thermogravimetric studies revealed the presence of drug molecules within the porous moieties of the carbon. The partial shifting of the decomposition peak of the drug adsorbed within the carbon pores was caused by the confinement of drug molecules within the narrow pore space of the carbon. The release profiles of both drugs were examined in simulated gastric fluid (pH = 1.2) and in three other release media with respective pH values of 4.5, 6.8 and 7.4, along with varying residence times to simulate the physiological conditions of the stomach, duodenum, small intestine and colon, respectively. All the release profiles manifested diffusion controlled sustained release that corroborates the effective role of micro-/mesoporous carbons as potential drug carriers.

  7. Micro-/mesoporous carbons for controlled release of antipyrine and indomethacin

    DOE PAGES

    Saha, Dipendu; Moken, Tara; Chen, Jihua; ...

    2015-02-24

    Here, we have demonstrated the potential of meso- and microporous carbons in controlled release applications and targeted oral drug delivery. We have employed two mesoporous and two microporous carbons for the sustained release of one water-soluble drug (antipyrine) and one water-insoluble drug (indomethacin), using these as models to examine the controlled release characteristics. The micro-/mesoporous carbons were characterized as having a BET surface area of 372–2251 m2 g–1 and pore volume 0.63–1.03 cm3 g–1. The toxicity studies with E. coli bacterial cells did not reveal significant toxicity, which is in accordance with our previous studies on human cells with similarmore » materials. Mucin adsorption tests with type III pork mucin demonstrated 20–30% mucin adsorption by the carbon samples and higher mucin adsorption could be attributed to higher surface area and more oxygen functionalities. Antipyrine and indomethacin loading was 6–78% in these micro-/mesoporous carbons. The signatures in thermogravimetric studies revealed the presence of drug molecules within the porous moieties of the carbon. The partial shifting of the decomposition peak of the drug adsorbed within the carbon pores was caused by the confinement of drug molecules within the narrow pore space of the carbon. The release profiles of both drugs were examined in simulated gastric fluid (pH = 1.2) and in three other release media with respective pH values of 4.5, 6.8 and 7.4, along with varying residence times to simulate the physiological conditions of the stomach, duodenum, small intestine and colon, respectively. All the release profiles manifested diffusion controlled sustained release that corroborates the effective role of micro-/mesoporous carbons as potential drug carriers.« less

  8. Intercalation and controlled release properties of vitamin C intercalated layered double hydroxide

    SciTech Connect

    Gao, Xiaorui; Lei, Lixu; O'Hare, Dermot; Xie, Juan; Gao, Pengran; Chang, Tao

    2013-07-15

    Two drug-inorganic composites involving vitamin C (VC) intercalated in Mg–Al and Mg–Fe layered double hydroxides (LDHs) have been synthesized by the calcination–rehydration (reconstruction) method. Powder X-ray diffraction (XRD), Fourier transform infrared (FTIR), and UV–vis absorption spectroscopy indicate a successful intercalation of VC into the interlayer galleries of the LDH host. Studies of VC release from the LDHs in deionised water and in aqueous CO{sub 3}{sup 2−} solutions imply that Mg{sub 3}Al–VC LDH is a better controlled release system than Mg{sub 3}Fe–VC LDH. Analysis of the release profiles using a number of kinetic models suggests a solution-dependent release mechanism, and a diffusion-controlled deintercalation mechanism in deionised water, but an ion exchange process in CO{sub 3}{sup 2−} solution. - Graphical abstract: Vitamin C anions have been intercalated in the interlayer space of layered double hydroxide and released in CO{sub 3}{sup 2−} solution and deionised water. - Highlights: • Vitamin C intercalated Mg–Al and Mg–Fe layered double hydroxides were prepared. • Release property of vitamin C in aqueous CO{sub 3}{sup 2−} solution is better. • Avrami-Erofe’ev and first-order models provide better fit for release results. • Diffusion-controlled and ion exchange processes occur in deionised water. • An ion exchange process occurs in CO{sub 3}{sup 2−} solution.

  9. Aurora A triggers Lgl cortical release during symmetric division to control planar spindle orientation.

    PubMed

    Carvalho, Cátia A; Moreira, Sofia; Ventura, Guilherme; Sunkel, Cláudio E; Morais-de-Sá, Eurico

    2015-01-05

    Mitotic spindle orientation is essential to control cell-fate specification and epithelial architecture. The tumor suppressor Lgl localizes to the basolateral cortex of epithelial cells, where it acts together with Dlg and Scrib to organize apicobasal polarity. Dlg and Scrib also control planar spindle orientation, but how the organization of polarity complexes is adjusted to control symmetric division is largely unknown. Here, we show that the Dlg complex is remodeled during Drosophila follicular epithelium cell division, when Lgl is released to the cytoplasm. Lgl redistribution during epithelial mitosis is reminiscent of asymmetric cell division, where it is proposed that Aurora A promotes aPKC activation to control the localization of Lgl and cell-fate determinants. We show that Aurora A controls Lgl localization directly, triggering its cortical release at early prophase in both epithelial and S2 cells. This relies on double phosphorylation within the putative aPKC phosphorylation site, which is required and sufficient for Lgl cortical release during mitosis and can be achieved by a combination of aPKC and Aurora A activities. Cortical retention of Lgl disrupts planar spindle orientation, but only when Lgl mutants that can bind Dlg are expressed. Hence, our work reveals that Lgl mitotic cortical release is not specifically linked to the asymmetric segregation of fate determinants, and we propose that Aurora A activation breaks the Dlg/Lgl interaction to allow planar spindle orientation during symmetric division via the Pins (LGN)/Dlg pathway.

  10. Controlled release evaluation of bacterial fertilizer using polymer composites as matrix.

    PubMed

    Wu, Chin-San

    2008-11-24

    The use of polybutylene succinate (PBSU)/starch-type composite as biodegradable matrix material for the controlled release of bacterial fertilizer was evaluated. The composites were prepared by a melting-blending method and various methods/instruments were applied to characterize composites and PBSU. The mechanical properties of the PBSU/starch composite were worse than PBSU alone because the former had poor compatibility between starch and the polymer matrix. Much better dispersion and homogeneity were observed in the composite when PBSU was replaced by acrylic acid grafted PBSU (PBSU-g-AA), hence leading to better mechanical properties of PBSU-g-AA/starch. Furthermore, PBSU-g-AA/starch was more easily processed. The bacterial fertilizer was encapsulated in PBSU and PBSU-g-AA/starch matrix. Increased blending of starch increased the biodegradability of matrix and the amount and rate of cell release from matrix suggesting that this composite is a promising candidate material for 'controlled release' bacterial fertilizer.

  11. Electrospun Micro/Nanofibers as Controlled Release Systems for Pheromones of Bactrocera oleae and Prays oleae.

    PubMed

    Kikionis, Stefanos; Ioannou, Efstathia; Konstantopoulou, Maria; Roussis, Vassilios

    2017-03-01

    New systems for the controlled release of 1,7-dioxaspiro[5.5]undecane and (Z)-7-tetradecenal, the sex pheromones of olive fruit fly, Bactrocera oleae, and olive moth, Prays oleae, respectively, were developed utilizing electrospun micro/nanofiber matrices from inexpensive, biodegradable polymers, namely polycaprolactone, cellulose acetate and polyhydroxybutyrate. The incorporation of the pheromones in 5, 10 and 20% w/w in the electrospinning polymer blends allowed for the production of fiber mats with variable loading levels and release rates, ensuring however in all cases the release of pheromones for more than 16 weeks. Laboratory bioassays and field trapping tests showed that the fiber mats obtained from electrospinning of polyhydroxybutyrate solution containing 5% w/w 1,7-dioxaspiro[5.5]undecane and polycaprolactone solution containing 5% w/w (Z)-7-tetradecenal were almost twice as effective in attracting B. oleae and P. oleae males, respectively, in comparison to the positive controls used.

  12. A possible link between sensation-seeking status and positive subjective effects of oxycodone in healthy volunteers.

    PubMed

    Zacny, James P

    2010-03-01

    Sensation-seeking is a personality trait that is linked to use and abuse of drugs. Laboratory studies have established that high sensation seekers, as measured by different instruments, are more likely to report abuse liability-related subjective effects from drugs such as nicotine, alcohol, and d-amphetamine than low sensation seekers. One class of drugs that has not been studied to date in this fashion is opioids. Accordingly, a retrospective analysis encompassing five studies that examined oxycodone effects, including its abuse liability-related effects, was conducted in subjects categorized as high or low sensation seekers. In addition, because there appear to be sex differences in how males and females respond to opioids, this factor was taken into account in the analysis. Seventy one subjects who scored on the lower end (15 and 19 low sensation-seeking males and females, respectively) or the higher end (23 and 14 high sensation-seeking males and females) of the Disinhibition subscale of the Sensation-Seeking Scale-Form V were studied for their responses to 0, 10, and 20mg of oral oxycodone. Ratings of "pleasant bodily sensations" were significantly higher after oxycodone administration than placebo only in male and female high sensation seekers. Ratings of "take again," "drug liking," "carefree," and "elated (very happy)" also tended to differentiate high from low sensation seekers although Group x Dose interactions were only marginally significant with the latter three ratings. Male and female low sensation seekers and female high sensation seekers reported dysphoric effects (e.g., ratings of nauseated) particularly after administration of the 20mg oxycodone dose. The results of this analysis provide suggestive evidence that high sensation seekers are more likely to experience greater positive subjective effects from oxycodone than low sensation seekers, but likelihood of experiencing negative effects is more complex (involving both sensation-seeking status

  13. Potential problems associated with the controlled release of anthelmintics in grazing animals.

    PubMed

    Herd, R P

    1984-11-01

    A high, constant and sustained release of drug appears to be a major requirement to avoid a late season rise in pasture infectivity that may result in production losses in calves in autumn or Type II osteragiasis in the following spring. The timing of administration is of crucial importance and will vary in regions of different epidemiology, such as between northern and southern United States. Lack of a standard and reliable technique for pasture larval counts has resulted in some negative or erratic results which are open to question. Although controlled release anthelmintics offer advantages of convenience, a comparison of the economic benefits at present favours prophylactic treatment of dairy heifers with conventional anthelmintics 3 and 6 weeks after spring turnout in northern regions of the Northern Hemisphere. There is a serious risk that boluses based on controlled release by diffusion will behave like slow decaying insecticides and select strongly for drug resistance, especially if farmers administer them in succession throughout the grazing season. There are, however, 2 features in the design of a controlled release device that in theory may minimize the risk of rapid selection for resistance: a high and constant release of anthelmintic followed by a rapid decline to zero as the device becomes exhausted. Under these conditions, the device may even prolong the useful life of an anthelmintic to which resistance has already developed. This paper was presented at Pfizer Symposium on The Application of Sustained Release Anthelmintic Dosage Forms in the Control of Parasites in Grazing Animals at the World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) 10th International Conference, 18-20 August 1983, Perth, W.A., Australia.

  14. Synthesis, characterization, and controlled release antibacterial behavior of antibiotic intercalated Mg–Al layered double hydroxides

    SciTech Connect

    Wang, Yi; Zhang, Dun

    2012-11-15

    Graphical abstract: The antibiotic anion released from Mg–Al LDHs provides a controlled release antibacterial activity against the growth of Micrococcus lysodeikticus in 3.5% NaCl solution. Highlights: ► Antibiotic anion intercalated LDHs were synthesized and characterized. ► The ion-exchange one is responsible for the release process. ► The diffusion through particle is the release rate limiting step. ► LDHs loaded with antibiotic anion have high antibacterial capabilities. -- Abstract: Antibiotic–inorganic clay composites including four antibiotic anions, namely, benzoate (BZ), succinate (SU), benzylpenicillin (BP), and ticarcillin (TC) anions, intercalated Mg–Al layered double hydroxides (LDHs) were synthesized via ion-exchange. Powder X-ray diffraction and Fourier transform infrared spectrum analyses showed the successful intercalation of antibiotic anion into the LDH interlayer. BZ and BP anions were accommodated in the interlayer region as a bilayer, whereas SU and TC anions were intercalated in a monolayer arrangement. Kinetic simulation of the release data indicated that ion-exchange was responsible for the release process, and the diffusion through the particles was the rate-limiting step. The antibacterial capabilities of LDHs loaded with antibiotic anion toward Micrococcus lysodeikticus growth were analyzed using a turbidimetric method. Significant high inhibition rate was observed when LDH nanohybrid was introduced in 3.5% NaCl solution. Therefore, this hybrid material may be applied as nanocontainer in active antifouling coating for marine equipment.

  15. Escitalopram versus paroxetine controlled release in major depressive disorder: a randomized trial

    PubMed Central

    Kishi, Taro; Matsuda, Yuki; Matsunaga, Shinji; Moriwaki, Masatsugu; Otake, Yoichiro; Akamatsu, Kaku; Okochi, Tomo; Hirano, Shigeki; Funahashi, Toshihiko; Okuda, Momoko; Tabuse, Hideaki; Fujita, Kiyoshi; Iwata, Nakao

    2017-01-01

    Objective There are no direct comparisons between escitalopram and paroxetine controlled release in patients with major depressive disorder (MDD). Methods We conducted a 24-week, rater-masked, randomized trial of escitalopram (5–20 mg/day) versus paroxetine controlled release (12.5–50 mg/day) in patients with MDD (UMIN000011191). Patients with the diagnosis of moderate-to-severe MDD (a 17-item Hamilton Rating Scale for Depression [HAMD-17], with total score at baseline being ≥20) were recruited to participate in a parallel, randomized, controlled trial. The primary outcome for efficacy was an improvement in the 21-item HAMD (HAMD-21) total score at 24 weeks. The secondary outcomes were the response, remission, and discontinuation rates and the incidence of individual adverse events. Results A total of 88 patients with MDD (males, 61.4%; mean age, 40.8±13.4 years) were recruited. The discontinuation rate was 58.0% (escitalopram, 55.8%; paroxetine controlled release, 60.0%). Both escitalopram and paroxetine controlled-release treatment groups exhibited significant reduction in the HAMD-21 total score at 2, 4, 8, 12, and 24 weeks from the baseline. However, there were no significant differences in the HAMD-21 total score, response rate, remission rate, and discontinuation rate at any time point between the groups. In addition, there were no significant differences in the incidence of any individual adverse events (eg, nausea, vomiting, and somnolence) between the treatment groups. Conclusion Our results suggest that escitalopram and paroxetine controlled release had similar efficacy and safety profiles in patients with MDD. One of the primary limitations of this study is the small sample size. PMID:28123299

  16. Biological control of tropical soda apple (Solanaceae) in Florida: Post-release evaluation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The leaf feeding beetle Gratiana boliviana Spaeth (Coleoptera: Chrysomelidae) was released as a biological control agent against tropical soda apple (TSA) (Solanum viarum Dunal (Solanaceae)) in Sumter County, FL in 2006. Evaluation of beetle feeding damage to TSA plants and changes in the beetle po...

  17. The effect of controlled-release ClO2 on the preservation of grapefruit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of controlled-release ClO2 gas on the safety and quality of grapefruit was studied. Three different tests were run: 1) isolated peel tissue with microorganism inoculation in a chamber system; 2) individual fruit with microorganism inoculation in a chamber; and 3) boxed fruit under commerc...

  18. Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot

    PubMed Central

    2016-01-01

    In this work we demonstrate that blood glucose can be controlled remotely through light stimulated release of insulin from an injected cutaneous depot. Human insulin was tethered to an insoluble but injectable polymer via a linker, which was based on the light cleavable di-methoxy nitrophenyl ethyl (DMNPE) group. This material was injected into the skin of streptozotocin-treated diabetic rats. We observed insulin being released into the bloodstream after a 2 min trans-cutaneous irradiation of this site by a compact LED light source. Control animals treated with the same material, but in which light was blocked from the site, showed no release of insulin into the bloodstream. We also demonstrate that additional pulses of light from the light source result in additional pulses of insulin being absorbed into circulation. A significant reduction in blood glucose was then observed. Together, these results demonstrate the feasibility of using light to allow for the continuously variable control of insulin release. This in turn has the potential to allow for the tight control of blood glucose without the invasiveness of insulin pumps and cannulas. PMID:27653828

  19. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    ERIC Educational Resources Information Center

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  20. EVALUATION OF BIOREMEDIATION STRATEGIES OF A CONTROLLED OIL RELEASE IN A WETLAND

    EPA Science Inventory

    A controlled petroleum release was conducted to evaluate bioremediation in a wetland near Houston, Texas. The 140-day study was conducted using a randomized, complete block design to test three treatments with six replicates per treatment. The three treatment strategies were in...

  1. Oil and drug control the release rate from lyotropic liquid crystals.

    PubMed

    Martiel, Isabelle; Baumann, Nicole; Vallooran, Jijo J; Bergfreund, Jotam; Sagalowicz, Laurent; Mezzenga, Raffaele

    2015-04-28

    The control of the diffusion coefficient by the dimensionality d of the structure appears as a most promising lever to efficiently tune the release rate from lyotropic liquid crystalline (LLC) phases and dispersed particles towards sustained, controlled and targeted release. By using phosphatidylcholine (PC)- and monolinoleine (MLO)-based mesophases with various apolar structural modifiers and water-soluble drugs, we present a comprehensive study of the dimensional structural control of hydrophilic drug release, including 3-d bicontinuous cubic, 2-d lamellar, 1-d hexagonal and 0-d micellar cubic phases in excess water. We investigate how the surfactant, the oil properties and the drug hydrophilicity mitigate or even cancel the effect of structure variation on the drug release rate. Unexpectedly, the observed behavior cannot be fully explained by the thermodynamic partition of the drug into the lipid matrix, which points out to previously overlooked kinetic effects. We therefore interpret our results by discussing the mechanism of structural control of the diffusion rate in terms of drug permeation through the lipid membrane, which includes exchange kinetics. A wide range of implications follow regarding formulation and future developments, both for dispersed LLC delivery systems and topical applications in bulk phase.

  2. Supramolecular Controlled Cargo Release via Near Infrared Tunable Cucurbit[7]uril-Gold Nanostars

    PubMed Central

    Han, Yanwei; Yang, Xiran; Liu, Yingzhu; Ai, Qiushuang; Liu, Simin; Sun, Chunyan; Liang, Feng

    2016-01-01

    The near infrared (NIR) absorption and average particle size of gold nanostars (GNSs) can be precisely controlled by varying the molar ratios of cucurbit[7]urils (CB[7]) and GNSs in aqueous solution. GNSs modified with CB[7] achieved high cargo loading with thermally activated release upon the NIR laser irradiation. PMID:26917240

  3. Longevity of controlled release fertilizer influences the growth of bedding Impatiens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled-release fertilizers (CRF) have not been extensively used in floriculture production, perhaps due to lack of grower experience and research-based information with their use in herbaceous plant production. Any information about the correct use of CRF should increase growers’ confidence in ...

  4. [Effects of applying controlled-release compound fertilizer on Platycodon grandiflorum growth].

    PubMed

    Zhu, Li-xiang; Wang, Jian-hua

    2010-09-01

    A pot experiment was conducted in 2008 to study the effects of applying controlled-release compound fertilizer (N:P2O5:K2O = 14:14:14) on the growth of Platycodon grandiflorum in the medicinal herbal farm of Shandong Agricultural University. Comparing with the application of common compound fertilizer (N:P2O5: K2O=15: 15: 15), applying equivalent amount of the controlled-release fertilizer increased the leaf chlorophyll content, root volume, root activity, and root diameter of P. grandiflorum at the late growth stage, but decreased the root length. When the N application rate was 0.24 and 0.32 g x kg(-1) soil, applying the controlled-release compound fertilizer increased the root yield by 26.78% and 22.50%, and the root soluble sugar, protein, and total saponin contents by 9.77% and 6.99%, 11.38% and 2.20%, and 8.85% and 5.47%, respectively, compared with applying the common compound fertilizer. More nitrogen application made the root soluble sugar content decreased but the total saponin content increased. Under our experimental condition, applying the controlled-release compound fertilizer with an application rate of 0.24 g N x kg(-1) soil could obtain the best effect for P. grandiflorum.

  5. Effects of Controlled Release Fertilizer on the Post-Production Performance of Impatiens Wallerana

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Controlled release fertilizers (CRF) in production systems have been known to reduce environmental contamination. However, there is a lot to be explored as per its use in bedding plant production. Bedding plant growers have not adapted CRF use because there is little information about its use and ...

  6. Controlled release of Pantoea agglomerans E325 for biocontrol of fire blight

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Microencapsulation and controlled release of Pantoea agglomerans strain E325 (E325), which is an antagonist to bacterial pathogen (Erwinia amylovora) of fire blight, a devastating disease of apple and pear, have been investigated. Uniform core-shell alginate microcapsules (AMCs), 60-300 µm in diamet...

  7. Preparation and controlled release of mesoporous MCM-41/propranolol hydrochloride composite drug.

    PubMed

    Zhai, Qing-Zhou

    2013-01-01

    This article used MCM-41 as a carrier for the assembly of propranolol hydrochloride by the impregnation method. By means of chemical analysis, powder X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy and low-temperature N(2) adsorption-desorption at 77 K, the characterization was made for the prepared materials. The propranolol hydrochloride guest assembly capacity was 316.20 ± 0.31 mg/g (drug/MCM-41). Powder XRD test results indicated that during the process of incorporation, the frameworks of the MCM-41 were not destroyed and the crystalline degrees of the host-guest nanocomposite materials prepared still remained highly ordered. Characterization by SEM and TEM showed that the composite material presented spherical particle and the average particle size of composite material was 186 nm. FT-IR spectra showed that the MCM-41 framework existed well in the (MCM-41)-propranolol hydrochloride composite. Low-temperature nitrogen adsorption-desorption results at 77 K showed that the guest partially occupied the channels of the molecular sieves. Results of the release of the prepared composite drug in simulated body fluid indicated that the drug can release up to 32 h and its maximum released amount was 99.20 ± 0.11%. In the simulated gastric juice release pattern of drug, the maximum time for the drug release was discovered to be 6 h and the maximum cumulative released amount of propranolol hydrochloride was 45.13 ± 0.23%. The drug sustained-release time was 10 h in simulated intestinal fluid and the maximum cumulative released amount was 62.05 ± 0.13%. The prepared MCM-41 is a well-controlled drug delivery carrier.

  8. Wireless platform for controlled nitric oxide releasing optical fibers for mediating biological response to implanted devices.

    PubMed

    Starrett, Michael A; Nielsen, Matthew; Smeenge, David M; Romanowicz, Genevieve E; Frost, Megan C

    2012-12-01

    Despite the documented potential to leverage nitric oxide generation to improve in vivo performance of implanted devices, a key limitation to current NO releasing materials tested thus far is that there has not been a means to modulate the level of NO release after it has been initiated. We report the fabrication of a wireless platform that uses light to release NO from a polymethylmethacrylate (PMMA) optical fiber coated with an S-nitroso-N-acetylpenicillamine derivatized polydimethylsiloxane (SNAP-PDMS). We demonstrate that a VAOL-5GSBY4 LED (λ(dominant)=460 nm) can be used as a dynamic trigger to vary the level of NO released from 500 μm diameter coated PMMA. The ability to generate programmable sequences of NO flux from the surface of these coated fibers offers precise spatial and temporal control over NO release and provides a platform to begin the systematic study of in vivo physiological response to implanted devices. NO surface fluxes up to 3.88 ± 0.57 × 10(-10)mol cm(-2)min(-1) were achieved with -100 μm thick coatings on the fibers and NO flux was pulsed, ramped and held steady using the wireless platform developed. We demonstrate the NO release is linearly proportional to the drive current applied to the LED (and therefore level of light produced from the LED). This system allow the surface flux of NO from the fibers to be continuously changed, providing a means to determine the level and duration of NO needed to mediate physiological response to blood contacting and subcutaneous implants and will ultimately lead to the intelligent design of NO releasing materials tailored to specific patterns of NO release needed to achieve reliable in vivo performance for intravascular and subcutaneous sensors and potentially for a wide variety of other implanted biomedical devices.

  9. Controlled release of ethacrynic acid from poly(lactide-co-glycolide) films for glaucoma treatment.

    PubMed

    Wang, Yong; Challa, Pratap; Epstein, David L; Yuan, Fan

    2004-08-01

    Ethacrynic acid (ECA) is a potential glaucoma drug that can reduce intraocular pressure. However, conventional methods of ECA administration may cause toxicity to normal eye tissues and are inconvenient to patients. Therefore, we developed and characterized an ECA loaded poly(lactide-co-glycolide) (PLGA) copolymer film, and quantified the therapeutic efficacy of the film implanted in the rabbit eye. In the aqueous medium, the release of ECA from the PLGA50:50 film was time dependent and more than 90% of ECA was released within a week. This release profile was consistent with the kinetics of water uptake and microstructural changes of PLGA50:50 films as revealed by an electron microscopy examination. ECA release and PLGA degradation caused a gradual pH decrease in the release medium. The total pH decrease was 0.4 unit in 3 days. We also observed that the initial rate of ECA release was positively correlated with the weight ratio of ECA versus PLGA and inversely correlated with the molar ratio of lactide versus glycolide in PLGA films. At the end of a 3-day incubation, the cumulative release of ECA from PLGA50:50, PLGA85:15 and PLGA100:00 films were 78.8%, 9.35% and 3.60%, respectively. When the PLGA50:50 film loaded with ECA was implanted into the sclera of rabbit eyes, the intraocular pressure was significantly reduced and the reduction was maintained for at least 10 days. These data indicate that PLGA films have a potential to be used as a controlled ECA release device for glaucoma treatment.

  10. Novel etherified locust bean gum-alginate hydrogels for controlled release of glipizide.

    PubMed

    Dey, Paramita; Maiti, Sabyasachi; Sa, Biswanath

    2013-01-01

    On many occasions, homopolysaccharide hydrogel networks alone are not suitable for controlled drug delivery. In this study, interpenetrating networks (IPNs) of sodium alginate (ALG) and etherified locust bean gum (ELBG) were developed through ionotropic gelation with Al(3+) ions, tested for glipizide release, and were compared with homopolymer hydrogel networks. The degree of reticulation in IPNs was explained by the neutralization equivalent, tensile strength measurement, and drying kinetics of drug-free hydrogels. IPNs afforded a maximum of 94.40 ± 0.35% drug entrapment efficiency and exhibited slower drug release profiles up to 8 h. Al(3+)-ALG network almost completed the release of embedded drug in 3.5 h; however, the homopolymer Al(3+)-ELBG network discharged their content at a slow, uniform rate up to 8 h like the IPNs. All the networks appeared spherical under scanning electron microscope. In all cases, a faster drug release rate was assumed in phosphate buffer (pH 7.4) than in KCl/HCl buffer (pH 1.2) solution. The pH-responsive swelling of the beads was responsible for the variable drug release rate in different media. NonFickian diffusion mechanism was operative for the transport of drug from the IPNs. Moreover, IPNs gained appreciation for their better mechanical strength (63.79 ± 1.59 MPa) than Al(3+)-ELBG network. Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, and X-ray diffraction analyses indicated a compatible environment for drug encapsualtion and release from the IPNs. The drug release curves of Al(3+)-ELBG and IPNs were found similar to a reference product. Hence, Al(3+)-ELBG and IPNs could be useful in controlling diabetes over longer periods.

  11. Development of floating chitosan-xanthan beads for oral controlled release of glipizide

    PubMed Central

    Kulkarni, Nilesh; Wakte, Pravin; Naik, Jitendra

    2015-01-01

    Introduction: The aim of the present work was to develop controlled release, floating and mucoadhesive beads of glipizide by using the polyionic complexation technique. Plasma half-life of glipizide being 2–4 h was selected for development of controlled release dosage form. Methods: Formulation batches were designed by employing chitosan as cationic and xanthan gum as anionic polymers. In vitro drug release was evaluated for the period of 24 h in phosphate buffer pH 7.4. Results: Sustained release of drug was observed in all formulation batches with % drug release ranging from 87.50% to 100.67%, no significant effect on the drug release was observed after varying chitosan to xanthan gum ratio. Encapsulation efficiency was found to be in the range of 79.48 ± 1.10–94.48 ± 1.52. In vitro bioadhesion studies showed that beads had satisfactory bioadhesive strength ranging from 67.11% ± 1.73% to 93.12% ± 1.56%. Buoyancy studies revealed that beads possess comparable floating capacity in the gastric fluids. Swelling kinetics was carried in pH 1.2 and 7.4 buffers. Significant difference (P < 0.05) in swelling kinetics was observed. Drug to polymer interaction was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry studies. Scanning electron microscopy studies revealed that formed beads were discrete with rough and wrinkled surfaces. Conclusions: In conclusion, beads were successfully formed by employing chitosan and xanthan gum and showed to possess sustained release effect. Beads also showed pH dependent swelling kinetics, this property can also be applied for the drugs which are susceptible to the acidic environment in the stomach, and comparable bioadhesive and floating properties were also observed. PMID:25838991

  12. A comparative study on long-term MTX controlled release from intercalated nanocomposites for nanomedicine applications.

    PubMed

    Alexa, Iuliana Florentina; Pastravanu, Cristina Giorgiana; Ignat, Maria; Popovici, Evelini

    2013-06-01

    The feasibility of some mesoporous materials such as SBA-15 and MCM-41 silica, LDH (layered double hydroxide) (Mg3Al-NO3) and MC (mesoporous carbon) have been comparatively evaluated for oral drug delivery applications, in order to broaden the range of matrices and implicitly to develop the class of drug delivery systems based on diffusion mechanism. As well known, methotrexate (MTX) is used widely to treat various neoplastic diseases such as acute lymphoblast leukemia, lymphoma and solid cancers and autoimmune diseases such as psoriasis and rheumatoid arthritis. The commercially available formulations of this drug have disadvantages due to the traditional release process that occurs in the body. Thus, this work is focused on the long-term controlled MTX delivery because this one could eliminate over or underdosing, could maintain drug levels in desired range, could increase patient compliance and prevent the side effects. Therefore, the mesoporous materials are used and efficient MTX-delivery systems, based on above-mentioned mesoporous materials, are successfully prepared by intercalation. The obtained drug carriers were tested in the controlled MTX-drug release process and the influence of the pore morphology and geometry on MTX release profiles was extensively studied comparatively. The prepared MTX delivery systems were characterized by FTIR and UV-vis spectroscopy, N2 sorption measurements. Then, the data obtained from the in vitro release studies have been analyzed, and in order to evaluate the MTX-release mechanism and kinetics, the Korsmeyer-Peppas equation has been applied.

  13. Okra (Hibiscus esculentus) gum-alginate blend mucoadhesive beads for controlled glibenclamide release.

    PubMed

    Sinha, Priyanka; Ubaidulla, U; Nayak, Amit Kumar

    2015-01-01

    The utility of isolated okra (Hibiscus esculentus) gum (OG) was evaluated as a potential sustained drug release polymer-blends with sodium alginate in the development of controlled glibenclamide release ionically-gelled beads for oral use. OG was isolated from okra fruits and its solubility, pH, viscosity and moisture content were studied. Glibenclamide-loaded OG-alginate blend beads were prepared using CaCl2 as cross-linking agent through ionic-gelation technique. These ionically gelled beads showed drug entrapment efficiency of 64.19 ± 2.02 to 91.86 ± 3.24%. The bead sizes were within 1.12 ± 0.11 to 1.28 ± 0.15 mm. These glibenclamide-loaded OG-alginate blend beads exhibited sustained in vitro drug release over a prolonged period of 8 h. The in vitro drug release from these OG-alginate beads were followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The swelling and degradation of these beads was influenced by the pH of the test medium. These beads also exhibited good mucoadhesivity with goat intestinal mucosa.

  14. Nano-Storage Wires for the Controlled Release of Biochemical Materials

    NASA Astrophysics Data System (ADS)

    Yoo, Haneul; Lee, Dongjun; Kim, Eunji; Kim, Daesan; Park, Juhun; Hong, Seunghun

    2015-03-01

    We herein report ``nano-storage wires'' (NSWs) that can store chemical species and release them at a desired moment by electrical stimulations. Here, we utilized the electrodeposition process through an anodized aluminium oxide template to fabricate multi-segmented nanowires which consisted of a polypyrrole (PPy) segment containing adenosine triphosphate (ATP) molecules, a ferromagnetic nickel segment, and a conductive gold segment. We could drive and deposit the NSWs onto desired positions on electrode surfaces via external magnetic fields. When the external electric potential was applied from the electrodes, the NSWs released ATPs from the PPy segments, and the released ATPs could change the activities of motor proteins near the NSWs. Furthermore, through direct writing or magnetic manipulation strategies, we could print NSWs onto various substrates such as flexible or three-dimensional structured substrates to build versatile chemical storage devices. Since our strategy enables the controllable storage and release of chemicals, our development should open up various applications such as drug delivery systems, biosensors and biochips for the controlled release of chemicals to biosystems.

  15. Temporally controlled release of multiple growth factors from a self-assembling peptide hydrogel

    NASA Astrophysics Data System (ADS)

    Bruggeman, Kiara F.; Rodriguez, Alexandra L.; Parish, Clare L.; Williams, Richard J.; Nisbet, David R.

    2016-09-01

    Protein growth factors have demonstrated great potential for tissue repair, but their inherent instability and large size prevents meaningful presentation to biologically protected nervous tissue. Here, we create a nanofibrous network from a self-assembling peptide (SAP) hydrogel to carry and stabilize the growth factors. We significantly reduced growth factor degradation to increase their lifespan by over 40 times. To control the temporal release profile we covalently attached polysaccharide chitosan molecules to the growth factor to increase its interactions with the hydrogel nanofibers and achieved a 4 h delay, demonstrating the potential of this method to provide temporally controlled growth factor delivery. We also describe release rate based analysis to examine the growth factor delivery in more detail than standard cumulative release profiles allow and show that the chitosan attachment method provided a more consistent release profile with a 60% reduction in fluctuations. To prove the potential of this system as a complex growth factor delivery platform we demonstrate for the first time temporally distinct release of multiple growth factors from a single tissue specific SAP hydrogel: a significant goal in regenerative medicine.

  16. Controlled release based on the dissolution of a calcium carbonate layer deposited on hydrogels.

    PubMed

    Ogomi, Daisuke; Serizawa, Takeshi; Akashi, Mitsuru

    2005-03-21

    It is possible that inorganic materials conjugated to suitable organic materials may induce unique mechanical, optical and other functional properties. Therefore, artificial conjugation of organic and inorganic components is attractive for preparing novel functional materials. Recently, we developed an alternate soaking process for calcium salt formation on/in polymer materials. In this study, a poly(vinyl alcohol) (PVA) hydrogel-calcium carbonate (CaCO(3)) composite was prepared by the aforementioned process as a controlled release support. Brilliant blue FCF (Mw = 794), FITC labeled BSA (Mw = 6.6 x 10(4)), FITC labeled dextran-10 k (Mw = 9.5 x 10(3)) and FITC labeled dextran-40 k (Mw = 4.3 x 10(4)) were loaded into the composite as model drugs. CaCO(3) dissolution and model drug release rates increased with a decrease in buffer pH. In addition, model drug release rates increased with a decrease in model drug molecular weight. These results show that CaCO(3) layers on hydrogels behave as capping layers for model drug release; the release rate of model drugs can be controlled by the dissolution rate of CaCO(3) and the molecular weight of the drug.

  17. Release and distribution of Lilioceris cheni (Coleoptera: Chrysomelidae), a biological control agent of air potato (Dioscorea bulbilfera: Dioscoreaceae), in Florida

    Technology Transfer Automated Retrieval System (TEKTRAN)

    From 2012 to 2015, 429,668 Lilioceris cheni Gressit and Kimoto (Coleoptera: Chrysomelidae) were released in Florida for biological control of air potato [Dioscorea bulbilfera L. (Dioscoreaceae)]. The spatial distribution of releases was highly aggregated, with several areas of high density releases ...

  18. Chitosan-genipin microspheres for the controlled release of drugs: clarithromycin, tramadol and heparin.

    PubMed

    Harris, Ruth; Lecumberri, Elena; Heras, Angeles

    2010-05-26

    The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1-10 microm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 °C for 5 h and with 5 mM genipin at 50 °C for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 °C, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

  19. Chitosan-Genipin Microspheres for the Controlled Release of Drugs: Clarithromycin, Tramadol and Heparin

    PubMed Central

    Harris, Ruth; Lecumberri, Elena; Heras, Angeles

    2010-01-01

    The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1–10 μm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 ºC for 5 h and with 5 mM genipin at 50 ºC for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 ºC, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs. PMID:20631867

  20. Controlled release of oral tetrahydrocurcumin from a novel self-emulsifying floating drug delivery system (SEFDDS).

    PubMed

    Setthacheewakul, Saipin; Kedjinda, Wichan; Maneenuan, Duangkhae; Wiwattanapatapee, Ruedeekorn

    2011-03-01

    The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9-32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations.

  1. Development of electrospun beaded fibers from Thai silk fibroin and gelatin for controlled release application.

    PubMed

    Somvipart, Siraporn; Kanokpanont, Sorada; Rangkupan, Rattapol; Ratanavaraporn, Juthamas; Damrongsakkul, Siriporn

    2013-04-01

    Thai silk fibroin and gelatin are attractive biomaterials for tissue engineering and controlled release applications due to their biocompatibility, biodegradability, and bioactive properties. The development of electrospun fiber mats from silk fibroin and gelatin were reported previously. However, burst drug release from such fiber mats remained the problem. In this study, the formation of beads on the fibers aiming to be used for the sustained release of drug was of our interest. The beaded fiber mats were fabricated using electrospinning technique by controlling the solution concentration, weight blending ratio of Thai silk fibroin/gelatin blend, and applied voltage. It was found that the optimal conditions including the solution concentration and the weight blending ratio of Thai silk fibroin/gelatin at 8-10% (w/v) and 70/30, respectively, with the applied voltage at 18 kV provided the fibers with homogeneous formation of beads. Then, the beaded fiber mats obtained were crosslinked by the reaction of carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS). Methylene blue as a model active compound was loaded on the fiber mats. The release test of methylene blue from the beaded fiber mats was carried out in comparison to that of the smooth fiber mats without beads. It was found that the beaded fiber mats could prolong the release of methylene blue, comparing to the smooth fiber mats without beads. This was possibly due to the beaded fiber mats that would absorb and retain higher amount of methylene blue than the fiber mats without beads. Thai silk fibroin/gelatin beaded fiber mats were established as an effective carrier for the controlled release applications.

  2. Mimicking Biological Delivery Through Feedback-Controlled Drug Release Systems Based on Molecular Imprinting

    PubMed Central

    Kryscio, David R.; Peppas, Nicholas A.

    2015-01-01

    Intelligent drug delivery systems (DDS) are able to rapidly detect a biological event and respond appropriately by releasing a therapeutic agent; thus, they are advantageous over their conventional counterparts. Molecular imprinting is a promising area that generates a polymeric network which can selectively recognize a desired analyte. This field has been studied for a variety of applications over a long period of time, but only recently has it been investigated for biomedical and pharmaceutical applications. Recent work in the area of molecularly imprinted polymers in drug delivery highlights the potential of these recognitive networks as environmentally responsive DDS that can ultimately lead to feedback controlled recognitive release systems. PMID:26500352

  3. Tinkering with topology: controlled constraint release in DNA solutions with topoisomerase II

    NASA Astrophysics Data System (ADS)

    Liverpool, T. B.; McLeish, T. C. B.; Betterton, M. D.

    2001-11-01

    The relaxation of stress in an entangled polymer solution is dominated by topological constraints. We propose using topoisomerase II to control the rate of constraint release in a DNA solution. The topoisomerase II enzyme can pass one DNA strand through another, thereby accelerating the relaxation of stress in the solution via a constraint-release Rouse process. We calculate the changes in the relaxation modulus due to the addition of topoisomerase II. We also discuss how spatial correlations in the enzyme concentration can lead to novel stress relaxation.

  4. Blood, sweat, tears and success of technology transfer long-term controlled-release of herbicides

    SciTech Connect

    Van Voris, P.; Cataldo, D.A.; Burton, F.G.; Skeins, W.E.

    1988-01-01

    The problems encountered, the technical difficulties that had to be overcome, and the successful transfer of technology related to controlled-release of pesticides is reviewed. Research on control-release of pesticides to date has resulted in products designed to extend bioactivity for periods of several days, months, or at most, several years. However, research supported by the U.S. Department of Energy directed toward solving problems associated with plant-root penetration through caps and liners engineered to minimize leaching or movement of buried nuclear and chemical wastes has resulted in development of a long-term controlled-release herbicide delivery system designed to stop root growth for periods of up to 100 years. Through the unique combination of polymers with a herbicidally active dinitroaniline, a cylindrical pellet was developed that continuously releases a herbicide for a period of up to 100 years. Equilibrium concentration of the herbicide in soil adjacent to the pellet and the bioactive lifetime of the device can be adjusted by changing the size of the pellet; the type of polymer; the type, quality, and quantity of carrier; and/or the concentration and type of dinitroaniline was used.

  5. Clean Photothermal Heating and Controlled Release from Near-Infrared Dye Doped Nanoparticles without Oxygen Photosensitization.

    PubMed

    Guha, Samit; Shaw, Scott K; Spence, Graeme T; Roland, Felicia M; Smith, Bradley D

    2015-07-21

    The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of (1)O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive (1)O2, leading to bleaching of the dye and also decomposition of coencapsulated payload such as the drug doxorubicin. Croc dye was especially useful as a photothermal agent for laser-controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water-soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications.

  6. Chitosan/alginate based multilayers to control drug release from ophthalmic lens.

    PubMed

    Silva, Diana; Pinto, Luís F V; Bozukova, Dimitriya; Santos, Luís F; Serro, Ana Paula; Saramago, Benilde

    2016-11-01

    In this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (alginate - CaCl2)/(chitosan+glyoxal) topped with a final alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved to have excellent features to control the release of the anti-inflammatory, diclofenac, while keeping or improving the physical properties of the lenses. The coating leads to a controlled release of diclofenac from SCL and IOL materials for, at least, one week. Due to its high hydrophilicity (water contact angle≈0) and biocompatibility, it should avoid the use of further surface treatments to enhance the useŕs comfort. However, the barrier effect of this coating is specific for diclofenac, giving evidence to the need of optimizing the chemical composition of the layers in view of the desired drug.

  7. Designing in vivo concentration gradients with discrete controlled release: a computational model

    NASA Astrophysics Data System (ADS)

    Walker, Edgar Y.; Barbour, Dennis L.

    2010-08-01

    One promising neurorehabilitation therapy involves presenting neurotrophins directly into the brain to induce growth of new neural connections. The precise control of neurotrophin concentration gradients deep within neural tissue that would be necessary for such a therapy is not currently possible, however. Here we evaluate the theoretical potential of a novel method of drug delivery, discrete controlled release (DCR), to control effective neurotrophin concentration gradients in an isotropic region of neocortex. We do so by constructing computational models of neurotrophin concentration profiles resulting from discrete release locations into the cortex and then optimizing their design for uniform concentration gradients. The resulting model indicates that by rationally selecting initial neurotrophin concentrations for drug-releasing electrode coatings in a square 16-electrode array, nearly uniform concentration gradients (i.e. planar concentration profiles) from one edge of the electrode array to the other should be obtainable. DCR therefore represents a promising new method of precisely directing neuronal growth in vivo over a wider spatial profile than would be possible with single release points.

  8. Chitosan-starch beads prepared by ionotropic gelation as potential matrices for controlled release of fertilizers.

    PubMed

    Perez, Jonas J; Francois, Nora J

    2016-09-05

    The present study examines the agrochemical application of macrospheres prepared with chitosan and chitosan-starch blends by an easy dripping technique, using a sodium tripolyphosphate aqueous solution as the crosslinking agent. These biopolymers form hydrogels that could be a viable alternative method to obtain controlled-release fertilizers (CRFs). Three different concentrations (ranging from 20 to 100wt/wt% of chitosan) and two crosslinking times (2 or 4h) were used. The resulting polymeric matrices were examined by scanning electron microscopy coupled with energy dispersive X-ray, X-ray diffraction, Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance, thermogravimetric analysis and differential scanning calorimetry. Ionotropic gelation and neutralization induced the formation of the macrospheres. The crosslinking time and the composition of the polymeric hydrogel controlled the crosslinking degree, the swelling behavior and the fertilizer loading capability. Potassium nitrate-loaded beads were shown to be useful as a controlled-release fertilizer. After 14days of continuous release into distilled water, the cumulative concentration in the release medium reached between 70 and 93% of the initially loaded salt, depending on the matrix used. The prepared beads showed properties that make them suitable for use in the agrochemical industry as CRFs.

  9. Yoctowells as a simple model system for the encapsulation and controlled release of bioactive molecules

    PubMed Central

    Bhosale, Sheshanath V.; Bhosale, Sidhanath V.

    2013-01-01

    The development of nanosized drug delivery systems to transport drugs to target cells, are promising tools to improve the drug therapeutic index. Transport systems should have a simple design to control the release of loaded drug to the target areas, thereby increasing concentration and prolonging retention. Herein, we demonstrate the use of yoctoliter wells (1 yL = 10−24 L) as simple model systems for the encapsulation and release of biologically active molecules, by manipulating pH. The drug molecule employed here is doxorubicin, which diffuses into the bottom of yoctowells from a bulk solution at pH 7. Capping of the yoctowells is achieved by addition of an anionic-porphyrin by electrostatic interaction. Furthermore, controlled release of the Doxorubcin and capping agent from the yoctowells is achieved by pH control. The effectiveness of the sustain release of the bioactive molecule from yoctowells, provides potential for development of a new generation of drug-delivery system for practical application. PMID:23760359

  10. Statistical correlation of the soil incubation and the accelerated laboratory extraction methods to estimate nitrogen release rates of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry; Obreza, Thomas; Leary, Emily; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release patterns of enhanced-efficiency fertilizers (EEFs) during the last few decades. These technologies have been developed mainly by manufacturers and are product-specific based on the regulation and analysis of each EEF product. Despite previous efforts to characterize nutrient release of slow-release fertilizer (SRF) and controlled-release fertilizer (CRF) materials, no official method exists to assess their nutrient release patterns. However, the increased production and distribution of EEFs in specialty and nonspecialty markets requires an appropriate method to verify nutrient claims and material performance. Nonlinear regression was used to establish a correlation between the data generated from a 180-day soil incubation-column leaching procedure and 74 h accelerated lab extraction method, and to develop a model that can predict the 180-day nitrogen (N) release curve for a specific SRF and CRF product based on the data from the accelerated laboratory extraction method. Based on the R2 > 0.90 obtained for most materials, results indicated that the data generated from the 74 h accelerated lab extraction method could be used to predict N release from the selected materials during 180 days, including those fertilizers that require biological activity for N release.

  11. Comparison of oxycodone and morphine on the proliferation, apoptosis and expression of related molecules in the A549 human lung adenocarcinoma cell line

    PubMed Central

    Tian, Mi; Jin, Li; Li, Renqi; Zhu, Sihai; Ji, Muhuo; Li, Weiyan

    2016-01-01

    The present study aimed to compare the effects of oxycodone and morphine hydrochloride on the proliferation, apoptosis and migration of A549 lung cancer cells. A549 human lung cancer cells were cultured in vitro and treated with oxycodone or morphine at various concentrations (10, 20 and 40 µg/ml). Cell migration was determined using a wound healing assay, whereas apoptosis was detected using flow cytometry. Reverse transcription quantitative-polymerase chain reaction was performed in order to assess the apoptosis-related gene expression levels, including p53, B-cell lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax). The levels of vascular endothelial growth factor (VEGF) and urokinase-type plasminogen activator (uPA) were detected using enzyme-linked immunosorbent assays. The expression levels of intercellular cell adhesion molecule (ICAM)-1 were determined by immunofluorescence. In the present study, oxycodone and morphine induced apoptosis in A549 lung cancer cells with similar potency; however, >20 µg/ml oxycodone was more effective at inhibiting cell proliferation (P<0.05) and migration (P<0.05), as compared with morphine at the same concentration. Oxycodone induced a dose-dependent increase in the expression levels of p53 and Bax apoptosis-related genes, whereas it decreased the gene expression levels of Bcl-2. Furthermore, oxycodone decreased, whereas morphine increased, the expression levels of ICAM-1 in a concentration-dependent manner. In addition, at 40 µg/ml, the expression levels of VEGF and uPA in the morphine group were significantly higher than those demonstrated in the oxycodone group (P<0.05). In conclusion, oxycodone was more effective in inhibiting the proliferation and migration of A549 lung cancer cells, as compared with morphine. PMID:27446244

  12. Coaxial electrospinning multicomponent functional controlled-release vascular graft: Optimization of graft properties.

    PubMed

    Yin, Anlin; Luo, Rifang; Li, Jiukai; Mo, Xiumei; Wang, Yunbing; Zhang, Xingdong

    2017-04-01

    Small diameter vascular grafts possessing desirable biocompatibility and suitable mechanical properties have become an urgent clinic demand. Herein, heparin loaded fibrous grafts of collagen/chitosan/poly(l-lactic acid-co-ε-caprolactone) (PLCL) were successfully fabricated via coaxial electrospinning. By controlling the concentration of heparin and the ratio of collagen/chitosan/PLCL, most grafts had the heparin encapsulation efficiency higher than 70%, and the heparin presented sustained release for more than 45 days. Particularly, such multicomponent grafts had relative low initial burst release, and after heparin releasing for 3 weeks, the grafts still showed good anti-platelet adhesion ability. In addition, along with the excellent cell biocompatibility, the fabricated grafts possessed suitable mechanical properties including good tensile strength, suture retention strength, burst pressure and compliance which could well match the native blood vessels. Thus, the optimized graft properties could be properly addressed for vascular tissue application via coaxial electrospinning.

  13. Coaxial electrospinning for encapsulation and controlled release of fragile water-soluble bioactive agents.

    PubMed

    Jiang, Hongliang; Wang, Liqun; Zhu, Kangjie

    2014-11-10

    Coaxial electrospinning is a robust technique for one-step encapsulation of fragile, water-soluble bioactive agents, including growth factors, DNA and even living organisms, into core-shell nanofibers. The coaxial electrospinning process eliminates the damaging effects due to direct contact of the agents with organic solvents or harsh conditions during emulsification. The shell layer serves as a barrier to prevent the premature release of the water-soluble core contents. By varying the structure and composition of the nanofibers, it is possible to precisely modulate the release of the encapsulated agents. Promising work has been done with coaxially electrospun non-woven mats integrated with bioactive agents for use in tissue engineering, in local delivery and in wound healing, etc. This paper reviews the origins of the coaxial electrospinning method, its updated status and potential future developments for controlled release of the class of fragile, water-soluble bioactive agents.

  14. Controlling the release of active compounds from the inorganic carrier halloysite

    NASA Astrophysics Data System (ADS)

    Tescione, F.; Buonocore, G. G.; Stanzione, M.; Oliviero, M.; Lavorgna, M.

    2014-05-01

    Halloysite (HNTs), a natural material characterized by a nanotube structure, has been used as an inorganic carrier of active compounds in several applications from medicine to anticorrosion coatings. In this present work, vanillin (VAN) used as a antimicrobial model, has been encapsulated within HNTs for exploiting its applicability in the active food packaging sector. The molecule release rate has been controlled by crosslinking at the tube ends the loaded vanillin with copper ions, thus producing a stopper network. The vanillin-loaded HNTs were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis. The antimicrobial release kinetics from the loaded nanoparticles (VAN/HNTs) in water was investigated using UV-vis spectroscopy. The results show that the vanillin crosslinked with cupper ions is a feasible method to tailor the release rate of antimicrobial model from HTNs nanoparticles.

  15. Controlling the release of active compounds from the inorganic carrier halloysite

    SciTech Connect

    Tescione, F.; Buonocore, G. G.; Stanzione, M.; Oliviero, M.; Lavorgna, M.

    2014-05-15

    Halloysite (HNTs), a natural material characterized by a nanotube structure, has been used as an inorganic carrier of active compounds in several applications from medicine to anticorrosion coatings. In this present work, vanillin (VAN) used as a antimicrobial model, has been encapsulated within HNTs for exploiting its applicability in the active food packaging sector. The molecule release rate has been controlled by crosslinking at the tube ends the loaded vanillin with copper ions, thus producing a stopper network. The vanillin-loaded HNTs were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis. The antimicrobial release kinetics from the loaded nanoparticles (VAN/HNTs) in water was investigated using UV-vis spectroscopy. The results show that the vanillin crosslinked with cupper ions is a feasible method to tailor the release rate of antimicrobial model from HTNs nanoparticles.

  16. Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size

    PubMed Central

    Toonen, Ruud F. G.; Wierda, Keimpe; Sons, Michèle S.; de Wit, Heidi; Cornelisse, L. Niels; Brussaard, Arjen; Plomp, Jaap J.; Verhage, Matthijs

    2006-01-01

    Prompt recovery after intense activity is an essential feature of most mammalian synapses. Here we show that synapses with reduced expression of the presynaptic gene munc18-1 suffer from increased depression during intense stimulation at glutamatergic, GABAergic, and neuromuscular synapses. Conversely, munc18-1 overexpression makes these synapses recover faster. Concomitant changes in the readily releasable vesicle pool and its refill kinetics were found. The number of vesicles docked at the active zone and the total number of vesicles per terminal correlated with both munc18-1 expression levels and the size of the releasable vesicle pool. These data show that varying expression of a single gene controls synaptic recovery by modulating the number of docked, release-ready vesicles and thereby replenishment of the secretion capacity. PMID:17110441

  17. Controlled-release cellulose esters matrices for water-soluble diclofenac sodium: compression and dissolution studies.

    PubMed

    Obeidat, W M; Alzoubi, N M

    2014-02-01

    Matrix tablets comprising of a blend of cellulose acetate butyrate (CAB) or cellulose acetate propionate (CAP) and alpha-lactose monohydrate were prepared by direct compression to control the release of diclofenac sodium. Tablet formulations containing CAP75000 or CAB50-54 exhibited highest extents, but lowest onsets of plastic deformation and lowest release rates in buffer medium, while tablets containing CAP15000 or CAB35-39 exhibited lowest extents, but highest rates of plastic deformation and highest release rates in buffer medium. The DA values obtained from Heckel plots and the DI values obtained from Kawakita plots showed similar trends. A plot of compression pressure or crushing strengths against T50% showed curvilinear relationship for all tablets. Tablets containing 40 % CAB35-39 (formulation F7D) was considered the best formulation in terms of T50%, compressibility and compactability.

  18. Biodegradable polymer based encapsulation of neem oil nanoemulsion for controlled release of Aza-A.

    PubMed

    Jerobin, Jayakumar; Sureshkumar, R S; Anjali, C H; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2012-11-06

    Azadirachtin a biological compound found in neem have medicinal and pesticidal properties. The present work reports on the encapsulation of neem oil nanoemulsion using sodium alginate (Na-Alg) by cross linking with glutaraldehyde. Starch and polyethylene glycol (PEG) were used as coating agents for smooth surface of beads. The SEM images showed beads exhibited nearly spherical shape. Swelling of the polymeric beads reduced with coating which in turn decreased the rate of release of Aza-A. Starch coated encapsulation of neem oil nanoemulsion was found to be effective when compared to PEG coated encapsulation of neem oil nanoemulsion. The release rate of neem Aza-A from the beads into an aqueous environment was analyzed by UV-visible spectrophotometer (214 nm). The encapsulated neem oil nanoemulsion have the potential for controlled release of Aza-A. Neem oil nanoemulsion encapsulated beads coated with PEG was found to be toxic in lymphocyte cells.

  19. Development of controlled release captopril granules coated with ethylcellulose and methylcellulose by fluid bed dryer.

    PubMed

    Stulzer, Hellen Karine; Silva, Marcos Antonio Segatto; Fernandes, Daniel; Assreuy, Jamil

    2008-01-01

    Captopril granules of controlled release with different polymers as ethylcellulose, ethyl/methylcellulose, and immediate release with polyvinylpyrrolidone (PVP) were developed by fluid bed dryer technique. The formulations were analyzed by scanning electron microscopy, X-ray powder diffraction, and dissolution profiles. To compare the formulations an in vivo setting rat blood pressure assay was performed, using angiotensin I as a vasoconstrictor agent. The scanning electron microscopy of granules showed differences in morphology, and X-ray powder diffraction technique presented some modification in crystalline structure of captopril in granules coated with PVP and ethyl/methylcellulose. The dissolution profile of granules coated with ethylcellulose showed a median time release of 4 hr whereas for granules coated with ethyl/methylcellulose, this time was 3.5 hr. The blockage of angiotensin I-induced hypertensive effect lasted 8 hr in granules coated with PVP and of more than 12 hr in the granules coated with ethylcellulose and ethyl/methylcellulose.

  20. Knowledge system and method for simulating chemical controlled release device performance

    DOEpatents

    Cowan, Christina E.; Van Voris, Peter; Streile, Gary P.; Cataldo, Dominic A.; Burton, Frederick G.

    1991-01-01

    A knowledge system for simulating the performance of a controlled release device is provided. The system includes an input device through which the user selectively inputs one or more data parameters. The data parameters comprise first parameters including device parameters, media parameters, active chemical parameters and device release rate; and second parameters including the minimum effective inhibition zone of the device and the effective lifetime of the device. The system also includes a judgemental knowledge base which includes logic for 1) determining at least one of the second parameters from the release rate and the first parameters and 2) determining at least one of the first parameters from the other of the first parameters and the second parameters. The system further includes a device for displaying the results of the determinations to the user.

  1. Controlled release and antibacterial activity of tetracycline hydrochloride-loaded bacterial cellulose composite membranes.

    PubMed

    Shao, Wei; Liu, Hui; Wang, Shuxia; Wu, Jimin; Huang, Min; Min, Huihua; Liu, Xiufeng

    2016-07-10

    Bacterial cellulose (BC) is widely used in biomedical applications. In this study, we prepared an antibiotic drug tetracycline hydrochloride (TCH)-loaded bacterial cellulose (BC) composite membranes, and evaluated the drug release, antibacterial activity and biocompatibility. The structure and morphology of the fabricated BC-TCH composite membranes were characterized using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The TCH release results show that the incorporation of BC matrix to load TCH is able to control the release. In vitro antibacterial assay demonstrate that the developed BC-TCH composites displayed excellent antibacterial activity solely associated with the loaded TCH drug. More importantly, the BC-TCH composite membranes display good biocompatibility. These characteristics of BC-TCH composite membranes indicate that they may successfully serve as wound dressings and other medical biomaterials.

  2. Release Mechanisms, Control Strategies, and Implementation Challenges of Controlling Lead in Drinking Water

    EPA Science Inventory

    Even minimally or moderately corrosive water can cause unacceptable and dangerous lead contamination to be released from common plumbing materials and devices into drinking water. Designing sampling programs to uncover the potential for ingestion of lead in water and to protect ...

  3. Polycaprolactone coated porous tricalcium phosphate scaffolds for controlled release of protein for tissue engineering

    PubMed Central

    Xue, Weichang; Bandyopadhyay, Amit; Bose, Susmita

    2010-01-01

    Polycaprolactone (PCL) was coated on porous tricalcium phosphate (TCP) scaffolds to achieve controlled protein delivery. Porous TCP scaffolds were fabricated using reticulated polyurethane foam as sacrificial scaffold with a porosity of 70–90 vol %. PCL was coated on sintered porous TCP scaffolds by dipping-drying process. The compressive strength of TCP scaffolds increased significantly after PCL coating. The highest strength of 2.41 MPa at a porosity of 70% was obtained for the TCP scaffold coated with 5% PCL solution. Model protein bovine serum albumin (BSA) was encapsulated efficiently within the PCL coating. The amount of BSA encapsulation was controlled by varying proteins’ composition in the PCL coating. The FTIR analysis confirmed that BSA retained its structural conformation and did not show significant denaturization during PCL coating. The release kinetics in phosphate buffer solution indicated that the protein release was controlled and sustained, and primarily dependant on protein concentration encapsulated in the PCL coating. PMID:19572301

  4. [Study on self-microemulsifying membrane controlled-release drop pill of hawthorn leaves flavonoids].

    PubMed

    Wang, Jin-Xuan; Huang, Hong-Zhang; Li, Ning; Gao, Chong-Kai

    2014-03-01

    To prepare the hawthorn leaves flavonoids self-microemulsifying membrane controlled-release coated drop pill, and to study its release rate in vitro and pharmacokinetics study in vivo. In order to improve the dissolution of hawthorn leaves flavonoids, self-microemulsifying technology was used to prepare the hawthorn leaves flavonoids self-microemulsion. Hawthorn leaves flavonoids self-microemulsifying drop pill was prepared with the PEG 6000. Studies were made on the in vitro release of flavonoids from hawthorn leaves self-micro-emulsifying membrane-moderated coated drop pills and the in vivo pharmacokinetic in rats. The prescription of flavonoids from hawthorn leaves self-micro-emulsifying drop pills was 0.25 g of flavonoids from hawthorn leaves, 0.25 g of iodophenyl maleimide, 0.375 g of polyethylene glycol 400, 0.375 g of cremophor RH 40 and 2 g of polyethylene glycol 6000. The optimized prescription was 4 g of ethyl cellulose 20, 0.64 g of polyethylene glycol 400, 1.8 g of diethyl phthalate, and the weight of coating materials increased by 3.5%. Flavonoids from hawthorn leaves self-micro-emulsifying membrane-moderated coated drop pills complied with the design of sustained-release in 12 h in terms of in vitro release and in vivo pharmacokinetic parameters in rats, and its bioavailability was 2.47 times of quick-release drop pills. Slightly soluble flavonoids from hawthorn leaves could be made into sustained-release preparations by the self-micro-emulsifying and coating technology.

  5. Diffusion-Controlled Drug Release From the Mesoporous Magnesium Carbonate Upsalite(®).

    PubMed

    Zhang, Peng; Zardán Gómez de la Torre, Teresa; Forsgren, Johan; Bergström, Christel A S; Strømme, Maria

    2016-02-01

    In vitro drug release from well-defined particle-size fractions of the mesoporous magnesium carbonate material Upsalite(®) was investigated in detail using ibuprofen, a biopharmaceutics classification system class II drug, as the model compound. The weight of loaded drug corresponded to 30% of the weight of the carrier and the pores were filled to approximately 80%. The incorporated ibuprofen was found to be in an amorphous state and was physisorbed, rather than chemisorbed, to the surfaces of the pore walls. In contrast to ibuprofen in mesoporous silica, there was no detectable drug on the outer surface of the carrier particles. Two ibuprofen doses were loaded into Upsalite(®) particles with size fractions ranging from 25 μm to more than 200 μm. The initial release rate was controlled by the particle size; the dissolution rate of the loaded ibuprofen during this period was more than four times faster than that of the crystalline drug. An extended-release period of about 24 h followed the initial rapid-release period. The features of this extended-release period were dependent on the total drug concentration in the release medium. Detailed analysis of the diffusion of ibuprofen in Upsalite(®) provided the ibuprofen diffusion coefficient (9.8 × 10(-8) cm(2)/s), the constrictivity of the diffusion process (0.47) and the tortuosity of the carrier (15). This relatively high tortuosity value indicates that Upsalite(®) can be used not only to enhance the dissolution rate of poorly soluble drugs but also as a carrier in sustained-release applications by using larger particle sizes or even pellets of the material.

  6. The Effect of Automatic Gain Control Structure and Release Time on Cochlear Implant Speech Intelligibility

    PubMed Central

    Khing, Phyu P.; Swanson, Brett A.; Ambikairajah, Eliathamby

    2013-01-01

    Nucleus cochlear implant systems incorporate a fast-acting front-end automatic gain control (AGC), sometimes called a compression limiter. The objective of the present study was to determine the effect of replacing the front-end compression limiter with a newly proposed envelope profile limiter. A secondary objective was to investigate the effect of AGC speed on cochlear implant speech intelligibility. The envelope profile limiter was located after the filter bank and reduced the gain when the largest of the filter bank envelopes exceeded the compression threshold. The compression threshold was set equal to the saturation level of the loudness growth function (i.e. the envelope level that mapped to the maximum comfortable current level), ensuring that no envelope clipping occurred. To preserve the spectral profile, the same gain was applied to all channels. Experiment 1 compared sentence recognition with the front-end limiter and with the envelope profile limiter, each with two release times (75 and 625 ms). Six implant recipients were tested in quiet and in four-talker babble noise, at a high presentation level of 89 dB SPL. Overall, release time had a larger effect than the AGC type. With both AGC types, speech intelligibility was lower for the 75 ms release time than for the 625 ms release time. With the shorter release time, the envelope profile limiter provided higher group mean scores than the front-end limiter in quiet, but there was no significant difference in noise. Experiment 2 measured sentence recognition in noise as a function of presentation level, from 55 to 89 dB SPL. The envelope profile limiter with 625 ms release time yielded better scores than the front-end limiter with 75 ms release time. A take-home study showed no clear pattern of preferences. It is concluded that the envelope profile limiter is a feasible alternative to a front-end compression limiter. PMID:24312408

  7. Antibiotic-releasing Porous Polymethylmethacrylate Constructs for Osseous Space Maintenance and Infection Control

    PubMed Central

    Shi, Meng; Kretlow, James D.; Nguyen, Anson; Young, Simon; Baggett, L. Scott; Wong, Mark E.; Kasper, F. Kurtis; Mikos, Antonios G.

    2010-01-01

    The use of a strategy involving space maintenance as the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite tissue defects in the craniofacial area, preserves the void volume of bony defects and could promote soft tissue healing prior to the subsequent definitive repair. One of the complications with a biomaterial-based space maintenance approach is local infection, which requires early, effective eradication, ideally through local antibiotic delivery. The purpose of this study is to develop a dual function implant material for maintaining osseous space and releasing an antibiotic to eliminate local infection in bony defects. Colistin, a polymyxin antibiotic, was chosen specifically to address infections with Acinetobacter species, the most common pathogen associated with combat-related traumatic craniofacial injuries. Porous polymethylmethacrylate (PMMA) constructs incorporating poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated by mixing a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid with a carboxymethylcellulose (CMC) hydrogel (40 or 50 wt%) to impart porosity and PLGA microspheres (10 or 15 wt%) loaded with colistin to control drug release. The PMMA/CMC/PLGA construct featured mild setting temperature, controllable surface/bulk porosity by incorporation of the CMC hydrogel, reasonably strong compressive properties, and continuous drug release over a period of 5 weeks with total drug release of 68.1-88.3%, depending on the weight percentage of CMC and PLGA incorporation. The concentration of released colistin was well above its reported minimum inhibitory concentration against susceptible species for 5 weeks. This study provides information on the composition parameters that enable viable porosity characteristics/drug release kinetics of the PMMA/CMC/PLGA construct for the initial space maintenance as part of a two-stage regenerative medicine

  8. Controlled-release panel traps for the Mediterranean fruit fly (Diptera: Tephritidae).

    PubMed

    Leonhardt, B A; Cunningham, R T; Chambers, D L; Avery, J W; Harte, E M

    1994-10-01

    Solid, controlled-release dispensers containing 2 g of the synthetic attractant trimedlure now are used in Jackson traps to detect the Mediterranean fruit fly, Ceratitis capitata (Wiedemann). Panel traps consisting of trimedlure mixed in a sticky substance and spread on the surfaces of a plastic panel are used to delineate the limits of discovered insect infestations in California. We describe the development of controlled-release, polymeric panels that prolong release of trimedlure and a highly attractive analog, ceralure. Attractants were incorporated in a polyethylene matrix to form panels and in a polymer coating on cardboard panels that then were evaluated by biological and chemical assay. In addition, commercial polymer matrix panels were evaluated. Field bioassay tests conducted in Hilo, HI, using released flies and in Guatemala in a natural population showed that the polyethylene matrix panel became brittle and cracked during field exposure and that release rates of the attractants were relatively low. The coated cardboard panels were stable under field conditions and yielded high fly captures for up to 6 wk. Farma Tech commercial panels containing 12.3 and 23.4 g of trimedlure remained highly attractive throughout a 134-d test in Hawaii and appear to be a long-lasting alternative to panels coated with trimedlure in Stikem. The cost of the relatively high dose of trimedlure is offset by the prolonged active life of the panel. Commercial panels from AgriSense (10 g trimedlure and 10 g ceralure) released the attractants at a slower rate and were less attractive.

  9. Modulation of Tenoxicam release from hydrophilic matrix: modulator membrane versus rate-controlling membrane.

    PubMed

    El-Nabarawi, Mohamed Ahmed

    2005-09-01

    This paper describes the preparation of two layered device comprising of tenoxicam containing layer and a drug free membrane layer based on Geomatrix Technology. Our device based on bilaminated films which produced by a casting/solvent evaporation technique. The drug-hydroxypropyl methylcellulose (HPMC) layer was covered by drug free membrane layer composed of a mixture of different ratios of HPMC and ethyl cellulose (EC). The prepared devices were evaluated for thickness, weight, drug content uniformity, water absorption capacity and in-vitro drug release. The films were also evaluated for appearance, smoothness and transparency. The influence of drug free membrane layer composition and thickness on the drug release pattern was studied on 12 devices (D1 to D12). The results indicate that, the release of drug from HPMC matrixes without the drug free membrane layer was fast and follows diffusion controlled mechanism. The release of drug from the devices D1, D4, D9 and D12 follow the same mechanism, while the release of drug from other devices become linear with time (zero order) and extended for long time especially when thickness and the ratio of EC was increased in the drug free membrane layer. From this study it is concluded that, changing the geometry of drug layer by addition of drug free membrane layer and changing its composition and thickness plays an important role in determining whether the drug free membrane layer is rate-controlling or modulator membrane. Hence it can facilitate the development of different pharmaceutical products with different release pattern.

  10. Continuous twin screw granulation of controlled release formulations with various HPMC grades.

    PubMed

    Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

    2016-09-25

    HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC.

  11. Hypoxia-induced angiogenesis is increased by the controlled release of deferoxiamine from gelatin hydrogels.

    PubMed

    Saito, Takashi; Tabata, Yasuhiko

    2014-08-01

    The objective of this study is to design biodegradable hydrogels for the controlled release of deferoxiamine (DFO) and evaluate their biological activity. When the DFO was added to human umbilical vein endothelial cells cultured in 5.0% O2, the level of hypoxia-inducible factor-1α and vascular endothelial growth factor significantly increased compared with that without DFO. The expression of angiogenesis-related genes was accordingly increased by the DFO addition. An aqueous solution of mixed gelatin and DFO was freeze-dried, and dehydrothermally treated at 140°C for 24h to prepare a gelatin hydrogel incorporating DFO. In the release test with phosphate-buffered saline solution (PBS) at 37°C, an initial DFO release of 60% was observed, followed by no release. When placed in PBS containing collagenase, the hydrogel was enzymatically degraded with time, and consequently released DFO in a degradation-dependent manner. After the hydrogel incorporating DFO was injected intramuscularly into a mouse model of hind limb ischemia, the number of new blood vessels formed was significantly higher than that with free DFO and DFO-free hydrogel. It is concluded that the DFO-containing hydrogel shows promising for inducing angiogenesis locally.

  12. Environmental Release Prevention and Control Plan (ERP and CP) annual review and update for 1993

    SciTech Connect

    Jannik, G.T.; Mamatey, A.; Arnett, M.

    1993-10-05

    In the Environmental Release Prevention and Control Plan (ERP and CP), WSRC made a commitment to conduct the following follow-up activities and actions: (1) Complete the action items developed in response to the findings and recommendation of the Environmental Release Prevention Taskteam (WSRC-RP-92-356). (2) Complete all batch and continuous release procedure revisions to incorporate the attributes that WSRC senior management required of each procedure. (3) DOE-SR Assistance Managers and WSRC counterparts to reach consensus and closure on the identified engineered solutions documented in the ERP and CP, develop and drive implementation of facility changes per the agreements. (4) Continue to analyze releases and monitor performance in accordance with the ERP and CP, and utilize the ALARA Release Guides Committee to drive improvements. (5) Conduct annual re-evaluations of the cost benefit analyses of the identified engineered solutions, and identify new options and alternatives for each outfall in response to site mission and facility changes. This report documents the efforts that have been completed over the past year in response to these commitments.

  13. Formulation and drying of alginate bead